Diagnostic Imaging-Obstetrics.pdf

DIAGNOSTIC IMAGING

OBSTETRICS

II

DIAGNOSTIC IMAGING

OBSTETRICS
Paula J. Woodward,

MD

Chief, Genitourinary
Radiology
Armed Forces Institute of Pathology
Washington DC
Adjunct Professor of Radiology
Adjunct Associate Professor of Obstetrics and Gynecology
University of Utah School of Medicine
Salt Lake City, Utah

Anne Kenned~ MD
Director of Women's Imaging
Associate Professor of Radiology
Adjunct Associate Professor of Obstetrics and Gynecology
University of Utah School of Medicine
Salt Lake City, Utah

Roya Sohaey, MD
Director of Ultrasound
Associate Professor of Radiology
Associate Professor of Obstetrics and Gynecology
Oregon Health and Science University
Portland, Oregon

Janice l.B. Byrne, MD
Associate Professor of Obstetrics and Gynecology
Division of Maternal-Fetal Medicine
Adjunct Associate Professor of Pediatrics
Division of Medical Genetics
University of Utah School of Medicine
Salt Lake City, Utah

Karen Y. Oh, MD
Assistant Professor of Radiology
Adjunct Assistant Professor of Obstetrics and Gynecology
Section of Women's Imaging
University of Utah School of Medicine
Salt Lake City, Utah

Michael D. Puchalski, MD
Director of Fetal Cardiac Program
Assistant Professor of Pediatrics
Division of Pediatric Cardiology
University of Utah School of Medicine
Salt Lake City, Utah

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AMIRSYS®
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First Edition
Text - Copyright Paula

J.

Woodward, MD 2005

Drawings - Copyright Amirsys Inc 2005
Compilation - Copyright Amirsys Inc 2005
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or media
or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from Amirsys Inc.

Composition by Amirsys Inc, Salt Lake City, Utah
Printed by Friesens, Altona, Manitoba, Canada
ISBN: 1-4160-2335-6
ISBN: 0-8089-2323-4 (International

English Edition)

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Library of Congress Cataloging-in-Publication

Data

Woodward, Paula J.
Diagnostic imaging-obstetrics
/ text, Paula J. Woodward.1st ed.
p. em.
Includes index.
ISBN 1-4160-2335-6 - ISBN 0-8089-2323-4 (International English ed.)
1. Prenatal diagnosis. 2. Diagnostic imaging. 3. Generative organs, Female--Imaging. I. Title: Obstetrics. II. Title.
RG628.W662005
618.2'0754-dc22
2005023220

IV

To my parents
who were so very proud of me. No kid could have been loved or supported more. They would have considered
this a coffee table book and foisted it upon all their unsuspecting friends.
PJW

To my parents
for giving me opporturiWes that they never had and to my wonderful family Neel, Jay, Tara and Bhupie for
looking after each other while I looked after "the book".

AK

To my husband
David R. Boston and my wonderful children, Haley and Brett, who mean everything to me. Thank you for your
patience, enthusiasm and support. I promise you the same for your adventures.

RS

v

VI

CONTRIBUTORS
Contributing Authors
Kathleen

H. Puglia, MD

Clinical Instructor of Radiology
Section of Women's Imaging
University of Utah School of Medicine
Salt Lake City, Utah

Jade Wong-You-Cheong,

MD

Director of Ultrasound and Genitourinary Radiology
Associate Professor of Radiology
University of Maryland School of Medicine
Baltimore, Maryland

Solange

Antonio

Ulrich Rassner, MD

M. Wyatt, MD

Assistant Professor of Obstetrics and Gynecology
Division of Maternal-Fetal Medicine
Oregon Health and Science University
Portland, Oregon

E. Frias, Jr, MD

Assistant Professor of Obstetrics and Gynecology
Division of Maternal-Fetal Medicine
University of Utah School of Medicine
Salt Lake City, Utah

Neuroradiology Fellow, Department of Radiology
University of Utah School of Medicine
Salt Lake City, Utah

Edward Quigley,
Maria A. Manning,

MD

Junior Scientist, Armed Forces Institute of Pathology
Body Imaging Fellow, George Washington University
Washington DC

Michael
Deborah

Arnold, MD

Clinical Instructor of Radiology
Oregon Health and Science University
Portland, Oregon

Maureen

P. Federle, MD, FACR

Chief, Abdominal Imaging
Professor of Radiology
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania

Harry Hatasaka, MD

S. Filipek, MD

Staff Radiologist
Legacy Health Systems
Emanual Hospital
Portland, Oregon

MD

Resident, Department of Radiology
University of Utah School of Medicine
Salt Lake City, Utah

Associate Professor of Obstetrics and Gynecology
Division of Reproductive Endocrinology and Infertility
University of Utah School of Medicine
Salt Lake City, Utah

Case Contributors
Catherine Babcook, MD
Michael Bamshad, MD
Zach Bland, MD
Susan Blaser, MD
Jessica Comstock, MD
Deborah Friedman, MD
Gary Hedlund, DO
H. Eugene Hoyme, MD
Ed Klatt, MD

Gael Lonergan, MD
Amy Lowichik, MD
Bryan Oshiro, MD
Kathleen O'Neil, MD
Angelica Putnam, MD
Nancy Rose, MD
Norman Silverman, MD
Julianna Szakacs, MD
Sandra Linne White, MD
Vll

VlIl

DIAGNOSTIC IMAGING: OBSTETRICS

We at Amirsys and Elsevier are proud to present Diagnostic Imaging: Obstetrics, the sixth volume in our acclaimed
Diagnostic Imaging (DI) series. This precedent-setting, image- and graphic-packed series began with David Stoller's DI:
Orthopaedics. The next four volumes, DI: Brain, DI: Head & Neck, DI: Abdomen and DI: Spine are now joined by Paula
Woodward's magnificent textbook DI: Obstetrics. The current practice of imaging in obstetrics covers a broad range of complex
subjects. Dr. Paula Woodward, one of the world's preeminent authorities in obstetrical imaging and her co-leads Drs. Anne
Kennedy and Roya Sohaey along with their team of experts have compiled an engrossing mixture of highly refined color
graphics, ultrasound, MR, clinical and gross pathology photos of obstetrical diseases the likes of which has not been seen before.
Again, the unique bulleted format of the Diagnostic Imaging series allows our authors to present approximately twice the
information and four times the images per diagnosis compared to the old-fashioned traditional prose textbook. All the
Diagnostic Imaging books follow the same format, which means the same information is in the same place: Every time! In every
organ system. The innovative visual differential diagnosis "thumbnail" that provides an at-a-glance look at entities that can
mimic the diagnosis in question has been highly popular. "Key Facts" boxes provide a succinct summary for quick, easy review.
In summary, Diagnostic Imaging: Obstetrics is a product designed with you, the reader, in mind. Today's typical practice
settings demand efficiency in both image interpretation and learning. We think you'll find this new DI: Obstetrics volume a
highly efficient and wonderfully rich resource that will significantly enhance your practice.
Enjoy!

Anne G. Osborn, MD
Executive Vice President & Editor-in-Chief, Amirsys Inc.
H. Ric Harnsberger, MD
CEO & Chairman, Amirsys Inc.

IX

x

FOREWORD

What
published.
fascinating
The format

a great book! I have long felt that most
However, Dr. Paula Woodward and her
book on fetal and perinatal ultrasound.
is concise, efficient, and the illustrations

textbooks were unattractive, boring, and out of date by the time they were
colleagues have succeeded in organizing an innovative, up-to-date, and
It is obvious that a great deal of careful planning has gone into this book.
are magnificent.

I know Dr. Woodward very well from her days at the University of Utah and that she has devoted her professional life to
medical education.
She has assembled an impressive team of co-authors who are experts in radiology, high-risk obstetrics,
genetics, prenatal diagnosis, pediatric cardiology, and perinatal pathology who all have extensive experience in fetal imaging,
disease processes, and patient care.
This is a book of differential diagnoses and actual cases that both experts and those of us with less expertise will all find
useful. Each image has been selected to illustrate an important point. The standardized format for rapid access to multiple
examples has resulted in a comprehensive and clinically useful resource. I know of no other textbook on this topic that is as
authoritative and rich in illustrations.
Diagnostic Imaging: Obstetrics is surely destined to become a "must have" for anyone
performing obstetric ultrasound.

James R. Scott, MD, Editor
Obstetrics & Gynecology
Professor and Chair Emeritus
Department of Obstetrics and Gynecology
University of Utah School of Medicine

Xl

Xli

PREFACE

I said I would never write a textbook. Why would I want to? There are a lot of textbooks out there on OB ultrasound; do
we really need another one? Also, quite frankly, I don't like to write prose (I know that is a sacrilege for someone who has chosen
an academic career, but it is the truth). There are those long, mandatory introductory paragraphs that prattle on but deliver little
actual usable information. There are strict restrictions on the number of images (which is the most important part) and you can
forget most of those color photographs. The writing/editing process is seemingly endless, and by the time it finally gets to print, it
is out-of-date. I definitely, didn't want to do that.
Although I have never enjoyed writing, I do love to lecture and can spend hours on the perfect word slide. The lecture
format, by its very nature, has to be compacted. The information is concise, bulleted, heavily illustrated, and with the right
finesse, will flow seamlessly.
No, I never wanted to write a textbook, and was on
and Ric Harnsberger approached me about participating
concept of writing was infectious (much like my process
on board. As it turns out, it is one of the most gratifying

record as such, with all my friends. My life changed when Anne Osborn
in the PocketRadiologist series. Their enthusiasm for this new template
for producing a lecture they said), and so I somewhat reluctantly came
things I have done.

The Amirsys Diagnostic Imaging series uses a highly structured, information dense, bulleted style that yields more "pearls per
pound" than a standard prose style textbook. Each diagnosis is richly illustrated including graphics, fetal MRI, 3D ultrasound as
well as conventional grayscale and Doppler imaging. Many diagnoses include pathologic and/or clinical correlation. The end
result is something unique and very different than any other OB ultrasound textbook.
The true joy for me in doing this book was the opportunity to put together an extraordinary team of fetal imagers, from
across the country. I have long believed patients are best served when a multidisciplinary team works in concert. I took that
approach in assembling my team, which includes experts in radiology, perinatology, cardiology, pathology and genetics. We have
collectively pored over thousands of images, selecting each one to illustrate an important clinical point.
I am indebted to everyone on the team for their hard work. I, especially, want to thank my two co-leads (and dear friends)
Anne Kennedy and Roya Sohaey, without whom I would have never undertaken this project. It is always a kick when we are
together. I also want to acknowledge Rich Coombs, the gifted illustrator, and the extraordinarily helpful staff at Amirsys for all
their assistance. Finally, on behalf of all of the authors, I want to thank all the sonographers who helped us to so richly illustrate
this book.
I hope you enjoy this textbook I said I would never write, or as I like to think of it, the world's longest word slide.
Paula J. Woodward, MD
Chief, Genitourinary Radiology
Armed Forces Institute of Pathology
Washington DC
Adjunct Professor of Radiology
Adjunct Associate Professor of Obstetrics and Gynecology
University of Utah School of Medicine
Salt Lake City, Utah

Xlll

XIV

ACKNOWLEDGMENTS
Illustrations
Richard Coombs, MS
Lane R. Bennion, MS

Art Direction and Design
Lane R. Bennion, MS
Richard Coombs, MS

Image/Text Editing
Angie O. Mascarenaz
Kaerli Main

Medical Text Editing
William Zwiebel, MO

Case Management
Eric Brinton
Roth LaFleur
David Harnsberger

Sonographers
Jeanne Baker, ROMS
Oscar del Barco, ROMS
Cherie Bunk, ROMS
Naomi Cummings, ROMS
Susan Oiston, ROMS
Kathy Donner, ROMS
Pam Guy, ROMS
Deanna Hecker, ROMS
Deborah Hogge, ROMS
Randy Lawson, ROMS
Adrian Lethbridge, ROMS
Ken Mattina, ROMS
Angie McDonald, ROMS
Katie Mullanix, ROMS
Sami Newman, ROMS
Mary Ellen Peterson, ROMS
Neda Razavi, ROMS
Brooke Roster, ROMS
Christine Sahn, ROMS
Chrissy Schutzer, ROMS
Lety Seals, ROMS
Jo Semon, ROMS
Fariba Tehranchi, ROMS
Catherine Townsend, ROMS
Becky Weintraub, ROMS
Ida Williams, ROMS
JoOee Winter, ROMS
Amy Young, ROMS
Ruth Zollinger, ROMS

Production lead
Melissa A. Hoopes

xv

XVI

SECTIONS
First Trimester
Brain
Spine

[I]

rn
rn

Face & Neck [1]
Chest ~
Heart

lliJ

Abdominal Wall [2]

rn:J

Gastrointestinal
Genitourinary

~

Musculoskeletal

[Q]

Umbilical Cord

[]

Placenta & Membranes
Multiple Gestations
Chromosomes

[11]
[TI]

IHl
[j]

Syndromes & Multisystem Disorders
Infection

[§]

Fluid, Growth and Well-Being
Maternal Conditions in Pregnancy

[ZJ
~
XVll

XV 111

TABLE OF CONTENTS
Acrania
Paula f.

SECTION 1
First Trimester

Occipital Encephalocele
Paula f. Woodward, MD & Edward

Introduction and Overview
Normal Early Pregnancy & Imaging

2-16

Karen Y. Oh, MD

1-2

2-18

Chiari II Malformation
Roya Sohaey, MD

Pregnancy

2-22

Aqueductal Stenosis
Paula f. Woodward, MD

First Trimester
1-6

Dandy- Walker Continuum:

Classic

2-26

Ulrich Rassner, MD & Karen Y. Oh, MD

Anne Kennedy, MD

Perigestational

2-12
Quigley, MD

Frontal Encephalocele

Anne Kennedy, MD

Anembryonic

2-10
Woodward, MD

Hemorrhage

1-10

Dandy-Walker

Continuum:

Variant

2-30

Ulrich Rassner, MD & Karen Y. Oh, MD

Roya Sohaey, MD

Tubal Ectopic

1-14

Mega Cisterna Magna

2-32

Karen Y. Oh, MD

Roya Sohaey, MD

Interstitial Ectopic
Paula f. Woodward, MD

1-18

Cervical Ectopic

1-22

Agenesis of the Corpus Callosum
Paula f. Woodward, MD

2-36

1-26

Mild Ventriculomegaly

2-40

Abdominal Ectopic
Karen Y. Oh, MD

Roya Sohaey, MD & Maureen S.Filipek, MD

C-section Scar Ectopic

1-28

Karen Y. Oh, MD

Alobar Holoprosencephaly

Pregnancy

1-30

Semilobar, Lobar Holoprosencephaly

2-46

Anne Kennedy, MD

Increased Nuchal Translucency

1-32

Septo-Optic Dysplasia

2-50

Anne Kennedy, MD

Roya Sohaey, MD

Ductus Venosus

1-36

Anne Kennedy, MD

Absent Cavum Septi Pellucidi

2-54

Karen Y. Oh, MD

2-56

Hydranencephaly
Kathleen H. Puglia, MD & Anne Kennedy, MD

SECTION 2
Brain

Encephalomalacia
Intracranial

& Imaging

2-60

Kathleen H. Puglia, MD & Anne Kennedy, MD

Introduction and Overview

Hemorrhage

2-2

Choroid Plexus Cyst

2-68

Roya Sohaey, MD

Arachnoid Cyst

2-72

Anne Kennedy, MD

Brain
Exencephaly, Anencephaly
Paula f. Woodward, MD

2-64

Kathleen H. Puglia, MD & Anne Kennedy, MD

Karen Y. Oh, MD

XIX

2-42

Anne Kennedy, MD

Karen Y. Oh, MD

Brain Development

2-34

Anne Kennedy, MD

Karen Y. Oh, MD

Heterotopic

Rhomben cephalosyna psis

Glioependymal
2-6

Cyst

Anne Kennedy, MD

2-76

2-80

Schizencephaly

Midface Anomalies

2-84

Microcephaly

Solange M. Wyatt, MD & Roya Sohaey, MD

Aprosencephaly

2-86

4-38

Hypertelorism
Solange M. Wyatt, MD & Roya Sohaey, MD

Janice L. B. Byrne, MD

2-90

Craniosynostosis

Orbital Tumors
Paula f. Woodward,

Janice L. B. Byrne, MD

2-94

Vein of Galen Malformation

4-42
MD

4-44

Scalp Masses
Anne Kennedy, MD

Karen Y. Oh, MD

Arteriovenous

4-34

Hypotelorism

Roya Sohaey, MD

Atelencephaly,

4-30

Roya Sohaey, MD

Karen Y. Oh, MD

2-98

Fistula

4-48

Cystic Hygroma
Roya Sohaey, MD

Anne Kennedy, MD

2-102

CNS Tumors

4-52

Goiter
Anne Kennedy, MD

Paula J. Woodward, MD

4-56

Cervical Teratoma

SECTION 3

I

Spine
Introduction
Karen Y. Oh, MD & Paula

f.

Woodw",d,

M:ECTION 5
Chest

and Overview

& Imaging

Spine Development

I P,ulal.

3-2

Woodward, MD

Introduction

Chest Development & Imaging
Paula f. Woodward, MD

Spine
3-6

Spina Bifida

Pulmonary Hypoplasia
Paula f. Woodward, MD

3-14

Congenital Diaphragmatic
Paula f. Woodward, MD

Hernia

5-10

3-18

Cystic Adenomatoid Malformation
Paula f. Woodward, MD

5-14

3-22

Bronchopulmonary
Paula f. Woodward,

5-18

Anne Kennedy, MD

Kyphosis, Scoliosis
Roya Sohaey, MD

Sacrococcygeal Teratoma
Paula f. Woodward, MD

5-6

3-10
MD & Edward Quigley, MD

Caudal Regression Sequence

Sequestration
MD

5-22

Pleural Effusion
Roya Sohaey, MD

SECTION 4
Face & Neck
Introduction
Facial Development

and Overview

& Imaging

4-2

Roya Sohaey, MD

5-26

Teratoma, Chest
Paula f. Woodward,

MD

Tracheal Atresia
Paula f. Woodward,

MD

5-28
5-30

Lymphangioma
Roya Sohaey, MD

SECTION 6
Heart

Face & Neck
4-6

Cleft Lip, Palate

5-2

Chest

Roya Sohaey, MD

Iniencephaly
Paula f. Woodward,

and Overview

Roya Sohaey, MD

Absent Nasal Bone

4-10

Solange M. Wyatt, MD & Roya Sohaey, MD

4-14

Micrognathia
Anne Kennedy, MD

Introduction
Cardiac Development

& Imaging

Heart

Anne Kennedy, MD

Epignathus
Paula f. Woodward,

4-22

Solange M. Wyatt, MD & Roya Sohaey, MD

xx

Echogenic Cardiac Focus

6-6

Roya Sohaey, MD

MD

Ear Anomalies

6-2

Anne Kennedy, MD

4-18

Macroglossia

and Overview

4-26

Foramen Ovale Aneurysm
Anne Kennedy, MD & Michael D. Puchalski, MD

6-8

XXI

Asphyxiating

Kidney
Renal Developmental

Variants

Thoracic Dysplasia

10-14

Janice L. B. Byrne, MD

9-6

Roya Sohaey, MD

Campomelic

Dysplasia

10-16

Janice L. B. Byrne, MD

Duplicated Collecting System

9-10

Kathleen H. Puglia, MD & Anne Kennedy, MD

Janice L. B. Byrne, MD

9-14

Mild Pelviectasis
Roya Sohaey, MD & Deborah Arnold, MD

Ureteropelvic Junction

Obstruction

10-18

Hypophosphatasia
Osteogenesis

10-20

Imperfecta

Janice L. B. Byrne, MD

9-18

Roya Sohaey, MD

10-24

Short Rib-Polydactyly
Janice L. B. Byrne, MD

Obstructive Cystic Dysplasia

9-22

Roya Sohaey, MD & Deborah Arnold, MD

Thanatophoric

10-26

Dysplasia

Janice L. B. Byrne, MD

9-26

Renal Agenesis
Anne Kennedy, MD

Multicystic Dysplastic Kidney

Extremity Malformations

9-30

10-30

Clubfoot

Roya Sohaey, MD

Autosomal Recessive Polycystic Kidney Disease

9-34

Rockerbottom

Anne Kennedy, MD

9-38

Mesoblastic Nephroma
Paula f. Woodward, MD

Roya Sohaey, MD

10-34

Foot

Roya Sohaey, MD

10-36

Sandal Gap Foot
Roya Sohaey, MD

Neuroblastoma
Paula f. Woodward,

10-38

Radial Ray Malformation

Adrenal

Anne Kennedy, MD

9-42
MD

10-42

Polydactyly
Paula J. Woodward, MD

Posterior Urethral Valves

Janice L. B. Byrne, MD

Clinodactyly

9-50

Ectrodactyly

9-52

Arthrogryposis,

9-56

Multiple Pterygium Syndrome

Karen Y. Oh, MD & Paula J. Woodward, MD

Ureterocele
Kathleen H. Puglia, MD & Anne Kennedy, MD

Urachal Anomalies
Paula f. Woodward, MD

Roya Sohaey, MD

10-52

Janice L. B. Byrne, MD

Akinesia Sequence

10-54

Janice L. B. Byrne, MD

10-58

Janice L. B. Byrne, MD

Genitalia

SECTION 11
Umbilic::al Cord

9-58

Ambiguous Genitalia

10-50

9-46

Kathleen H. Puglia, MD & Anne Kennedy, MD

Prune Belly Syndrome

10-46

Syndactyly

Bladder

Roya Sohaey, MD & Maureen S. Filipek, MD

9-62

Hypospadias
Roya Sohaey, MD

9-64

Hydrocele
Roya Sohaey, MD

Introduction

Normal Umbilical Cord & Doppler

Umbilical Cord

Roya Sohaey, MD

9-68

Ovarian Cyst
Kathleen H. Puglia, MD & Paula f. Woodward, MD

Abnormal Cord Doppler

Umbilical Cord Cyst
Umbilical Cord Aneurysms
10-2

Persistent Right Umbilical Vein

10-6

Vasa Previa

Janice L. B. Byrne, MD

XXll

11-18

Anne Kennedy, MD

Janice L. B. Byrne, MD

Janice L. B. Byrne, MD

11-14

Roya Sohaey, MD

Dysplasias

Amelia, Micromelia

11-10

Roya Sohaey, MD

SECTION 10
Musc::uloskeletal

Achondroplasia

11-6

Anne Kennedy, MD

Single Umbilical Artery

Achondrogenesis

11-2

Anne Kennedy, MD

9-66

Testicular Torsion

and Overview

10-10

11-22

Roya Sohaey, MD

11-24

Roya Sohaey, MD

Nuchal Cord
Paula J. Woodward, MD

11-26

SECTION 12
Placenta & Membranes

SECTION 14
Chromosomes

Placenta & Membranes

14-2

Trisomy 21

Introduction and Overview

Roya Sohaey, MD

12-2

Roya Sohaey, MD

14-6

Trisomy 18
Roya Sohaey, MD

Placental Sonolucencies

Roya Sohaey, MD

12-6

Roya Sohaey, MD

Chorioamniotic

Separation

12-10
12-12

Roya Sohaey, MD

Velamentous Cord

Turner Syndrome (XO)

14-14

Roya Sohaey, MD

14-18

Triploidy
Paula J. Woodward, MD

Roya Sohaey, MD & Maureen S. Filipek, MD

Placenta Previa

14-10

Trisomy 13

Placenta & Membranes

14-22

Monosomy 21
Kathleen H. Puglia, MD

12-16

Roya Sohaey, MD

Placental Abruption

12-18

Roya Sohaey, MD

Succenturiate Lobe

12-22

Roya Sohaey, MD

Circumvallate Placenta

12-24

Roya Sohaey, MD & Deborah Arnold, MD

Battledore Placenta

12-26

Roya Sohaey, MD

Placentomegaly

12-28

Roya Sohaey, MD

Placenta Accreta Spectrum

12-30

Kathleen H. Puglia, MD & Paula J. Woodward, MD

Chorioangioma

12-34

Paula J. Woodward, MD

Complete Hydatidiform Mole

12-38

Roya Sohaey, MD

Invasive Mole

12-42

Roya Sohaey, MD

Choriocarcinoma

12-44

Roya Sohaey, MD

SECTION 15
Syndromes & Multisystem
Disorders
Aicardi Syndrome

15-2

Janice L. B. Byrne, MD

Amniotic Band Syndrome

15-4

Kathleen H. Puglia, MD & Paula J. Woodward, MD

Apert Syndrome

15-8

Janice L. B. Byrne, MD

Beckwith- Wiedemann Syndrome

15-10

Janice L. B. Byrne, MD

Carpenter Syndrome

15-12

Janice L. B. Byrne, MD

Cornelia de Lange Syndrome

15-14

Janice L. B. Byrne, MD

Cystic Fibrosis

15-16

Paula J. Woodward, MD

Fryns Syndrome

15-18

Janice L. B. Byrne, MD

Joubert Syndrome

15-20

Anne Kennedy, MD

SECTION 13
Multiple Gestations
Dichorionic Diamniotic Twins

Meckel-Gruber Syndrome
Pierre Robin Syndrome
13-2

Diamniotic Twins

13-6

Monochorionic

Monoamniotic

15-28

Janice L. B. Byrne, MD

Smith-Lemli-Opitz Syndrome

Anne Kennedy, MD

Twins

13-10
13-14

Twin-Twin Transfusion Syndrome

15-36

Karen Y. Oh, MD

VACTERLAssociation

Anne Kennedy, MD

13-18

15-32

Janice L. B. Byrne, MD

Tuberous Sclerosis

Anne Kennedy, MD

Discordant Twin Growth

15-26

Janice L. B. Byrne, MD

Sirenomelia

Anne Kennedy, MD

Monochorionic

15-22

Paula J. Woodward, MD

15-40

Janice L. B. Byrne, MD

Anne Kennedy, MD

Twin Reversed Arterial Perfusion

13-22

SECTION 16
Infection

Anne Kennedy, MD

Conjoined Twins

13-26

Anne Kennedy, MD

Triplets and Beyond

13-30

Cytomegalovirus

16-2

Janice L. B. Byrne, MD

Janice L. B. Byrne, MD

XXlll

16-6

Parvovirus

Incidental

Ovarian Mass

16-8

Toxoplasmosis

Torsion

18-38

Paula J. Woodward, MD & Maria A. Manning, MD

Janice L. B. Byrne, MD

Varicella

16-10

Janice L. B. Byrne, MD

Teratogens
Fetal Alcohol Syndrome

SECTION 17

Janice L. B. Byrne, MD

17-6

Oligohydramnios

Warfarin (Coumadin)

18-46

Janice L. B. Byrne, MD

Roya Sohaey, MD

17-10

Symmetric IUGR

Miscellaneous

Anne Kennedy, MD

17-14

Asymmetric IUGR
Anne Kennedy, MD

Acute Abdomen in Pregnancy

18-48

Anne Kennedy, MD

17-18

Macrosomia
Roya Sohaey, MD

Diabetes

18-52

Janice L. B. Byrne, MD

17-20

Biophysical Profile
Roya Sohaey, MD

Maternal Hydronephrosis

18-56

Anne Kennedy, MD

17-24

MCA Doppler
Anne Kennedy, MD

HELLP Syndrome

18-60

Michael P. Federle, MD

17-28

Uterine Artery Doppler
Anne Kennedy, MD

Ovarian Vein Thrombosis

18-64

Paula J. Woodward, MD & Maria A. Manning, MD

Hydrops

17 -32

Roya Sohaey, MD

Rh Incompatibility
Antonio E. Frias Jr., MD & Karen Y. Oh, MD

SECTION 18

Maternal Conditions in
Pregnancy
Uterus
18-2

Cervix

Roya Sohaey, MD

18-6

Uterine Duplication
Paula J. Woodward, MD

18-10

Leiomyoma
Paula J. Woodward, MD & Maria A. Manning, MD

18-14

Synechiae
Paula J. Woodward, MD & Maria A. Manning, MD

18-16

Uterine Rupture
Kathleen H. Puglia, MD & Anne Kennedy, MD

Retained Products of Conception

18-20

Paula J. Woodward, MD & Maria A. Manning, MD

18-22

Endometritis
Paula J. Woodward, MD & Maria A. Manning, MD

Ovary
Corpus Luteum Cyst

18-24

Karen Y. Oh, MD

Hyperstimulation

18-44

Valproic Acid
Janice L. B. Byrne, MD

Roya Sohaey, MD

Incompetent

18-42

Hydantoin
17-2

Polyhydramnios

18-40

Janice L. B. Byrne, MD

Fluid, Growth and Well-Being

Syndrome

18-26

Karen Y. Oh, MD & Harry Hatasaka, MD

Theca Lutein Cysts
Karen Y. Oh, MD & Paula J. Woodward, MD

XXIV

18-34

Karen y. Oh, MD & Antonio E. Frias Jr., MD

Janice L. B. Byrne, MD

18-30

18-66

xxv

XXVI

DIAGNOSTIC IMAGING

OBSTETRICS

XXVll

XXVIII

SECTION 1: First Trimester

Introduction

and Overview

Normal Early Pregnancy & Imaging

1-2

First Trimester
Anembryonic Pregnancy
Perigestational Hemorrhage
Tubal Ectopic
Interstitial Ectopic
Cervical Ectopic
Abdominal Ectopic
C-section Scar Ectopic
Heterotopic Pregnancy
Increased Nuchal Translucency
Ductus Venosus

1-6
1-10
1-14

1-18
1-22
1-26
1-28
1-30
1-32
1-36

:~~: I

NORMAL

EARLY PREGNANCY

Graphic shows the DOSS. Decidua parietalis (arrow)
lines the uterine cavity and decidua capsularis (open
arrow) covers the gestational sac. The decidua basalis is
the site of the developing placenta (curved arrow).

ITerminology
Definitions
• First trimester: From fertilization of ovum to end of
13th post-menstrual week

IAnatomy-Based

Imaging Issues

Key Concepts or Questions
• Sonographic signs of intrauterine pregnancy (IUP)
important to recognize
• Intradecidual sac sign (lOSS), earliest sign of IUP
o Seen by 4-4.5 weeks after last menstrual period
(LMP) by endovaginal ultrasound
o Fertilized ovum implants into decidualized
endometrium
o Gestational sac "burrows" into endometrium
o Echogenic ring is seen eccentric to linear interface of
endometrial surfaces
• Double decidual sac sign (DDSS)
o Described as earliest transabdominal sign of IUP
o Two echogenic rings seen within endometrial cavity
o Decidua parietalis
• Outer ring, decidual lining of uterine cavity
o Decidual capsularis
• Inner ring, covering free margin of gestational sac
o Decidua basalis
• Endometrial "base" of sac
• Decidua basalis + chorionic frondosum forms
placenta
• Development of yolk sac
o Presence of a yolk sac within a gestational scan
confirms IUP
o Seen by 5-5.5 weeks after LMP
o Round and echogenic
o Amnion develops embryologically before yolk sac,
but yolk sac is easier to see
o Number of yolk sacs = number of amnions
• In multiple gestations, count yolk sacs to
determine amnionicity
• Embryo

& IMAGING

Endovaginal ultrasound shows the earliest appearances
of an IUP The gestational sac (curved arrow)"burrows"
into the endometrium forming the lOSS. Two echogenic
rings (arrows) form the DOSS.

o First seen as focal thickening on yolk sac
o "Diamond ring" sign
• Embryo appears as echogenic "diamond" on top of
yolk sac
o "Double bleb" sign
• Yolk sac and amniotic sac
• Embryo is in amniotic sac, immediately adjacent
to yolk sac
o Distinct embryo with cardiac activity seen by 6-6.5
weeks
• 5 mm is discriminatory value for presence of heart
beat
• "5 alive" rule: If heartbeat no present by 5 mm '*
demise

Imaging Approaches
• Endovaginal ultrasound is mainstay of early pregnancy
imaging
o Well-established developmental stages, excellent
resolution
• Transabdominal ultrasound
o Used in trials of first trimester screening
o Excellent for rapid confirmation of live IUP
• Doppler
o Use of pulsed Doppler avoided in first trimester
• Concerns regarding heating/embryonic damage
o Limited color Doppler may be used
o "Ring of fire" appearance described as circle of
increased flow on color Doppler
• Nonspecific finding
• Seen in normal trophoblastic tissue around
embryo
• Seen with ectopic gestation (lack of flow does not
rule out ectopic)
• Seen in ovary, surrounding normal corpus luteum
• M-mode: Used to document cardiac activity in embryo
• MRI: Current recommendations are to avoid MRI
during first trimester, as effects on developing embryo

unknown
• CT: Ionizing radiation
o May still use depending on clinical circumstance
(e.g. trauma)

NORMAL EARLY PREGNANCY & IMAGING
Key Facts
Normal Early Pregnancy Milestones
•
•
•
•
•
•

lntradecidual sac sign (IDSS): 4-4.5 wks
Yolk sac: 5-5.5 wks
Embryo with heart beat: 6-6.5 wks
Double bleb sign: Yolk sac + amniotic sac
Embryo forms within amnion
Must determine chorionicity/amnionicity
in multiple
gestations
umber of yolk sacs = number of amnions

Failed 1st Trimester Pregnancy
• Normal milestones
normal pregnancy
• Mean sac diameter
• Mean sac diameter
• If embryo ~ 5mm:

are clear and must be met for
development
~ 10 mm: Must see yolk sac
~ 18 mm: Must see embryo
Cardiac activity must be seen

o Even with fetus in beam, radiation dose below
threshold for concern
• In author's institution abdominopelvic CT dose
approximates 14mGy; threshold for concern is >
100 mGy

Imaging Protocols
• Measure mean sac diameter (MSD)
o Measure sonolucent area only, do not include
echogenic chorionic rim
o Measure diameter in 3 planes, average of these
measurements = MSD
• Measure crown rump length (CRL)
o Most accurate method to date pregnancy from 6-10
weeks
o Use CRL as soon as embryo is visible
o Measure longest axis of embryo
• Be careful not to include yolk sac
o Biological variation does not become significant
until> 12 weeks
• Evaluate yolk sac
o Look for sac outside amnion
o Shape should be spherical, diameter :$ 6 mm
o Thin-walled
• Crenelated, calcified or thick wall abnormal
o Becomes obliterated as amnion fuses with chorion at
"" 14 weeks
• Do not just measure IUP, look at anatomy
o Many anomalies may be detected in 1st trimester
• Anencephaly, acrania, holoprosencephaly
• Cystic hygroma
• Abdominal wall defects, be cautious about
omphalocele before 12 weeks

Normal Measurements
•
•
•
•
•

MSD increases by about 1mm per day
Sac diameter should be about 1cm longer than CRL
Cord length approximates embryo length
Nuchal translucency < 3 mm (11-14 weeks)
Embryonic heart rate
o < 6 weeks, 110-115 beats per min
o By 8 weeks, 144-159 beats per min
o > 9 weeks, 137-144 beats per min

• Failure to meet any of the above ~ failed pregnancy

Potential Pitfalls
• Mistaking yolk sac for embryo
• Mistaking subchorionic hemorrhage for gestational
sac
• Missing multiple gestational sacs
• Pseudosac of ectopic pregnancy
Fluid collection central within endometrial cavity
• Normal rhombencephalon
for cystic brain mass
• Physiologic bowel herniation for omphalocele

First Trimester Screening For Aneuploidy
• Nuchal translucency
• Ductus venosus flow
• Nasal bone

oRate < 90 bpm = embryonic bradycardia
• Screening for aneuploidy
o Nuchal translucency
• < 3 mm by strict standardized measuring
techniques
o Ductus venosus
• Should be continuous forward flow throughout
cardiac cycle
• Triphasic waveform
o Nasal bone
• Should see nasal bone separate from skin

I Pathology-Based Imaging Issues
Key Concepts or Questions
•
•
•
•
•
•

Is there an intrauterine gestation?
Is there an ectopic gestation?
How many gestational sacs are there?
If multiple sacs, what is chorionicity, amnionicity?
Is there a yolk sac?
Is there a normal embryo?

I Embryology
Embryologic

Events

• Embryo
o Fusion of ovum + sperm ~ zygote
o Cleavage of zygote => formation of morula
o Central fluid-filled space in morula ~ blastocystic
cavity, which separates trophoblast from inner cell
mass
• Trophoblast ~ embryonic part of placenta
• Inner cell mass (embryoblast ) ~ primordium of
embryo
o Embryoblast ~ bilaminar embryonic disc
o Embryonic disc ~ three dimensional, C-shaped
embryo by beginning of 6th post-menstrual week
• Undergoes cranial, caudal, lateral folding
o Neural tube closes
• Caudal neuropore closes embryonic day 26
(5th-6th post-menstrual week)

NORMAL EARLY PREGNANCY

Sagittal ultrasound shows normal features that may be
mistaken for pathology The rhombencephalon
(arrows)
is a precursor of normal posterior fossa structures.
Curved arrow shows physiologic bowel herniaUon.

•

•

•

•

o Heart partitioned by end of 8th post-menstrual week
• Cardiac activity seen before partitioning complete
• Cardiac activity should be present once embryo =
5 mm in length
o Limb buds
• Visible by 8-9 post-menstrual weeks
• Movement seen by 9-10 post-menstrual weeks
o Embryo is recognizably "human" by end of 10th
week
Placenta
o Anatomic arrangements for maternofetal exchange
are present by end of 5th post-menstrual week
Cord fully formed with established coiling of vessels
by 9 weeks
o Cord formed by fusion of vitelline duct, body stalk,
yolk sac, allantois
Bowel herniation
o Bowel grows rapidly, volume greater than embryo
therefore herniates into base of cord
o Bowel undergoes rotation within cord, then returns
to abdominal cavity
o Liver never herniates normally
Multiple gestations: Type of twinning depends on
number of zygotes and timing of division
o Dizygotic twins: Two fertilized ova
• All dichorionic, diamniotic
o Monozygotic: Chorionicity and amnionicity
determined by timing of zygote division
• Before 3rd day post conception ~ dichorionic,
diamniotic
• 4th-8th days post conception => monochorionic,
diamniotic
• Cleavage of inner cell mass of blastocyst after 8th
day post conception => monochorionic,
monoamniotic
• Incomplete cleavage of embryonic disc after 13th
day post conception => conjoined twins

Practical Implications
• Rhombencephalon
is normal
o Lucency in back of head where hindbrain is forming
o Not to be confused with intracranial cyst, posterior
fossa mass

& IMAGING

Axial color Doppler ultrasound shows a "physiologic
omphalocele"
(arrow) due to normal herniation or
bowel loops into the base of the umbilical cord. Gawel
returns 10 the abdominal cavity by 72 weeks.

• Physiologic bowel herniation is normal < 12 weeks
o Do not confuse with omphalocele
o Presence of herniated liver is never normal, and if
seen, indicates and omphalocele
• Do not confuse normal unfused amnion for skin when
performing nuchal thickness measurements

I Clinical Implications
Human chorionic gonadotropin (hCG)
• Normal pregnancy results in t hCG
• Discriminatory level of hCG can be very useful in
triage of pain and bleeding in early pregnancy
o If hCG > 2,000 IU (3rd internation reference
preparation) expect to see IUP
• Triage decision tree
o Empty uterus with hCG > 2,000
• Differential diagnosis is ectopic pregnancy vs
spontaneous abortion
• If signs of ectopic pregnancy => methotrexate vs.
surgery
• If patient is stable, with no sonographic features
of ectopic pregnancy, follow with serial hCG, US
• Empty uterus with hCG < 2,000
o Differential diagnosis is ectopic pregnancy vs.
spontaneous abortion vs. normal early pregnancy
o Look for signs of ectopic, if present treat accordingly
o If no signs ectopic follow with serial hCG, US
o In a normal early 1st trimester pregnancy hCG
should double every 2-3 days
• Hydatidiform mole has markedly elevated hCG

I Related References
1.

2.
3.

Fong KW et al: Detection of fetal structural abnormalities
with US during early pregnancy. Radiographies.
24(1):157-74,2004
Demianczuk NN et al: The use of first trimester ultrasound.
J Obstet Gynaecol Can. 25(10):864-75, 2003
Hata T et al: Assessment of embryonic anatomy at 6-8
weeks of gestation by intrauterine and transvaginal
sonography. Hum Reprod. 12(9):1873-6, 1997

NORMAL EARLY PREGNANCY

& IMAGING

IIMAGE GALLERY
(Left) Endovaginal
ultrasound shows the
embryonic disc (curved
arrow) between the yolk sac
(arrow) and amnion (open
arrow). All of these
structures are within the
chorionic sac. (Right)
Endovaginal ultrasound
shows the ease with which
chorionicity and amnionicity
can be determined in the
first trimester. There are 2
chorionic sacs and 3 yolk
sacs (implying 3 amnions),
therefore this is a
dichorionic, triamniotic
triplet gestation.

(Left) Endovaginal
ultrasound shows an 8 week
embryo inside the amnion
(curved arrow), with the
yolk sac (arrow) being
obliterated as the amnion
approaches the chorion. The
fluid in the extra-amniotic
space (open arrow) is
echogenic. (Right) Color
Doppler ultrasound shows
normal coiling of umbilical
cord vessels in a 9 week
gestation.

(Left) Transabdominal
ultrasound shows a normal
nuchal translucency
measurement
(curved arrow)
and normal ductus venosus
waveform (open arrows) in
the first trimester. (Right) 3D
ultrasound clearly shows the
"human" appearance of the
embryo at the end of the first
trimester. The nose (arrow),
limbs (curved arrows) and
loops of cord (open arrow)
are easily identified.

ANEMBRYONIC

Color Doppler ultrasound shows an anembryonic
gestation. There is very little trophoblastic flow and a
poor decidual
reaction,
surrounding
a flattened
gestational sac with no internal structures.

ITERMINOLOGY
Abbreviations

and Synonyms

• Anembryonic pregnancy
• Blighted ovum

(AP)

Definitions
• Anembryonic pregnancy
o Gestational sac without visible embryo
• Failure of embryo to develop
• Early demise and resorption of embryonic pole
• Embryonic demise
o Gestational sac with visible dead embryo
• Consider term "failed first trimester pregnancy"
o Avoids confusion
o Simplifies terminology
o Why "blame" the ovum with terms such as blighted
ovum

IIMAGING FINDINGS
General Features
• Gestational sac without identifiable embryo
o Sac size must have reached discriminatory threshold
• Discriminatory criteria for anembryonic pregnancy by,
endovaginal (EV) ultrasound
o Mean sac diameter> 10 mm without a yolk sac

PREGNANCY

Endovaginal ultrasound in a normal pregnancy of similar
gestational age for comparison shows thick decidual
reaction (black arrows), embryo (curved arrow), yolk
sac (white arrow) and amnion (open arrow).

• Some authors use 8 mm
o Mean sac diameter> 18 mm without an embryo
• Some authors use 16 mm
• Discriminatory criteria for anembryonic pregnancy by
transabdominal ultrasound
o Mean sac diameter> 20 mm without a yolk sac
o Mean sac diameter> 2S mm without an embryo
• Very few indications for performing transabdominal
scan alone: Resolution much better with EV scans
o Victims of abuse
o Pelvic/perineal trauma

Ultrasonographic

Findings

• Grayscale Ultrasound
o Empty amnion
• Specific sign of anembryonic gestation
• Amniotic sac without an embryo
• Yolk sac may be visible: Outside amnion
o Yolk sac forms after amnion but is easier to see
• Embryo first seen as focal thickening on yolk sac
• Amnion then becomes visible
• Amnion enlarges rapidly and envelops embryo
• Yolk sac eventually obliterated as amnion fuses
with chorion
o Signs of abnormal pregnancy
• Irregular sac shape, may be "tear-drop" shaped
• Poor decidual reaction
• Sac position low in uterus

DDx: Uterine Finding With Pain Or Bleeding In First Trimester

Ectopic-Cornual

CTO-Invasive Mole

CTO-Complete Mole

Perigestational Bleed

ANEMBRYONIC

PREGNANCY

Key Facts
Terminology

Pathology

• Gestational sac without visible embryo
• Consider term "failed first trimester pregnancy"

• 60% of spontaneous abortions < 12 weeks due to
abnormal chromosomes

Imaging Findings

Clinical Issues

•
•
•
•
•

• No specific recurrence risk
• Most will spontaneously aDort without treatment

Sac size must have reached discriminatory threshold
Mean sac diameter> 10 mm without a yolk sac
Mean sac diameter> 18 mm without an embryo
Empty amnion
Poor color Doppler signal around sac

Top Differential

Diagnostic Checklist
• Abnormalities common in early pregnancy
• Diagnosis depends on knowledge of normal early
pregnancy milestones
• If in doubt, wait and see
• "Empty amnion sign" is a specific indicator of
anembryonic gestation

Diagnoses

• Normal early intrauterine pregnancy (IUP)
• Retained products of conception (RPOC)
• Gestational trophoblastic disease (GTD)

• Color Doppler
o Poor color Doppler signal around sac
• Use with caution to support abnormal diagnosis
• Doppler delivers greater energy with theoretic
risks to developing embryo from heating and
cavitation
• If possibility of normal early gestation, follow-up
with grayscale rather than use Doppler

Imaging Recommendations
• Use EV sonography
o Better resolution
o More confidence in diagnosis
• Be sure to scan through entire uterus in longitudinal
and transverse planes
o Must look carefully for yolk sac, embryo
o Avoids missing multiple gestations
• Measure sac diameter in 3 planes
o Measurement does not include chorionic reaction
o Mean sac diameter = average of these three
measurements
• Follow-up if possible normal early pregnancy
o Check menstrual history ~
• Verify date of last menstrual period (LMP)
• Is cycle regular?
• What is cycle length?
o Know anatomy and developmental stages
• "Double bleb": Embryonic disc between amnion
and yolk sac
• Yolk sac and amnion should be visible by 7 weeks
post LMP
• Embryo lies inside amniotic cavity
• Yolk sac lies outside amniotic cavity
• Normal yolk sac round in shap~
• Normal yolk sac ::s; 6 mm diameter

I

DIFFERENTIAL DIAGNOSIS

Normal early intrauterine

pregnancy (lUP)

• Double decidual sac sign (DDSS)
• Thick echogenic decidual reaction
• Yolk sac may not be seen if MSD < 10 mm EV

o > 10 mm + no yolk sac = failed lUP
• Prominent color flow around sac
• Low-resistance, high-velocity flow on spectral analysis
of chorion
• Remember to use Doppler sparingly in early gestation

Pseudosac of ectopic pregnancy
• Sac central in endometrial cavity
• No DDSS
• Doppler: Absent or low velocity flow
o Peak systolic velocity < 8 cm/sec

Retained products of conception

(RPOC)

• Disorganized material in uterine cavity
• Echogenic material with flow on color Doppler -+
most likely RPOC
• Retained clot is usually hypoechoic, non-perfused
• No recognizable gestation sac

Gestational

trophoblastic

disease (GTD)

• Classic hydatidiform mole has "swiss cheese"
appearance
• May see abnormal appearing gestational sac
o Can mimic anembryonic sac
• May see associated ovarian theca lutein cysts

Perigestational

hemorrhage

• Usually crescentic around periphery of gestational sac
• +/- Living embryo
I

PATHOLOGY

General Features
• General path comments
o 60% of spontaneous abortions < 12 weeks due to
abnormal chromosomes
• Trisomies
• Triploid/tetraploid
• 4S XO
• Translocations
• Mosaics
• Epidemiology

ANEMBRYONIC
o 30-60% documented elevations of beta human
chorionic gonadotrophin end as failed pregnancy
• Pregnancy "diagnosis" biochemical not clinical
o Up to 20% of confirmed first trimester pregnancies
end in spontaneous abortion
o Pathology series of abnormal early pregnancies
• 35% anembryonic
• 54% early loss (cause not specified)
• 11% molar (partial or complete)
o Groups with increased incidence of early pregnancy
failure
• Advanced maternal age
• History recurrent abortions
• Poor diabetic control

Microscopic

Features

• Chorionic villi present in uterine curettings
• Significant reduction in number of vessels per
chorionic villus when compared to normal pregnancy
• Vessel abnormally located within chorionic villi:
Remain as central cords
o Thought to relate to inadequate vasculogenesis,
abnormal development of vasculosyncitial
membrane
o Vessels marginalize to periphery of villus in normal
pregnancy
• Nuclear DNA abnormal in high proportion (up to
40%)
• Suggests that chromosomal aberrations -+ abnormal
embryogenesis -+ anembryonic gestation

I CLINICAL ISSUES
Presentation
• May be asymptomatic with diagnosis made during
routine first trimester scan
• If spontaneous miscarriage imminent
o Vaginal bleeding
o Pelvic pain
o Uterine contractions
• Patient perception
o Diminished breast tenderness
o Decrease of morning sickness
o "Doesn't feel like other pregnancies"

Natural History & Prognosis
• Random event
• No specific recurrence risk
• Threatened abortion occurs in 25% first trimester
pregnancies
o Presents with pain and bleeding after missed
menstrual period

Treatment
• "Wait and see"
o Most will spontaneously abort without treatment
• Vaginal misoprostol
o Successful evacuation of uterus in majority of
patients
o Many patients prefer definitive treatment to
expectant management
o Some will require curettage but overall expect 50%
reduction in need for surgical management

PREGNANCY
• Suction curettage
o Small associated risk of excessive bleeding, uterine
rupture, Asherman syndrome

I DIAGNOSTIC

CHECKLIST

Consider
• Abnormalities common in early pregnancy
• Anembryonic pregnancy often due to chromosomal
aberration
• Diagnosis depends on knowledge of normal early
pregnancy milestones
• If in doubt, wait and see
o Normal pregnancies grow in a predictable manner
o MSD increases by 1 mm per day
o Schedule follow-up for a time when gestational sac
should have reached discriminatory threshold

Image Interpretation

Pearls

• "Empty amnion sign" is a specific indicator of
anembryonic gestation
o Gestational sac with amnion but no visible embryo
o YSmay be visible

I SELECTED

REFERENCES

Lisman BA et al: Abnormal development of the
vasculosyncytial membrane in early pregnancy failure.
Fertil Steril. 82(3):654-60, 2004
Luise C et al: Expectant management of incomplete,
2.
spontaneous first-trimester miscarriage: outcome according
to initial ultrasound criteria and value of follow-up visits.
Ultrasound Obstet Gynecol. 19(6):580-2, 2002
3. Carbillon Let al: Doppler ultrasonography and
implantation: a critical review. Fetal Diagn Ther.
16(6):327-32,2001
Sebire NJ et al: The diagnostic implications of routine
4.
ultrasound examination in histologically confirmed early
molar pregnancies. Ultrasound Obstet Gynecol.
18(6):662-5, 2001
5. Ozeren M et al: Ploidy analysis and S-phase fraction
determination by flow cytometry in anembryonic
pregnancy and spontaneous abortions. Gynecol Obstet
Invest. 48(2):104-7, 1999
6. Brajenovic-Milic B et al: Chromosomal anomalies in
abnormal human pregnancies. Fetal Diagn Ther.
13(3):187-91, 1998
Kurjak A et al: Doppler assessment of the intervillous blood
7.
flow in normal and abnormal early pregnancy. Obstet
Gynecol. 89(2):252-6, 1997
Pandya PP et al: The prevalence of non-viable pregnancy at
8.
10-13 weeks of gestation. Ultrasound Obstet Gynecol.
7(3):170-3,1996
Sohaey R et al: First trimester ultrasound: The essentials.
9.
Semin Ultrasound, CT and MR. 17:2-14, 1996
10. Chao KH et al: Decidual natural killer cytotoxicity
decreased in normal pregnancy but not in anembryonic
pregnancy and recurrent spontaneous abortion. Am J
Reprod Immunol. 34(5):274-80, 1995
11. McKenna KM et al: The empty amnion: a sign of early
pregnancy failure. J Ultrasound Med. 14(2): 117-21, 1995
12. Salim A et al: Corpus luteum blood flow in normal and
abnormal early pregnancy: evaluation with transvaginal
color and pulsed Doppler sonography. J Ultrasound Med.
13(12):971-5, 1994
1.

ANEMBRYONIC

PREGNANCY

IIMAGE GALLERY
Typical
(Left) Endovaginal
ultrasound shows an empty
gestational sac with poor
decidual reaction (arrows).
The sac is also irregular in
shape. (Right) Endovaginal
ultrasound in a normal
pregnancy for comparison
shows the double decidual
sac sign created by the
apposition of the decidua
capsularis (curved arrow)
and decidua parietalis
(arrow). The open arrow
marks the decidua basalis.

Typical
(Left) Endovaginal
ultrasound shows the empty
amnion sign. The amnion
(arrow) is seen within the
gestational sac (curved
arrows) but there is no
embryo or identifiable yolk
sac. (Right) Endovaginal
ultrasound shows another
example of an empty amnion
sign (arrow). In this case, a
yolk tan be seen (curved
arrow).

(Left) Endovaginal
ultrasound shows a
"tear-drop" shaped
gestational sac (cursors),
with surrounding
hemorrhage (arrows). The
patient had a spontaneous
abortion the next day.
(Right) Transabdominal
ultrasound shows a large
gestational sac with poor
decidual reaction and
internal debris (arrow) but
no embryo. A sac of this size
would be expected to
contain an embryo with a
crown rump length of
approximately
6 cm.

PERIGESTATIONAL

Sagittal ultrasound shows a perigestational hemorrhage
(open arrows) and a living 10 wk fetus (curved arrow).
The inferior placenta edge (arrows) has been lifted off
the uterus. Outcome was normal.

ITERMINOlOGY
Abbreviations

and Synonyms

Perigestational hemorrhage (PGH)
Subchorionic hematoma
Intrauterine hematoma
Abruption
o Term more often reserved for 2nd/3rd trimester
• Breus mole
o Massive PGH

Definitions
• Hematoma adjacent to gestational sac in first trimester
(first 13 wks of gestation)
o Bleeding often from chorionic frondosum (CF')
• CF is early placenta

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Intrauterine fluid collection
separate from and adjacent to gestational sac (GS)
• Location: Often near CF
• Size: Variable
• Morphology: Depends on size and age of hemorrhage

CA Separation

Cross pathology shows fetal demise at 7 7 weeks and a
large perigestational hemorrhage. A large blood clot
(arrows) extends from behind the membranes (curved
arrow). PCH is most commonly subchorionic.

Ultrasonographic

•
•
•
•

DDx: Intrauterine

HEMORRHAGE

Findings

• Hematoma appearance depends on age of bleed
o Acute hematoma
• Isoechoic to CF
o Subacute hematoma
• More hypoechoic than acute
• Complex fluid collection
• Fibrin strands resemble septations
o Resolving hematoma
• Sonolucent
• May see fluid-fluid level
• Hematoma size .J. with time
o Eventually resolves
• Curvilinear shape often seen
o Follows contour of uterus
• May extend completely around GS
o Blood in subchorionic space
o Can often be traced to edge of CF
• May see edge of placenta lifted
• Mass-like hematoma
o May significantly compress GS
• Distorted GS
o PGH may be larger than GS
• Difficult to find GS
• Mimic anembryonic sac
o May mimic a second GS
• PGH may extend beyond subchorionic space

Fluid Collection

Normal

CA Separation

Dichorionic

Twinning

Pseudogestational

Sac

PERIGESTATIONAL

HEMORRHAGE

Key Facts
• Pseudogestational

Terminology

sac (ectopic pregnancy)

• Subchorionic hematoma

Pathology

Imaging Findings

• 3.1% of all first trimester cases have PGH
• 20% of patients with vaginal bleeding have PGH.

• Best diagnostic clue: Intrauterine fluid collection
separate from and adjacent to gestational sac (GS)
• Hematoma appearance depends on age of bleed
• Curvilinear shape often seen
• May see edge of placenta lifted
• Distorted GS
• 90-95% have good outcomes when living embryo
present
• PGH may mimic GS or twin gestation

Top Differential

Diagnoses

• Chorioamniotic (CA) separation
• Diamniotic twinning

o May extend into placenta
• Large intraplacental hematoma
• Appears as placental thickening when acute
o Blood in amniotic cavity
• Floating echogenicities in amniotic fluid
• Often present with large PGH
• Fetus swallows blood '* echogenic bowel
• Findings associated with poor prognosis
o Large hematoma
• > 50% CF detached
• GS appears floating in uterine cavity
• Misshapen GS
o GS located in lower uterine segment
• GS detached completely
• + Cervical os dilatation '* miscarriage
o GS without normal intra sac anatomy
• No yolk sac when GS > 8-10 mm
• No embryo when GS > 16-18 mm
• Anembryonic GS
o Bradycardia
• Embryo heart rate ~ 90 beats/minute
• Most PGH resolves, with delivery of a normal infant
o 90-95% have good outcomes when living embryo'
present
• Role of color Doppler
o Helps show isoechoic PGH
• PGH without flow
• CF has blood flow
o Helps identify detached CF
• Subplacental veins show areas of attachment

Imaging Recommendations
• Best imaging tool: Transvaginal ultrasound with color
Doppler
• Protocol advice
o Look carefully at GS size and morphology
o PGH may mimic GS or twin gestation
o Short term follow-up helpful
• Normal GS grows 1 mm/day
• Hematoma should l in size
• Hematoma will become less echogenic

Clinical Issues
• PGH may be an incidental finding
• 10-15% spontaneous abortion rate with PGHt

Diagnostic

Checklist

• Use transvaginal ultrasound to carefully assess
morphology of PGH and GS
• High-risk of pregnancy failure if GS < 16 mm at time
of diagnosis'
• Beware of twins mimicking PGH and vice versa
• 1st trimester PGH '* t fetal/maternal morbidity later
in pregnancy

I DIFFERENTIAL DIAGNOSIS
Chorioamniotic

(CA) separation

• Amnion seen separate from uterine wall
o Normal before 14 wks
o Membranes should fuse by 16 wks
o Chorionic fluid more echogenic than amniotic fluid
• Fluid less complex than PGH
• Causes of CA separation> 16 wks
o Invasive procedure (amniocentesis)
o Delayed CA fusion
• Associated with aneuploidy
• Trisomy 21 most common
• Placental edge well attached
o Placental edge often lifted with PGH

Diamniotic

twinning

• Second GS can mimic PGH
• Dichorionic
o 2 GS with 2 decidual rings
• Thick "separating" tissue
• PGH without decidual lining
• Monochorionic twins less likely to mimic PGH
o Only one chorionic sac
o Thin separating membrane
• GS round while PGH often curvilinear
• Follow-up to see yolk sac/embryo development in sac

Pseudogestational

sac (ectopic pregnancy)

• Endometrial blood
o Centrally located in endometrium
• No associated intrauterine gestational sac
• Adnexal mass
o Ectopic ring
o Hematoma
• Cul-de-sac echogenic fluid
o Intraperitoneal hemorrhage

I PATHOLOGY
General Features
• General path comments

PERIGESTATIONAL
o Blood usually collects in subchorionic space
• Potential space between chorion and uterus
• Can extend freely around GS in this space
o Large PGH
• Blood may extend into chorioamniotic space
• Blood may extend into amniotic space
o Pregnancy failure associated with CF detachment
• Blood dissects under placenta
• May detach GS completely
• Etiology
o Bleeding from CF
• Most common
• Less likely from endometrial decidua
o Self-limited process
• Epidemiology
o 3.1% of all first trimester cases have PGH
o 20o/il of patients with vaginal bleeding have PGH
• Associated abnormalities: Abnormal placentation

HEMORRHAGE
o Advise patient to seek care if bleeding worsens
• Most often self-limited process
o Follow-up 2nd/3rd trimester scan
• Follow human chorionic gonadotropin (HCG) levels
o Normally doubles every 48 hours in first trimester
o Should see GS when HCG levels are> 2,000 mIU/mL
IRP (international reference preparation)
• Pregnancy failure
o Diagnosis
• Embryonic demise
• Falling HCG levels
• Anembryonic GS
o Treatment
• Expectant management and miscarriage
• Dilatation and evacuation of uterus

I DIAGNOSTIC

CHECKLIST

Consider

I CLINICAL

ISSUES

Presentation
• Threatened abortion
o Bleeding
o Uterine cramping
o Closed cervical os
• Abortion in progress
o Open cervical os + bleeding/pain
• PGH may be an incidental finding
o Patient without symptoms
• Elevated maternal serum alpha-fetoprotein
(AFP)
o Mixing of fetal and maternal blood at time of PGH
o May see residua of PGH at screen for t AFP

Natural History & Prognosis
• 10-15% spontaneous abortion rate with PGH
o Severity of symptoms do not necessarily correlate
with outcome
• Excellent prognosis if living embryo + small PGH
o > 90% pregnancy success rate.
• Guarded prognosis if early PGH
o GS < 16 mm + PGH
o 64% loss rate
o Short term follow-up
• Guarded prognosis with large PGH
o 20% loss rate even if living embryo present
• Poor prognosis if retroplacental hematoma
o > 50% of CF detachment greatest loss rate
• Poor prognosis if associated embryo bradycardia
o 80% loss rate
• Cervical os dilatation '* near 100% loss rate
o Cervical os dilatation is clinical diagnosis
• PGH associated with maternal/fetal morbidity
o 2nd trimester abruption (5.6x t risk)
o Preeclampsia (4.0x t risk)
o Fetal growth restriction (2.4x t risk)
o Preterm delivery (2.3x t risk)
o Pregnancy induced hypertension (2.1x t risk)
o Cesarean section (l.4x t risk)

Treatment
• Follow-up ultrasound
o Look for normal first trimester landmarks

• Use transvaginal ultrasound to carefully assess
morphology of PGH and GS

Image Interpretation

Pearls

• Presence of a living embryo is most reassuring sign
when PGH seen
o > 90<V" pregnancy success rate if PGH not large
• Follow-up ultrasound in 5-7 days helpful in early cases.
o Blood evolves quickly _
o GS grows 1 mm/day
o High-risk of pregnancy failure if GS < 16 mm at time
of diagnosis
• Beware of twins mimicking PGH and vice versa
• Careful pregnancy assessment in 2nd/3rd trimester
o 1st trimester PGH '* t fetal/maternal morbidity later
in pregnancy
o Associated with abnormal placentation

I SELECTED
1.
2.

3.

4.

5.

6.

REFERENCES

Dogra V et al: First trimester bleeding evaluation.
Ultrasound Q. 21(2):69-85; quiz 149-50, 153-4,2005
Nishijima K et al: Massive subchorionic hematoma:
peculiar prenatal images and review of the literature. Fetal
Diagn Ther. 20(1):23-6, 2005
Falco Pet al: Sonography of pregnancies with
first-trimester bleeding and a small intrauterine gestational
sac without a demonstrable embryo. Ultrasound Obstet
Gynecol. 21(1):62-5, 2003
Nagy S et al: Clinical significance of subchorionic and
retroplacental hematomas detected in the first trimester of
pregnancy. Obstet Gynecol. 102(1 ):94-100, 2003
Bennett GL et al: Subchorionic hemorrhage in
first-trimester pregnancies: prediction of pregnancy
outcome with sonography. Radiology. 200(3):803-6, 1996
Dickey RP et al: Relationship of first trimester subchorionic
bleeding detected by color Doppler ultrasound to
subchorionic fluid, clinical bleeding, and pregnancy
outcome. Obstet Gynecol 80:415-20,1992

PERIGESTATIONAL
IIMAGE

HEMORRHAGE

GALLERY
(Left) Axial ultrasound shows
PGH and an anembryonic
GS. The large misshapen GS
(open arrows) is empty and
the curvilinear, echogenic
fluid collection (arrows) is
blood. (Right) Axial
ultrasound shows a large,
circumferential PGH
(arrows) and a small GS
(curved arrow). Color
Doppler shows a living
embryo (open arrow) Large
PGHs have a poor prognosis
especially when the sac is <
16 mm. The patient
miscarried 2 days later.

(Left) Sagittal color Doppler
ultrasound shows a
hypoechoic curvilinear PGH
(arrows) in a 72 wk
pregnancy presenting with
bleeding. The placenta
(open arrows) is well
attached. (Right) Ultrasound
performed at 18 weeks in the
same case shows residual
PGH (arrows) in front of the
cervix (calipers),
echogenicities in the
amniotic fluid (open arrows)
and echogenic bowel
(curved arrows) from
swallowed blooe/.

Variant
(Left) Ultrasound images
from a transabdominal scan
show 2 fluid collections
(arrows) within the uterus
mimicking the appearance of
a twin gestation. (Right)
Sagittal endovaginal
ultrasound shows that the
smaller fluid collection
(arrows) is actually a PGH
adjacent to an otherwise
normal appearing GS with a
living embryo (curved
arrow). The PGH is
thin-walled and lifis the edge
of the chorionic frondosum
(open arrows).

TUBAL ECTOPIC

Sagittal endovaginal ultrasound shows a tubal ring
(open arrows) by the uterine fundus, an empty uterus
(curved arrow) and a large amount of echogenic pelvic
fluid (arrows) in this case of ruptured tubal ectopic.

I TERMI NOlOGY
Abbreviations

and Synonyms

• Ectopic pregnancy (EP)
• Tubal pregnancy

Definitions
• Ectopic gestation developing in fallopian tube

IIMAGING FINDINGS
General Features
• Best diagnostic clue: No intrauterine pregnancy (IUP)
+ tubal mass + echogenic cul-de-sac fluid
• Location: Separate from ovary
• Morphology
o Complex adnexal mass
• From hemorrhage
o Tubal ring
• Similar to IUP gestational sac (GS)

Ultrasonographic

Findings

• Uterine findings vary
o Thin endometrium
• Empty uterus
o Thick echogepic endometrium
• Decidual reaCtion of pregnancy

Intra-operative photograph from the same case shows
the ectopic pregnancy has distended the fallopian tube
(open arrows). A large amount of peritoneal blood
(arrow) is seen. Focal rupture was present.

o Endometrial cysts
• Often small and multiple
• Large cyst may mimic early IUP
o "Pseudo gestational sac" sign
• Decidual cast
• Endometrial fluid (blood)
• Lacks double-decidual sac sign of normal IUP
o Heterotopic pregnancy (rare)
• IUP + EP
• Tubal findings
o Adnexal abnormality in 80-95%
o Tubal hematoma (40-60%)
• Nonspecific mass
• Heterogeneous echotexture
o Tubal ring (50%)
• Echogenic ring separate from ovary
• +/- Yolk sac
• +/- Embryo +/- cardiac activity
o Tubal ring "lights up" with color Doppler
• "Ring of fire"
• May show small EP missed otherwise
o Pulsed Doppler findings
• High-velocity, low-resistance flow
• Trophoblastic flow velocity> ovarian velocity
• > 2-4 kHz common for trophoblastic flow
• Ovary findings
o Identify which ovary contains corpus luteum (CL)
• 85% of ectopics on same side as CL

DDx: Adnexal Mass In Pregnancy

CL Cyst

Hemorrhagic CL

Cornual Ectopic

Ovarian Neoplasm

TUBAL ECTOPIC
Key Facts
Top Differential

Terminology
• Ectopic gestation developing

Imaging

in fallopian tube

Findings

• Best diagnostic clue: No intrauterine pregnancy (lUP)
+ tubal mass + echogenic cul-de-sac fluid
• "Pseudogestational sac" sign
• Adnexal abnormality in 80-95%
• Tubal hematoma (40-60%)
• Tubal ring (50%)
• "Ring of fire"
• 85% of ectopics on same side as CL
• Ultrasound completely negative in 5-10% of cases
• 91% of EP accurately diagnosed
• Suspect EP if no lUP and hCG > 2,000 mlU/mL IRP
• Use endovaginal probe as a palpation tool

o Corpus luteum appearance is variable
• Echogenic ring
• Hypoechoic cyst
• Anechoic cyst
• Complex cyst from hemorrhage
o Corpus luteum can mimic EP
• CL is within ovary and tubal EP is outside of ovary
o Corpus luteum Doppler findings
• Similar to "ring of fire" but in ovary
• CL flow velocity < trophoblastic tissue velocity
• Low-resistive flow-like EP flow
• Echogenic fluid in cul-de-sac
o Blood within peritoneal space
• Between uterus and rectum
o Echogenic fluid
• May need t gain settings to see echoes
• Small amount of anechoic fluid considered
physiologic
• Clotted blood may be mass-like and complex
o Blood may be an isolated finding
• 42% will have EP if small amount of fluid seen
• 73% will have EP if large amount of fluid seen
o Role of transabdominal ultrasound
• Look for upper abdomen fluid
• Paracolic gutters
• Morrison pouch (between liver and kidney)
• Ultrasound completely negative in 5-10% of cases
o No IUP, normal adnexa, no cul-de-sac fluid

Imaging

Recommendations

• Best imaging tool
o Transvaginal ultrasound + color Doppler
• 91% of EP accurately diagnosed
• Protocol advice
o Correlate findings with human chorionic
gonadotropin (hCG) levels
• Should see IUP when hCG levels are> 2,000
mlU/mL IRP (international reference preparation)
• Suspect EP if no lUP and hCG > 2,000 mlU/mL
IRP
o Lack of IUP at low hCG levels does not rule out EP
• EP's have lower hCG levels/gestational age
o Obtain sagittal cul-de-sac view in every case

Diagnoses

• IUP
• Cornual pregnancy
• Incidental adnexal mass

Pathology
• 1.4% of all pregnancies are ectopic
• 95% of all ectopics are tubal

Clinical

Issues

• Medical treatment

Diagnostic

with methotrexate

preferred

Checklist

• Presence of lUP is best negative predictor of EP
• Can often find EP with hCG levels < 2,000 mlU/mL
• CL can mimic EP

• Transvaginal probe angled towards rectum
• Adjust gain settings to see echoes
o Look for CL in every case
• EP often on same side as CL
• CL hemorrhage or rupture may be cause of pain
• Do not confuse CL for EP
o Use color Doppler
• Look for small EP
• Rule out ovarian torsion as cause of pain
o Use endovaginal probe as a palpation tool
• Gently wedge probe between mass and ovary
• Free hand on abdomen palpates same area
• EP moves independent of ovary
• CL moves with ovary

I DIFFERENTIAL DIAGNOSIS
IUP
• Gestational sac
o Double decidual sac sign
• Perigestational hemorrhage common
o Resembles pseudosac
• CL appearance variable
o Hemorrhagic CL
• Echogenic cul-de-sac fluid if ruptured
o Presence of IUP makes EP less likely

Cornual

pregnancy

• Pregnancy in intersitial (cornual) portion of tubl}
• Eccentric gestational sac
o Incomplete myometrial coverage
o Sac within 5 mm of uterine serosa
• At risk for rupture
o Often later than EP
o Can cause massive intraperitoneal hemorrhage
• Treatment
o Ultrasound guided injection preferable to surgery
o Methotrexate or potassium chloride

Incidental

adnexal

mass

• Paraovarian cyst
o Unilocular and anechoic

TUBAL ECTOPIC
• Incidental ovarian mass
o Most often teratoma
o Neoplasm rare

I PATHOLOGY
General Features
• Etiology
o Normal blastocyst implantation
• Within uterus on day 7 after ovulation
o Abnormal blastocyst implantation in tube
• Delayed transport ~ tubal implantation
o Abnormal tube is a risk factor for EII
• Chronic salpingitis
• Salpingitis isthmica nodosa
• Tubal surgery
• Prior EP
• Epidemiology
o 1.4% of all pregnancies are ectopic
o 95% of all ectopics are tubal
o 10-40% risk in fertility patients
o 5-20% incidence if patient presents with
pain/bleediftg

o Early, unruptured, small ectopic
• 90% success rate
• EP < 4 cm
• HCG levels < 5,000 mlU/mL
• ::S; 8 wks gestation
o 70% success rate if living embryo
o Multiple doses may be necessary
o Ultrasound after treatment is often confusing
• t Hemorrhage around EP
• t Size of EP
• Use only if suspect tubal rupture
• Surgical therapy
o Salpingectomy
• Segment of tube removed
• Ends reconnected if possible
• Only choice for ruptured EP
o Salpingotomy
• Small lengthwise incision in tube
• Removal of EP
• Ultrasound guided local injection
o Methotrexate or potassium chloride (KCl}
• Injected directly into GS
o Live ectopic + unruptured tube
• 30% fail systemic treatment
o Preferred method for cornual and cervical ectopics

ICLINICALISSUES
Presentation
• Most common signs/symptoms: First trimester
pain/bleeding
• Other signs/symptoms
o Palpable adnexal mass
o Cardiovascular shock
o Incidental diagnosis
o No IUP and hCG > 2,000 mlU/mL IRlJ,
• EP vs. failing lUP
o Low hCG level and negative ultrasound
• EP vs. early lUP vs. failed lUP
o Maternal serum progesterone levels
• Helps predict normallUP vs. EP/failing lUP
• Can not differentiate EP from failed lUP
• < 5 ng/ml = nonviable pregnancy in 100%
• Office curettage can rule out failed lUP
• > 25 ng/ml excludes ectopic with 97.5%
sensitivity

I DIAGNOSTIC

CHECKLIST

Consider
• Serial hCG levels in indeterminate cases
o Levels double every 2 days with normallUP
o Repeat ultrasound if hCG levels are rising
o Dropping levels suggest failing pregnancy

Image Interpretation

Pearls

• Presence of lUP is best negative predictor of EP
• Can often find EP with hCG levels < 2,000 mlU/mL
o Do not delay ultrasound
• Look for "ring of fire" in adnexa with color Doppler
o May detect a small EP when grayscale findings are
negative
• Be aware and beware of corpus luteum
o CL can mimic EP
o Often on same side as EP
o Can be cause of pain

Natural History & Prognosis
• Delayed diagnosis ~ morbidity and death
o Case fatali~rate has ~ from 3.5 to 1:1,000.
• 2° to earlier diagnosis with ultrasound
• Prognosis for future pregnancies
o 80% will have future IUP
o 15-20% will have future EP
• EP may resolve on own
o More likely if hCG levels are < 1,000 mlU/mL IRP
o Must follow dropping hCG levels very carefully
o 24% of all EP may spontaneously resolve

I SELECTED
1.

2.

3.
4.

Treatment
• Medical treatment with methotrexate preferred
o Patient must be hemodynamically stable
o No evidence for tube rupture
• Little or no peritoneal fluid

5.

REFERENCES

Blaivas M et al: Reliability of adnexal mass mobility in
distinguishing
possible ectopic pregnancy from corpus
luteum cysts. J Ultrasound Med. 24(5):599-603; quiz 605,
2005
Condous G et al: The accuracy of transvaginal
ultrasonography
for the diagnosis of ectopic pregnancy
prior to surgery. Hum Reprod. 20(5):1404-9, 2005
Dogra V et al: First trimester bleeding evaluation.
Ultrasound Q. 21(2):69-85; quiz 149-50, 153-4,2005
Monteagudo
A et al: Non-surgical management
of live
ectopic pregnancy with ultrasound-guided
local injection:
a case series. Ultrasound Obstet Gynecol. 25(3):282-8, 2005
Dialani V et al: Ectopic pregnancy: a review. Ultrasound Q.

20(3):105-17,2004
6.

Sowter MC et al: Ectopic pregnancy:
Obstet Gynecol. 16(4):289-93, 2004

an update.

Cun Opin

TUBAL ECTOPIC
IIMAGE GALLERY
Typical
(Left) Sagittal endovaginal
ultrasound shows a
pseudogestational sac
(arrows). Only one layer of
decidua (decidual cast)
surrounds the fluid. Complex
cul-de-sac fluid (curved
arrow) is also seen. (Right)
Endovaginal ultrasound of
the right adnexa in the same
case shows a heterogeneous
adnexal mass (arrows)
adjacent to the ovary (open
arrows). Nonspecific adnexal
mass is common with tubal
EP

(Left) Endovaginal
ultrasound images of a living
embryo in a tubal ectopic.
The tubal ring (arrows) is
adjacent to the ovary (open
arrows) and contains a
distinguishable embryo
(calipers) and yolk sac
(curved arrow). M-mode
confirmed cardiac activity.
(Right) Cross pathology from
the same case shows a well
formed embryo (arrow)
within the tubal gestational
sac. Note the presence of
extensive trophoblastic tissue
(curved arrow).

(Left) Endovaginal
ultrasound shows an
echogenic ring (arrows) next
to the ovary (curved arrow).
This ring" lights up" with
power Doppler and exhibits
the typical high-velocity,
low-resistance flow of an EP
(Right) Endovaginal
ultrasound of the right
adnexa shows a CL (arrows)
within the ovary (cursors)
but no other obvious
findings. Color Doppler
shows a "ring of fire" from
an EP Color Doppler may
aid in finding a small EP that
might otherwise be missed.

INTERSTITIAL ECTOPIC

Axial endovaginal ultrasound shows the interstitial line
sign (curved arrow). There is severe thinning of the
myometrium (arrows) and marked trophoblastic flow is
seen with power Doppler (inset).

ITERMINOlOGY
Abbreviations

and Synonyms

• Interstitial ectopic pregnancy
o Preferred term
• Cornual ectopic pregnancy
o Often used interchangeably
o More appropriately applied to pregnancies in a
rudimentary horn
• Intramural ectopic pregnancy
• Angular pregnancy
o Pregnancy implanted at lateral angle of uterine
cavity by ostium
o Medial to interstitial portion of tube and round
ligament

Definitions
• Pregnancy occurring in interstitial portion of fallopian
tube

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Combination of findings
• Interstitial line sign: Echogenic line from
endometrium to ectopic sac

DDx: Uterine Duplication

Uterus Didelphys

Intra-operative photograph shows the bulging, thinned
myometrium at the site of the ectopic (curved arrow).
The gestational sac was resected (inset) and has a
clearly defined embryo (arrow) and adjacent yolk sac.

• Myometrium thinned to < 5 mm
• Location
o Interstitial (intramural) portion of fallopian tube
• Connects uterine cavity to isthmus (extrauterine
portion of tube)
• 1 cm in length, 1 mm in diameter
• Size: Covered by myometrium so can grow to larger
size than tubal ectopics
• Early interstitial pregnancy often difficult to diagnose
o 42% of cases missed in one large series

Ultrasonographic

Findings

• Gestational sac located high in fundus
o Eccentrically located with respect to endometrial
cavity
• Appearance of sac contents quite variable
o Gestational sac +/- yolk sac, embryo
• Gestational sac and embryo can be quite large
o May appear as echogenic mass within cornua
• Combination of trophoblastic tissue, hematoma
• No definable sac
• Thinned myometrium
o < 5 mm of surrounding myometrium very suggestive
o May have areas where no definable myometrium is
seen
o Normal myometrium may be seen early and does
not exclude an interstitial ectopic

Anomalies

Bicornuate

Septate

Septate

INTERSTITIAL ECTOPIC
Key Facts
Top Differential

Terminology
• Pregnancy occurring in interstitial
fallopian tube

portion of

Diagnoses

• Normal intrauterine
• Uterine duplications

pregnancy

Imaging Findings

Pathology

• Interstitial line sign: Echogenic line from
endometrium to ectopic sac
• Gestational sac located high in fundus
• Eccentrically located with respect to endometrial
cavity
• Gestational sac and embryo can be quite large
• May appear as echogenic mass within cornua
• < 5 mm of surrounding myometrium very suggestive
• Normal myometrium may be seen early and does not
exclude an interstitial ectopic
• Interstitial line sign has reported sensitivity of 80%
and specificity of 98%

• 2-4% of ectopic pregnancies
• Mortality rate 2-2.5%

• Interstitial line sign has reported sensitivity of 80%
and specificity of 98%
o Echogenic line can be followed from endometrium
to ectopic sac
• 3D ultrasound
o Multiple case reports show improved diagnosis
o Improved spatial orientation of ectopic in relation to
uterine cavity
• Doppler findings
o Trophoblastic tissue is highly vascular
o Marked flow identified on color and power Doppler
o Pulsed Doppler shows high-velocity, low-resistance
waveform
o May see prominent arcuate vessels in outer third of
myometrium

MR Findings
• Has been shown accurate in diagnosis
o Eccentric sac separated from endometrium by
junctional zone
• Generally not necessary
• Consider when ultrasound findings are equivocal or
pre-operative planning for large ectopics
• Generally avoided in first trimester unless clinical
situation warrants

Imaging Recommendations
• Always document location of sac with respect to
endometrium in both transverse and longitudinal
views
• Measure surrounding myometrium if it appears thin
o < 5 mm more likely to be an interstitial ectopic
• Look for echogenic line leading to myometrium
(interstitial line sign)
• Use 3D ultrasound if available
• If unclear, short term follow-up with careful
instructions to patient to return immediately if
symptoms occur
• May consider MR if still unclear

are interstitial

Clinical Issues
• Hypotension and shock if presenting with rupture
• Significantly greater morbidity and mortality than for
tubal ectopics
• Uterine rupture most commonly occurs at 9-12 weeks

Diagnostic Checklist
• Despite technical advances, diagnosis of interstitial
ectopic pregnancy remains difficult

I DIFFERENTIAL DIAGNOSIS
Normal intrauterine

pregnancy

• High, eccentric implantation may be confusing
• Should always have normal myometrial coverage
• Follow-up scan shows normal development

Uterine duplications
• Duplication of endometrial cavity
• Implantation within one horn gives eccentric
appearance
• Myometrium will completely surround gestational sac
in all types
• May give false appearance of interstitial line sign
o Can follow an echogenic line to main cavity
• Close evaluation shows it is curved, rather than
straight
• Classification system based on external contour
o Uterus didelphys
• Two separate uteri
• Easiest to distinguish from interstitial ectopic
o Bicornuate
• External contour of uterus is concave
• Must obtain views of uterine fundus to adequately
evaluate contour
o Septate
• External uterine contour is normal
• Most likely congenital anomaly to be confused
with interstitial ectopic
• Septum extends for variable lengths (subseptate
vs. complete)

Tubal ectopic
• Can occasionally be confusing if adjacent to cornua of
uterus
• Use ultrasound probe to gently separate structures

I

PATHOLOGY

General Features
• Etiology
o Risk factors

INTERSTITIAL ECTOPIC
• History of prior tubal surgery, especially
salpingectomy
• Prior ectopic pregnancy
• Assisted reproductive technology (ART)
pregnancies
• May see heterotopic pregnancy with ART with one
sac in cornua
o Intrauterine contraceptive devices (IUD) are not
associated with interstitial ectopics
• Ectopic pregnancies more likely to be in tube
when IUD present
• Epidemiology
o 2-4% of ectopic pregnancies are interstitial
o Mortality rate 2-2.5%

Microscopic

Features

• Interstitial portion of tube composed of multiple layers
o Endosalpinx (mucosa)
o Myosalpinx
• 3 layers of muscle
• Highly vascularized
o Serosa is directly contiguous with peritoneum

o Considered only if small sac and no living embryo
• Rupture may require hysterectomy
o May consider uterine artery embolization prior to
surgery

I DIAGNOSTIC
Consider
• 3D ultrasound
to endometrial

ISSUES

Presentation
• Most common signs/symptoms
o Pelvic/abdominal pain
o Vaginal bleeding
• Other signs/symptoms
o Hypotension and shock if presenting with rupture
o May be an incidental finding on routine 1st
trimester scan
• Easy to miss on early scan

Natural History & Prognosis
• Significantly greater morbidity and mortality than for
tubal ectopics
o Surrounding myometrium is distensible, allowing
for greater gestational sac size
o Uterine rupture most commonly occurs at 9-12
weeks
• May occur earlier
o Potential exsanguination
• Large accurate vessels run in outer third of
myometrium
• Good outcome, with preserved future fertility, with
appropriate treatment

Treatment
• Systemic methotrexate
o Follow human chorionic gonadotropin (hCG) after
initial dose
o May require second dose if levels do not fall
appropriately
o Failed treatment goes to surgery
• Sac injection
o Generally with methotrexate
• Via laparoscopy or ultrasound guidance
o Potassium chloride, etoposide also used
• Cornuostomy with sac excision
o May be done with laparoscopy or laparotomy
• Expectant management

for improved spatial orientation
cavity

Image Interpretation

I SELECTED

of sac

Pearls

• Despite technical advances,
ectopic pregnancy remains
o Must have a high degree
high-risk patient
o Short term follow-up for
and eccentric

1.

I CLINICAL

CHECKLIST

diagnosis of interstitial
difficult
of suspicion, especially in a
any sac which appears high

REFERENCES

Filhastre M et al: Interstitial
pregnancy:
role of MRI. Eur
Radiol. 15(1):93-5,
2005
2.
Lee GS et al: Diagnosis
of early intramural
ectopic
pregnancy.
J Clin Ultrasound.
33(4):190-2,
2005
3.
Anandakumar
C et al: Three-dimensional
transvaginal
sonographic
diagnosis
of asymptomatic
interstitial
pregnancy
at 6 weeks of gestation.
Acta Obstet Gynecol
Scand. 83(4):408-10,
2004
Coric M et al: Laparoscopic
approach
to interstitial
4.
pregnancy.
Arch Gynecol Obstet. 270(4):287-9,
2004
5.
Jermy K et al: The conservative
management
of interstitial
pregnancy.
BJOG. 111(11):1283-8,2004
Tarim E et al: Angular pregnancy.
J Obstet Gynaecol
Res.
6.
30(5):377-9,2004
Tulandi T et al: Interstitial
pregnancy:
results generated
7.
from the Society of Reproductive
Surgeons Registry. Obstet
Gynecol.
103(1):47-50,2004
Akrivis Ch et al: Early ultrasonographic
diagnosis
of
8.
unruptured
interstitial
pregnancy:
a case report and review
of the literature.
Clin Exp Obstet Gynecol.
30(1):60-4,
2003
Chan LY et al: Pitfalls in diagnosis
of interstitial
pregnancy.
9.
Acta Obstet Gynecol Scand. 82(9):867-70,
2003
10. Izquierdo
LA et al: Three-dimensional
transvaginal
sonography
of interstitial
pregnancy.
J Clin Ultrasound.
31(9):484-7,2003
11. Bouyer J et al: Sites of ectopic pregnancy:
a 10 year
population-based
study of ] 800 cases. Hum Reprod.
17(12):3224-30,2002
treatment
for
12. Chen CL et al: Successful conservative
advanced
interstitial
pregnancy.
A case report. J Reprod
Med. 47(5):424-6,
2002
13. Sagiv R et al: Three conservative
approaches
to treatment
of interstitial
pregnancy.
J Am Assoc Gynecol Laparosc.
8(1):154-8,200]
]4. Lawrence A et al: Three-dimensional
ultrasound
diagnosis
of interstitial
pregnancy.
Ultrasound
Obstet Gynecol.
14(4):292-3,
]999
]5. Takeuchi K et al: Comparison
of magnetic
resonance
imaging and ultrasonography
in the early diagnosis
of
interstitial
pregnancy.
J Reprod Med. 44(3):265-8,
1999
16. Ackerman
TE et al: Interstitial
line: Sonographic
finding in
interstitial
(cornual)
ectopic pregnancy.
Radiology.
]89:83-7,
1993

INTERSTITIAL ECTOPIC
I IMAGE GALLERY
Typical
(Left) Axial endovaginal
ultrasound shows the
interstitial line sign (arrow),
which extends from the
endometrium to the ectopic
gestational sac (curved
arrow). The surrounding
myometrium is thinned.
(Right) Axial color Doppler
ultrasound in another case
shows flow around the
interstitial ectopic (arrowendometrium). Prominent
arcuate vessels (open
arrows) are seen in the outer
third of the myometrium.
Exsanguination may occur if
the uterus ruptures.

Typical
(Left)

Ultrasound of a 73.5
week interstitial ectopic with
questionable myometrial
coverage around the lateral
aspect of the sac (arrow).
(Right) Axial T2WI MR was
likewise concerning for areas
of absent myometrium
(arrows).

(Left) Sagittal T2WI MR in
the same case shows the
normal myometrium rapidly
thinning (arrows) and
becoming a thin membrane
(curved arrow) around the
large ectopic sac. Blood
(open arrow) is seen in the
cul-de-sac. (Right)
Intra-operative photograph
of the right cornua shows
two areas of rupture
(arrows). Catastrophic
hemorrhage may occur
without prompt medical
treatment.

CERVICAL ECTOPIC

Sagittal endovaginal ultrasound of a cervical ectopic
pregnancy shows a retroverted uterus with a gestational
sac distending the cervix (open arrow). Decidual
reaction of the endometrium is present (arrows).

o Marked peritrophoblastic flow around sac
• Can be deceiving as early demise can also have
some persistent vascularized tissue

ITERMINOlOGY
Definitions
• Implantation

of gestational sac within cervical stroma

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Gestational sac within cervical
stroma with live embryo
• Morphology
o Gestational sac usually round
• Similar appearance to normal pregnancy
• Can be elliptical or flattened making diagnosis
more difficult

Ultrasonographic

Endovaginal ultrasound focused on the cervix shows the
yolk sac with an adjacent live embryo (arrow). This
patient was treated successfully with potassium chloride
injection into the sac and systemic methotrexate.

Findings

• Grayscale Ultrasound
o Eccentric sac within cervical stroma
• Endometrial/cervical canal visualized separately,
adjacent to sac
o "Hourglass" shaped uterus
• Secondary to cervical distention from pregnancy
o Embryo with heartbeat often present
o Internal os closed
o Decidual reaction of endometrium
• Color Doppler

Imaging Recommendations
• Transabdominal ultrasound aids in identifying
anatomic landmarks
o Uterine shape
o Uterine position
o Internal os
o Bladder and bladder wall
• Transvaginal ultrasound helpful to characterize early
gestational sac
o Aids in evaluating uterine cavity to differentiate
from abortion in progress
o Can also better evaluate adnexa
o Rare, but should exclude heterotopic pregnancy
• Especially in the setting of assisted reproductive
technology or hormonal stimulation
• Ultrasound localization for medical treatment
o Used for guidance of needle into sac
o Subsequent injection for termination
• Methotrexate
• Potassium chloride

DDx: Cervical Mass

Spontaneous

Abortion

Prolapsed

Polyp

C-section

Ectopic

Nabothian

Cysts

CERVICAL ECTOPIC
Key Facts
Imaging Findings
•
•
•
•

Eccentric sac within cervical stroma
"Hourglass" shaped uterus
Internal os closed
Marked peri trophoblastic flow around sac

Top Differential
•
•
•
•

Diagnoses

Normal pregnancy with low uterine implantation
Spontaneous abortion
Cesarean section (C-section) scar ectopic
Nabothian cyst

Pathology
• Prior instrumentation
key risk factor
• Endometrium is injured, adversely impacting
implantation of pregnancy
• Epidemiology: - 1% of ectopic pregnancies

I DIFFERENTIAL

DIAGNOSIS

Normal pregnancy with low uterine
implantation
• Sac will be above internal os
• Eccentric location in decidualized endometrium
• Normal pregnancy milestones should be identified
o Early sac correlates with serial human chorionic
gonadotropin (hCG) levels
• Should double every 48 hours in early pregnancy
o Look for normal yolk sac
• Should be seen by m~an sac diameter of 10 mm
• Normal diameter :5 6 mm
• Located outside amnion
o Identify presence of embryo
• Should be seen by mean sac diameter of 18 mm
• Must have a heart beat if ~ 5 mm

Spontaneous abortion
• Irregular, deformed, flattened sac
o Centered in cervical canal
o Mobile with gentle pressure ("sliding sign")
• Use transvaginal probe to visualize
o Lacks surrounding echogenic ring
• May see spontaneous movement of sac through
endocervical canal
o Repeat scan in a few hours may show complete
passage
• No embryo/fetal heart beat
• Enlarged globular uterus
o Typical hourglass shape of cervical ectopic not seen
• Internal os open
o External os mayor may not be open at time of
clinical exam
• Correlate with serial hCG
o Should be decreasing with miscarriage

Cesarean section (C-section) scar ectopic
• Can be difficult to distinguish from cervical ectopic
• Correlate with prior history of C-section
• Look for thinned or absent myometrium at scar

• Cervical mucosa vulnerable
proliferation

to trophoblast

Clinical Issues
• Potentially fatal if unrecognized
• Preservation of fertility usually successful when
treated conservatively
• Medical management advisable if possible
• Hysterectomy, if conservative therapy fails

Diagnostic Checklist
• Always consider if gestational sac has a low
implantation
• Be suspicious of a cervical ectopic if a gestational sac
in or near the cervix is round instead of flattened
• A living embryo within a cervical sac is highly
suspicious for an ectopic pregnancy

o Trophoblastic tissue may invade into adjacent
bladder
• Medical treatment is similar to cervical ectopic
o Helpful to distinguish if surgery planned
• May require scar revision

Nabothian

cyst

• Obstructed mucous secreting endocervical glands
o Thought to result from prior inflammation
• Asymptomatic, incidentally noted on pelvic
ultrasound
• Eccentric within cervical stroma
• Anechoic or low-level echoes
• May be single or multiple
• Usually 2-10 mm but may be larger
• No surrounding increased vascularity on Doppler
evaluation
• Generally follows fluid signal intensity on MRI
o Low signal T1 WI, high signal T2WI
o Occasionally mucin causes high signal on Tl WI

Cervical mass
• Cervical fibroid
o Hypoechoic cervical mass
o Can be pedunculated from myometrium
• If passes into cervix can present with pain
• Can protrude into vagina
o MRI

• Intermediate signal Tl WI, low signal T2WI
• Cervical polyp
o Either from cervix or prolapsed from endometrium
o Solid lesion in cervical canal
• Polyps may have cystic areas
o Vascularity seen with color Doppler ultrasound
• May have dominant feeding vessel
• Cervical carcinoma
o Irregular cervical mass
o Better evaluated with pelvic MR
• Intermediate signal mass invading cervical stroma

CERVICAL ECTOPIC
I PATHOLOGY
General Features
• Etiology
o Prior instrumentation
key risk factor
• Endometrium is injured, adversely impacting
implantation of pregnancy
o Multiple etiologies of endometrial injury
• Dilatation and curettage
• In vitro fertilization with embryo transfer
• Previous cervical procedure: Loop electrosurgical
excision procedure (LEEP), conization, cryosurgery
• Prior C-section
• Previous uterine surgery
• Asherman syndrome
• Epidemiology: - 1% of ectopic pregnancies

Gross Pathologic & Surgical Features
• Trophoblastic invasion into cervical stroma
• Insufficient vascularity within cervix to support
gestation

Microscopic

Features

• Cervical mucosa vulnerable to trophoblast
proliferation
o Allows deep penetration of chorionic villi

ICLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Bleeding
• Usually painless
• Other signs/symptoms
o May be incidental finding on early viability scan
• Often larger and presents later than tubal ectopic
o Abdominal/pelvic pain
o Hypotension and shock if ruptured
o Urinary problems
o Distended cervix
o External os dilatation

Natural History & Prognosis
• Potentially fatal if unrecognized
o May rupture
o Uncontrolled hemorrhage can result
• Good with appropriate treatment
• Preservation of fertility usually successful when treated
conservatively

Treatment
• Medical management advisable if possible
o Methotrexate
• Injected into sac
• Systemic administration
o Potassium chloride injection into sac
o May use combined approach of sac injection
followed by systemic methotrexate
o Close follow-up required to document regressing
pregnancy

• Follow-up ultrasound to show embryonic demise
and/or sac involution
• Serial hCG should show declining levels

• Uterine artery embolization
o Can be used to attempt hemostasis if significant
bleeding occurs
o May be required even if medical therapy initiated
• Hysterectomy, if conservative therapy fails
o Required in setting of uncontrolled, massive
hemorrhage
o Large ectopic
• Other methods also reported
o Curettage of endocervical remnants of pregnancy
• Following injection of sac
o Hysteroscopic resection of sac and tissue

I DIAGNOSTIC

CHECKLIST

Consider
• Always consider if gestational
implantation

Image Interpretation

sac has a low

Pearls

• Be suspicious of a cervical ectopic if a gestational sac in
or near the cervix is round instead of flattened
• A living embryo within a cervical sac is highly
suspicious for an ectopic pregnancy
• A follow-up scan in a few hours will show change or
passage of the sac in a spontaneous abortion

I SELECTED

REFERENCES

Hassiakos D et al: Cervical pregnancy treated with
transvaginal ultrasound-guided
intra-amniotic instillation
of methotrexate. Arch Gynecol Obstet. 271(1):69-72, 2005
Mesogitis S et al: Management of early viable cervical
2.
pregnancy. BJOG. 112(4):409-11,2005
3. Doubilet PM et al: Sonographically guided minimally
invasive treatment of unusual ectopic pregnancies. J
Ultrasound Med. 23(3):359-70, 2004
Hidalgo LA et al: Management of cervical pregnancy: risk
4.
factors for failed systemic methotrexate. J Perinat Med.
32(2):184-6,2004
Kung IT et al: Differential diagnosis of suspected cervical
5.
pregnancy and conservative treatment with the
combination of Iaparoscopy-assisted
uterine artery ligation
and hysteroscopic endocervical resection. Fertil Steril.
81(6):1642-9,2004
6. Papaloucas CD: "Hour-glass" shape of the uterus in the
diagnosis and treatment of cervical pregnancy. Clin Anat.
17(8):658-61,2004
Gun M et al: Cervical ectopic pregnancy: a case report and
7.
literature review. Ultrasound Obstet Gynecol.
19(3):297-301,2002
Pascual MA et al: Cervical ectopic twin pregnancy:
8.
diagnosis and conservative treatment: case report. Hum
Reprod. 16(3):584-6, 2001
Kung IT et al: Subsequent reproduction and obstetric
9.
outcome after methotrexate treatment of cervical
pregnancy: a review of original literature and international
collaborative follow-up. Hum Reprod. 12(3):591-5, 1997
10. Jurkovic D et al: Diagnosis and treatment of early cervical
pregnancy: a review and a report of two cases treated
conservatively. Ultrasound Obstet Gynecol. 8(6):373-80,
1996
11. Frates MC et al: Cervical ectopic pregnancy: results of
1.

conservative treatment. Radiology. 191(3):773-5, 1994

CERVICAL ECTOPIC
I IMAGE GALLERY
(Left) Color Doppler
ultrasound of the uterus
shows mild vascularity
surrounding a gestational sac
in the cervical canal (arrow).
The sac has a flattened
appearance, suggestive of a
spontaneous
abortion.
(Right) M-mode ultrasound
shows a heartbeat however,
making a cervical ectopic
more likely. A repeat exam in
a few hours would confirm
the diagnosis. The heartbeat
would be gone and sac
either changed or passed
with a spontaneous
abortion.

Variant
(Left) Sagittal ultrasound of a
large cervical ectopic shows
a 73.5 week living fetus
(curved arrow) and placenta
(arrow) implanted within the
cervix (uterus - open arrow).
(Right) Coronal TlWI MR
shows the fetus (arrow)
within the cervix. Open
arrows show the vagina. The
uterus is out of the plane of
section. The patient
underwent a hysterectomy.

Variant
(Left) Cross pathology from
the case above shows
marked enlargement of the
cervix (arrows) with
variegated, hemorrhagic
trophoblastic tissue (uterus open arrows, ovary - curved
arrow). (Right) Sagittal T2WI
MR from a different case
shows trophoblastic invasion
into the cervical stroma
(arrows) from a cervical
ectopic (external os - curved
arrow). There is also blood
within the endometrial cavity
(open arrow).

ABDOMINAL

Sagittal ultrasound of the pelvis shows the fetal head
(arrows) located within the abdominal cavity, above the
uterus (open arrow). The endometrium
demonstrates
an echogenic decidual reaction (curved arrow).

ITERMINOlOGY
Definitions
• Pregnancy outside of the uterus and within the
peritoneal cavity

IIMAGING

ECTOPIC

An image slightly higher shows the intra-abdominal fetus
and placenta, which is implanted on the anterior
abdominal wall (arrows). This should not be confused
with the normal hypoechoic myometrial wall.

o Identify location of placenta(s)
o Plan surgical intervention
• Peritoneal entry site
o Assess for secondary complications
• Uterine/solid organ invasion
• Bowel obstruction, hydronephrosis
• Consider MR angiography to identify vascular supply

FINDINGS

General Features

[DIFFERENTIAL DIAGNOSIS

• Best diagnostic clue
o Gestational sac with embryo or fetus in abdomen
o Uterus identified separately

Tubal ectopic pregnancy

Ultrasonographic

Findings

• Lack of normal, hypoechoic rim of myometrium
surrounding gestational sac
• Most often in pouch of Douglas or posterior uterine
wall
• Implantation sites also include various abdominal
structures
o Omentum, mesentery, bowel
o Liver, spleen
o May implant on multiple sites
• Echogenic free fluid (hemorrhage) may be present

• Less likely to see a large embryo/fetus
• Echogenic tubal ring or hematoma most common
findings

Intrauterine
• Hypoechoic

pregnancy
endometrium

surrounds

gestational

[PATHOLOGY
General Features
• Epidemiology:
pregnancies

Approximately

1% of all ectopic

Gross Pathologic & Surgical Features

Imaging Recommendations

• Primary abdominal pregnancy
o Extremely uncommon

• Abdominal MR useful

DDx: Other Ectopic Pregnancies

Heterotopic

Pregnancy

Live Tubal Ectopic

Ruptured

Ectopic

Interstitial Ectopic

sac

ABDOMINAL

ECTOPIC

Key Facts
Imaging Findings

Pathology

• Gestational sac with embryo or fetus in abdomen
• Lack of normal, hypoechoic rim of myometrium
surrounding gestational sac
• Most often in pouch of Douglas or posterior uterine
wall

• Epidemiology: Approximately 1% of all ectopic
pregnancies

Top Differential

Diagnoses

Clinical Issues
• Significant rate of maternal morbidity and mortality
• Placental embolization reported to be successful in
decreasing placental mass

• Tubal ectopic pregnancy
• Intrauterine pregnancy
o Studdiford criteria
• Normal tubes and ovaries present
• No evidence of uteroperitoneal fistula
• Pregnancy related exclusively to peritoneal surface
from early gestation
• Secondary abdominal pregnancy
o More common type
o Tubal ectopic pregnancy ruptures into peritoneal
cavity
o Subsequent implantation in abdomen
I CLINICAL

ISSUES

o Placental embolization reported to be successful in
decreasing placental mass
o CT used to follow regression of residual placental
tissue in abdomen
• Serial beta hCG after evacuation to document
appropriately declining levels

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Always assess for hypoechoic myometrium around
developing pregnancy to prove intrauterine location

Presentation
• Most common signs/symptoms
o Abdominal pain
o Hypotension
• Hypovolemic shock may occur secondary to
massive hemorrhage
o Incidentally noted on routine viability sonogram or
anatomic survey

I SELECTED REFERENCES

Natural History & Prognosis

4.

• Significant rate of maternal morbidity and mortality
o Higher maternal mortality rate than with other
types of ectopic pregnancy
• Most will cause intraperitoneal bleeding
• Spontaneous demise of embryo/fetus occurs when
blood supply becomes insufficient
• Rarely sufficient blood supply to carry pregnancy to
viability

1.

2.
3.

5.

Onan MA et al: Primary omental pregnancy: case report.
Hum Reprod. 20(3):807-9, 2005
Xiao GH et al: Abdominal pregnancy: full-term viable
baby. Eur J Obstet Gynecol Reprod BioI. 118(1):117-8, 2005
Kalof AN et al: Splenic pregnancy: a case report and review
of the literature. Arch Pathol Lab Med. 128(11):e146-8,
2004
Veerareddy S et al: Non-surgical management of a
mid-trimester abdominal pregnancy. BJOG. 111(3):281-3,
2004
Oelabrousse E et al: Intrahepatic pregnancy: sonography
and CT findings. AJR AmJ Roentgenol. 173(5):1377-8,
1999

I IMAGE GAllERY

Treatment
• First trimester
o Potassium chloride injection into sac or embryo
o Methotrexate
• Systemic dose or injection into sac
o Surgical evacuation of pregnancy may be necessary
if bleeding persists
• Second trimester
o Consider presurgical embolization of placental
vessels
o Surgical evacuation of fetus
• Third trimester (rare)
o Consider watchful waiting if near viability
• Immediate delivery for signs of bleeding
o Surgical delivery of fetus
• Placenta not necessarily removed surgically

(Left) Axial T2WI MR of a second trimester abdominal pregnancy
shows the fetal head and a placental mass (arrow) displacing the
uterus (open arrows) posteriorly. (Right) Axial CECT after delivery at
28 weeks shows heterogeneous enhancement of one of the residual
placental masses (curved arrows). These spontaneously regressed
over time on follow-up CT scans.

C-SECTION SCAR ECTOPIC

Sagittal endovaginal ultrasound in a patient with vaginal
bleeding shows a gestational sac (curved arrow), which
is low and eccentric to the endometrial cavity (arrows).
She has a history of 2 prior C-sections.

Gross pathology of the opened uterus after emergency
hysterectomy shows the implantation site (arrow). This
corresponded to the site of her C-section scar.

• Consider MR to evaluate local anatomy
trophoblastic invasion of bladder

ITERMINOlOGY

and possible

Definitions
• Ectopic pregnancy
(C-section) scar

developing

at the cesarean section

I DIFFERENTIAL DIAGNOSIS
Cervical ectopic

IIMAGING

FINDINGS

General Features
• Best diagnostic clue
o Eccentric gestational sac within anterior
myometrium at site of cesarean section (CS) scar
• Empty uterine cavity and cervical canal
• Thinned or absent myometrium at scar between
sac and bladder
• Color Doppler shows marked peritrophoblastic
flow
around sac
o Generally low-impedance, high-velocity flow
o Useful to detect invasion into bladder

Imaging Recommendations
• Assess for other associated complications
C-section
o Placenta accreta, in creta or percreta
o Placenta previa
o Placental abruption

of prior

• Located within cervical stroma
• Can be difficult to distinguish from C-section scar
ectopic, especially if sac is large
• May be lateral or posterior, not just anterior as with
C-section scar ectopic

Prominent C-section scar
• Varied appearances
o Wedge-shaped anechoic defect in anterior
myometrium
o Cystic fluid collection within incision site
• Consider evaluation of C-section scar and uterine wall
integrity prior to conception in patients at high-risk of
complications
o In vitro fertilization patients
o Multiple prior C-sections

Adenomyosis
• Ill-defined, hypoechoic, thickened junctional zone
• Ectopic glands create small cysts, which could be
confused with C-section ectopic
o Most cysts are 2-3 mm but can be as large as 4 em

DDx: C-Section Scar Variations And Ectopic Mimics

Prominent

CS Defect

Adenomyosis,

Cyst

C-section

Scar Cyst

Cervical

Ectopic

C-SECTION SCAR ECTOPIC
Key Facts
Imaging Findings

Clinical

• Eccentric gestational sac within anterior myometrium
at site of cesarean section (CS) scar
• Thinned or absent myometrium at scar between sac
and bladder

• Can be asymptomatic initially
• Massive bleeding usually occurs by late first trimester
if not treated
• High risk for uterine rupture
• Avoid isolated dilatation and curettage

Top Differential

Diagnoses

• Cervical ectopic
• Prominent C-section scar
• Adenomyosis
o Appearance may change over menstrual cycle

I PATHOLOGY
General Features
• Epidemiology
o Rarest form of ectopic pregnancy
o True incidence difficult to assess due to so few
reported cases

Issues

Diagnostic Checklist
• Prominent, cystic C-section scar can mimic early
ectopic gestational sac
o Revision/resection of C-section scar
• Avoid isolated dilatation and curettage
o Trophoblastic tissue invading myometrium unlikely
to be fully removed
o Risk of perforating uterine wall and/or damaging
bladder
o May lead to massive bleeding

I DIAGNOSTIC

CHECKLIST

Gross Pathologic & Surgical Features

Image Interpretation

• Two types of C-section scar ectopic pregnancies
o Implantation at scar, with progression toward
uterine cavity
• Rarely can lead to viable fetus
o Deep implantation into defect, with subsequent
rupture and life-threatening bleeding
• Diagnosis and symptoms usually in first trimester
of pregnancy

• Look for sac at the C-section scar and thinned or
absent anterior myometrium
• Prominent, cystic C-section scar can mimic early
ectopic gestational sac

I CLINICAL

ISSUES

I SELECTED
1.

2.

Presentation

Pearls

REFERENCES

Maymon R et al: Ectopic pregnancies in a Caesarean scar:
review of the medical approach to an iatrogenic
complication. Hum Reprod Update. 10(6):515-23,2004
Seow KM et al: Cesarean scar pregnancy: issues in
management. Ultrasound Obstet Gynecol. 23(3):247-53,
2004

• Most common signs/symptoms
o Can be asymptomatic initially
o Vaginal bleeding
o Abdominal or pelvic pain
o Hypotension due to hemorrhage

3.

Natural History & Prognosis

IIMAGE

]urkovic IJ et al: First-trimester diagnosis and management
of pregnancies implanted into the lower uterine segment
Cesarean section scar. Ultrasound Obstet Gynecol.
21(:{):220-7,2003

GALLERY

• Life-threatening condition
o Massive bleeding usually occurs by late first
trimester if not treated
• High risk for uterine rupture
• Multiple prior C-sections may increase risk of
C-section scar ectopic

Treatment
• Goal is to preserve future fertility
• Medical treatment
o Systemic or locally injected methotrexate
o Local injection of potassium chloride into sac or
embryo
o Rupture of scar and bleeding may still occur
• Consider concurrent uterine artery embolization
or vasopressin injection
• Surgical management
o Laparotomy with excision of pregnancy

(Left) Sagillal endovaginal ultrasound shows the gestational sac
(arrows) within the wall of the lower uterine segment in a patient
with a history of prior C-section (bladder - open arrow). (Right) A
closer view clearly shows it is anterior to the endometrial cavity
(arrows). It may be difficult to differentiate a C-section from cervical
ectopic but the distinction is not critical as treatment is the same.

HETEROTOPIC

Endovaginal ultrasound of a heterotopic pregnancy
shows an intrauterine gestational sac (arrows) with a
yolk sac, and embryo. Echogenic fluid (open arrows) is
seen within the endometrial cavity.

PREGNANCY

Additionally, in the left adnexa there is an echogenic
mass (arrows) adjacent to the ovary (open arrow). A
large amount of echogenic free fluid was also present. A
ruptured tubal ectopic was found at surgery.

I DIFFERENTIAL DIAGNOSIS

ITERMINOlOGY
Definitions

Ectopic pregnancy

• Two concurrent pregnancies, at least one of which is
ectopic in location
o Tubal, cervical, cornual, abdominal, cesarean section
scar
• Usually one intrauterine pregnancy with tubal ectopic
pregnancy
o Triplet heterotopic pregnancies reported

• Much more common
• Pseudosac may mimic a true gestational sac simulating
a heterotopic pregnancy
o Central fluid collection
• Normal sac is eccentric to endometrial cavity
o No double decidual sac sign

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Intrauterine embryo/fetus with
second ectopic pregnancy

Imaging Recommendations
• Identify intrauterine pregnancy
• Look for echogenic free fluid or adnexal mass/ring
• Use color Doppler whenever ectopic is suspected
o Increased trophoblastic flow creates "ring of fire"
o Helpful for identifying small ectopic pregnancies,
which might otherwise be missed

Uterine duplications
• May appear as heterotopic pregnancy
o Twins with one sac in each horn
o Single sac with fluid in other horn
• Myometrium completely surrounds each sac
• No adnexal masses
• Types of anomalies
o Didelphys: 2 separate uteri
o Bicornuate: Concave fundal contour
o Septate: Normal fundal contour

I PATHOLOGY
General Features
• Epidemiology
o < 1:30,000 naturally conceived pregnancies
• Incidence is increasing

DDx: Two

Sacs Simulating Heterotopic

Ectopic, Pseudosac

Ectopic, Adnexa

Pregnancy

Bicornuate Twins

Bicornuate Twins

HETEROTOPIC

PREGNANCY

Key Facts
Terminology
• Two concurrent pregnancies, at least one of which is
ectopic in location

Top Differential

Diagnoses

• Ectopic pregnancy
• Uterine duplications

Pathology
• < 1:30,000 naturally conceived pregnancies
o 1:100-500 following assisted reproductive
technology (ART)pregnancies
• Damage to endometrium or fallopian tubes
predisposes to ectopic pregnancy implantation
o Tubal damage
• Prior ectopic pregnancy
• Endometriosis
• Prior salpingectomy
• Pelvic inflammatory disease
o History of pelvic surgery
o Intrauterine contraceptive device
o Uterine anomalies

• 1:100-500 following assisted reproductive technology
(ART)pregnancies
• Damage to endometrium or fallopian tubes
predisposes to ectopic pregnancy implantation

Clinical Issues
• Approximately 66% of treated heterotopic
pregnancies deliver live fetus
• Surgical management treatment of choice, to preserve
intrauterine pregnancy

I DIAGNOSTIC

Image Interpretation

I SELECTED REFERENCES

ISSUES

Presentation
• Most common signs/symptoms
o Abdominal pain
o Adnexal mass
o Vaginal bleeding
o Hypovolemic shock if ruptured

2.

3.

4.

Natural History & Prognosis
• Depends on size and location of ectopic
• Approximately 66% of treated heterotopic pregnancies
deliver live fetus

Pearls

• Careful evaluation of high-risk patients warranted to
exclude heterotopic pregnancy
o Always carefully check adnexa, even if intrauterine
pregnancy identified
o Especially important if patient presents with pelvic
pain

1.

I CLINICAL

CHECKLIST

5.

Rabbani I et ai: Heterotopic pregnancy is not rare. A case
report and literature review. J Obstet Gynaecol.
25(2):204-5, 2005
Chin HY et al: Heterotopic pregnancy after in vitro
fertilization-embryo
transfer. Int J Gynaecol Obstet.
86(3):411-6,2004
Yazicioglu HF et al: An unusual case of heterotopic twin
pregnancy managed successfully with selective feticide.
Ultrasound Obstet Gynecol. 23(6):626-7, 2004
Varras M et al: Heterotopic pregnancy in a natural
conception cycle presenting with tubal rupture: a case
report and review of the literature. Eur J Obstet Gynecol
Reprod Biol. 106(1):79-82,2003
Tal J et al: Heterotopic pregnancy after ovulation induction
and assisted reproductive technologies: a literature review
from 1971 to 1993. Fertil Steril. 66(1):1-12, 1996

Treatment
• Surgical management treatment of choice, to preserve
intrauterine pregnancy
o Salpingotomy
• Small lengthwise incision in tube
• Removal of ectopic pregnancy
o Salpingectomy
• Segment of tube removed
• Ends reconnected if possible
• Only choice for ruptured ectopic
• Medical treatment
o Potassium chloride (KCI) injection into ectopic sac
• Does not affect trophoblastic tissue
o Methotrexate injection into sac
• Slows trophoblastic tissue growth
• Less favored due to potential risk of toxicity to
intrauterine embryo
o Combination of KCI and methotrexate injection
• Serial beta hCG measurements
o May be misleading, as normal pregnancy placental
production will be high

I IMAGE GALLERY

(Left) Sagittal ultrasound shows an eccentric gestational sac (arrow)
within the uterus. A decidual reaction is present, however no yolk sac
or embryo is identified,
consistent with a failed intrauterine
pregnancy.
(Right) Endovaginal
ultrasound
reveals a second
gestational sac in the right adnexa, adjacent to the ovary (open
arrow). A well-defined yolk sac (curved arrow) is seen and there is
echogenic free fluid (arrows).

INCREASED NUCHAL TRANSLUCENCY

Lateral graphic sho\l's ho\1' the nuchal trallSlucency
should be measured. The calipers are placed such that
the largest measurement of subcutaneous fluid is
obtained.

o Variable
• Most often t NT is minimal
• Morphology:
Usually simple fluid without

ITERMINOlOGY
Abbreviations
• Increased
• Increased
• Thickened

and Synonyms

nuchal translucency
nuchal lucency
nuchal fold

(t NT)

Ultrasonographic

Definitions
• t Fluid under skin in back of fetal neck
o Measurement
performed
at 11-14 wks menstrual
o Marker for aneuploidy
• Trisomy 21 ('1'21) most common
o Marker for congenital
heart defect (CH D)

IIMAGING FINDINGS
General

Features

• Best diagnostic
clue
o NT> 95th percentile
for menstrual
age (MA)
o NT:::: 3 mm always abnormal
(11-14 wks MA)
• Location
o Fluid is underneath
skin
o May extend beyond neck
• Inferiorly to back
• Superiorly to scalp
• Anteriorly
to abdomen
• Size

DDx: Pitfalls

In NT Measurements

Sagittal ultrasound shOlI'S increased NT in a 72 week
fetus. The transverse portion of the "+" calipers are
correctly placed at the margins of fluid. The amnion
(arrows) is seen separale from the skin.

age

septations

Findings

• NT measurement
technique
o Transabdominal
ultrasound
often adequate
• > 95')1, success rate
• 5% require transvaginal
exam
o Success rate for obtaining
accurate NT near lOO'!1,
• Takes time and patience
o Small window of opportunity
for NT screening
• 11-14 wks MA
• Crown rump length (CRL) of 45-84 mm
• Biparietal diameter < 27 mm
o Midsagittal
plane
• Beam perpendicular
to skin
• Maximizes ability to discern skin
o Image magnification
crucial
• Head, neck, upper chest occupies::::
75%) of image
o Fetal head in neutral position
• Flexion minimizes
NT
• Extension
falsely maximizes
NT
o Beware of amnion
• Gravity dependent
fetus may lie on amnion
• Wait for fetus to move away
• Show amnion and skin on same image
o Correct caliper placement
critical

INCREASED NUCHAL TRANSLUCENCY
Key Facts
• Poor measurement
• Cystic hygroma

Terminology
• Increased nuchal translucency (t NT)
• t Fluid under skin in back of fetal neck
• Measurement performed at 11-14 wks menstrual
• Marker for aneuploidy
• Trisomy 21 (T21) most common
• Marker for congenital heart defect (CHD)

Pathology
age

Imaging Findings
• Success rate for obtaining accurate NT near 100%
• Correct caliper placement critical
• t NT associated with hydrops
• Ultrascreen testing: NT + maternal serum screen
• 90% detection rate for aneuploidy

Top Differential
• Chorioamniotic

Diagnoses
separation

• Use "+" calipers only
• Can not use "x" calipers
• Calipers border anechoic space
• Transverse caliper line excludes skin
• True measurement of fluid only
• Measure largest fluid depth
o Accurate and sensitive calibration necessary
• Incremental increase in calipers of 0.1 mm
• Example: Can measure 2.1 vs. 2.2 mm
o Machine must have cine-loop ability
• 1st trimester fetal movement is "spastic"
• Abrupt flexion and extension common
• Cine to appropriate neutral position
• Measurement criteria for t NT
o NT measurement>
95th percentile for MA
• Certified labs have software to calculate percentile
o NT ~ 3 mm always abnormal
o NT < 3 mm may be abnormal
• t NT and chromosome abnormalities
o Trisomy 21
• Most common
• t NT leads to t nuchal skin fold in 2nd trimester
o Trisomy 18 (T18)
• Early intrauterine growth restriction may be
present
o Trisomy 13 (T13)
• Other anomalies are detectable in 1st trimester
• Cardiac defects
• Intracardiac echogenic focus
• Holoprosencephaly
• Severe facial anomaly
o Turner syndrome
• Often with largest NT
• Septations may be seen
• Associated hydrops
• t NT and non-chromosome
abnormalities
o CHD

• 24x t risk if NT > 99th percentile (normal
chromosomes)
• Cardiac defect rarely obvious at 11-14 wks
o Syndromes and t NT
• Skeletal dysplasia

technique

• Abnormal lymphatic
• Early heart failure

drainage

Clinical Issues
• 90% normal outcome if no aneuploidy
• Larger NT has worse prognosis

Diagnostic Checklist
• Perform NT screening only in certified lab
• Fetal echocardiography
if t NT and normal
chromosomes
• Amniotic membrane is a potential pitfall in
measuring NT

• Myotonic dystrophy
• Many other syndromes
• t NT associated with hydrops
o t NT + skin edema
• +/- Ascites
• +/- Pleural effusion
o More common with Turner syndrome
o Can be seen regardless of cause of t NT
• Pitfalls
o Amniotic membrane
• Gravity dependent fetus lies on amnion
• Can mimic fetal skin
• Wait for fetus to move away from amnion
o Nuchal cord
• 5-10% incidence in 1st trimester
• Presence makes NT measurement difficult
• Measure below and above nuchal cord
• Report smallest NT number

Imaging Recommendations
• Best imaging tool: NT measurement by certified
sonogra pher /sonologist
• Protocol advice
o Fetal medicine foundation (FMF) certification
should be obtained before performing
• Certifies individuals to perform NT measurement
• Education course required
• Image and video tape review required
o Ultrascreen testing: NT + maternal serum screen
• Obligatory FMF certification
o First trimester maternal serum screen
• Free ~-human chorionic gonadotropin (~-hCG)
• Pregnancy-associated plasma protein A (PAPP-A)
• t B-hCG, + PAPP-A with T21
o Can add nasal bone assessment
• Look for absence of nasal bone
• Part of ultrascreen program now
• Improves detection rates for aneuploidy
o Aneuploidy detection rates using NT alone
• 82% for T21
• 82% for T18
• 80% for T13
• 89% for Turner syndrome

INCREASED NUCHAL TRANSLUCENCY
o Improved detection rates using ultrascreen test
• 90% detection rate for aneuploidy
o Second trimester follow-up in screened population
• Detailed anatomic ultrasound
• Controversial if repeat serum screen necessary
• Echocardiography if t NT and normal
chromosomes

I DIFFERENTIAL
Chorioamniotic

DIAGNOSIS
separation

• Normal at 11-14 wk MA
• Amnion confused for fetal skin
• Fetus lies supine upon amnion
o Measurement taken from fetus to amnion
• NT measurement requires patience
o Wait to see fetus move away from amnion

Poor measurement
•
•
•
•

technique

Image not adequately magnified
Calipers not correctly placed
Obliquely oriented fetus
Measurement performed late (> 14 wks)

Cystic hygroma
• Large fluid collection behind fetal neck
o Septations common
o Can mimic amniotic fluid
• Often with associated hydrops
• More often second trimester diagnosis
o 2/3 with chromosome abnormality
• Turner syndrome most common
• Trisomy 21

I PATHOLOGY
General Features
• Genetics
o Trisomy 21
o Trisomy 18
o Trisomy 13
o Turner syndrome
o Most often normal chromosomes
• Etiology
o Abnormal lymphatic drainage
• Delayed lymphatic development
• Absent lymphatic channels
• Genetic abnormality
• Movement disorder
o Early heart failure
• Cardiac defect
• Congenital infection
• Fetal anemia
o Abnormal extracellular matrix
• Proteins encoded on chromosomes 21, 18, 13
• Associated abnormalities
o Non-chromosomal structural anomalies
• Cardiac defects
• Myotonic dystrophy
• Skeletal dysplasia
• Diaphragmatic hernia
• Omphalocele

• VACTERLassociation

ICLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Incidentally seen during first trimester ultrasound
o Detected during ultrascreen test

Demographics
• Age
o Associated with advanced maternal age (AMA)
• AMA = ~ 35 year old at time of delivery
• Trisomies associated with AMA
• Turner not associated with AMA

Natural History & Prognosis
• Variable prognosis dependent upon chromosome
results and presence of other abnormalities
o 90% normal outcome if no aneuploidy
• 8% with CHD
• 2% with other anomalies/syndrome
• Larger NT has worse prognosis
o CHD: 3% if NT 3.5-5.4 mm -+ 15% if NT ~ 5.5 mm
o Largest NTs associated with Turner syndrome
• t NT natural history
o Often resolve spontaneously
o Progress to 2nd trimester t nuchal fold
o Progress to 2nd trimester cystic hygroma
o Progress to hydrops

Treatment
• Chorionic villus sampling (CVS)
• Amniocentesis

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Perform NT screening only in certified lab
o Should be able to offer CVS
o Should be able to offer genetic counseling
• Fetal echocardiography if t NT and normal
chromosomes
• Amniotic membrane is a potential pitfall in measuring

NT

I SELECTED REFERENCES
1.

2.
3.

4.

5.

Avgidou K et al: Prospective first-trimester
screening for
trisomy 21 in 30,564 pregnancies.
Am] Obstet Gynecol.
192(6):1761-7,2005
Souka AP et al: Increased nuchal translucency
with normal
karyotype. Am] Obstet Gynecol. 192(4):1005-21,2005
Nicolaides KH: Nuchal translucency
and other
first-trimester
sonographic
markers of chromosomal
abnormalities.
Am] Obstet Gynecol. 191(1):45-67, 2004
Platt LD et al: Sequential pathways of testing after
first-trimester
screening for trisomy 21. Obstet Gynecol.
104(4):661-6,2004
Nicolaides KH et al: Nuchal translucency
and chromosome
defects, in Diploma in Fetal Medicine Series: The 11-14
week scan. Parthenon
Publishing group. 1:1-50, 1999

INCREASED NUCHAL TRANSLUCENCY
I IMAGE GAllERY
(Left) Sagittal ultrasound
shows t NT (arrows) in a
fetus with trisomy 21. The
amnion (curved arrow) is
not included in the NT
measurement. The nasal
bone is absent (open arrow).
(Right) Sagittal ultrasound
shows a markedly t NT
(arrows) in a fetus with
Turner syndrome. Very large
NT and hydrops are often
seen with Turner syndrome.

Typical
(Left) Sagittal ultrasound
shows a 13 wk fetus with t
NT (arrows) that extends
down the back. There is also
a distended bladder (curved
arrow). (Right) Ultrasound
performed prior to
amniocentesis (at 16 wks)
shows t nuchal fold
thickening (arrows) and club
foot (curved arrow points to
toes and open arrows point
to shin). This fetus with
multiple anomalies had
trisomy 18.

(Left) Sagittal ultrasound
shows t NT (curved arrow)
and body wall edema (open
arrow). Chromosomes were
normal and
echocardiography was
performed in the second
trimester. (Right) Axial
ultrasound shows a severely
hypoplastic left heart. Only
the right atrium (open
arrow) and right ventricle
(curved arrow) are visible. t
NT is associated with cardiac
defects, with or without
chromosome abnormalities.

DUCTUS VENOSUS

Color Doppler ultrasound shows the umbilical vein
(open arrow) in the fetal abdomen. The ductus venosus
is easily seen as an area of aliasing (curved arrow)
between the portal vein and IVC (arrow).

ITERMINOlOGY
Abbreviations

and Synonyms

• Ductus venosus (DV)

Definitions
• Fetal vascular connection from portal vein (PV) to
inferior vena cava (IVe)
o Brings oxygenated blood from placenta to heart
o Shunts oxygenated stream - foramen ovale - left
atrium - ascending aorta

IIMAGING FINDINGS
General Features
• Size
o Maximum length DV 3 mm, in first trimester
o Diameter at isthmus (narrowest portion of inlet) ::5 2
mm throughout pregnancy
• Morphology
o DV is funnel-shaped
• Focal narrowing creates a "jet effect" - at least
50% of UV blood shunted toward foramen ovale
• Ensures blood with higher oxygen saturation goes
to ascending aorta - coronary/cerebral
circulations
• Applications of DV ultrasound

Pulsed Doppler ultrasound in a 73 week fetus shows the
normal triphasic ductus venosus waveform, with an 5,
D and A wave (arrows). Flow is always forward (in this
case below the baseline).

o First trimester screening for aneuploidy
o 2nd/3rd trimester
• Evaluation of cardiac function
• Information on fetal response to hostile
environment with growth restriction
• Normal waveform is triphasic, with continuous
forward flow
o S wave: Ventricular systole
o D wave: Early ventricular diastole
o A wave: Atrial contraction
• Physiology
o Waveform reflects pressure gradient between right
atrium and umbilical vein
o Ventricular contraction = maximum atrial filling S wave
o Early ventricular diastole = atria empty into
ventricles - atrial inflow increases - D wave
o Atrial contraction = highest atrial pressure = lowest
atrial inflow - A wave
• Abnormal waveform
o Reduction of forward flow during A wave
o Reversed flow during A wave
o Abnormal indices: Normative data available
• Pulsatility index (PI), S:A ratio, peak velocity index

Imaging Recommendations
• Best imaging tool: Pulsed Doppler
• First trimester

DDx: Conditions Associated With Abnormal

Trisomy 18

Trisomy 21

DV Flow

CHD-Pulm Atresia

Placental Insufficiency

DUCTUS VENOSUS
Key

Facts

Terminology

Top Differential

• Fetal vascular connection from portal vein (PV) to
inferior vena cava (IVC)
• Brings oxygenated blood from placenta to heart

• Absence of ductus venosus

Imaging Findings
• DV is funnel-shaped
• Focal narrowing creates a "jet effect" -. at least 50% of
UV blood shunted toward foramen ovale
• Ensures blood with higher oxygen saturation goes to
ascending aorta -. coronary/cerebral circulations
• Normal waveform is triphasic, with continuous
forward flow
• Beware of pitfalls in Doppler evaluation of DV
• Incorrect placement of sample volume may give
spurious results

o Most cases can be imaged transabdominally
• Use endovaginal scans for difficult maternal
habitus
o Sagittal section
o Place cursor in midline beneath diaphragm
o Move cursor while listening for sound: Sample at
site of "machinery murmur" sound
o May use Color Doppler to assist with direct
visualization of DV
• In general, try to avoid extensive use of color
Doppler in first trimester due to safety concerns
• Limit exposure to < 5 minutes
o Sample volume 1 mm, high-pass filter set at 50Hz
o Obtain three good waveforms
• 2nd/3rd trimester use Color Doppler
o Sagittal section in midline
• Follow umbilical vein from cord insertion site into
left portal vein (PV)
• Focal narrowing of DV (between PV and IVC) -.
aliasing on color Doppler
o Oblique transverse section
• Cursor beneath diaphragm, right of midline
• DV identified by characteristic sound
o Place sample volume in DV inlet, avoiding PV and
IVC
o For velocity measurements have angle of insonation
< 60°

• Velocity ratios are independent of angle
• Pulsed Doppler: Multiple parameters can be measured
o Peak velocity: Maximum velocity during S wave
o Peak velocity index: Peak velocity S wave minus
peak velocity A wave/peak velocity D wave
o S:Aratio = peak velocity S wave/peak velocity A
wave (can not be measured if reversed flow in A
wave)
o PI: Peak velocity S wave minus peak velocity A
wave/time-averaged velocity (many published
studies use mean PI)
• Beware of pitfalls in Doppler evaluation of DV
o Incorrect placement of sample volume may give
spurious results
o If sample volume includes IVC or hepatic veins

Diagnoses

Clinical Issues
• Published incidence of aneuploidy associated with
abnormal DV flow varies from 65-90%

Diagnostic Checklist
• Published data is based on study of high-risk
populations
• Value of DV assessment in fetuses with normal NT,
normal growth is unclear
• Changes in DV flow in 2nd/3rd trimester imply
severe fetal compromise and imminent demise
• In first trimester, abnormal DV flow is associated with
aneuploidy and increased risk for adverse outcome,
even if chromosomes are normal

• May see apparent reversal of flow in diastole
o If sample volume includes portal or umbilical vein
• May cause spurious appearance of forward flow or
obscure decreased flow during A wave
o May see intrafetal variation, especially with
movement, breathing

I DIFFERENTIAL DIAGNOSIS
Absence of ductus venosus
• Very rare but 3 subtypes described
o UV connects directly to right atrium, bypassing liver
• Color Doppler shows aberrant vessel crossing
diaphragm
• Courses between liver and right abdominal wall
o UV connects to IVC via iliac or renal vein (bypasses
liver)
• UV courses inferiorly if connected to iliac vein
• IVC enlarged
.
o UV connects to PV without development of DV
• Color Doppler fails to identify DV
• Hepatic veins may be distended
• Strong association with aneuploidy (25%)
o Trisomy 21, 18, Turner syndrome
• Strong association with adverse outcome
o Hydrops 33%
o Polyhydramnios
o Surviving infants: 50% have absent portal veins

I PATHOLOGY
General Features
• Epidemiology
o DV waveform abnormal in 7.7% of series 1, 217
un selected patients presenting for first trimester
screening
• Maternal age> 35 yrs in 45% of group
• Nuchal translucency (NT) > 95th percentile for
CRL in 49% of cases with abnormal DV flow
• First trimester

DUCTUS VENOSUS
o Cardiac impairment thought to be cause of
abnormal NT and abnormal DV flow
o Significant correlation observed between DV PI and
NT measurement
• 2nd/3rd trimester conditions that affect DV flow
o Diminished cardiac contractility
• Severe placental insufficiency, arrhythmia, anemia
-+ hypoxia
-+ subendocardial
ischemia
• Extrinsic compression by pericardial/pleural
fluid
o Increased afterload
• Abnormal placental resistance
• Obstruction to cardiac outflow (e.g. pulmonary
atresia with intact ventricular septum)
o Increased preload (increased venous return)
• Shunt lesions: Vascular tumors, arteriovenous
malformations
• Recipient twin in twin-twin transfusion syndrome
• Physiology of abnormal placental resistance
o Increased cardiac work required to perfuse
abnormally resistive placenta
o Right ventricle (RV) is systemic ventricle in fetus
o RV decompensation,
tricuspid regurgitation
o Tricuspid regurgitation => increased right atrial
pressure
o Increased right atrial (RA) pressure transmitted to
venous structures
o Eventually RA pressures prevent forward flow from
DV

o A wave Doppler tracing reaches baseline, with
further decompensation
causing flow reversal

IClINICALISSUES
Presentation
• First trimester screening for aneuploidy
• Second/third trimester evaluation of abnormal
cardiac function

growth,

Natural History & Prognosis
• Published incidence of aneuploidy associated with
abnormal DV flow varies from 65-90%
• Abnormal NT but normal chromosomes in un selected
group presenting for first trimester screening
o Abnormal DV flow -+ 77% live birth
o Normal DV flow -+ 94% live birth
• Abnormal NT + normal chromosomes + abnormal DV
flow
o 27-64% congenital heart disease (CHD)
• First trimester high-risk fetuses with abnormal NT +
abnormal DV but normal chromosomes
o 9 fold risk of adverse outcome compared to those
with abnormal NT + normal chromosomes + normal
DV

o Management of growth restriction depends on
gestational age at diagnosis
• > 32 weeks, consider delivery
• < 32 weeks, risks associated with severe
prematurity are considerable

I DIAGNOSTIC
Consider

• DV Doppler adds additional physiologic information
to anatomic survey
o First trimester
• Detection of aneuploidy
• Fetuses at risk for adverse outcome including
congenital heart disease
o Second/third trimester
• Fetal response to adverse intrauterine
environment in placental insufficiency
• Cardiac compromise/impending
hydrops
• Published data is based on study of high-risk
populations
o First trimester with abnormal NT
o 2nd/3rd trimester fetuses with growth restriction,
cardiac compromise
• Value of DV assessment in fetuses with normal NT,
normal growth is unclear

Image Interpretation

Pearls

• DV has characteristic triphasic waveform
• Ratios of flow velocities have less interobserver
variability than direct velocity measurements
• Changes in DV flow in 2nd/3rd trimester imply severe
fetal compromise and imminent demise
• In first trimester, abnormal DV flow is associated with
aneuploidy and increased risk for adverse outcome,
even if chromosomes are normal
I SELECTED
1.

2.

3.

4.

5.

Treatment
• First trimester
o Offer karyotype: Chorionic villus sampling or early
amniocen tesis
o If normal chromosomes
• Formal fetal echocardiography
at 16-18 weeks
• Consider repeat echo later, in third trimester
• Monitor closely, as increased risk adverse outcome
• Second/third trimester

CHECKLIST

6.

7.

REFERENCES

Baschat AA et al: Venous Doppler in the prediction of
acid-base status of growth-restricted fetuses with elevated
placental blood flow resistance. Am J Obstet Gynecol.
191(1):277-84, 2004
Muller T et al: Arterial and ductus venosus Doppler in
fetuses with absent or reverse end-diastolic flow in the
umbilical artery: correlation. with short-term perinatal
outcome. Acta Obstet Gynecol Scand. 81(9):860-6, 2002
Hsu TY et al: Waveforms of the ductus venosus blood flow
in normal human fetuses aged 8-38 weeks. Chang Gung
Med]. 24(11):717-23, 2001
Bahlmann F et al: Reference values of ductus venosus flow
velocities and calculated waveform indices. Prenat Diagn.
20(8):623-34, 2000
Matias A et al: Haemodynamic evaluation of the first
trimester fetus with special emphasis on venous return.
Hum Reprod Update. 6(2):177-89, 2000
Selam B et al: Fetal arterial and venous Doppler parameters
in the interpretation of oligohydramnios in postterm
pregnancies. Ultrasound Obstet Gynecol. 15(5):403-6, 2000
Hecher K et al: Assessment of fetal compromise by Doppler
ultrasound investigation of the fetal circulation. Arterial,
intracardiac, and venous blood flow velocity studies.
Circulation. 91(1):129-38, 1995

DUCTUS VENOSUS
I IMAGE GAllERY
(Left) Pulsed Doppler
ultrasound shows the normal
triphasic waveform seen in
the ductus venosus. The S
wave (arrow) occurs during
ventricular systole, the D
wave (open arrow) in
ventricular diastole and the
A wave (curved arrows)
during atrial contraction.
(Right) Pulsed Doppler
ultrasound shows an
abnormal ductus venosus
waveform with reversed flow
(arrows) during the A wave.

(Left) Pulsed Doppler
ultrasound shows reversed
flow (arrows) during the A
wave in a 7 week 5 day
embryo. This pregnancy was
considered high-risk due to a
history of previous abnormal
pregnancies. (Right)
Follow-up ultrasound at 73
weeks in the same case
shows increased nuchal
translucency demarcated by
the cursors. The amnion is
seen separately (arrow).
Further scans showed short
limbs. The infant was born
with mild, short-limbed
dwarfism.

Variant
(Left) Sagittal ultrasound
shows an abnormal nuchal
translucency (arrows).
(Right) Pulsed Doppler
ultrasound in the same case
shows forward flow during
the A wave (arrows) but
apparent flow reversal
(curved arrows) is also seen.
The normal triphasic /VC
waveform contaminates the
tracing, with two phases
visible beneath the baseline
(curved and open arrows).
Inclusion of the /VC can give
a false positive result and
should be avoided.
Chromosomes were normal.

SECTION 2: Brain

Introduction and Overview
Brain Development

& Imaging

2-2

Brain
Exencephaly, Anencephaly
Acrania
Occipital Encephalocele
Frontal Encephalocele
Chiari II Malformation
Aqueductal Stenosis
Dandy-Walker Continuum: Classic
Dandy-Walker Continuum: Variant
Mega Cisterna Magna
Rhombencephalosyna
psis
Agenesis of the Corpus Callosum
Mild Ventriculomegaly
Alobar Holoprosencephaly
Semilobar, Lobar Holoprosencephaly
Septo-Optic Dysplasia
Absent Cavum Septi Pellucidi
Hydranencephaly
Encephalomalacia
Intracranial Hemorrhage
Choroid Plexus Cyst
Arachnoid Cyst
Glioependymal Cyst
Schizencephaly
Microcephaly
Atelencephaly, Aprosencephaly
Craniosynostosis
Vein of Galen Malformation
Arteriovenous Fistula
CNSTumors

2-6
2-10
2-12
2-16
2-18
2-22
2-26

2-30
2-32
2-34
2-36

2-40
2-42
2-46
2-50
2-54
2-56
2-60
2-64
2-68
2-72
2-76
2-80
2-84
2-86
2-90
2-94
2-98
2-102

BRAIN DEVELOPMENT

Sagittal graphic shows the cystic appearance of the
normal developing rhombencephalon in the embryo
(arrow). The rhombencephalon eventually gives rise to
the pons, medulla, and cerebellum.

I Imaging Anatomy
Ultrasound
• Brain parenchyma
o Cerebral hemispheres
• Hypoechoic parenchyma
• Increasing gyration/sulcation visible with
maturation
o Cerebellum
• Bilobed structure
• Linear echogenic folia
o Midline cerebellar vermis
• Most echogenic intracranial structure
o With increasing gestational age, visible anatomic
detail increases
• Thalamus, brainstem, corpus callosum
• Ventricles
o Anechoic cerebral spinal fluid (CSF)
o Homogeneously echogenic choroid plexus fills
lateral ventricles
• Cavum septi pellucidi (CSP)
o CSF-filled structure between frontal horns
o Important marker of normal brain development
• Cisterna magna
o CSF-filled space behind cerebellum
o May see dural folds in subarachnoid space
• Linear echogenic structures extending from
cerebellum to inner table of skull
• May represent inferior attachments of falx
cerebelli
• Normal anatomic finding
• Skull
o Echogenic with posterior acoustic shadowing
• Evaluation of skull shape
• Orbit
• Nasal bone
• Osseous palate
• Tooth buds

Doppler Ultrasound
• Identify Circle of Willis

& IMAGING

Sagittal ultrasound shows the cystic appearance of the
developing hindbrain at 11 weeks gestation (arrows).
This should not be confused with hydrocephalus or a
cystic mass.

o Critical for measuring middle cerebral artery (MCA)
velocity
o Seen on oblique axial imaging of brain
• Can be used to identify callosomarginal and
pericallosal arteries in sagittal plane
o Used to confirm presence of corpus callosum

MRI
• Helpful for optimal visualization of anatomy
o Consider when screening ultrasound shows
abnormality
o Can uncover additional anomalies or clarify
ultrasound diagnosis
• May affect prognosis of fetus
• Rapid acquisition techniques with T2WI are most
useful
o Gray matter
• Low signal on T2WI
o White matter
• High signal on T2WI
• May use Tl WI as well
o Helpful to identify blood products
• High signal material in ventricles or parenchyma
o Myelination documented by high signal on T1WI
• Can help show evidence of fetal brain maturation
• More helpful as pregnancy/myelination progresses
• Sulcation, gyration, and myelination progress with
increasing gestational age
o Cortex appears relatively smooth at 22 weeks
• Do not mistake for lissencephaly
o Interhemispheric fissure should be visible
o Sylvian fissure widely open at 22 weeks
• Opercularization occurs back --+ front from 22-38
weeks
• Closure complete at 40 weeks gestation

IAnatomy-Based

Imaging Issues

Imaging Protocols
• American Institute of Ultrasound in Medicine (AlUM)
evaluation
o Head and neck

BRAIN DEVELOPMENT

& IMAGING

Key Facts
Imaging Issues
• AlUM requirements
o Measure BPD and HC at level of thalami and
cavum septi pellucidi
o Fetal anatomic survey must include
• I-lead and neck
• CerebelJum
• Choroid plexus
• Cisterna magna
• Lateral cerebral ventricles
• Midline falx
• Cavum septi pellucidi
• Normal lateral ventricles < 10 mm
• Normal cisterna magna::;; 10 mm
• Cavum septi pellucidi important marker for normal
brain development

o Brain
• Cerebellum
• Choroid plexus
• Cisterna magna
• Lateral cerebral ventricles
• Midline falx
• Cavum septi pellucidi (CSP)
• Fetal profile useful to document
o Nasal bone, micrognathia, frontal bossing

Imaging Pitfalls
• Normally developing rhombencephalon
o Seen in first trimester
o Sonolucent area in dorsal cranial end of embryo
o Should not be mistaken for hydrocephalus or cystic
mass
• Posterior fossa
o Imaging in steep oblique axial plane
• May simulate mega cisterna magna or
Dandy-Walker variant
o Dural folds in subarachnoid space of cisterna magna
• Normal finding, do not mistake for cystic mass
o Cerebellar vermis is not complete until 18 weeks
• Caution in diagnosing Dandy-Walker continuum
before formation complete
• Skull
o Unilateral petrous ridge seen in axial plane
• Can mimic echogenic mass in fetal brain
• Caused by angling slightly oblique in axial plane
o Posterior acoustic shadowing from skull in occipital
region
• Can mimic osseous defect in axial plane due to
dropout
• Change transducer angle to verify

Normal Measurements
• Routine measurements required by AlUM
o Biparietal diameter (BPD)
• Measure at level of thalami and CSP
• Cerebellar hemispheres should not be visible
• Measurement taken from outer edge proximal
skull -+ inner edge distal skull
o Head circumference (HC)

• Consider fetal MRI for detailed visualization
anatomy

of

Clinical Issues
• BPD may underestimate gestational
dolichocephaly
• HC less affected by skuU shape

age in

Avoid Imaging Pitfalls
• Normal developing rhombencephalon
appears cystic
• Steep oblique imaging simulates posterior fossa
abnormalities
• Be cautious diagnosing Dandy-Walker continuum
before vermis is fully formed (18 weeks)
• Cortex appears relatively smooth until late 2nd
trimester on fetal MRI
o Do not mistake for lissencephaly

• Measure at same level as BPD
• Circumference taken along outer edge of skull
o BPD and HC used in calculation of gestational age
(GA) and estimated fetal weight (EFW)
• Lateral ventricles
o Normal < 10 mm
o Measured inner edge to inner edge
• At level of glomus of choroid plexus
• Measure perpendicular to long axis of ventricle
(not midline)
o Generally stable measurement between 14-40 weeks
gestation
o Male fetuses have slightly larger ventricle
measurements than female fetuses
• Cisterna magna
o Normal::;; 10 mm
o Size varies slightly with gestational age

I

Pathology-Based

Imaging Issues

Imaging Protocols
• Head shape has greater effect on BPD than HC
o Dolichocephaly
• Relative flattened appearance of fetal skull
• BPD tends to underestimate gestational age
• Can be seen in normal fetuses, breech
presentation, oligohydramnios,
myelomeningocele
o Brachycephaly
• Rounded appearance of fetal skull
• Relatively shortened anteroposterior diameter
• BPD may overestimate fetal age
• Can be seen in normal fetuses, trisomy 21
• HC more reliable in calculating GA and EFW in these
conditions

I Embryology
Embryologic Events
• 3rd-4th week
o Neural plate and folds appear

BRAIN DEVELOPMENT & IMAGING

Coronal T2WI MR shows a normal 23 week fetus. Note
the sylvian fissures are still open (arrows), and the brain
surface lacks the normal sulci and gyri seen later in
gestation. This should not be mistaken for lissencephaly.

o Conversion of neural plate to neural tube
(neurulation)
• Broad cranial portion (neuropore) becomes brain
o 3 major divisions (vesicles) of brain demarcated by
indentations in neural folds
• Prosencephalon (forebrain)
• Mesencephalon (midbrain)
• Rhombencephalon
(hindbrain)
o Cranial neuropore closes day 24
• 5th week
o Further division of 3 primary brain vesicles to 5
vesicles
o Prosencephalon divides
• Telencephalon
• Diencephalon
o Rhombencephalon
divides
• Metencephalon
• Myelencephalon
o Pontine flexure forms
o Primitive ventricle forms
• Telencephalon cavity -+ lateral ventricles
• Diencephalon cavity -+ 3rd ventricle
• Mesencephalic cavity -+ aqueduct of Sylvius
• Rhombencephalon
cavity -+ 4th ventricle
o Ventricles fill with CSF
• 5th week to term
o Further differentiation of 5 brain vesicles
o Telencephalon
• Cerebral hemispheres
• Choroid plexus
• Internal capsule
• Olfactory bulbs and tracts
o Diencephalon
• Thalamus, optic nerves
• Geniculate and mamillary bodies
• Pineal and pituitary glands
o Mesencephalon
• Midbrain
o Metencephalon
• Pons, cerebellum
o Myelencephalon
• Medulla

Sagittal T2WI MR of a 3rd !rimester fetus shows
increasing sulcalion. Midline structures, including the
corpus callosum (white arrows) and cerebellar vermis
(black arrow), are nicely demonstrated.

I Clinical

Implications

Clinical Importance
• Brain abnormalities have significant impact on
intellect and developmental growth postnatally
• Pregnancy management may be affected by results
o Termination may be considered based on prognosis
o Karyotyping may be offered
o Consider neonatology or pediatric neurosurgery
consultation if pregnancy continued
• Delivery issues
o Massive hydrocephalus
• Requires close monitoring of BPD
• BPD > 10 cm may inhibit vaginal delivery
o May require immediate resuscitation/intervention
at
birth
• Delivery at tertiary medical center optimal
o Supportive care for lethal malformations

I

Related References

1.
2.

3.

4.

5.

6.
7.
8.

9.

Barnewolt
CE et al: Sonography
of the fetal central nervous
system. Neuroimaging
Clin N Am. 14(2):255-71,
viii, 2004
Blaicher W et al: Magnetic
resonance
imaging and
ultrasound
in the assessment
of the fetal central nervous
system. J Perinat Med. 31 (6):459-68,
2003
Lan LM et al: Normal fetal brain development:
MR imaging
with a half-Fourier
rapid acquisition
with relaxation
enhancement
sequence.
Radiology. 215(1):205-]
0, 2000
Babcook CJ et al: Sonographic
anatomy
of the developing
cerebellum:
normal embryology
can resemble pathology.
AJR AmJ Roentgenol.
166(2):427-33,
1996
Laing FC et al: Sonography
of the fetal posterior fossa: false
appearance
of mega-cisterna
magna and Dandy-Walker
variant. Radiology.
192(1):247-51,
1994
Larsen WJ: Human embryology.
New York, Churchill
Livingstone.
375-408,
1993.
Pretorius DH et al: Linear echoes in the fetal cisterna
magna.J
Ultrasound
Med. 11(4):125-8,
1992
Heiserman
J et al: Effect of measurement
errors on
sonographic
evaluation
of ventriculomegaly.
J Ultrasound
Med. 10(3):121-4,
1991
Hadlock FP et al: Estimating
fetal age: effect of head shape
on BPD. AJR AmJ Roentgenol.
137(1):83-5,
198]

BRAIN DEVELOPMENT & IMAGING
IIMAGE GAllERY
(Left) Graphic sho\ 1'5 the
routine scan planes lor
evaluation o( the t~·tal brain.
These include the lateral
ventricles (A), the level o(
the BPD and lie (/3), and an
angled view o( the posterior
(ossa (C). (Right) Axial
ultrasound corresponds to
scan plane A and shows the
normal, uni(ormly echogenic
appearance o( the choroid
plexus, which (ills the lateral
ventricles.

(Left) Axial ultrasound
corresponding
to plane B
shows the normal thalami
(open arrows) and cavum
septi pellucid (arrow). This is
the plane in which IIC and
BPD are measured. Note the
cerebellum is not included.
(Right) Axial oblique
ultrasound corresponding
to
plane C shows a normal
bi/obed cerebellum. Linear
echoes are present in the
cisterna magna (arrows),
representing dural folds in
the subarachnoid space.

(Left) Sagittal ultrasound o( a
3rd trimester (etus shows the
corpus callosum (arrows)
forming a hypoechoic
band
above the cavum sepli
pellucidi. (Right) Sagillal
color Doppler ultrasound
shows flow in the pericallosal
artery, which infers the
presence of the corpus
callosum.

EXENCEPHALY, ANENCEPHALY

Coronal ultrasound
of a 2nd trimester case of
anencephaly shows prominent eyes (arrows) with no
calvarium or neural tissue seen above the orbital ridge
(curved arrow).

and Synonyms

• Exencephaly
• Anencephaly
• Exencephaly/anencephaly

sequence

Definitions
• Absence of cranial vault and varying amounts
supratentorial brain

IIMAGING

of
to

• Neural tissue present
• Remaining tissue abnormal with an irregular
contour
• Typically seen in first trimester
o Anencephaly
• No organized neural tissue remaining
• Cranial defect is covered by angiomatous stroma
(area cerebrovasculosa)

ITERMINOLOGY
Abbreviations

Cross pathology
shows
the classic findings
anencephaly. The eyes are protuberant secondary
shallow orbits and the calvarium is absent.

of

FINDINGS

General Features
• Best diagnostic clue
o No calvarium with absence of neural tissue above
orbits
• Diagnosis should never be missed with routine
views
• Morphology
o Exencephaly/anencephaly
sequence
• Neural tissue "wears away" during gestation
• Result of fetal movement and exposure to
amniotic fluid
• Small amounts of dysmorphic tissue may still be
present in 2nd trimester
o Exencephaly

DDx: Abnormal

Calvarium

1st Tri Encephalocele

2nd

Tri Encephalocele

Ultrasonographic

Findings

• First trimester
o Neural tissue is still present (exencephaly)
o Normal head contour is absent
o Head has an irregular, flattened, splayed appearance
• Exposed brain has a lobulated ( "Mickey Mouse")
or spiked ("Bart Simpson") appearance
o Crown-rump length (CRL) less than expected
• Second and third trimester
o Neural tissue has dissolved
o No soft tissue above orbits
o Remaining surface is irregular
• Area cerebrovasculosa
• Face
o Protuberant eyes
• Secondary to shallow orbits
• Eyes themselves normally formed
• "Frog-like" appearance when face viewed in
coronal plane

Microcephaly

Acrania

EXENCEPHALY, ANENCEPHALY
Key Facts
Terminology

Top Differential

• Exencephaly/anencephaly
sequence
• Absence of cranial vault and varying amounts
supratentorial brain

•
•
•
•

of

Imaging Findings
• Cranial defect is covered by angiomatous stroma (area
cerebrovasculosa)
• Crown-rump length (CRL) less than expected
• Protuberant eyes
• Often contiguous with cervical spine defect
• Polyhydramnios common
• Amniotic fluid often echogenic seCONdary to
dissolved neural tissue
• Should be able to pick up routinely 10-14 weeks
• Routine 2nd trimester cranial views detect 100% of
cases
o Cleft lip/palate may be seen
• Often have other open neural tube defects (ONTD)
o Often contiguous with cervical spine defect
o Lumbar myelomeningocele
• Polyhydramnios common
o Secondary to impaired swallowing
o Amniotic fluid often echogenic secondary to
dissolved neural tissue
• 3D ultrasound
o More detailed depiction of cranial contour
o May potentially increase accuracy in first trimester

MR Findings
• Not generally needed for diagnosis
• May be useful if ultrasound is compromised
equivocal
• Obvious cranial defect
• Little or no supratentorial brain remains
• Brainstem and cerebellum often dysplastic

or

Imaging Recommendations
• Endovaginal scanning in 1st trimester for earlier
diagnosis
o Often difficult before 10 weeks
o Should be able to pick up routinely 10-14 weeks
o Examine cranial contour carefully
• Splayed
• Flattened
• Lobular
• Spiked
o Can measure crown-chin length (CCL)
• 77% of anencephaly < 5th percentile
o CCL/CRL ratio
• 62% of anencephaly < 5th percentile
o Short term follow-up if any suspicions
o Correlate with maternal serum alpha-fetoprotein
• Routine 2nd trimester cranial views detect 100% of
cases

Diagnoses

Acrania
Encephalocele
Amniotic band syndrome
Atelencephaly/aprosencephaly

Pathology
• Multifactorial disorder that likely results from a
combination of etiologic agents

Clinical Issues
• Lethal malformation
• Preconceptual folic acid should be given for future
pregnancies

Diagnostic Checklist
• CRL < expected is not always incorrect dates

I DIFFERENTIAL DIAGNOSIS
Acrania
• Defined neural tissue still present
• Brain better seen than normal
o Secondary to absent skull
• Considered part of anencephaly spectrum
• Lethal

Encephalocele
• Cranium present
• Neural tissue protrudes through defect
o Most commonly occipital
• May be difficult to differentiate in first trimester
o Becomes obvious with advancing gestational age

Amniotic band syndrome
•
•
•
•

Defect is asymmetric
Slash defects
Other body parts often affected
Bands may be visible

Atelencephaly / aprosencephaly
• Severe microcephaly with or without limb
abnormalities
• No normal cerebral structures
• Facial anomalies
o Micrognathia
o Midline malformations including cyclopia
o Cleft lip/palate
• Cranium intact

Severe microcephaly
• Cranium intact
• Sloped forehead
• Cerebrum present

I PATHOLOGY
General Features
• General path comments

EXENCEPHALY, ANENCEPHALY

•

•

•

•

o Multifactorial disorder that likely results from a
combination of etiologic agents
• Genetic
• Environmental
• Metabolic
• Nutritional
Genetics
o Multifactorial
o Risk of recurrence increased if positive family history
• Greatest risk if first degree relative
Etiology
o Risk factors
• Folic acid deficiency
• Insulin-dependent
diabetes
• Hyperthermia
• Methotrexate, valproic acid, carbamazepine,
aminopterin (folic acid antagonists)
o Embryology
• Anterior neuropore closes on day 23
• Failure of closure results in cranial defects
including anencephaly, encephaloceles and
iniencephaly
• Skull complete by 10 weeks
Epidemiology
o 1:1,000
• United Kingdom greatest incidence
oM:F=1:4
Associated abnormalities
o Reported in 41 % but lack importance given lethality
of condition
oSpina bifida: 27%
• +/- Myelomeningocele
• Most commonly involves cervical spine
o Genitourinary: 16%
o Cleft lip/palate: 10%
o Gastrointestinal: 6%
o Cardiac: 4%

Gross Pathologic & Surgical Features

Treatment
•
•
•
•

I DIAGNOSTIC

• CRL < expected is not always incorrect dates
o May be early indicator of neural tube malformation
o Short term follow-up for any case when the head
looks asymmetric or irregular

Image Interpretation

I SELECTED
1.

2.

3.

4.

ICLINICALISSUES

7.

5.

Presentation

Natural History & Prognosis

Pearls

• Diagnosis may be made in first trimester with
endovaginal ultrasound
• Exencephaly evolves into anencephaly

6.

• Lethal malformation
o May live hours to days
o < 10% live to one week
• 2-3% risk of recurrence of any ONTD

CHECKLIST

Consider

• Absent calvarium and telencephalon
• Brainstem and rhombencephalic
structures remain
• Defect is covered by angiomatous stroma (area
cerebrovasculosa)

• Abnormal first trimester scan
o Can be reliably diagnosed by 10-14 weeks
• Elevated maternal serum alpha-fetoprotein
(MSAFP)
o > 2.5 multiples of the median (MOM) considered
abnormal
o Detects 90% of anencephaly
• Large-for-dates secondary to polyhydramnios
• Obvious finding on routine midtrimester scan

Termination offered
Supportive care for family
Genetic counseling
Preconceptual folic acid should be given for future
pregnancies
o 4 mg/day beginning at least 1 month prior and
continuing through first trimester
• Decreases risk of all ONTD by approximately 70%
o 0.4 mg/day recommended for all women attempting
pregnancy

8.

9.
10.

11.
12.

13.

REFERENCES

Cafici D et al: First-trimester
echogenic
amniotic fluid in
the acrania-anencephaly
sequence. J Ultrasound
Med.
22(10):1075-9;
quiz 1080-1, 2003
Becker R et al: Sonographic
markers of exencephaly
at 9 + 3
weeks of gestation.
Ultrasound
Obstet Gynecol.
16(6):582-4,2000
Hata T et al: Three-dimensional
sonographic
features of
fetal central nervous system anomaly. Acta Obstet Gynecol
Scand. 79(8):635-9, 2000
Chatzipapas
IK et al: The 'Mickey Mouse' sign and the
diagnosis of anencephaly
in early pregnancy.
Ultrasound
Obstet Gynecol. 13:196-9, 1999
Johnson SP et al: Ultrasound
screening for anencephaly
at
10-14 weeks of gestation.
Ultrasound
Obstet Gynecol.
9:14-6, 1997
Sepulveda W et al: Crown-chin
length in normal and
anencephalic
fetuses at 10 to 14 weeks' gestation. Am J
Obstet Gynecol. 176(4):852-5,
1997
Timor-Tritsch
IE et al: Exencephaly-anencephaly
sequence:
Proof by ultrasound
imaging and amniotic fluid cytology. J
Matern Fetal Med. 5:182-5,1996
Wilkins-Haug
L et al: Progression of exencephaly
to
anencephaly
in the human fetus--an ultrasound
perspective.
Prenat Diagn. 11 (4):227-33, 1991
Goldstein RB et al: Sonography
of anencephaly:
pitfalls in
early diagnosis. J Clin Ultrasound.
17(6):397-402,
1989
Hendricks SK et al: ExencephalYhclinical
and ultrasonic
correlation
to anencephaly.
Obstet Gynecol. 72(6):898-901,
1988
Baird PA et al: Survival in liveborn infants with
anencephaly.
Am J Med Genet. 28(4):1019-20,
1987
Toriello HV et al: Occurrence
of neural tube defects among
first-, second-, and third-degree
relatives of probands:
results of a United States study. Am J Med Genet.
15(4):601-6,1983
David TJ et al: Congenital
malformations
associated with
anencephaly
and iniencephaly.
J Med Genet. 13(4):263-5,
1976

EXENCEPHALY, ANENCEPHALY
I IMAGE GALLERY
(Left) Coronal endovaginal
ultrasound of an embryo
with exencephaly.
The head
shape is abnormal and the
neural tissue has a splayed,
spiked appearance (arrows).
(Right) Coronal endovaginal
ultrasound of another
embryo with exencephaly
shows a more flattened,
lobular appearance of the
exposed neural elements
(arrows). Recognition of the
first trimester appearance of
anencephaly
is important for
early diagnosis of this lethal
malformation.

(Left) Coronal 3D ultrasound
in the 2nd trimester shows
no remaining neural tissue.
The irregular surface (arrow)
is the area cerebrovasculosa.
(Right) Coronal ultrasound in
a twin pregnancy with one
normal twin and one
anencephalic
twin. Some
neural tissue is still remaining
(arrow). The amniotic fluid
(inset) is markedly
echogenic (curved arrow)
when compared to the
adjacent sac of the normal
twin. This is common in
anencephaly
and represents
dissolved neural tissue.

(Left) Coronal ultrasound of
the cervical spine in a fetus
with anencephaly
shows the
defect continuing inferiorly
to involve the cervical spine
(arrows). Spina bifida,
especially cervical, is often
seen with anencephaly.
(Right) Lateral gross
pathology shows that the
defect is covered with
angiomatous stroma, the
area cerebrovasculosa
(arrow). This tissue accounts
for the irregular contour seen
on ultrasound.

ACRANIA

Sagittal ultrasound of a fetus with acrania. The calvarium
is absent but the brain is at least partially covered with
meninges (curved arrow). A large cyst is seen anteriorly
(arrow).

o Meninges may be present
• May provide protective barrier from erosion
• Face
o Similar to anencephaly
o Shallow orbits with protuberant eyes
o Orofacial clefts if amniotic bands
• Polyhydramnios common
o Fluid often echogenic

ITERMINOLOGY
Abbreviations

and Synonyms

• Acrania
• Acalvaria

Definitions
• Absent calvarium above orbits
• Considered part of exencephaly/anencephaly
sequence

IIMAGING

30 ultrasound of a fetus with acrania (arrow) caused by
amniotic bands. It is important to differentiate acrania
from amniotic bands versus a primary neural tube
defect to counsel regarding recurrence risk.

Imaging Recommendations
• Look for amniotic bands as cause
o Asymmetric skull defects
o Look closely for bands associated-with defect
o Other body parts frequently affected

FINDINGS

General Features
• Best diagnostic clue: Exposed brain with no cranium

Ultrasonographic

Findings

• Calvarium
o Absent above orbits
• Defect may be asymmetric with amniotic bands
o Affects membranous flat bones
o Skull base intact
• Brain
o Brain seen "too well"
o Distortion of parenchyma with loss of landmarks
o May "wear away" during gestation
• Can appear identical to anencephaly at delivery

I DIFFERENTIAL DIAGNOSIS
Exencephaly / anencephaly
• Exposed, irregular neural tissue first trimester
• Little or no cerebral tissue above orbits by second
trimester

Encephalocele
• Cranium present
• Neural tissue protrudes through defect
o Most commonly occipital

DDx: Acrania

01

Encephalocele

Exencephaly

ACRANIA
Key Facts
• Encephalocele
• Amniotic band syndrome
• Osteogenesis imperfecta (01)

Terminology
• Absent calvarium above orbits

Imaging Findings
• Skull base intact
• Brain seen "too well"
• Shallow orbits with protuberant

Top Differential

Clinical Issues
eyes

Diagnoses

• Determination of cause imperative for genetic
counseling
• If primary neural tube defect, recurrence risk 2-3%
• No recurrence risk with amniotic bands

• Exencephaly/anencephaly

I DIAGNOSTIC

Amniotic band syndrome
• Defect asymmetric
• "Slash" defects affecting other body parts
• Bands may be visible

Body stalk anomaly (Iimb-body-wall
complex)
• Fetus adherent to placenta
• No free floating cord
• Scoliosis major feature

Osteogenesis imperfecta

(01)

• Poor skull ossification may mimic acrania
o Brain still looks "contained"
• Skull deforms under scan pressure
• Underlying brain usually normal
• Entire skeleton involved, often with fractures

Image Interpretation

General Features
• Etiology
o Risk factors same as anencephaly
o Proposed mechanisms
• Failure of anterior neuropore to close
• Primary failure of membranous bone formation
• Epidemiology
o 1:1,000 quoted incidence
• Includes anencephaly so true incidence much less

Pearls

• Isolated acrania
o Primary neural tube defect
• Part of exencephaly/anencephaly
• Acrania + body defects
o Destructive process
• Amniotic bands
• Body stalk anomaly

I SELECTED
1.

2.

3.

/PATHOLOGY

CHECKLIST

4.

5.

sequence

REFERENCES

Chen CP et al: Prenatal sonographic diagnosis of acrania
associated with amniotic bands. J Clin Ultrasound.
32(5):256-60, 2004
Cincore V et al: Prenatal diagnosis of acrania associated
with amniotic band syndrome. Obstet Gynecol. 102(5 Pt
2):1176-8,2003
Chen CP et al: Prenatal diagnosis of acrania associated with
facial defects, amniotic bands and limb-body wall complex.
Ultrasound Obstet Gynecol. 20(1):94-5, 2002
Chandran 5 et al: Fetal acalvaria with amniotic band
syndrome. Arch Dis Child Fetal Neonatal Ed. 82(1):Fll-3,
2000
Harrington BJ et al: A counseling dilemma involving
anencephaly, acrania and amniotic bands. Genet Couns.
3(4):183-6,1992

I IMAGE

GALLERY

ICLINICALISSUES
Presentation
• Most common signs/symptoms
o Elevated maternal serum alpha-fetoprotein
o Found on routine views
o Polyhydramnios

Natural History & Prognosis
• Lethal malformation

Treatment
• Termination offered
• Determination of cause imperative
counseling

for genetic

o If primary neural tube defect, recurrence risk 2-3%
o No recurrence risk with amniotic bands

(Left) Coronal ultrasound shows obvious neural tissue without a
surrounding calvarium (arrow). The brain was attached to the
placenta (curved arrow). There were multiple other body wall defects
in this case of amniotic band syndrome. (Right) Coronal ultrasound of
a midtrimester fetus with acrania shows no bones above the skull
base (arrow). A large amount of disorganized neural tissues remains
(curved arrow). This may "wear away" over time appearing similar to
anencephaly at birth.

OCCIPITAL ENCEPHALOCELE

Axial ultrasound shows an obvious cranial defect
(arrows). The cephalocele
is purely cystic (curved
arrow) with only herniation of meninges. Contents of a
cephalocele directly impact resectability and prognosis.

Clinical photograph shows a large occipital cephalocele.
Postnatal work-up showed no brain contents within the
sac and reseclion was possible.

ITERMINOlOGY

IIMAGING FINDINGS

Abbreviations

General Features

and Synonyms

•
•
•
•
•

Encephalocele
Cephalocele
Cranial meningocele
Cranium bifidum, cranioschisis, cranioraschisis
Encephalomeningocele,
encephalomeningocystocele,
gliocele
• Chiari III

Definitions
• Herniation of intracranial structures through
defect
o Cephalocele
• More generic term
• Herniation of intracranial contents
o Encephalocele
• Meninges + brain
• Most common
o Cranial meningocele
• Meninges only
o Chiari III
• Hindbrain malformation
• Cerebellum herniated into cephalocele
• Very rare

skull

• Best diagnostic clue: Paracranial mass with boney
defect
• Location
o Associated with sutures
• Occipital
• Parietal
• Vertex
• Frontal
o 80% are occipital in western hemisphere
• Size
o Variable
• May be atretic and mistaken for scalp mass

Ultrasonographic

Findings

• First trimester
o Head may look small or irregular
o Must do endovaginal examination
• Can see cranial defect in late first trimester
• Brain
o Diverse appearance of herniated tissue
o Gyral pattern may be identified
o Mixed cystic/solid mass
o Purely cystic
o "Cyst within a cyst" or "target" sign
• Suggests prolapsed 4th ventricle

DDx: Encephalocele

ExC'ncC'phdly

Metopic

l\idgC'

Scalp

11i'/7Jdngio/7Ja

/\crania

OCCIPITAL ENCEPHALOCELE
Key Facts
Terminology
• Herniation
defect

of intracranial

structures through

skull

Imaging Findings
•
•
•
•
•
•
•
•

Diverse appearance of herniated tissue
Gyral pattern may be identified
"Cyst within a cyst" or "target" sign
Ventriculomegaly in 70-80%
Microcephaly in 25%
Osseous defect should be demonstrated
Both polyhydramnios
and oligohydramnios
described
Oligohydramnios more likely to have concurrent
defects

Top Differential

Diagnoses

• Amniotic band syndrome
• Anencephaly/acrania
• Cystic hygroma

Pathology
• Associated with multiple syndromes
• Meckel-Gruber syndrome most common
disorder

genetic

Diagnostic Checklist
• If encephalocele is not associated with cranial sutures
consider amniotic bands as cause
• Edge artifacts may simulate a cranial defect
• For isolated encephaloceles, prognosis most impacted
by volume of herniated parenchyma, microcephaly,
and ventriculomegaly

• Scalp masses

o Normal intracranial landmarks distorted
o Ventriculomegaly in 70-80%
• Impaired cerebral spinal fluid (CSF) flow
• Primary brain malformation
o Microcephaly in 25%
o Other central nervous system (CNS) anomalies
common
• Agenesis of corpus callosum
• Dandy-Walker continuum
• Neuronal migrational anomalies
• Spina bifida
• Cranium
o Osseous defect should be demonstrated
• Usually midline: Occipital
• Lateral: Parietal, inferior temporal
• May be difficult to see with small defect
o "Lemon sign" in 30%
• Depression of frontal bones
• Both polyhydramnios and oligohydramnios
described
o Oligohydramnios more likely to have concurrent
defects
• Polycystic kidneys
• Multiple other anomalies described

MR Findings
• Best modality for evaluating brain parenchyma
• Contents of cephalocele
o Major determining factor in prognosis
• Define relationship with dural sinuses
o Look for patentcy

CT Findings
• Not usually done in utero
• Best for evaluating boney defect postnatally

Imaging Recommendations
• Endovaginal scan in first trimester
• Follow-up scans
o Herniated contents may become more cystic over
time
o Small cephaloceles may "disappear"
• Atretic connection found after delivery
o Monitor head size

• Microcephaly poor prognostic sign
• Ventriculomegaly may be progressive
• Fetal MRI best for evaluation of herniated contents
and associated parenchymal malformations

I DIFFERENTIAL

DIAGNOSIS

Scalp masses
• Hemangioma, epidermal cyst, cephalohematoma
• Cranium intact
o Must scan from multiple angles for confirmation
• Edge artifact may give erroneous appearance of
cranial defect
• May be located anywhere on scalp
o Cephaloceles associated with sutures

Amniotic band syndrome
• May cause cranial defect and cephalocele
• Not associated with sutures
• Facial "slash" defects common
o Large, obliquely oriented facial clefts
• Bands may be visible
• Other body parts often affected

Anencephaly/acrania
• No cranium
• Variable amounts

of brain tissue

Cystic hygroma
•
•
•
•

Septated cystic neck mass
Cranium intact
No neural tissue
Hydrops common

Body stalk anomaly (Iimb-body-wall
complex)
• Severe disorganization with multiple body wall defects
• Scoliosis
• Absent/short umbilical cord

Iniencephaly
• Encephalocele

OCCIPITAL ENCEPHALOCELE
• Rachischisis involving spine
• Absent cervical vertebrae
• Neck in hyperextension ("stargazer" position)

Metopic ridge
• Closure of metopic suture
• Causes trigonocephaly
• Cranium intact

I PATHOLOGY
General Features
• Genetics
o Multifactorial, many sporadic
o Genetic: Multiple syndromes
• Many autosomal recessive
o Chromosomal
• Trisomy 13, 18
o Teratogens
• Warfarin syndrome: Nasal hypoplasia, ocular
defects, thrombocytopenia, multiple CNS
anomalies including cephalocele
o Maternal obesity implicated as risk factor
• Etiology
o Several proposed mechanisms
• Primary failure of cranial neuropore closure
• Secondary event with pressure erosion and
herniation of neural tissue
• Failure of induction of membranous bone
formation
• Epidemiology
o 1-3:10,000 in United States
• Majority occipital
o Frontal encephaloceles more common in Southeast
Asia
• Associated abnormalities
o Body malformations common
• Isolated or part of syndrome
• Associated with multiple syndromes'
o Meckel-Gruber syndrome most common genetic
disorder
• Encephalocele, polydactyly, polycystic kidneys
• Autosomal recessive
o Walker-Warburg syndrome
• Lissencephaly, hydrocephalus, encephalocele,
microphthalmia, cataracts
• Autosomal recessive
o Knobloch syndrome
• Vitreoretinal degeneration and encephalocele
• Autosomal recessive

Gross Pathologic & Surgical Features
• Herniated brain dysplastic

ICLINICAL

ISSUES

Presentation
• Cranial defect
• Meninges generally intact so maternal serum
alpha-fetoprotein (MSAFP)usually not elevated

Natural History & Prognosis
• Varies with amount of brain tissue in defect and
associated malformations
• 40% mortality in neonatal series
o Isolated cranial meningocele better prognosis
• 79% mortality in fetal series
• Survivors: 80% neurologic impairment
o Developmental delay, often significant
o Seizures
• 2-5% recurrence risk, unless associated with syndrome
• 25% recurrence risk for autosomal recessive disorders

Treatment
•
•
•
•

All fetuses should be karyotyped
Termination offered
Thorough family history and genetic counseling
Referral to neurosurgery prior to delivery for surgical
planning
• Deliver at tertiary care facility
• Cesarean section considered to reduce birth trauma

I DIAGNOSTIC

CHECKLIST

Consider
• If encephalocele is not associated with cranial sutures
consider amniotic bands as cause

Image Interpretation

Pearls

• Edge artifacts may simulate a cranial defect
• For isolated encephaloceles, prognosis most impacted
by volume of herniated parenchyma, microcephaly,
and ventriculomegaly

I SELECTED REFERENCES
Mittermayer C et al: Prenatal diagnosis of the
Meckel-Gruber syndrome from 11th to 20th gestational
week. Ultraschall Med. 25(4):275-9, 2004
2.
Kojima K et al: Antenatal evaluation of an encephalocele in
a dizygotic twin pregnancy using fast magnetic resonance
imaging. Fetal Diagn Ther. 18(5):338-41,2003
3. Haberle 1 et al: Cervical encephalocele in a
newbornnChiari III malformation. Case report and review
of the literature. Childs Nerv Syst. 17(6):373-5,2001
4.
Bannister CM et al: Can prognostic indicators be identified
in a fetus with an encephalocele? Eur 1 Pediatr Surg 10
SuppL 1:20-3,2000
Budorick NE et al: Cephalocele detection in utero:
5.
Sonographic and clinical features. Ultrasound Obstet
GynecoL 5:77-85,1995
Wininger S1et al: Syndromes identified in fetuses with
6.
prenatally diagnosed cephaloceles. Prenat Diagn.
14(9):839-43, 1994
7.
Goldstein RB et al: Fetal cephaloceles: Diagnosis with US.
Radiology. 180:803-8, 1991
8.
1eanty P et al: Prenatal diagnosis of fetal cephalocele: a
sonographic spectrum. Am 1 PerinatoL 8(2):144-9, 1991
9.
Queisser-Luft A et al: [Does maternal obesity increase the
risk of fetal abnormalities? Analysis of 20,248 newborn
infants of the Ma;nz Birth Register for detecting congenital
abnormalities. Ultra schall Med. 19(1)40-4, 1988
10. Simpson DA et al: Cephaloceles: treatment, outcome and
antenatal diagnosis. Neurosurgery. 15(1):14-21, 1984
L

OCCIPITAL ENCEPHALOCELE
IIMAGE

GALLERY

Typical
(Left) Axial ultrasound shows
a large encephalocele
(curved arrow) protruding
through a cranial defect
(arrows). (Right) Axial
oblique ultrasound shows a
"cyst within a cyst" or
"target" sign, which is
created when the 4th
ventricle (curved arrow)
herniates into the
cephalocele (arrow).

(Left) Axial ultrasound shows
a small cephalocele (curved
arrow). Note there is also
ventriculomegaly (arrow).
Other CNS abnormalities are
commonly present, even if
the cephalocele is small.
(Right) Axial T2WI MR
through the posterior fossa
shows a large cystic sac
(white arrow) with
herniation of a small amount
of cerebellar tissue (black
arrow). MRI can be very
helpful in determining extent
of brain involvement and
associated parenchymal
abnormalities.

(Left) Sagittal
transabdominal ultrasound in
the first trimester in which
the head (arrow) appears
irregular and small. (Right)
Axial endovaginal ultrasound
of the same fetus shows an
obvious, large encephalocele
(arrows). Cephaloceles may
be identified in the first
trimester and any head
irregularity on a
transabdominal scan should
be further investigated with
endovaginal sonography.

FRONTAL ENCEPHALOCELE

Sagittal graphic shows a nasofrontal encephalocele (A)
extending through the fonticulus frontalis. (8) Shows
parenchyma herniating through the foramen cecum,
seen in nasoethmoidal encephaloceles.

ITERMINOlOGY
Definitions
• Defect of the skull in the frontoethmoidal
herniation of intracranial structures

IIMAGING

region with

• No role prenatally
• Used to identify skull defect prior to surgical repair

General Features
• Best diagnostic clue: Brain parenchyma
through an anterior skull defect
• Location: Frontoethmoidal
skull

herniating

I DIFFERENTIAL DIAGNOSIS
Amniotic band syndrome

Findings

• Many are likely missed on prenatal ultrasound
small size
• Facial mass
• Look for associated midline anomalies
o Hypertelorism
o Dysgenesis/agenesis of the corpus callosum
o Interhemispheric
lipoma
o Heterotopia

MR Findings
• Consider in utero MRI
• Most useful tool to characterize
o Size

o Location
o Communication
with intracranial structures
• Used to distinguish cephaloceles from other
frontonasal masses
o Nasal dermoid/epidermoid
o Nasal glioma

CT Findings

FINDINGS

Ultrasonographic

Sagillal ultrasound of the face shows an osseous defect
and frontal encephalocele (arrows) in a fetus who also
had aprosencephaly Autopsy confirmed this was
dysplastic brain tissue.

due to

• Should have other limb and body abnormalities
• Externalized portions of brain tissue due to amniotic
bands

Nasal glioma
• Collection of dysplastic brain tissue
• Located in nasal cavity or subcutaneous tissue
• Herniation of brain tissue into dural tract
o Subsequent resorption of intervening tissue

Dermoid
cephalocele

cyst

• Persistent dural projection through foramen cecum
o Dermoid or epidermoid develops along tract
• Can have connection with intracranial contents

DDx: Facial Masses

Rhabdomyosarcoma

Amniotic Bands

Nasal Teratoma

FRONTAL ENCEPHALOCELE
Key Facts
• Nasal glioma
• Dermoid cyst

Terminology
• Defect of the skull in the frontoethmoidal
with herniation of intracranial structures

region

Pathology
• More commonly

Imaging Findings
• Facial mass
• Hypertelorism

seen in Southeast Asia

Diagnostic Checklist

Top Differential

• Consider when unexplained hypertelorism
especially in Asian population

Diagnoses

present,

• Amniotic band syndrome

Other facial masses

Natural History & Prognosis

•
•
•
•

• Prognosis better for frontoethmoidal
encephaloceles
than occipital or parietal locations
o Depends on the presence of other congenital brain
anomalies

Nasal teratoma
Facial neoplasm
Vascular malformation
Dacryocystoceles

Treatment

I PATHOLOGY

• Surgical excision with closure of the dural defect and
reconstruction of the skull defect
• Repair should be performed soon after delivery to
minimize the risk of meningitis

General Features
• Etiology
o Late neurulation defect during fourth gestational
week
o Herniation of intracranial parenchyma through
persistent embryologic relationships
• Failure of fonticulus frontalis to close
• Persistent dural projection through the foramen
cecum
• Epidemiology
o Rare condition
o More commonly seen in Southeast Asia
• Incidence of about 1:5,000
• Associated abnormalities
o Microcephaly
o Hydrocephalus
o Microphthalmos

I DIAGNOSTIC

Image Interpretation

I CLINICAL

Pearls

• Consider when unexplained hypertelorism
especially in Asian population

present,

I SELECTED REFERENCES
1.

Hoving EW: Nasal encephaloceles.

Childs Nerv Syst.

]6(10-11):702-6,2000

2.

3.

Gross Pathologic & Surgical Features
• Extracraniallocation
of brain parenchyma
o Nasofrontal: Between frontal and nasal bones
o Nasoethmoidal: Between nasal bones and nasal
cartilage
o Nasoorbital: Through medial orbital defect
• Bordered anteriorly by frontal process of maxilla
• Posteriorly confined by lacrimal bone and lamina
papyracea

CHECKLIST

Budorick NE et al: Cephalocele detection in utero:
so'nographic and clinical features. Ultrasound Obstet
Gynecol. 5(2):77-85, 1995
Barkovich A] et al: Congenital nasal masses: CT and MR
imaging features in 16 cases. A]NR Am] Neuroradiol.
12(1):105-16,

I

1991

IMAGE GALLERY

ISSUES

Presentation
• Prenatal
o Incidental facial mass ± hypertelorism
• Postnatal
o Skin-covered facial or nasal mass
o Nasal congestion

(Left) Sagittal T2WI MR performed post-natally shows brain
parenchyma herniating through the fonticulus frontalis in a child with
a nasofrontal encephalocele (arrows). (Right) Axial NECT in bone
windows shows the osseous defect in the frontal skull (arrows).

CHIARI II MALFORMATION

Sagittal graphic of Chiari /I malformation
with
meningomyelocele (open arrow). Hindbrain herniation
is the hallmark finding. The cerebellum is herniated
(arrow) and the cisterna magna is obliterated.

• Morphology
o Posterior fossa compression
o Frontal bone concavity

ITERMINOLOGY
Abbreviations
•
•
•
•

Sagittal T2WI MR shows a Chiari /I malformation (arrow
points to cerebellar herniation) and meningocele (open
arrow) in a second trimester fetus. A small syrinx is
identified within the spinal cord (curved arrow).

and Synonyms

Chiari II
Arnold Chiari II
Spina bifida
Open neural tube defect (ONTD)

Ultrasonographic

Findings

• First trimester findings
o "Acorn" shaped calvarium
• Dolichocephaly = small biparietal diameter (BPD)
• Narrow frontal bones
• Flat occiput on sagittal view
o Parallel cerebral peduncles on BPD view
• Posterior fossa compression
o Cisterna magna (CM) obliteration
• Most common finding
• CM is small or gone « 3 mm)
• Seen on routine axial posterior fossa view
o Cerebellar compression
• Cerebellum curves around midbrain ("banana")
• Absent cerebellum rare
• Ventriculomegaly
o Atrial width ~ 10 mm
• Seen on routine axial ventricle view
• Ventricle measured at atrium
• Usually borderline or mild
o May develop during pregnancy
• 55% at time of diagnosis
• 33% progress during pregnancy
• 90% at birth

Definitions
• Symptomatic hindbrain herniation
o Contents herniate through foramen magnum
• Virtually 100% association with ONTD

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Posterior fossa "banana sign"
o Calvarial "lemon sign"
o Ventriculomegaly
o ONTD
• Location
oSpina bifida
• 73% lumbar
• 17% sacral
• 9% thoracic
• 1% cervical

DDx: Hydrocephalus

,.
Aqueductal Stenosis

Aqueductal Stenosis

OW Continuum

OW Continuum

CHIARI II MALFORMATION
Key Facts
Terminology

Pathology

• Symptomatic hindbrain herniation
• Virtually 100% association with ONTD

• 4% aneuploidy

Imaging Findings

• t Maternal

•
•
•
•
•
•
•

•
•
•
•
•
•

Clinical

Posterior fossa "banana sign"
Calvarial "lemon sign"
Ventriculomegaly
Cisterna magna (CM) obliteration
Head size remains normal or small
Look for ONTD when Chiari II seen
Follow-up ultrasound for ventriculomegaly

Top Differential

• Useful when maternal habitus limits ultrasound
• Required for fetal surgery
• Large field of view
o Spine and brain seen on one image
• Occasional cord syrinx more likely seen with MR

Imaging Recommendations
• Best imaging tool: Routine axial cranial views
• Protocol advice

serum alpha-fetoprotein
(AFP)
High morbidity and mortality
Cesarean section delivery at term
Immediate postnatal ONTD surgery
80% need ventriculoperitoneal
shunt
Chiari II can reverse with in utero surgery
Preventive treatment with folic acid

• Genetic amniocentesis
• Compressed CM may be only finding
• Cranial findings often easier to see than ONTD

• Sacrococcygeal teratoma (SC teratoma)
• Aqueductal stenosis
• Isolated frontal bone concavity

MR Findings

Issues

Diagnostic Checklist

Diagnoses

o Head size remains normal or small
• Frontal bone scalloping
o Frontal bone concavity ("lemon")
o Nonspecific finding
• Found in 1% of normal fetuses
o Resolves in 3rd trimester regardless of +/- spina
bifida
• ONTD
o Bony dorsal arch defect + neural content exposure
• No Chiari II with skin covered spina bifida
o Vertebral findings
• Splayed dorsal ossification centers
• "U" shaped vertebra on axial view
• Coronal view best for evaluating extent
• Sagittal view best for seeing soft tissue sac
• 80% with overlying sac
o Meningocele sac
• Anechoic cystic mass
• Sac contains meninges only
o Myelomeningocele
• Complex cystic mass
• Sac contains meninges + neural elements
o Myeloschisis
• No associated sac
• Open spinal cord part of defect
• Associated findings
o Lower extremity anomalies
• 24% clubfoot
o Scoliosis and kyphosis
• Seen at level of ONTD
o 40% with additional anomalies
• 67% aneuploid fetuses with other anomalies

rate with spina bifida

o Look for fluid-filled CM in all 2nd trimester cases
o Look for ONTD when Chiari II seen
o Follow-up ultrasound for ventriculomegaly

I

DIFFERENTIAL DIAGNOSIS

Sacrococcygeal teratoma

(SC teratoma)

• Germ cell neoplasm
• Exophytic complex mass from sacrum
o Rarely purely cystic
• Spine may be deformed
• Rarely associated with ONTD

Aqueductal

stenosis

• Obstruction of aqueduct of Sylvius
o Noncommunicating
hydrocephalus
• Moderate and severe hydrocephalus most common
o > 15 mm atria measurement
o Dangling choroid plexus
• Fetal head enlarged

Dandy-Walker

continuum

(OW continuum)

• Dysgenesis of cerebellar vermis
o May be partial or complete
o Fourth ventricle communicates with CM
• Cisterna magna is enlarged
o > 10 mm on routine axial posterior fossa view
o "Keyhole" CM with partial vermis absence
• Hydrocephalus

Isolated frontal bone concavity
• Seen in 1% of normal fetuses
• Resolves in third trimester
• Normal cisterna magna

I PATHOLOGY
General Features
• General path comments
o Posterior fossa compression
• Cerebellar vermis herniates via foramen magnum

CHIARI II MALFORMATION

•

•

•

•

• Fourth ventricle displaced inside neural canal
• Tentorium pulled downward
• Medulla displaced inferiorly and kinked
Genetics
o 4% aneuploidy rate with spina bifida
• Trisomy 18 (TI8)
• Trisomy 13 (TI3)
Etiology
o Prolonged prenatal cerebral spinal fluid (CSF) leak
• Fluid escapes from cranial vesicles via ONTO
• 4th ventricle blocked
• Low cerebellum blocks reentry of fluid
o ONTO
• Mostly sporadic and multifactorial
• Folate deficiency
• Teratogens: Anticonvulsants
o Arrhaphia theory of ONTO
• Primary failure of neuropore closure
• Absent skin/muscle from failed induction
o Hydromelic theory of ONTO
• CSF imbalance
• Excess CSF accumulates in closed neural tube
• Secondary separation of dorsal wall
Epidemiology
o 0.4:1,000
o 3% all spontaneous abortions
o 1-2% recurrence risk
Associated abnormalities
o All Chiari II with spina bifida
o 40% with other anomalies

Gross Pathologic & Surgical Features
• ONTO
o Bony defect with exposed neural elements

Staging, Grading or Classification Criteria
• Chiari I
o Cerebellar tonsil herniation
o Usually asymptomatic
o Not diagnosed prenatally
• Chiari III
o Hindbrain herniation
o Low occipital/upper cervical bony defect
• Spina bifida
oSpina bifida aperta (85%)
oSpina bifida occulta (15%)
• No Chiari II with occulta

• Hispanic> Caucasian, African-American, Asian

Natural History & Prognosis
• High morbidity and mortality
o 35% live-born die within first 5 yrs
• Chiari II main cause of death < 2 yrs old
o 50% with IQ > 80
o In utero findings do not predict outcome
• Obstructive hydrocephalus
o From posterior fossa compression
• Musculoskeletal dysfunction
o 25% complete lower limb dysfunction
• Gastrointestinal/genitourinary
dysfunction
o 17% with normal continence

Treatment
• Cesarean section delivery at term
o ! Infection rate
o !Meningomyelocele sac rupture rate
• Immediate postnatal ONTO surgery
o Cover exposed spinal cord
o 80% need ventriculoperitoneal shunt
• In utero surgery in clinical trials
o Chiari II can reverse with in utero surgery
o ! Shunt dependence
• 54% vs. 80%
o Paralysis and continence rates unchanged
o t Preterm delivery risk
• Preventive treatment with folic acid
o Preconceptual therapy best
o 4 mg/day reduces recurrence risk by 70%
o 0.4 mg/day for all women

I DIAGNOSTIC
Consider

• Genetic amniocentesis
• Search for ONTO when Chiari II seen

Image Interpretation

I SELECTED
1.

ISSUES

Presentation

3.

• Most common signs/symptoms
o t Maternal serum alpha-fetoprotein (AFP)
• > 2.5 multiples of median (MOM) detects 80%
ONTO

4.
5.

Demographics
• Age
o Advanced maternal age (AMA) slightly higher risk
• ~ 35 yrs at time of delivery
• Secondary to association with TI8 and TI3
• Ethnicity
o United States data

Pearls

• Compressed CM may be only finding
• Cranial findings often easier to see than ONTO

2.

I CLINICAL

CHECKLIST

6.
7.

REFERENCES

Stevenson
KL: Chiari Type II malformation:
past, present,
and future. Neurosurg
Focus. 16(2):£5,2004
Tubbs RS et al: Treatment
and management
of the Chiari II
malformation:
an evidence-based
review of the literature.
Childs Nerv Syst. 20(6):375-81,
2004
Adzick NS et al: Myelomeningocele:
prenatal diagnosis,
pathophysiology
and management.
Semin Pediatr Surg.
12(3):168-74,2003
.
Beuls £ et al: The Arnold-Chiari
type II malformation
at
midgestation.
Pediatr Neurosurg.
39(3):149-58,
2003
Buisson 0 et al: Sonographic
diagnosis
of spina bifida at 12
weeks: Heading towards indirect signs. Ultrasound
Obstet
Gynecol.
19:290-2, 2002
Coleman
BG et al: Fetal Therapy: State of the art. J
Ultrasound
Med. 21:1257-88,
2002
Jobe AH: Fetal surgery for myelomeningocele.
N Engl J
Med. 347:230-1,
2002

CHIARI II MALFORMATION
IIMAG~ GALLERY
Typical
(Left) Axial ultrasound shows
Chiari II malformation. The
cerebellum is banana shaped
(arrows) as it wraps around
the midbrain. Frontal bone
concavity (open arrows)
gives the calvarium a lemon
shape. (Right) Axial NECT
after birth in a baby with
Chiari II shows that the
frontal concavity resolves
(open arrows). The midbrain
(arrows) remains angulated
and abnormally positioned
posteriorly.

Typical
(Left) Axial ultrasound shows
significant obstructive
hydrocephalus in a fetus
with a meningocele. The
third ventricle (curved
arrow) and lateral ventricles
(arrows) are dilated. Note
the dangling choroid plexus.
(Right) Sagittal ultrasound of
the spine in the same fetus
shows a small sacral
meningocele (arrow).
Calvarial findings are often
easier to see and more
obvious than the spine
findings.

(Left) Sagittal T2WI MR
shows a Chiari II
malformation and
myeloschisis. Cerebellar
tonsil herniation (open
arrow), ventriculomegaly
(arrow) and open spinal
defect (curved arrow) are all
seen in one view. (Right)
Clinical photograph shows
another myeloschisis. The
absence of a sac makes the
diagnosis more difficult.
However, Chiari II
malformation findings are
present and trigger a search
for spina bifida.

AQUEDUCTAL STENOSIS

Coronal graphic shows narrowing at the aqueduct of
Sylvius (curved arrow). There is dilatation of the 3rd and
lateral ventricles with thinning of the cortical mantle.
The posterior fossa is normal (arrows).

Coronal T2WI MR shows severe hydrocephalus from
AS. When this severe, individual ventricles can not be
identified. The cerebral cortex is thinned (arrows) but
the posterior fossa is normal (open arrows).

ITERMINOlOGY

[IMAGING FINDINGS

Abbreviations

General Features

and Synonyms

• Aqueductal stenosis (AS)
• Isolated hydrocephalus

Definitions
• Narrowing or occlusion at aqueduct of Sylvius
• Important to differentiate hydrocephalus from
ventriculomegaly
• Hydrocephalus
o Increased intraventricular pressure
o Increased ventricular size
o Increased head size
o Noncommunicating (obstructive)
• Cerebral spinal fluid (CSF) flow blocked within
ventricular system
o Communicating
• Failure of CSF resorption
• Ventriculomegaly
o Normal intraventricular pressure
o Increased ventricular size
o Head size normal or small
• True aqueductal stenosis blocks CSF flow causing
obstructive hydrocephalus

DDx: Fluid-Filled

Hydranencepha/y

• Best diagnostic clue: Hydrocephalus with normal
posterior fossa
• Location
o Aqueduct of Sylvius connects 3rd and 4th ventricles
• More proximal stenoses cause greater
hydrocephalus
• Size
o Normal diameter of aqueduct at birth 0.5 mm2
(range 0.2-1.8 mm2)
o Narrowest portion of ventricular system

Ultrasonographic

Findings

• Moderate to severe ventricular dilatation (> 15 mm)
o Often extreme
o Cortical mantle thinned
• May be severe mimicking hydranencephaly
• "Dangling" choroid
o Choroid plexus does not fill lateral ventricle
o Choroid from opposite side may fall through dilated
foramen of Monroe into dependent ventricle
• "Double dangle"
• 3td ventricle dilated
o Dilatation may be so extreme normal ventricular
anatomy may not be discernible
• Posterior fossa normal

Cranium

Hydranencepha/y

A/abar Ha/apros

A/abar Ha/apros

AQUEDUCTAL STENOSIS
Key Facts
Terminology
• Narrowing or occlusion at aqueduct of Sylvius
• True aqueductal stenosis blocks CSF flow causing
obstructive hydrocephalus

Imaging Findings
• Best diagnostic clue: Hydrocephalus with normal
posterior fossa
• Moderate to severe ventricular dilatation (> 15 mm)
• Cortical mantle thinned
• "Dangling" choroid
• 3rd ventricle dilated
• Dilatation may be so extreme normal ventricular
anatomy may not be discernible
• Corpus callosum often thinned or not visible
• Cavum septi pellucidi (CSP) may be absent
• Head size often large

•
•

•
•

•

o Cisterna magna can be compressed with severe
hydrocephalus
Corpus callosum often thinned or not visible
Cavum septi pellucidi (CSP) may be absent
o Severe hydrocephalus causes fenestrations within
walls of CSP
Head size often large
o May be severe
Color Doppler
o Look for flow in compressed cerebral mantle
o Follow middle cerebral artery (MCA)
Additional findings in X-linked hydrocephalus
o Male fetus
o Adduction-flexion deformity of thumbs
• Present in 50% of cases

• If history of prior child with AS, continue
even if initial scans are normal

Top Differential

Diagnoses

• Hydranencephaly
• Holoprosencephaly
• Dandy-Walker continuum

Clinical Issues
•
•
•
•
•
•
•

Developmental delay in up to 90%
X-linked hydrocephalus severe mental retardation
X-linked recurrence risk 50% for male fetuses
4% recurrence risk for all others
Large head size may cause dystocia
Genetic counseling for future pregnancies
In utero shunting not proven effective

• Be suspicious of X-linked form
o Document gender
o Carefully image hands
• Adducted thumbs have been reported in first
trimester
• Complete genetic work-up and amniocentesis
• Follow-up scans every 2-3 weeks for progression
• If history of prior child with AS, continue to follow
even if initial scans are normal
o Hydrocephalus may not develop until late in
pregnancy or neonatal period
• Fetal MRI

I DIFFERENTIAL DIAGNOSIS

MR Findings

Hydranencephaly

• Better for assessing presence of thinned cortical mantle
• More precise anatomic evaluation
o Midline sagittal view best for evaluating aqueduct of
Sylvius
• May see aqueduct "funnel" to point of obstruction
o Posterior fossa, 4th ventricle are normal
o Third ventricle dilated with displacement of both
roof and floor
o Corpus callosum thinned
o Periventricular interstitial edema may be present
o Evaluate for other brain anomalies
• Often see flow artifacts with very distended ventricles
o CSF is turbulent within obstructed systems

• No cerebral tissue
o Use Doppler
o MRI may be necessary for confirmation
• Head size usually normal

Imaging Recommendations
• Use endovaginal probe if head is cephalic
• Rule out other causes of ventriculomegaly
o Posterior fossa images of critical importance
• Normal in AS, although can be compressed if
hydrocephalus is severe
• Often abnormal with other malformations
• Carefully assess remaining cortical mantle
o Differentiates AS from destructive lesions or other
congential malformations
o Doppler to look for flow in MCA and compressed
parenchyma

to follow

Holoprosencephaly
• Absent falx
• Fused thalami
• Facial malformations

Dandy-Walker

often present

continuum

• Dysgenesis of cerebellar vermis
o May be partial or complete
• Posterior fossa cyst
• 4th ventricle appears "open" and contiguous with cyst
• Hydrocephalus may be present but more typically
develops postpartum

Chiari II malformation
• Hindbrain herniation with posterior fossa compression
o Obliteration of cisterna magna
o Cerebellum curves around midbrain ("banana" sign)
• Frontal bone concavity ("lemon" sign)
• Myelomeningocele
• Ventriculomegaly
o Usually borderline or mild

AQUEDUCTAL STENOSIS
• Head size not typically large

Ence p hal 0 m alad a/ po re nce p haly
•
•
•
•
•

Destructive process of brain parenchyma
Most commonly ischemic or infection
Focal areas of destruction
Progressive ventriculomegaly
Head size not en larged

I PATHOLOGY
General Features
• General path comments
o Pathophysiology
• Aqueductallumen
normally decreases throughout
gestation
• Narrowing secondary to growth of adjacent
mesencephalic structures
• AS obstructs normal CSF flow
• CSF production continues in lateral and 3rd
ventricles
• Ventricular fluid pressure increases compressing
adjacent parenchyma, stretching corpus callosum
• Pressure may disrupt ependymal cell junctions
causing periventricular edema
o Some postulate AS may develop from
communicating
hydrocephalus
• External compression of quadrigeminal plate by
dilated cerebral hemispheres
• Genetics
o Most sporadic
oX-linked
• X-linked hydrocephalus (Bickers-Adams
syndrome)
• Mutation of Xq28 which produces Ll, a neural
cell adhesion molecule
• < 5% of AS
• Males
• Adducted thumbs
• Mental retardation
• Etiology
o Incompletely understood and likely multifactorial
• Stenosis may result from inflammation or
infection in 50%
• Disruption of ependymal lining
• White matter edema
• Gliosis and fibrosis (irreversible at this point)
• Infections: Cytomegalovirus (CMV),
toxoplasmosis, rubella, influenza, mumps, syphilis
• Hemorrhage and tumors also implicated
• Epidemiology
o 0.3-1.5:1,000 births
o M:F=2:1

• Associated abnormalities
o CRASH: Callosal hypoplasia, mental Retardation,
Adducted thumbs, Spastic paraplegia, X-linked
Hydrocephalus
oMASA: Mental retardation, Aphasia, Shuffling gait,
Adducted thumbs
o 30% may have extracranial abnormalities

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms: Hydrocephalus on
routine scan
• May have history of prior child with AS
o Hydrocephalus may not seen be seen until 3rd
trimester or neonatal period

Natural History & Prognosis
•
•
•
•
•

10-30% neonatal mortality
Developmental delay in up to 90%
X-linked hydrocephalus severe mental retardation
X-linked recurrence risk 50% for male fetuses
4% recurrence risk for all others

Treatment
• Amniocentesis
o Karyotype
o Infection screen
• Large head size may cause dystocia
• Genetic counseling for future pregnancies
• Ventricular shunting after delivery
o Thickness of cortical mantle improves after shunting
o In utero shunting not proven effective
• Endoscopic ventriculostomy

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Careful search for other anatomic
aqueductal stenosis is diagnosed

I SELECTED

causes before

REFERENCES

Senat MV et al: Prenatal diagnosis of
hydrocephalus-stenosis
of the aqueduct of Sylvius by
ultrasound in the first trimester of pregnancy. Report of
two cases. Prenat Diagn. 21(13):1129-32, 2001
Schrander-Stumpel C et al: Congenital hydrocephalus:
2.
nosology and guidelines for clinical approach and genetic
counselling. Eur J Pediatr. 157(5):355-62, 1998
3.
Kenwrick S et al: X linked hydrocephalus and MASA
syndrome. J Med Genet. 33(1):59-65, 1996
Timor-Tritsch IE et al: Transvaginal sonographic detection
4.
of adducted thumbs, hydrocephalus, and agenesis of the
corpus callosum at 22 postmenstrual weeks: the masa
spectrum or Ll spectrum. A case report and review of the
literature. Prenat Diagn. 16(6):543-8, 1996
Levitsky DB et al: Fetal aqueductal stenosis diagnosed
5.
sonographically: How grave is the prognosis? AJR Am J
Roentgenol 164:725-30, 1995
Gupta J K et al: Management of apparently isolated fetal
6.
ventriculomegaly. Obstet Gynecol Surv 49:716-21, 1994
7.
Brocard 0 et al: Prenatal diagnosis of X-linked
hydrocephalus. J Clin Ultrasound 21:211-4, 1993
Schwanitz G et al: Chromosomal findings in fetuses with
8.
ultrasonographically
diagnosed ventriculomegaly. Ann
Genet. 36(3):150-3, 1993
Varadi Vet al: Heterogeneity and recurrence risk for
9.
congenital hydrocephalus (ventriculomegaly): a
prospective study. Am J Med Genet. 29(2):305-10, 1988
10. Halliday Jet al: X linked hydrocephalus: a survey of a 20
year period in Victoria, Australia. J Med Genet. 23(1):23-31,
1986
1.

AQUEDUCTAL STENOSIS
I IMAGE GALLERY
(Left) Axial ultrasound shows
severe hydrocephalus
with a
dangling choroid (arrow) in
a fetus with X-linked
hydrocephalus.
The foramen
of Monroe is so massively
dilated that the choroid from
the other ventricle has fallen
through to the dependent
side (curved arrow). (Right)
Axial oblique ultrasound
through the posterior fossa
shows a normal cerebellum
and 4th ventricle (arrow)
ruling out other causes of
hydrocephalus
such as
Dandy-Walker or Chiari /I
malformation.

(Left) Sagittal T2WI MR
shows severe hydrocephalus.
Note the markedly enlarged
head (curved arrow) as
compared to the face. The
posterior fossa is normal,
with the vermis and 4th
ventricle (arrow) well seen.
(Right) Axial ultrasound
confirms a normal
cerebellum and 4th ventricle
(arrow). The point of
obstruction has to be above
this level. These findings are
typical of aqueductal
stenosis.

Typical
(Left) Axial ultrasound in a
case of aqueductal stenosis
shows severe hydrocephalus
and a markedly thinned
cortical mantle (arrow)
(curved arrow - dangling
choroid). Cerebral cortex in
the near field could not be
evaluated. (Right) Axial
T2WI MR shows
symmetrically
thinned
parenchyma
(arrows)
compressed against the
calvarium. MRI can be very
helpful in evaluating the
remaining cortical mantle.

DANDY-WALKER CONTINUUM:

Sagittal graphic shows a superiorly rotated vermian
remnant (open arrow) with communication of the 4th
ventricle with the PF cyst. The torcular Herophili is
characteristically elevated (arrow).

Sagittal T2WI MR shows an elevated torcular Herophili
(open arrow), vermian remnant (arrow), and large PF
cyst. There is also agenesis of the corpus callosum with
an interhemispheric cyst (curved arrow).

o Vermis severely hypoplastic or absent
• If present, superiorly displaced
o Enlarged posterior fossa (PF)
o Abnormal configuration of 4th ventricle

ITERMINOLOGY
Abbreviations

and Synonyms

• Dandy-Walker continuum (DWC)
o Newest terminology
o Reflects developmental spectrum of findings
• Dandy-Walker malformation (DWM), Dandy-Walker
complex, Dandy-Walker spectrum

Definitions
• Group of cystic posterior fossa malformations
(most-to-least severe): Dandy-Walker malformation,
Dandy-Walker variant (DWV), persistent Blake pouch
cyst (BPC), mega cisterna magna (MCM)
• Posterior fossa (PF) malformation characterized by
o Dysgenesis of cerebellar vermis
o Cystic dilatation of 4th ventricle (4V)

IIMAGING

FINDINGS

General Features
• Best diagnostic clue
o Large PF with big cerebrospinal fluid (CSF) cyst
o 4V appears "open" and contiguous with PF cyst
• Location: Posterior fossa
• Size: Varies widely
• Morphology

DDx: Cystic Appearance

Mega Cisterna Magna

CLASSIC

Ultrasonographic

Findings

• Agenesis or severe hypoplasia of echogenic vermis
• Communication
of 4V with PF cyst/cisterna magna
• Hydrocephalus may be present but more typically
develops postpartum
o Requires follow-up to evaluate for development or
progression
• Associated findings
o Central nervous system (CNS)
• Ventriculomegaly
• Dysgenesis of corpus callosum
• Encephaloceles
• Neural tube defects
o Extracranial
• Cleft lip/palate
• Cardiac defects
• Polycystic kidneys

MR Findings
•
•
•
•
•

Problem solving tool
Better definition of PF abnormalities
Identifies associated supratentorial anomalies
Midline sagittal view best demonstrates vermis
T2WI images most useful

Of Posterior Fossa

Dandy-Walker

Variant

Arachnoid

Cyst

/oubert

Syndrome

DANDY-WALKER CONTINUUM:

CLASSIC

Key Facts
Terminology

Top Differential

•
•
•
•

• Mega cisterna magna
• Arachnoid cyst (AC)
• Dandy-Walker continuum:

Dandy-Walker continuum (DWC)
Newest terminology
Reflects developmental spectrum of findings
Dysgenesis of cerebellar vermis

• Large PF with big cerebrospinal fluid (CSF) cyst
• 4V appears "open" and contiguous with PF cyst
• Torcular herophili elevated (mechanical hindrance
normal descent by PF cyst)
• Hydrocephalus may be present but more typically
develops postpartum
• Diagnosis should not be made before 18 weeks
gestation

• Approximately 70-90% have additional supratentorial
or extracranial anomalies
• Chromosomal abnormalities in approximately 50%
of

Imaging Recommendations

I DIFFERENTIAL DIAGNOSIS
Mega cisterna magna

Arachnoid cyst (AC)

Dandy-Walker

continuum:

Variant

Persistent Blake pouch cyst
• Most recently added diagnosis to DWC
• Lack of formation of foramen of Magendie

4th

or

o Ballooning of 4th ventricular roof during
development, results in inferior PF cyst
• No primary vermian hypoplasia or cerebellar dysplasia
• Mild pressure-related vermian and/or cerebellar
atrophy may be present
• May be indistinguishable
from AC prenatally

• Consider gestational age
o Formation of vermis somewhat variable
• Open vermis in 56% at 14 weeks gestation, in 6%
at 17 weeks gestation
o Diagnosis should not be made before 18 weeks
gestation
o Normal rhombencephalon
appears cystic in first
trimester

• Cisterna magna> 10 mm
• Vermis intact
• Thought to be mildest form of Dandy-Walker
continuum
• Vast majority considered normal variant, although
long-term studies
• No associated anomalies

Clinical Issues
• Extremely variable, ranging from normal
psychomotor development to severe handicap
death
• 40% mortality in infancy and early childhood
• All fetuses should be karyotyped

o Agenesis or hypoplasia of vermis
• If vermis hypoplastic, then inferior vermis
deficient
o Torcular herophili elevated (mechanical hindrance
of normal descent by PF cyst)

• Milder vermian hypoplasia than DWM
• Small or no PF cyst
• Posterior fossa not enlarged
o Normal location of torcular Herophili
• Keyhole appearance of 4th ventricle

Variant

Pathology

Imaging Findings

• Vermis intact
• Displacement of cerebellum and compressed
ventricle
• Not traversed by falx cere belli

Diagnoses

Congenital

vermian hypoplasia

• Synonym: Molar tooth malformation
• Absent or hypoplastic vermis
• Abnormal superior cerebellar peduncles with vermian
dysgenesis resulting in "molar tooth" configuration
• No posterior fossa cyst
• Difficult to confirm on ultrasound
o MRI preferred for diagnosis
• Complex group of syndromes
o Prototype: Joubert syndrome

I PATHOLOGY
General Features
no

• Genetics
o Majority sporadic
o Many syndromes with DWC
• Etiology
o Embryology
• Not fully understood
• 5th week: Neural tube develops sharp bend
(pontine flexure), resulting in large 4th ventricle
with thin rhombencephalic
roof
• 6th week: 2 areas in rhombencephalic
roof form
ependymal cells: Anterior area membranacea
(AMA), posterior area membranacea (PMA)
• AMA normally incorporated into vermis and/or
tela choroidea
• PMA eventually perforates and forms foramen of
Magendie
o Dandy-Walker continuum
• Spectrum of diseases caused by abnormalities of
4th ventricular roof
• Defective formation of AMA thought to cause
classic and variant forms

DANDY-WALKER CONTINUUM:
• Defective formation of PMA thought to cause
MCM and BPC
o Environmental factors implicated but not proven
• Maternal diabetes
• Alcohol
• Early in utero infections
• Epidemiology
o 1:25,000-35,000 live births
o Higher incidence in utero
o 10% of infantile hydrocephalus
• Associated abnormalities
o Approximately 70-90% have additional
supratentorial or extracranial anomalies
o CNS
• Callosal dysgenesis
• Encephalocele
• Neural tube defects
• Holoprosencephaly
• Polymicrogyria
• Heterotopias
o Extracranial
• Cleft lip/palate
• Cardiac anomalies
• Polycystic kidneys
• Extremity defects
o Chromosomal abnormalities in approximately 50%
• Trisomy 13, 18, 21
• Turner syndrome (45XO)
o Meckel-Gruber syndrome
• Encephalocele, polydactyly, polycystic kidneys
• Autosomal recessive
o Walker-Warburg syndrome
• Lissencephaly, hydrocephalus, encephalocele,
microphthalmia,
and cataracts
• Autosomal recessive

Natural History & Prognosis
• Extremely variable, ranging from normal psychomotor
development to severe handicap or death
• 40% mortality in infancy and early childhood
• Intellectual development dependent on vermian
abnormality, associated supratentorial anomalies and
associated syndromes
o Intelligence normal in 35-50% of cases
• Large vermian remnant with normal lobulation
and absence of supratentorial abnormalities =>
more favorable outcome
• Absent or small vermis with abnormal lobulation,
supratentorial abnormalities => poor outcome
• Recurrence risk 1-5%
o Unless associated with syndrome

Treatment
• All fetuses should be karyotyped
• Hydrocephalus in 75% at 3 months postpartum
o May require ventricular and/or cyst shunt

I DIAGNOSTIC

• Fetal MRI to detect associated anomalies

Image Interpretation

I SELECTED
1.

2.

3.

ISSUES

Presentation
• Prenatal
o Incidental finding on routine antenatal ultrasound
o Hydrocephalus
• Subsequent workup shows DWC
• Postnatal
o Enlarging head circumference or signs and
symptoms of hydrocephalus
• No hydrocephalus in approximately 80% at birth
• Hydrocephalus present in 90% at time of
postnatal presentation
o Developmental delay

Demographics
• Gender: Female preponderance

Pearls

• Assure appropriate scanning plane
o Too steep of scanning angle can simulate DWC

4.

I CLINICAL

CHECKLIST

Consider

Gross Pathologic & Surgical Features
• Large PF with CSF-containing cyst
o Inferior margin of vermian remnant continuous
with cyst wall
o Choroid plexus of 4th ventricle absent or displaced
into lateral recesses

CLASSIC

5.

6.

7.

8.

9.

REFERENCES

Gleeson JG et al: Molar tooth sign of the
midbrain-hindbrain
junction: occurrence in multiple
distinct syndromes. Am J Med Genet A. 125(2):125-34;
discussion 117, 2004
Has R et al: Dandy-walker malformation: a review of 78
cases diagnosed by prenatal sonography. Fetal Diagn Ther.
19(4):342-7,2004
Boddaert N et al: Intellectual prognosis of the
Dandy-Walker malformation in children: the importance
of vermian lobulation. Neuroradiology. 45(5):320-4, 2003
ten Donkelaar HJ et al: Development and developmental
disorders of the human cerebellum. J Neurol.
250(9):1025-36, 2003
Patel Set al: Analysis and classification of cerebellar
malformations. AJNR Am J Neuroradiol. 23(7):1074-87,
2002
Calabro F et al: Blake's pouch cyst: an entity within the
Dandy-Walker continuum. Neuroradiology. 42(4):290-5,
2000
Ecker JL et al: The sonographic diagnosis of Dandy-Walker
and Dandy-Walker variant: associated findings and
outcomes. Prenat Diagn. 20(4):328-32, 2000
Ulm Bet al: Dandy-Walker malformation diagnosed before
21 weeks of gestation: Associated malformations and
chromosomal abnormalities. Ultrasound Obstet Gynecol.
10:167-70, 1997
Bromley B et al: Closure of the cerebellar vermis:
evaluation with second trimester US. Radiology.
193(3):761-3,1994

DANDY-WALKER CONTINUUM:
IIMAGE

CLASSIC

GALLERY
(Left) Axial ultrasound of the
brain shows two very
hypoplastic cerebellar
hemispheres
(arrows) with
an enlarged posterior fossa.
(Right) Axial T2WI MR
shows the open
communication
of the fourth
ventricle (curved arrow)
with the large posterior fossa
cyst. This is a severe
presentation of the
Dandy-Walker continuum.

(Left) Coronal ultrasound of
the posterior fossa shows
splaying of the cerebellar
hemispheres
(arrows) with a
midline cyst (open arrow).
Hydrocephalus
(curved
arrows) is also present in this
case. (Right) Gross
pathology from the autopsy
demonstrates
the cyst
(arrow) between the two
cerebellar hemispheres
confirming the prenatal
diagnosis of a Dandy-Walker
malformation.

Typical
(Left) Axial ultrasound shows
an absent cavum septi
pellucidi (open arrow) as
well as an absent vermis
(arrows). Hydrocephalus
is
present, which is seen
antenatally in up to 20% of
Dandy-Walker
malformations.
It typically
progresses, being present in
90% of cases that present
postnatally. (Right) Axial
ultrasound shows the
hypoplastic cerebellar
hemispheres displaced
anterolaterally (curved
arrows).

DANDY-WALKER CONTINUUM:

Axial oblique ultrasound shows absence of the inferior
vermis (arrows). Other images demonstrated the
presence of the superior portion of the vermis. The
cavum septi pellucidi is present (curved arrow).

ITERMINOlOGY
Abbreviations

and Synonyms

• Dandy-Walker variant (DWV)
• Part of the Dandy-Walker continuum (DWC),
Dandy-Walker complex, Dandy-Walker spectrum
o DWC is newest terminology
o Group of cystic posterior fossa malformations
(most-to-Ieast severe): Dandy-Walker malformation,
Dandy-Walker variant, Persistent Blake pouch cyst,
mega cisterna magna (MCM)

VARIANT

Sagittal T2WI MR obtained postnatally confirms the
absence of the inferior vermis (open arrow). The
torcular Herophili is in a normal location (arrow), in
comparison to the classic form of the OWe.

• Posterior fossa not enlarged
• "Keyhole" appearance of 4th ventricle
• Avoid imaging in steep coronal plane
o May lead to incorrect diagnosis of DWV

MR Findings
• Midline sagittal T2WI image best for diagnosis
• Inferior vermis deficient

I DIFFERENTIAL DIAGNOSIS

Definitions

Dandy-Walker

• Partial agenesis or hypoplasia of inferior vermis
• Cystic dilation of fourth ventricle

•
•
•
•

IIMAGING

Mega cisterna magna

FINDINGS

Ultrasonographic

Normal early development
with cisterna magna

Findings

• Hypoplasia of echogenic vermis
o Less extensive than classic form

DDx: Cystic Appearance

Steep Coronal Plane

Classic

• Cisterna magna> 10 mm
• Vermis intact
• Vast majority considered normal variant

General Features
• Best diagnostic clue
o Posterior fossa (PF) defect
• Inferior vermis absent
• 4th ventricle communicates

continuum:

More severe vermian dysgenesis than DWV
Large posterior fossa cyst
Abnormal 4th ventricle communicates with PF cyst
Enlarged PF with elevation of torcular Herophili

of vermis

• Formation of vermis variable
o Open vermis in 56% at 14 weeks gestation, in 6% at
17 weeks gestation
• Incomplete vermis before 18 weeks may be normal

Of Posterior Fossa

Arachnoid Cyst

Mega Cisterna Magna

owe:

Classic

DANDY-WALKER CONTINUUM:

VARIANT

Key Facts
Terminology
• Partial agenesis or hypoplasia

of inferior vermis

• 4th ventricle communicates with cisterna magna
• "Keyhole" appearance of 4th ventricle

Diagnoses

• Dandy-Walker continuum:
• Mega cisterna magna

of vermis

Pathology

Imaging Findings

Top Differential

• Normal early development
• Arachnoid cyst (AC)

Classic

• Mostly sporadic
• Abnormal karyotype in approximately

Clinical Issues
• Extremely variable prognosis
• All fetuses should be karyotyped

o Ranges from normal psychomotor development
severe handicap or death
• Strongly influenced by associated anomalies

Arachnoid cyst (AC)
• Vermis intact
• Mass effect with displacement of cerebellum,
compression of 4th ventricle
• Not traversed by falx cere belli

30%

to

Treatment
• All fetuses should be karyotyped

Persistent Blake pouch cyst
• No primary vermian hypoplasia or cerebellar dysplasia
• Mild pressure related vermian and/or cerebellar
atrophy may be present

Congenital vermian hypoplasia
• Synonym: Molar tooth malformations
• Absent or hypoplastic vermis
• Abnormal superior cerebellar peduncles in
conjunction with vermian dysgenesis resulting in
molar tooth configuration
• No PF enlargement or PF cyst
• Prototype: Joubert syndrome

I PATHOLOGY

I DIAGNOSTIC

Image Interpretation

Pearls

• Avoid imaging posterior fossa in steep coronal plane
o Can mimic DWV

I SELECTED REFERENCES
1.

2.

3.

General Features
• Genetics
o Mostly sporadic
o Abnormal karyotype in approximately 30%
• Etiology: Dandy-Walker continuum thought to arise
from defect in area membranacea in rhombencephalic
roof
• Associated abnormalities
o Similar in frequency and type to classic form of
DWC
• Brain: Ventriculomegaly, callosal dysgenesis
• Extracranial: Cardiac defects, genitourinary
abnormalities, limb defects
• Can be associated with syndromes

CHECKLIST

4.

Malinger G et al: The fetal cerebellar vermis: normal
development as shown by transvaginal ultrasound. Prenat
Diagn. 21(8):687-92, 2001
Ecker JL et al: The sonographic diagnosis of Dandy-Walker
and Dandy-Walker variant: associated findings and
outcomes. Prenat Diagn. 20(4):328-32, 2000
Chang MC et al: Sonographic detection of inferior vermian
agenesis in Dandy-Walker malformations: prognostic
implications. Radiology. 193(3):765-70, 1994
Laing FC et al: Sonography of the fetal posterior fossa: false
appearance of mega-cisterna magna and Dandy-Walker
variant. Radiology. 192(1):247-51, 1994

I IMAGE GAllERY

IClINICAllSSUES
Presentation
• Most common signs/symptoms
o Prenatal diagnosis on routine screening
o Postnatal presentation
• Developmental delay
• Signs and symptoms of hydrocephalus

Natural History & Prognosis
• Extremely variable prognosis

(Left) Axial oblique ultrasound in a late 3rd trimester fetus wilh a
Dandy-Walker variant shows a characteristic "keyhole" deformity
(arrow).
The superior vermis was intact and there was no
hydrocephalus. (Right) Sagittal T2WI MR in a different third trimester
fetus shows communication of the fourth venlricle with an enlarged

cisterna magna and a hypoplastic inferior vermis (arrow). Note the
torcular Herophili is not displaced (open arrow).

MEGA CISTERNA MAGNA

Axial ultrasound shows a relatively mature third
trimester brain in a fetus with trisomy 18. An enlarged
cisterna magna, measuring > 10 mm, is identified
(arrow).

Sagittal ultrasound at midline in the same patient shows
an intact, echogenic vermis (curved arrow) along with
the enlarged cisterna magna (arrow).

!TERMINOLOGY

MR Findings

Abbreviations

• Enlarged cisterna magna
• Sagittal view shows vermis completely covering fourth
ventricle
o Rules out Dandy-Walker malformation/variant
• May show scalloping of inner table of skull
o Due to CSF pulsations

and Synonyms

• Mega cisterna magna (MCM)

Definitions
• Cisterna magna measuring>

IIMAGING

10 mm

Imaging Recommendations

FINDINGS

General Features
• Best diagnostic clue: Enlarged posterior fossa cerebral
spinal fluid (CSF) space
• Location: Posterior fossa

Ultrasonographic

Findings

• Measured in axial oblique plane at level of cerebellar
hemispheres
o Avoid angled semi-coronal plane
• Mimics MCM or Dandy-Walker variant
• Cisterna magna measuring> 10 mm
• Fourth ventricle is normal
• Cerebellar hemispheres normally formed
• Cerebellar vermis is complete and normal
o Can be difficult to differentiate from mild
Dandy- Walker va riant

• Evaluate carefully for associated abnormalities
o Trisomy 18
• Cardiac defects
• Choroid plexus cysts
• Omphalocele
• Clenched hands
• Rocker-bottom feet

I DIFFERENTIAL DIAGNOSIS
Dandy-Walker

malformation

• Absent vermis
• Cystic dilation of fourth ventricle in direct
communication
with enlarged cisterna magna
• Hydrocephalus commonly present
• Associated with agenesis of the corpus callosum

DDx: Cystic lesions Of The Posterior Fossa

Dandy-Walker Variant

Arachnoid Cyst

Too Steep An Angle

MEGA CISTERNA

MAGNA

Key Facts
Terminology
• Cisterna magna measuring>

10 mm

Imaging Findings
• Measured in axial oblique plane at level of cerebellar
hemispheres
• Evaluate carefully for associated abnormalities

Top Differential
• Dandy-Walker

Diagnoses

malformation

Dandy-Walker

variant

• Partially absent inferior vermis
• Torcular Herophili not elevated
• Hydrocephalus typically absent

Normal early cerebellar development
• Inferior vermis may appear absent
o Vermis incompletely formed before 18 weeks

Arachnoid cyst
• 1/3 infratentorial
• Extraaxial CSF-containing lesion
• Mass effect on adjacent brain

Vein of Galen malformation

• Dandy-Walker variant
• Normal early cerebellar development

Clinical

Diagnostic Checklist
• Too steep a scanning angle may simulate a MCM
• Carefully document vermis to rule out Dandy-Walker
variant

[DIAGNOSTIC

Image Interpretation

1.

2.

I PATHOLOGY

5.

ICLINICAL

Pearls

I SELECTED REFERENCES

3.

• Thought to be in same spectrum as Dandy-Walker
malformation and variant
• Torcular Herophili is in normal position
o Elevated in Dandy-Walker malformation
• Completely formed vermis and cerebellar hemispheres

CHECKLIST

• Too steep a scanning angle may simulate a MCM
• Carefully document vermis to rule out Dandy-Walker
variant

• Doppler flow identifiable in lesion
• Other associated abnormalities present
o Cardiomegaly
o Hydrocephalus
o Dilated neck vessels
o Hydrops

General Features

Issues

• If isolated likely has no adverse clinical outcome

4.

Serhatlioglu S et al: Sonographic measurement of the fetal
cerebellum, cisterna magna, and cavum septum
pellucidum in normal fetuses in the second and third
trimesters of pregnancy. J Clin Ultrasound. 31(4): 194-200,
2003
Haimovici JA et al: Clinical significance of isolated
enlargement of the cisterna magna (> 10 mm) on prenatal
sonogr"aphy. J Ultrasound Med. 16(11):731-4; quiz 735-6,
1997
Rosati Pet al: Transvaginal sonographic measurement of
cisterna magna in fetuses with abnormal karyotype. Fetal
Diagn Ther. 11(4):260-3, 1996
Nyberg DA et al: Prenatal sonographic findings of trisomy
18: review of 47 cases. J Ultrasound Med. 12(2):103-13,
1993
Nyberg DA et al: Enlarged cisterna magna and the
Dandy-Walker malformation: factors associated with
chromosome abnormalities. Obstet Gynecol. 77(3):436-42,
1991

I IMAGE GALLERY

ISSUES

Presentation
• Usually an incidental finding
• Part of multiple findings seen with trisomy 18

Demographics
• Gender
o Isolated MCM
• No specific sex predilection
o MCM associated with trisomy 18
• More often seen in male fetuses

Natural History & Prognosis
• If isolated likely has no adverse clinical outcome

(Left) Axial ultrasound-shows an enlarged cisterna magna (arrow) in a
fetus with trisomy 18. This fetus had other anomalies including a
cardiac defect. (Right) Axial ultrasound shows a mega cisterna magna
in a third trimester fetus. The cerebellum is normally formed. This was
an isolated finding in an otherwise normal fetus

RHOMBENCEPHALOSYNAPSIS

Coronal graphic demonstrates the appearance of
rhombencephalosynapsis.
There is a single-lobed
cerebellum with no vermis (arrow). The folia (curved
arrows) are horizontally aligned.

Coronal ultrasound shows rhombencephalosynapsis
(open arrow). The cerebellum is small and the
hemispheres are fused. There is also holoprosencephaly
with a large monovenlricle (arrows).

o Posterior "pointing" of 4th ventricle described on
postnatal axial MRI
• Not an open defect as in Dandy-Walker
continuum

ITERMINOlOGY
Definitions
• Congenital fusion of cerebellar lobes, dentate nuclei
and superior cerebellar peduncles
• Agenesis of cerebellar vermis

IIMAGING

FINDINGS

Imaging Recommendations
• Best imaging tool: Fetal MRI
• Protocol advice: Look carefully for presence of vermis,
rhombencephalosynapsis
most likely diagnosis if
vermis not identified and cerebellar hemispheres fused

General Features
• Best diagnostic clue: Single-lobed cerebellum

Ultrasonographic

I DIFFERENTIAL DIAGNOSIS

Findings

Dandy-Walker

• Cerebellum looks small
o Steep scanning angle can make cerebellum look
abnormal
o Real time evaluation will confirm appropriate
appearance on correct axial oblique plane
• May be other intracranial anomalies
o Hydrocephalus
o Holoprosencephaly
o Callosal dysgenesis/agenesis
o Septooptic dysplasia

•
•
•
•

MR Findings

Cerebellar

•
•
•
•

continuum

Congenital vermian hypoplasia

• Fused cerebellar hemispheres
• Abnormal shape 4th ventricle

Joubert syndrome prototype
Abnormal vermis
"Molar tooth" cerebellar peduncles
Cerebellar lobes not fused

hypoplasia

• Transverse diameter small for gestational
• Intact vermis, cerebellar lobes not fused

DDx: Abnormal Cerebellum

OW Continuum

(DWC)

Inferior vermian defect
Posterior fossa cyst in DWC
Cyst in continuity with 4th ventricle
Cerebellar lobes not fused

OW Continuum

Joubert Syndrome

age

RHOMBENCEPHALOSYNAPSIS
Key Facts
Terminology

Top Differential

• Congenital fusion of cerebellar lobes, dentate nuclei
and superior cerebellar peduncles
• Agenesis of cerebellar vermis

• Dandy-Walker continuum

Imaging Findings
• Best diagnostic clue: Single-lobed cerebellum
• Cerebellum looks small
• May be other intracranial anomalies

Diagnoses
(DWC)

Clinical Issues
• Often short lifespan, occasional survivors to early
adulthood

Diagnostic Checklist
• Fetal MRI invaluable to clarify posterior fossa
malformations

I PATHOLOGY

Treatment

General Features

• Offer karyotype
• Careful postnatal evaluation by pediatric neurologist
and endocrinologist

• Genetics
o FGF8 and Lmxla genes being considered
• Defective "isthmic organizer" ~ abnormal dorsal
patterning
o Interstitial deletion 2qo Consanguinity: Possible autosomal recessive
inheritance
• Etiology
o Teratogens
• Maternal diabetes mellitus
• Maternal hyperpyrexia
• Phenylcyclidine
• Epidemiology
o Extremely rare but becoming more recognized on
postnatal MRI
o Increasing postnatal recognition ~ prenatal
identification
• Embryology
o Very early defect, probably 33-34 days gestation
o Failure induction/differentiation
midline structures
o Lateral structures relatively preserved
o Cerebellar hemispheres form but fuse due to absent
vermis

I DIAGNOSTIC
Consider

• Fetal MRI invaluable to clarify posterior fossa
malformations

I SELECTED REFERENCES
1.

2.
3.

4.

S.

I CLINICAL ISSUES
Presentation
• Most common signs/symptoms:
fossa on routine antenatal US

I
Abnormal posterior

CHECKLIST

Boltshauser E: Cerebellum-small brain but large confusion:
a review of selected cerebellar malformations and
disruptions. Am J Med Genet. 126A(4):376-85, 2004
Sener RN et al: Rhombencephalosynapsis and a Chiari II
malformation. J Com put Assist Tomogr. 27(2):257-9, 2003
Patel S et al: Analysis and classification of cerebellar
malformations. AJNR Am J Neuroradiol. 23(7):1074-87,
2002
Toelle SP et al: Rhombencephalosynapsis: clinical findings
and neuroimaging in 9 children. Neuropediatrics.
33(4):209-14,2002
Yachnis AT: Rhombencephalosynapsis with massive
hydrocephalus: case report and pathogenetic
considerations. Acta Neuropathol (Bert). 103(3):301-4,
2002

IMAGE GALLERY

Natural History & Prognosis
• Depends on associated anomalies
• Often short lifespan, occasional survivors to early
adulthood
• Older survivors
a Bipolar disorder
o Self injurious behavior
o Hyperactivity
• Neurological defects
o Ataxia
o Cerebral palsy
o Seizures
o Developmental delay
• Hydrocephalus may require shunt placement
• Hypothalamic pituitary axis dysfunction

(Left) Axial oblique ultrasound shows a small cerebellum with fused
hemispheres (arrow). It no longer has a bilobed contour. (Right) Axial
T2WI MR shows the fused cerebellar lobes (arrow). This could be
easily be confused with a Dandy-Walker malformation but there is no
communication
with the 4th ventricle. This is a key differentiating
feature. Holoprosencephaly also present.

AGENESIS OF THE CORPUS CALLOSUM

Coronal graphic shows corpus callosal agenesis with
widely spaced laleral venlricles (arrows). The 3rd
venlricle is elevated and is contiguous dorsally wilh lhe
inlerhemispheric fissure (curved arrow).

o Normally forms hypoechoic
pellucidi et vergae

ITERMINOLOGY
Abbreviations

and Synonyms

• Agenesis of the corpus callosum (ACC)
• Callosal dysgenesis

Definitions
• Failure ofaxons to cross midline and form corpus
callosum (CC)
o May be complete or partial

IIMAGING

Coronal T2WI MR shows the classic "triden/-shaped"
ventricles (arrows). The 3rd ventricle is high-riding and
is contiguous with the interhemispheric fissure (curved
arrow) where the corpus callosum is normally seen.

FINDINGS

General Features
• Best diagnostic clue
o Teardrop-shaped ventricles most consistent finding
on routine axial views
o Absent cavum septi pellucidi (CSP) and CC complex
on coronal and midline sagittal views
• Location
o Corpus callosum is midline structure composed of
four parts (from front to back)
• Rostrum
• Genu
• Body
• Splenium

Ultrasonographic

band over cavum septi

Findings

• Mild ventriculomegaly
o Look at shape of ventricles
• Colpocephaly
o Teardrop-shaped ventricles
o Lateral ventricles widely spaced anteriorly
• Medial wall of ventricle is further from midline at
frontal horn
o Enlargement of ventricular atria and occipital horns
• Prominent interhemispheric
fissure
• Elevation of 3rd ventricle
o Contiguous with interhemispheric
fissure
o Best seen in coronal plane
• Multiple descriptors for ventricular configuration
o "Trident-shaped"
o "Steer horn"
o "Viking helmet"
o "Moose head"
• Gyri
o Cingulate gyrus absent
o Radial, "spoke-wheel", "sunray" appearance in
sagittal plane
o Radiate to 3rd ventricle
• Absent CSP
• Other CNS anomalies in 50%

DDx: Agenesis Of The Corpus Callosum

Lobar Holopros

Lobar Holopros

Ventriculomegaly

Septa-Optic Dysplasia

AGENESIS OF THE CORPUS CALLOSUM
Key Facts
Top Differential

Terminology
• Failure ofaxons
callosum (CC)

to cross midline and form corpus

Imaging Findings
• Teardrop-shaped ventricles most consistent finding
on routine axial views
• Absent cavum septi pellucidi (CSP) and CC complex
on coronal and midline sagittal views
• Elevation of 3rd ventricle
• Other CNS anomalies in 50%
• Lipomas
• Interhemispheric
cyst
• Fetal MRI recommended in routine work-up
• Detection of other abnormalities negatively impacts
prognosis
• Absence of other abnormalities reassuring
o Lipomas
• Hyperechoic midline mass
• 50% of lipomas have ACC
o Interhemispheric
cyst
• Cystic mass centered around falx
• Most are likely glioependymal cysts
o Dandy-Walker continuum (DWC)
o Heterotopias and gyral abnormalities
• May manifest as asymmetry of cerebral
hemispheres
o Microcephaly
o Encephalocele
o Myelomeningocele
• Body anomalies
o Cardiac defects
o Genitourinary
• Renal malformations
• Undescended testes
o Congenital diaphragmatic hernia
• Color Doppler
o May have azygous anterior cerebral artery
• Single unpaired vessel arising from confluence of
left and right anterior cerebral arteries
• Abnormal course, running under frontal bones
o Abnormal course of peri callosal artery

MR Findings
• Sagittal
o Absent CC
o Absent cingulate gyrus
o Abnormal radially oriented gyri
• Converge toward 3rd ventricle
• Coronal
o Absent CC
o Widened interhemispheric
fissure
o "High-riding" 3rd ventricle
o "Trident-shaped" ventricles
• Lateral ventricles pointed superiorly
• May see Probst bundles
o Non-crossing commisural fibers that would have
normally formed CC
• Run front to back instead of crossing midline
o Indent medial wall of lateral ventricle

Diagnoses

• Mild ventriculomegaly
• Lobar holoprosencephaly
• Septo-optic dysplasia

Pathology
• Chromosomal anomalies in 10-20%
• Multiple syndromes described

Clinical Issues
• 3% of mild ventriculomegaly cases have ACC
• Karyotype recommended even if isolated finding

Diagnostic Checklist
• Diagnosis may be missed before 18-20 weeks
• Absent cavum septi pellucidi should raise suspicion
for ACC

Imaging Recommendations
• Best imaging tool
o Fetal MRI recommended in routine work-up
• Detection of other abnormalities negatively
impacts prognosis
• Absence of other abnormalities reassuring
• Meticulous sonographic technique needed to make
diagnosis
o Often missed or misdiagnosed as hydrocephalus
• Look for CSP
o Should be seen on routine views
o Absence very concerning for multiple conditions
including ACC
• If fetal presentation is cephalic, perform endovaginal
scan for better evaluation
• Midline sagittal and coronal planes often more helpful
than routine transverse planes
• Look for associated anomalies

I DIFFERENTIAL DIAGNOSIS
Mild ventriculomegaly
• Ventricles have normal configuration
• cSP present
• Normal gyral pattern

Lobar holoprosencephaly
•
•
•
•
•
•

Falx may be absent or abnormal
Fused frontal horns
Fused fornices
Fused thalami
Absent CSP
Facial anomalies may be present

Septo-optic
•
•
•
•

dysplasia

Fontal horns have "flat" or "squared-off" appearance
Downward point of frontal horns
Fused frontal horns
CC present but may be thinned

• Absent CSP

AGENESIS OF THE CORPUS CALLOSUM
I PATHOLOGY

Natural History & Prognosis

General Features

• Isolated (pediatric data)
o 75% normal or near-normal at 3 years
o Subtle cognitive defects may develop later
• Large, long-term studies for fetal diagnosis lacking
• Poor prognosis if associated with other malformations,
syndrome or chromosomal abnormalities

• Genetics
o Most felt to be sporadic
o Autosomal dominant, recessive and X-linked
described
o Chromosomal anomalies in 10-20%
• Trisomy 18, 13, 8
• Triploidy
• Etiology
o Multiple case reports implicating a variety of
etiologic agents
o Teratogens
• Alcohol, cocaine, valproate
o Infections
• Cytomegalovirus (CMV), rubella
o Destructive etiologies
• Ischemia, bleed
• Epidemiology
o 0.3-0.7% of general population
o Fetal incidence not known
oM> F
• Associated abnormalities
o Fetal body anomalies seen in 60%
• Cardiac
• Genitourinary
• Gastrointestinal
• Musculoskeletal
• Embryology
o Complete formation of CC is late embryologic event
o CC forms in midline lamina between 8-20 weeks
o Develops from anterior to posterior except rostrum
which is last
• Genu ~ body ~ splenium ~ rostrum
o Thickening continues until after birth
o Partial agenesis, splenium and rostrum missing
• Genu and body present to varying degrees
• Multiple syndromes described
o Aicardi syndrome
• Dandy-Walker continuum, ACC, ocular
abnormalities, choroid plexus cysts
o Apert syndrome
• Craniosynostosis, syndactyly
o Fryns syndrome
• Diaphragmatic hernia, micrognathia, facial
anomalies, distal limb hypoplasia
o Meckel-Gruber syndrome
• Encephalocele, polydactyly, polycystic kidneys
o Walker-Warburg syndrome
• Microcephaly, encephalocele, ocular abnormalities

!ClINICALISSUES
Presentation
• Most common signs/symptoms
o Mild ventriculomegaly
• Diagnosis easily missed
• 3% of mild ventriculomegaly
cases have ACC
o Discovered with other more obvious findings
o Incidental finding

Treatment
• Karyotype recommended even if isolated finding
• Full work-up after delivery

I

DIAGNOSTIC

CHECKLIST

Consider
• In setting of mild ventriculomegaly
• MRI very helpful in making diagnosis and evaluating
for associated anomalies

Image Interpretation

Pearls

• Diagnosis may be missed before 18-20 weeks
o Formation is not complete
• Absent cavum septi pellucidi should raise suspicion for
ACC
• Other brain and systemic anomalies common

I SELECTED

REFERENCES

Woodward P] et al: From the archives of the AFIP: a
comprehensive review of fetal tumors with pathologic
correlation. Radiographies. 25(1):215-42, 2005
2.
Blaicher W et al: Magnetic resonance imaging in foetuses
with bilateral moderate ventriculomegaly and suspected
anomaly of the corpus callosum on ultrasound scan.
Ultraschall Med. 24(4):255-60, 2003
3.
Weinstein AS et al: In utero disappearance of the corpus
callosum secondary to extensive brain injury.] Ultrasound
Med. 22(8):837-40, 2003
4.
Goodyear PW et al: Outcome in prenatally diagnosed fetal
agenesis of the corpus callosum. Fetal Diagn Ther.
16(3):139-45,2001
5.
d'Ercole C et al: Prenatal diagnosis of fetal corpus callosum
agenesis by ultrasonography
and magnetic resonance
imaging. Prenat Diagn.18:247-53, 1998
6.
Bennett GL et al: Agenesis of the corpus callosum: prenatal
detection usually is not possible before 22 weeks of
gestation. Radiology. 199(2):447-50, 1996
7.
Gupta JK et al: Assessment and management of fetal
agenesis of the corpus callosum. Prenat Diagn 15:301-12,
1995
8.
Vergani Pet al: Prognostic indicators in the prenatal
diagnosis of agenesis of corpus callosum. Am J Obstet
GynecoI170:753-8,1994
9.
Malinger G et al: The corpus callosum: normal fetal
development as shown by transvaginal sonography. AJR
Am J Roentgenol. 161(5):1041-3, 1993
10. Filly RA et al: Fetal ventricle: importance in routine
obstetric sonography. Radiology. 181(1):1-7, 199]
11. Barkovich AJ et al: Anomalies of the corpus callosum:
correlation with further anomalies of the brain. AJR Am J
Roentgenol. ]5](]):171-9, ]988
1.

AGENESIS OF THE CORPUS CALLOSUM
IIMAGE

GALLERY

(Left) Axial ultrasound of
colpocephaly in a case of
ACe. Note that the medial
wall of the frontal horn (a) is
further from the midline than
the occipital horn (b). The
3rd ventricle is elevated
(arrow). This was shown to
better advantage in the
coronal plane. (Right)
Coronal ultrasound after
delivery shows classic
"trident-shaped" lateral
ventricles (arrows) with an
elevated 3rd ventricle.

Typical
(Left) Coronal ultrasound
shows an echogenic midline
mass in the region of the
interhemispheric fissure
(arrow). This is characteristic
of a lipoma raising a strong
suspicion for ACe. (Right)
Coronal gross pathology
shows a lipoma (arrow)
corresponding to the mass
seen on ultrasound. Note the
absence of the corpus
callosum, which would
normally connect the two
hemispheres. 50% of
lipomas have associated
ACe. (Also shown in
Radiographies, ref 1).

Typical
(Left) Sagittal T2WI MR of
callosal dysgenesis showing
a very atretic portion of the
corpus callosum anteriorly
(arrow). The cingulate gyrus
is absent, with the remaining
gyri arranged in a radial
pattern. (Right) Axial
ultrasound shows an
interhemispheric cyst
(arrow) associated with
ACe. The ventricles have a
classic "teardrop" shape,
with pointing of the frontal
horns (curved arrow) and
widening of the atria and
occipital horns.

MILD VENTRICULOMEGALY

Axial ultrasound shows a second trimester fetus with a
lateral ventricular measurement of 72 mm (calipers).
The choroid plexus (arrow) is displaced from the medial
wall of the ventricle. This finding was isolated.

o Most are stable during pregnancy
o Some progress during pregnancy
o Rarely unilateral
• Isolated finding at time of ultrasound
o 4% with subsequent brain anomaly
• Progressive hydrocephalus
• Cystic brain lesion
o 9% with a malformation not diagnosed in utero

ITERMINOlOGY
Abbreviations

Axial T2WI MR in the same case shows Ule frontal horns
(arrows) and cavum septi pellucidi (curved arrow) to
better advantage. No additional brain anomalies were
detected and the infant was normal.

and Synonyms

• Mild ventriculomegaly (MV)
• Borderline ventriculomegaly

Definitions
• Atrium of lateral ventricle measures 10-12 mm

MR Findings
• Additional intracranial
• Best after 28 weeks

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Enlarged atria of lateral ventricle
on routine axial view
• Location: Bilateral> unilateral
• Size
o Normal atria is < 10 mm
• Mean diameter of 7.6 mm (+/- 0.6)
• 70% of hemicalvarium at 18 wks
• 30% of hemicalvarium at 28 wks

Ultrasonographic

Findings

~.

5

seen in 8%

Imaging Recommendations
• Best imaging tool: Routine transverse atrial assessment
• Protocol advice
o Measure atria of lateral ventricle in every case
• < 10 mm in 2nd/3rd trimester
o Serial ultrasounds to follow mild ventriculomegaly
o Fetal MR
o Look for markers of trisomy 21

I DIFFERENTIAL DIAGNOSIS

• Dilated lateral ventricular atria
o Axial plane through lateral ventricle
• Internal wall-to-internal wall measurement
• ~ 10 mm and ~ 12 mm considered MV
o 30% resolve in utero

DDx: Obstructive

anomalies

Agenesis of corpus callosum (CC)
• Complete or partial absence of CC
• MV + colpocephaly
o Teardrop-shaped ventricles

Hydrocephalus

-

~~-_.
~.~

.

~
l\quecluct<ll

Stenosis

/\quccluctal

Stenosis

IC Ilcl110rrhage

OW Continuul11

MILD VENTRICULOMEGALY
Key Facts
Terminology

Top Differential

• Borderline ventriculomegaly
• Atrium of lateral ventricle measures 10-12 mm

• Agenesis of corpus callosum (CC)
• Obstructive hydrocephalus

Imaging Findings

Pathology

•
•
•
•

• 4% with aneuploidy
• 90% idiopathic

Internal wall-to-internal wall measurement
30% resolve in utero
Rarely unilateral
Serial ultrasounds to follow mild ventriculomegaly

• Absent cavum septi pellucidi

Obstructive

hydrocephalus

• Aqueductal stenosis
• Dandy-Walker continuum (DW continuum)
• Intracranial hemorrhage (IC hemorrhage)

I

Diagnoses

PATHOLOGY

General Features
• Genetics
o 4% with aneuploidy
• Trisomy 21 most common
• Etiology
o 90% idiopathic
• Normal outcome
o Maternal infection
• Rare cause
• Cytomegalovirus (CMV)
o Chromosome anomaly
o Intracranial hemorrhage
o Other cerebral anomaly

Clinical Issues
• M:F

Presentation
• Most common signs/symptoms: Abnormal second
trimester routine ultrasound screen
• Other signs/symptoms: Abnormal maternal serum
screen for trisomy 21

3:1

I DIAGNOSTIC

CHECKLIST

Consider
•
•
•
•

Idiopathic MV is a diagnosis of exclusion
Genetic amniocentesis
Maternal infection screen
Fetal MR

Image Interpretation

Pearls

• More likely idiopathic in male fetuses, especially when
presenting> 20 weeks

I SELECTED REFERENCES
1.

2.

3.

4.

I CLINICAL ISSUES

=

Signorelli M et al: Width of the fetal lateral ventricular
atrium between 10 and 12 mm: a simple variation of the
norm? Ultrasound
Obstet Gynecol. 23(1):14-8, 2004
Valsky DV et al: The role of magnetic resonance imaging in
the evaluation
of isolated mild ventriculomegaly.
J
Ultrasound
Med. 23(4):519-23;
quiz 525-6,2004
Kinzler WL et al: Outcome of prenatally diagnosed mild
unilateral cerebral ventriculomegaly.
J Ultrasound Med.
20(3):257-62,
2001
Mercier A et al: Isolated mild fetal cerebral
ventriculomegaly:
a retrospective
analysis of 26 cases.
Prenat Diagn. 21(7):589-95,
2001

IIMAGE GALLERY

Demographics
• Age: Mean maternal age is 28
• Gender
o M:F = 3:1
• Larger calvarial volume in males
• More likely idiopathic in males

Natural History & Prognosis
• 9% with abnormal outcome when isolated
• 4% aneuploidy
• Better prognosis when unilateral

Treatment
• Postnatal assessment
o Imaging surveillance
o Developmental follow-up at least until 6 yrs old

(Left) Axial ultrasound shows ventriculomegaly in a 18 week fetus.
Calipers measure the atrium of the lateral ventricle. The choroid
plexus (arrow) is displaced peripherally. (Right) Axial ultrasound of
the heart in the same fetus shows a moderate-sized ventricular septal
defect (arrow). Civen the presence of two markers for aneuploidy,
amniocentesis was performed and revealed trisomy 21.

ALOBAR HOLOPROSENCEPHALY

Coronal ultrasound shows a monoventricle with a very
thin mantle of brain (arrows) and thalamic fusion
(curved arrow) in a fetus with trisomy 73. Also note the
absence of a falx.

• Flattened nose

ITERMINOlOGY
Abbreviations

Cross pathology in a similar case shows the typical
features of alobar holoprosencephaly. A thin mantle of
brain surrounds a large monoventricle
(arrows).
Thalamic fusion (curved arrow) is also present.

and Synonyms

IIMAGING FINDINGS

• Alobar holoprosencephaly
• Holoprosencephaly (HPE)

General Features

Definitions
• Severe brain malformation due to early arrest in brain
cleavage and rotation
• Nomenclature for associated facial malformations
o Cyclopia
• Single midline eye
• Arrhinia (absent nose)
• Proboscis may be present
o Ethmocephaly
• Severe hypotelorism
• Arrhinia
• Proboscis
o Cebocephaly
• Hypotelorism
• Nose with single nostril
o Face with median cleft lip
• Cleft lip and palate
• Hypotelorism
• Flattened nose
o Face with median philtrum premaxilla anlage and
flat nose
• Bilateral cleft lip

• Best diagnostic clue
o First trimester
• Absent "butterfly" sign (see below): Abnormal
appearance of choroid plexus
o Second/third trimester
• Fused thalami with monoventricle

Ultrasonographic

Findings

• Grayscale Ultrasound
o "Butterfly" sign
• Both choroids normally seen as "butterfly wings"
• Used in the first trimester
• If absent increases suspicion for HPE
o Single ventricle
o Absent midline structures
• Cavum septi pellucidi
• Falx cerebri
• 3rd ventricle
• Corpus callosum
o Fused thalami
o Dorsal sac
• Cystic extension of monoventricle
• Herniation of telea choroidea

DDx: Alobar Holoprosencephaly

Hydranencephaly

Arachnoid Cyst

Aqueduct Stenosis

Aqueduct Stenosis

ALOBAR HOLOPROSENCEPHALY
Key Facts
• Aprosencephaly/atelencephaly

Terminology
• Severe brain malformation
cleavage and rotation

due to early arrest in brain

Imaging Findings
•
•
•
•

Single ventricle
Fused thalami
Dorsal sac
Remaining brain has 3 appearances:
and "ball"
• Facial anomalies

Top Differential
•
•
•
•

"Pancake", "cup"

Clinical Issues
• Karyotype all fetuses
• Termination offered

Diagnoses

Hydranencephaly
Aqueductal stenosis
Porencephaly
Arachnoid/glioependymal

Diagnostic Checklist
• "The face predicts the brain"
• Facial malformations of any kind should trigger a
very careful evaluation of the brain

cyst

• Can be large
a Remaining brain has 3 appearances: "Pancake", "cup"
and "ball"
a "Pancake"
• Mantle flattened at skull base
• Large dorsal monoventricle/cyst
a "Cup"
• Brain mantle anterior and at base of skull
• Partial crescent around monoventricle
a "Ball"
• Brain mantle surrounds monoventricle
a Facial anomalies
• Cyclopia
• Proboscis
• Hypotelorism
• Cleft lip and palate
a Helps to define severity of malformation
a Useful to characterize associated facial
malformations
• 72% have facial anomalies

MR Findings
• Very helpful when US is equivocal
• Fused thalami easily demonstrated

Imaging Recommendations
• Protocol advice
a Look for features of trisomy 13
• Congenital heart disease
• Renal anomalies
• Musculoskeletal anomalies
• Gastrointestinal anomalies
• Intrauterine growth restriction,
a MRI for difficult cases

Aqueductal
•
•
•
•

stenosis

Head often large
Dilated 3rd ventricle
Thalami not fused
Cavum septi pellucidi present
a May be thinned or obliterated
hydrocephalus

in severe

Porencephaly
• Usually asymmetric ventricular enlargement
• May see evidence of residual hematoma which evolves
over time

Arachnoid/glioependymal

cyst

Ap rosen cep haly / atel encephaly
• Rare severe malformation
• Absent brain above the tentorium
• Maldevelopment of face
a May have complete absence of orbits +/- nose
• Facial skin tags cause confusion with facial c1efting

I PATHOLOGY
General Features

often early onset

I DIFFERENTIAL DIAGNOSIS
Hydranencephaly

• Brainstem may bulge superiorly and mimic fused
thalami

• Can be confused with dorsal sac if large

• 3D

• No cerebral tissue
• Falx present
• ormal facial development

Pathology
• Isolated HPE often normal karyotype
• Trisomy 13 (T13) most common chromosomal
association
• At least 12 different chromosomal regions contain
genes involved in HPE pathogenesis
• Infants of diabetic mothers have 1% risk

• Genetics
a Most cases sporadic
• Isolated HPE often normal karyotype
a Chromosomal abnormalities
• Trisomy 13 (T13) most common chromosomal
association
• Also trisomy 18, triploidy, monosomy 21
a Autosomal recessive, dominant, and X-linked forms
described
a At least 12 different chromosomal regions contain
genes involved in HPE pathogenesis
• Sonic hedgehog (SHH) gene was the first gene
identified (1996)
• SHH mutations in 33% of familial HPE

ALOBAR HOLOPROSENCEPHALY

•

•

•

•

•

•
•
•
•

• SHH mutation in < 5% of sporadic cases
o Other implicated genes
• ZIC2
• SIX3
• TGIF
Etiology
o Maternal diabetes
• Infants of diabetic mothers have 1% risk
o Teratogens
• Retinoic acid
• Alcohol
Epidemiology
o 1:16,000 births
o More common in utero
• 1:250 in terminated pregnancies
Associated abnormalities
o Part of multiple syndromes
• Smith-Lemli-Opitz syndrome
• Aicardi syndrome
• Fryns syndrome
Embryology
o Primitive brain develops 3 vesicles at day 22-24
• Prosencephalon
• Mesencephalon
• Rhombencephalon
Cleavage of prosencephalon gives rise to
telencephalon and diencephalon at 32 days
o Telencephalon gives rise to
• Cerebral hemispheres
• Putamen
• Caudate nucleus
o Diencephalon gives rise to
• Thalamus
• Hypothalamus
• Globus pallidus
• Optic vesicles
Abnormal cleavage of prosencephalon
results in
spectrum of brain malformations
Anatomists prefer term "abnormal cleavage" to "fusion"
Abnormal budding of optic vesicles => eye and orbit
malformations
Associated general defect in midline cranial cartilage
differentiation rostral to notochord
o Midface anomalies

o Feeding difficulties
o Seizure disorder

Treatment
•
•
•
•

I DIAGNOSTIC

• Fetal MRI if findings equivocal
o Differentiates from other entities with better
prognoses

Image Interpretation

I SELECTED
1.

2.

3.

4.

5.

6.
7.

8.

9.

• Other signs/symptoms
o May have an abnormal triple screen (Tl3)
o May be diagnosed in 1st trimester

Natural History & Prognosis
• Stillbirth common
• Liveborn infants have short lifespan

REFERENCES

Aguilella C et al: Molecular
screening
of the TGIF gene in
holoprosencephaly:
identification
of two novel mutations.
Hum Genet. 112(2):131-4,2003
Chen CP et al: Molecular
diagnosis
of a novel heterozygous
268C-->T (R90C) mutation
in TGIF gene in a fetus with
holoprosencephaly
and premaxillary
agenesis. Prenat
Diagn. 22(1):5-7, 2002
Kjaer I et al: Midline skeletodental
morphology
in
holoprosencephaly.
Cleft Palate Craniofacj.
39(3):357-63,
2002
Situ 0 et al: Investigation
of a cyclopic, human,
term fetus
by use of magnetic
resonance
imaging (MRI). J Anal.
200(5):431-8,2002
Cannistra
C et al: Cyclopia: a radiological
and anatomical
craniofacial
post mortem study. J Craniomaxillofac
Surg.
29(3):150-5,2001
Chasen ST et al: The role of cephalocentesis
in modern
obstetrics.
Am J Obstet Gynecol.
185(3):734-6,2001
]eng LB et al: Genetic advances
in central nervous system
malformations
in the fetus and neonate.
Semin Pediatr
Neurol. 8(2):89-99,
2001
Nowaczyk
MJ et al: Smith-LemJi-Opitz
(RHS) syndrome:
holoprosencephaly
and homozygous
IVS8-1G-->C
genotype.
Am J Med Genet. 103(1):75-80,2001
Lai TH et al: Prenatal diagnosis
of alobar
holoprosencephaly
by two-dimensional
and
three-dimensional
ultrasound.
Prenat Diagn. 20(5):400-3,

2000

ISSUES

Presentation

Pearls

• "The face predicts the brain"
o Facial malformations of any kind should trigger a
very careful evaluation of the brain

10.

ICLINICAL

CHECKLIST

Consider

Gross Pathologic & Surgical Features
• Malformations of midline structures anterior to sella
turcica
o Compromised suture and cartilage development.
• Single central incisor
• Single nasal bone
• Absent crista galli

Karyotype all fetuses
Termination offered
Fetal intervention not indicated
Consider cephalocentesis to allow vaginal delivery if
pregnancy carried
o Avoids maternal morbidity of cesarean section for
non-viable fetus

11.
12.

Leonard NJ et al: Prenatal diagnosis
of holoprosencephaly
(HPE) in a fetus with a recombinant
(18)dup(18q)inv(18)(pl1.31ql1.2)mal.
Prenat Diagn.
20(12):947-9,2000
Armbruster-Moraes
E et al: Holoprosencephaly
in a
1999
Klinefelter
fetus. Am J Med Genet. 85(5):511-2,
Arnold WH et al: Cranio-facial
skeletal development
in
three human synophthalmic
holoprosencephalic
fetuses.
Anat Anz. 180(1):45-53,
1998

ALOBAR HOLOPROSENCEPHALY
I IMAGE GALLERY
(Left) Sagittal ultrasound
shows an abnormal facial
profile in a fetus with trisomy
13. There was no normal
nose; instead a proboscis
(arrow) extends from the
forehead. No orbits seen
sonographically. (Right)
Coronal T2WI MR shows
facial appearance of the
same fetus on an autopsy
MRI. There are rudimentary
globes (arrows) in a single
orbit. No normal nose is seen
and the proboscis (open
arrow) is above the orbit.

Typical
(Left) Coronal ultrasound
shows a midline facial cleft
(open arrow) in a fetus with
holoprosencephaly. The
orbits (arrows) were
abnormally close and the
nose appeared "flattened".
(Right) Cross pathology
shows similar appearances in
another fetus with
hypotelorism (open arrow),
single nostril nose (arrow),
and midline facial cleft
(curved arrow). This fetus
had trisomy 73.

(Left) Axial ultrasound shows
a remarkably clear image of
the fetal tongue (arrow). The
tongue is well seen because
of the virtual absence of the
palate in this fetus with a
midline facial cleft and
alobar holoprosencephaly.
(Right) Sagittal T2WI MR
shows a large dorsal sac
(arrows) in a fetus with
alobar holoprosencephaly
and a midline facial cleft
(secondary to diabetic
embryopathy). The brain is
in the "cup" morphology
(curved arrow).

SEMILOBAR, LOBAR HOLOPROSENCEPHALY

Coronal T2WI MR shows a monoventricle (arrows), but
some attempt at cleavage as there is a Falx present
(curved arrow). Other Findings included incomplete
thalamic Fusion and absent cavum septi pellucidi.

• Single unpaired vessel arising from confluence
left and right ACAs

ITERMINOlOGY
Abbreviations

Cross pathology
of a similar case of semilobar
holoprosencephaly
shows the monoventricle (arrows).
Note the incomplete
hemispheric
cleavage
with
rudimentary FalxFormation (curved arrow).

and Synonyms

• Semilobar holoprosencephaly
• Lobar holoprosencephaly
• Holoprosencephaly
(HPE) developmental spectrum
o Continuum with no sharp division among types

Definitions
• Less severe entities within holoprosencephaly
spectrum
• Semilobar HPE
o Incomplete interhemispheric
fissure
o Rudimentary cerebral lobes
• Fused anteriorly
o Olfactory tracts and bulbs absent or hypoplastic
o Abnormal corpus callosum
o Thalami completely/partly
fused
• Lobar HPE
o Interhemispheric
fissure present
o Well formed lobes
• May be normal size
• Frontal lobes most likely to be hypoplastic
o Often midline continuity of one or more gyri
o Thalami normal/partly fused
o Fornices fused
o Azygos anterior cerebral artery (ACA)

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Semilobar HPE
• Anterior hemispheric fusion
o Lobar HPE
• Fused fornices, specific sign when present

Ultrasonographic

Findings

• Grayscale Ultrasound
o Monoventricle anteriorly
• Separate occipital horns
o Absent cavum septi pellucidi (CSP)
o Callosal dysgenesis
• Deficient anteriorly
• Abnormal course of ACA
o Thalami
• May be partly cleaved
o Forniceal fusion
• Creates a round "mass" in third ventricle
o Brachycephaly
• Rounded head secondary to frontal lobe
hypoplasia
o Macrocephaly

DDx: Holoprosencephaly

Aqueduct Stenosis

Septa-Optic Dysplasia

Septa-Optic Dysplasia

Schizencephaly

of

SEMILOBAR, LOBAR HOLOPROSENCEPHALY
Key Facts
Terminology

Pathology

• Less severe entities within holoprosencephaly
spectrum

• Infants of diabetic mothers have 10/0risk
• Overall HPE 1:16,000 births

Imaging Findings

Clinical Issues

•
•
•
•

• Depends on type and severity
• Semilobar HPE worse than lobar HPE
• Karyotype all fetuses

Monoventricle anteriorly
Absent cavum septi pellucidi (CSP)
Callosal dysgenesis
Facial anomalies

Top Differential
•
•
•
•
•

Diagnoses

Aqueductal stenosis
Agenesis of the corpus callosum
Schizencephaly
Septo-optic dysplasia
Syntelencephaly

• Associated aqueductal stenosis
• Disrupted cerebral spinal fluid (CSF) circulation
• Large dorsal cyst
o Microcephaly
• Fundamental abnormality of brain
o Facial anomalies
• Less severe than those seen with alobar
holoprosencephaly
• Cleft lip/palate
• Cebocephaly (hypotelorism, single nostril)
o If fetus has trisomy 13
• Congential heart disease
• Renal anomalies
• Musculoskeletal anomalies
• Gastrointestinal anomalies
• Intrauterine growth restriction, often early onset
• Color Doppler
o Azygos anterior cerebral artery (ACA)
• Abnormal course ACA
• Runs under frontal bone
• Single rather than paired vessel
• 3D

o May help determine extent of hemispheric fusion
o Useful for assessment of facial malformations

MR Findings
• Semilobar HPE
o Falx incomplete/deficient
anteriorly
o Monoven tricle
o Absent CSP
o Partial development of corpus callosum (CC)
• HPE spectrum is only condition in which anterior
CC is deficient
• Lobar HPE
o Falx often complete
o Absent CSP
o Fornices fused
o Single flow void for azygos ACA

Imaging Recommendations
• Best imaging tool; Fetal MRI very helpful for
characterizing brain malformation

Diagnostic Checklist
•
•
•
•

Fetal MRI if findings equivocal
Frontal lobe hypoplasia in all forms
Round appearance to head in multiple scan planes
Communication
between frontal horns of lateral
ventricles is never normal
• Fused fornices is specific sign of lobar
holoprosencephaly

I DIFFERENTIAL DIAGNOSIS
Aqueductal

stenosis

• Interhemispheric
fissure present
• Dilated 3rd ventricle
o Thalami not fused
o Fornices not fused
• CSP present
o May be thinned or obliterated in severe
hydrocephalus
• Normal face
• Abducted thumbs seen in X-linked recessive form

Absent cavum septi pellucidi
• Agenesis of the corpus callosum
o Interhemispheric
fissure present
o Lateral ventricle parallel
o Colpocephaly
o "Trident-shaped" appearance to anterior horns
o Abnormal course callosomarginal/pericallosal
arteries
• Schizencephaly
o Interhemispheric
fissure present
o Cerebral cortical cleft lined by grey matter
• Septo-optic dysplasia
o Downward point to anterior horns
o Flat-top or squared-off appearance of frontal horns

Syntelencephaly
• Midline interhemispheric
fusion
• Anterior and posterior horns separate
o Hemispheres fused centrally
• Associated with 13q- deletion
o Hypoplastic thumbs and syndactyly with 13q-

I PATHOLOGY
General Features
• Genetics
o Most cases sporadic
o Autosomal dominant,
described

recessive and X-linked forms

SEMILOBAR, LOBAR HOLOPROSENCEPHALY

•

•

•

•

o At least 12 different chromosome regions contain
genes involve in HPE pathogenesis
o Known genes include
• Sonic hedgehog (SHH)
• ZIC2
• SIX3
• TGIF
o Also seen in trisomies 13, 18, & triploidy
Etiology
o Maternal diabetes
• Infants of diabetic mothers have 1% risk
o Teratogens
• Retinoic acid
• Alcohol
Epidemiology
o Overall HPE 1:16,000 births
o Hard to separate alobar/semilobar/lobar
• Milder forms may not be recognized
• All forms commoner in fetus than livebirths
• HPE seen in 1:250 terminated pregnancies
Embryology
o Primitive brain develops 3 vesicles day 22-24
• Prosencephalon
• Rhombencephalon
• Mesencephalon
Cleavage of prosencephalon
gives rise to
telencephalon and diencephalon at 32 days
o Telencephalon gives rise to
• Cerebral hemispheres
• Putamen
• Caudate nucleus
o Diencephalon gives rise to
• Thalamus
• Hypothalamus
• Globus pallidus
• Optic vesicles
o Abnormal cleavage of prosencephalon
results in
spectrum of brain malformation

• Essential before embarking on extensive surgical
repair of facial malformations

I DIAGNOSTIC
Consider

• Fetal MRI if findings equivocal
o Characterize degree brain malformation
o Assists with parental counseling

Image Interpretation

I SELECTED
1.

2.
3.

4.

5.

6.

7.

ISSUES

Presentation
• Most common signs/symptoms: Abnormal
communication
between frontal horns of lateral
ventricles

Natural History & Prognosis
• Depends on type and severity
• Semilobar HPE worse than lobar HPE
o Mental retardation
o Developmental delay
o Seizure disorder
o Hypothalamic pituitary malfunction
o Visual problems

Treatment
• Prenatal
o Karyotype all fetuses
o Offer termination
• Postnatal
o Careful evaluation by pediatric neurology
o Postnatal imaging to define brain abnormality

Pearls

• Frontal lobe hypoplasia in all forms
o Brachycephaly
o Round appearance to head in multiple scan planes
• Communication
between frontal horns of lateral
ventricles is never normal
• Fused fornices is specific sign of lobar
holoprosencephaly

8.

I CLINICAL

CHECKLIST

9.

10.

11.

12.
13.

14.
15.

16.

REFERENCES

Blin G et al: Prenatal diagnosis of lobar holoprosencephaly
using color Doppler: three cases with the anterior cerebral
artery crawling under the skull. Ultrasound Obstet
Gynecol. 24(4):476-8, 2004
Hahn JS et al: Evaluation and management of children
with holoprosencephaly.
Pediatr Neurol. 31(2):79-88, 2004
Hendi JM et al: Plastic surgery considerations for
holoprosencephaly
patients. J Craniofac Surg. 15(4):675-7,
2004
Kinsman SL: White matter imaging in holoprosencephaly
in children. Curr Opin Neurol. 17(2):115-9,2004
Sepulveda Wet al: First-trimester sonographic diagnosis of
holoprosencephaly:
value of the "butterfly" sign. J
Ultrasound Med. 23(6):761-5; quiz 766-7, 2004
Takahashi TS et al: Holoprosencephaly--topologic
variations in a liveborn series: a general model based upon
MRI analysis. J Neurocytol. 33(1):23-35, 2004
Thakur S et al: Spectrum of holoprosencephaly.
Indian J
Pediatr. 71(7):593-7, 2004
Takahashi T et al: Semilobar holoprosencephaly
with
midline 'seam': a topologic and morphogenetic model
based upon MRI analysis. Cereb Cortex. 13(12):1299-312,
2003
Bernard JP et al: A new clue to the prenatal diagnosis of
lobar holoprosencephaly:
the abnormal pathway of the
anterior cerebral artery crawling under the skull.
Ultrasound Obstet Gynecol. 19(6):605-7,2002
Blaas HG et al: Brains and faces in holoprosencephaly:
preand postnatal description of 30 cases. Ultrasound Obstet
Gynecol. 19(1):24-38, 2002
Kjaer I et al: Midline skeletodental morphology in
holoprosencephaly.
Cleft Palate Craniofac J. 39(3):357-63,
2002
Witters I et al: Semi lobar holoprosencephaly
in a 46,XY
female fetus. Prenat Diagn. 21(10):839-41, 2001
Sztriha Let al: Mediobasal and mantle defect of the
prosencephalon:
lobar holoprosencephaly,
schizencephaly
and diabetes insipidus. Neuropediatrics. 29(5):272-5, 1998
Chow BH et al: Holoprosencephaly
and chromosomal
anomalies. Singapore Med J. 37(4):394-7, 1996
Kuhn MJ et al: Absence of the septum pellucidum and
related disorders. Comput Med Imaging Graph.
17(2):137-47,1993
McGahan JP et al: Sonography of facial features of alobar
and semilobar holoprosencephaly.
AJR Am J Roentgenol.
154(1):143-8, 1990

SEMILOBAR, LOBAR HOLOPROSENCEPHALY
IIMAGE

GALLERY

Typical
(Left) Axial oblique
ultrasound shows a single
ventricle with
communication anteriorly
(open arrow) but with
differentiation of the
occipital horns (arrows).
(Right) Coronal ultrasound
after delivery shows the
monoventricle (arrows) but
some cleavage of thalami
(curved arrows) in this case
of semilobar
holoprosencephaly.

(Left) Coronal ultrasound
shows ventricular
communication and an
apparent "mass" (arrow)
within third ventricle. The
"mass" is formed by fused
fornices and is an important
finding in lobar
holoprosencephaly. (Right)
Coronal T2WI MR of fetal
brain shows classic findings
of lobar holoprosencephaly.
There is an absent cavum
septi pellucidi with
communication of ventricles.
Fused fornices (arrow) are
well demonstrated.

Typical
(Left) Coronal ultrasound on
day one of life shows
separation of the thalami
(curved arrows). Fused
fornices run
anterior-to-posterior in the
third ventricle (arrow).
(Right) Coronal T2WI MR in
the same infant shows well
developed cerebral
hemispheres and
interhemispheric fissure
(arrow), absent CSP and
fused fornices (open arrow),
consistent with lobar
holoprosencephaly.

SEPTO-OPTIC

Coronal graphic shows the downward point of the
frontal horns (curved arrow). The fornices (white arrow)
are not fused. Corpus callosum is present (black arrow)
but cavum septi pellucidi is absent.

DYSPLASIA

Coronal T2WI MR shows absent cavum septi pellucidi
with "flat top" appearance (arrow) to anterior horns of
the lateral ventricles. The absence of fused fornices
helps differentiate SOD from lobar holoprosencephaly.

[TERMINOLOGY

IIMAGING

Abbreviations

General Features

and Synonyms

• Septo-optic dysplasia (SOD)
o De Morsier syndrome
• First described condition in 1956
o Kaplan Grumbach Hoyt syndrome
o Suprasellar dysgenesis
o Septo-optic-pituitary
dysgenesis
• SOD "plus"
o Term coined for cases with additional
malformation
• Cortical dysplasias
• Schizencephaly

• Best diagnostic clue: Absent cavum septi pellucidi

Ultrasonographic

brain

Definitions
• Heterogeneous group of disorders with anomalies
including:
o Hypoplasia optic nerves and tracts
o Absence of cavum septi pellucidi
o Hypothalamic pituitary dysfunction
• Some consider SOD mildest form of
holoprosencephaly

DDx: Septo-Optic

Agenesis CC

FINDINGS

Findings

• CSP absent
o CSP normally seen as parallel echogenic lines in
anterior midline of brain
o Seen on standard axial view for biparietal diameter
and head circumference measurements
• Mild ventriculomegaly
o Look at ventricular wall for nodularity
o Nodules => heterotopia
• Anterior horns lateral ventricles have "flat" or
"squared-off" appearance
• Anterior horns are connected across the midline
• Corpus callosum present but may be thinned

MR Findings
• Fetal MRI does not yet have sufficient resolution to
evaluate optic chiasm and tracts
o Confirms absent cavum septi pellucidi (CSP)
• Excludes agenesis of corpus callosum as cause
o Demonstrates associated brain malformation
• Schizencephaly (seen in 50-70% postnatal cases)
• Heterotopia
• Axial

Dysplasia

Dysgenesis CC

Schizencephaly

Lobar Holopros

SEPTO-OPTIC
Key

DYSPLASIA
Facts

Terminology

Clinical Issues

• Some consider SOD mildest form of
holoprosencephaly

• Isolated optic nerve hypoplasia ~ good
developmental outcome
• Associated hemispheric anomalies ~ more guarded
prognosis
• 75-90% have brain abnormalities
• 45% pituitary insufficiency
• Visual defects vary

Imaging Findings
• Best diagnostic clue: Absent cavum septi pellucidi
• Downward point to anterior horns of lateral
ventricles
• "Squared-off" appearance to frontal horns
• Anterior horns are connected across the midline
• Corpus callosum present but may be thinned

Top Differential

Diagnoses

• Agenesis of the corpus callosum
• Lobar holoprosencephaly

o Frontal horns communicate across midline
o "Flat" or "squared-off" appearance to frontal horn
confluence
• Sagittal
o Corpus callosum usually present in simple SOD
• May be thinned
• Coronal
o Absent or rudimentary CSP
o Downward point to anterior horns of lateral
ventricles
o "Squared-off" appearance to frontal horns

Imaging Recommendations
• Best imaging tool: Fetal MRI
• Protocol advice
o Endovaginal ultrasound useful if cephalic fetal
presentation
• Use anterior fontanelle as acoustic window to fetal
brain
o Thorough evaluation of midline structures
• CSP
• Corpus callosum (CC)
o Evaluate ventricular morphology
• Especially useful in coronal plane
• Squared frontal horns coming to point inferiorly
• Document that fornices are not fused

I DIFFERENTIAL DIAGNOSIS
Agenesis of the corpus callosum
•
•
•
•
•

Absent CSP
Parallel lateral ventricles
Abnormal course callosomarginal/pericallosal
arteries
"Trident-shaped" appearance of anterior horns
Colpocephaly
o Teardrop-shaped ventricles
• Radial configuration of gyri
• May be associated with interhemispheric cyst

Lobar holoprosencephaly
• Fused fornices run anteroposterior
• Azygos anterior cerebral artery

in third ventricle

Diagnostic Checklist
• Fetal MRI for complete evaluation in all cases
• CSP is a marker of normal fetal central nervous
system development
• Lack of fused fornices helps differentiate from lobar
holoprosencephaly

o Single rather than paired anterior cerebral arteries
o Runs under frontal bone
• Facial anomalies
• If associated trisomy 13
o Omphalocele
o Congenital heart disease
o Polydactyly
o Cystic renal disease

Schizencephaly
• Absent CSP
• Cleft in cerebral parenchyma lined
o Cleft extends from brain surface
o Ventricular wall may be "tented"
o Unilateral or bilateral defect
• Small unilateral defect may not be
ultrasound
• May occur with SOD
o SOD "plus"

I

with grey matter
to ventricular wall
toward defect
apparent on

PATHOLOGY

General Features
• Genetics
o Most cases are sporadic
o Autosomal dominant and recessive types described
o Mutation in homeobox gene Hesxl/HESXl
• Homozygous mutation ~ full syndrome
• Heterozygous mutation ~ milder form
o Inactivation Hesxl by an Arg53Cys substitution
• Deficient anterior lobe of pituitary
o 18q- deletion
• Etiology
o Teratogens
• Valproate
• Ethanol
• Maternal diabetes mellitus
• Cytomegalovirus (CMV) infection
o Maternal drug abuse
• Possible early vascular insult
• Cocaine
• Heroin

SEPTO-OPTIC
• Amphetamine
• Epidemiology
o 1:50,000
o M=F

o Younger mothers and first born infants

Gross Pathologic & Surgical Features
• Small optic chiasm and nerves
o Sparse/absent myelinated fibers
o Optic nerve hypoplasia unilateral in 20%
• Deficient or absent CSP
• Pituitary hypoplasia common

DYSPLASIA
• If absent, significant neurological conditions to
consider include
o SOD
o Agenesis of the corpus callosum
o Schizencephaly
• Lack of fused fornices helps differentiate from lobar
holoprosencephaly

I SELECTED REFERENCES
1.

2.

I CLINICAL ISSUES
Presentation

3.

• Most common signs/symptoms
o Absent CSP
o Fused anterior horns of ventricles

4.

5.

Natural History & Prognosis
• Depends on degree of severity and associated
abnormalities
o Isolated optic nerve hypoplasia ~ good
developmental outcome
• Optic nerve hypoplasia occult on neuroimaging in
50% cases after birth
• Clinical diagnosis by ophthalmologic examination
• Fetal presentation probably implies more severe
end of spectrum
o Associated hemispheric anomalies ~ more guarded
prognosis
• 75-90o;h have brain abnormalities
• 4591> pituitary insufficiency
o Secondary to hypothalamic malformation
o Short stature
o Mental retardation
o Anosmia
• 709'6bilateral optic nerve hypoplasia
o Optic nerve hypoplasia can be unilateral
o Visual defects vary
• Color blindness to complete visual loss
• Nystagmus
• Strabismus

6.
7.

8.
9.
10.

11.

12.

13.

14.
15.

Treatment
• Not indication for early delivery
• Careful assessment of infant by pediatric
endocrinologist and ophthalmologist

I DIAGNOSTIC

CHECKLIST

16.

17.

18.

Consider

19.

• Fetal MRI for complete evaluation in all cases
o Identify associated malformations
o Not yet adequate to evaluate optic chiasm and tracts

20.

Image Interpretation

Pearls

• Do not assume an absent CSP is "technical"
• CSP is a marker of normal fetal central nervous system
development

Singh V et al: Septo-optic dysplasia and dentato-olivary
dysplasia in a case of 18q deletion/3p trisomy. Clin
Neuropathol. 23(1):28-33, 2004
Stevens CA et al: Septo-optic dysplasia and amniotic bands:
further evidence for a vascular pathogenesis. Am J Med
Genet. 125A(I):12-6, 2004
Camino R et al: Septo-optic dysplasia plus. Lancet Neurol.
2(7):436, 2003
Campbell CL: Septo-optic dysplasia: a literature review.
Optometry. 74(7):417-26, 2003
Cohen RN et al: Enhanced repression by HESXl as a cause
of hypopituitarism and septooptic dysplasia. J Clin
Endocrinol Metab. 88(10):4832-9, 2003
Gasparetto EL et al: Septo-optic dysplasia plus: case report.
Arq Neuropsiquiatr. 61(3A):671-6, 2003
Minami K et al: Septo-optic dysplasia with congenital
hepatic fibrosis. Pediatr Neurol. 29(2):157-9, 2003
Ang CS: Septooptic dysplasia. MedJ Malaysia. 57(4):487-9,
2002
Dattani MT et al: HESXl and Septo-Optic Dysplasia. Rev
Endocr Metab Disord. 3(4):289-300, 2002
Orrico A et al: Septo-optic dysplasia with digital anomalies
associated with maternal multidrug abuse during
pregnancy. Eur J Neurol. 9(6):679-82, 2002
Parker KLet al: Septo-optic dysplasia/optic nerve
hypoplasia: data from the National Cooperative Growth
Study (NCGS). J Pediatr Endocrinol Metab. 15 Suppl
2:697-700,2002
McMahon CL et al: Septo-optic dysplasia as a
manifestation of valproic acid embryopathy. Teratology.
64(2):83-6, 2001
Thomas PQ et al: Heterozygous HESXl mutations
associated with isolated congenital pituitary hypoplasia
and septo-optic dysplasia. Hum Mol Genet. 10(1):39-45,
2001
Dattani ML et al: Molecular genetics of septo-optic
dysplasia. Horm Res. 53 Suppll:26-33, 2000
Hsu HC et al: Septo-optic dysplasia with unilateral optic
nerve hypoplasia: case report. Changgeng Yi Xue Za Zhi.
23(5):303-8, 2000
Miller SP et al: Septo-optic dysplasia plus: a spectrum of
malformations of cortical development. Neurology.
54(8):1701-3,2000
Tanaka T et al: Genetics of brain development and
malformation syndromes. Curr Opin Pediatr. 12(6):523-8,
2000
Brodsky MC et al: Sudden death in septo-optic dysplasia.
Report of 5 cases. Arch Ophthalmol. 115(1):66-70, 1997
Lubinsky MS: Hypothesis: septo-optic dysplasia is a
vascular disruption sequence. Am J Med Genet.
69(3):235-6, 1997
Sener RN: Septo-optic dysplasia associated with cerebral
cortical dysplasia (cortico-septo-optic dysplasia). J
Neuroradiol. 23(4):245-7, 1996

SEPTO-OPTIC

DYSPLASIA

IIMAGE GAllERY
Typical
(Left) Coronal ultrasound
shows absence of the cavum
septi pellucidi and
downward pointing of the
frontal horns (arrows) which
communicate
across the
midline and are
"squared-off"
(open arrow)
superior/yo (Right) Coronal
T2WI MR confirms prenatal
sonographic findings of
downward pointing frontal
horns (arrows), and
communicating,
"squared-off" ventricles
(open arrow). Ophthalmic
examination confirmed SOD.

Typical
(Left) Axial ultrasound shows
continuity of the frontal
horns across the midline
(arrow) where the cavum
septi pellucidi is absent.
Additional images showed
mild ventriculomegaly.
SOD
confirmed at birth. (Right)
Axial T2WI MR shows an
absent cavum septi pellucidi
with ventricles in continuity
across the midline. Note the
"flat top" appearance
(curved arrow) of the frontal
horns and mild
ventriculomegaly
(arrows).

Variant
(Left) Axial ultrasound in a
poorly controlled diabetic
admitted in ketotic coma
shows an absent CSP and
squared frontal horns
(arrow). (Right) Axial
oblique ultrasound of the
posterior fossa. A CSP should
be seen on this scan plane,
in the region of the arrow.
Septooptic dysplasia
diagnosed at birth. SOD can
have profound
consequences
for the
neonate. Always look for the
CSP

ABSENT CAVUM SEPTI PELLUCIDI

Axial oblique ultJasound demonstJates an absent cavum
septi pellucidi and mild ventJiculomegaly.
There is
continuity of the frontal horns across the midline
(arrow) where the CSP should be seen.

Coronal T2WI MR in the same fetus confirms absent
CSP The ventricles are enlarged (arrows) and there is
fusion of the fornices (curved arrow) in this fetus with
lobar holoprosencephaly as a cause of absent CSP

DIFFERENTIAL DIAGNOSIS

ITERMINOLOGY

I

Abbreviations

Septo-optic

and Synonyms

Definitions
• Absence of cerebrospinal fluid (CSF) filled space
between frontal horns

IIMAGING

FINDINGS

Holoprosencephaly

General Features
• Best diagnostic clue: Nonvisualization of CSP
• Location: CSP normal fluid collection between frontal
horns of lateral ventricles

Ultrasonographic

Findings

• Continuity of frontal horns across midline
• Almost always associated with other anomalies
o Holoprosencephaly spectrum
o Agenesis of the corpus callosum
o Schizencephaly

MR Findings
• Can often make more specific diagnosis than
ultrasound
• Identify associated parenchymal abnormalities
o Heterotopias

DDx: Conditions

Semilobar

Holopros

dysplasia (SOD)

• Some consider this mildest form of holoprosencephaly
• Absent CSP most important fetal finding
• Hypoplastic optic nerves
o In utero imaging not adequate to evaluate
o Requires postnatal MRI and ophthalmic
examination
• May present in childhood with seizures

• Absent cavum septi pellucidi (CSP)

• Alobar
o Monoventricle without midline structures
(including absent CSP)
o Absent falx
o Mantle of brain tissue surrounding monoventricle
o May have dorsal sac
• Semilobar
o Absent CSP
o Some differentiation of occipital horns
• Lobar
o Absent CSP
o Further differentiation of ventricles, communication
only between frontal horns
o Fused fornices most specific finding
• All may have varying degrees of facial malformations

With An Absent CSP

Agenesis

CC

Schizencephaly

Septo-Optic

Dysplasia

ABSENT CAVUM SEPTI PELLUCIDI
Key Facts
Imaging Findings

• Chiari II malformation

• Continuity of frontal horns across midline
• Almost always associated with other anomalies

Clinical Issues

Top Differential Diagnoses
•
•
•
•
•

Septo-optic dysplasia (SOD)
Holoprosencephaly
Agenesis of the corpus callosum
Schizencephaly
Chronic severe hydrocephalus

• CSP should be documented
• Rarely an isolated finding

Diagnostic Checklist
• CSP is an important marker for normal fetal central
nervous system development

• Possibly related to developmental
the limbic system

Agenesis of the corpus callosum
• Absence of CSP
• Agenesis may be complete or partial
o Presence of CSP excludes complete agenesis
• Colpocephaly
o Teardrop-shaped ventricles
• Can have associated interhemispheric cyst or lipoma

Schizencephaly
• Absent CSP in about 70%
• Focal defect in the brain parenchyma
from surface of brain to ventricle

which extends

Chronic severe hydrocephalus
• Chronic hydrocephalus leads to fenestrations or
thinning of walls of septum pellucidum
• CSP appears absent

I DIAGNOSTIC

Image Interpretation Pearls
• CSP is an important marker for normal fetal central
nervous system development
• Never assume absent CSP is "technical", can be a
marker of serious brain malformation
I SELECTED
1.

Supratentorial space filled with CSF
Absent normal brain parenchyma
Falx present
Normal posterior fossa
Absent middle and anterior cerebral artery flow

CHECKLIST

• Fetal MRI to clarify findings
• Postnatal MRI if isolated to look for optic tracts and
other findings of SOD

• Absent CSP concerning for associate callosal agenesis
or dysgenesis
• Abnormal corpus callosum present in up to 90% of
Chiari II patients

Hydranencephaly

pathology of

Consider

Chiari II malformation

•
•
•
•
•

on every scan

2.

3.

4.

REFERENCES

Supprian T et al: Isolated absence of the septum
pellucidum. Neuroradiology. 41 (8):563-6, 1999
Cohen HI. et al: Ultrasound of the septum pellucidum.
Recognition of evolving fenestrations in the hydrocephalic
infant.) Ultrasound Med. 9(7):377-83, 1990
Barkovich A) et al: Absence of the septum pellucidum: a
useful sign in the diagnosis of congenital brain
malformations. A)R Am) Roentgenol. 152(2):353-60, 1989
Sarwar M: The septum pellucidum: normal and abnormal.
1989
A)NR Am) Neuroradiol. 10(5):989-1005,

IIMAGE GALLERY
I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Absence on routine views
o CSP should be documented on every scan

Natural History & Prognosis
• CSP usually seen in all fetuses
o Subsequently regresses with age
o May persist into adulthood as a normal variant
• Absent CSP has variable prognosis according to
associated condition
• Rarely an isolated finding
o May have no neurologic manifestations
o Some reports suggest association with schizophrenia
• Both absence of and persistent CSP

(Left) Axial T2WI MR in lobar holoprosencephaly shows anterior
continuity of the lateral ventricles, no cavum septi pellucidi was
identified. The arrow marks where the CSP should be seen at this
level. (Right) Axial ultrasound shows colpocephaly (cursors measure
ventricle at 72 mm) and absent CSP (arrow marks where it should be
seen) in this fetus with agenesis of the corpus callosum.

HYDRANENCEPHALY

Coronal T2WI MR
tissue, with the
fluid-tilled. The falx
brainstem is bulging

shows total absence of cerebral
supratentorial
space
completely
is present (curved arrow) and the
upward (arrow).

Cross pathology with the calvarium retracted shows
translucent meninges but no underlying cerebral cortex.
The falx (arrow) is seen between the two hemispheres.

IIMAGING FINDINGS

• Macrocephaly may occasionally be seen
o Continued cerebral spinal fluid (CSF) production
o Lack of CSF resorption
o Falx may be absent
• Increased pressure ~ rupture of falx
• May be mistaken for holoprosencephaly
• Structural survey usually normal apart from brain
o Occasional association with other anomalies
• Color Doppler
o Middle/anterior cerebral artery flow absent
• Circle of Willis intact in hydrocephalus

General Features

MR Findings

• Best diagnostic clue
o Fluid-filled supratentorial space
• Falx present
• Normal posterior fossa

• Cerebral hemispheres/cortical
mantle not present
• Occasionally, orbital surface of frontal lobes remain
• Medial temporal or inner occipital lobes also may be
present
o Supplied by posterior circulation
o Anterior temporal lobes supplied by carotids
• If present, hydranencephaly
is unlikely
• Thalamus and basal ganglia usually present, although
may be incomplete
o Separated thalami
o Thalamus may herniate into supratentorial
space
o Thalamic tissue may be nodular in appearance,
mimicking fusion
• Normal cerebellum
• Normal/atrophic
brainstem

ITERMINOlOGY
Abbreviations

and Synonyms

• Hydranencephaly

Definitions
• Complete destruction of cerebral hemispheres
o Normal cerebellum and brainstem

Ultrasonographic

Findings

• Replacement of cerebral hemispheres by fluid
o End stage of process
o May be seen at presentation
• Variable early intracranial findings
o Focal hemorrhage ~ echogenic mass
o Diffuse parenchymal destruction ~ diffusely
abnormal intracranial echoes
o Loss of normal landmarks
• Head size usually normal

DDx: Hydranencephaly
Tl~~~

-- -' ~.

~--:

~~~'

Aqueducta/

Stenosis

'

..

Bi/at Schizencepha/y

H%prosencepha/y

C/ioependyma/

Cyst

HYDRANENCEPHALY
Key Facts
Terminology
• Complete destruction of cerebral hemispheres

Imaging Findings
•
•
•
•

Fluid-filled supratentorial space
Falx present
Normal posterior fossa
Medial temporal or inner occipital lobes also may be
present
• Head size usually normal
• Macrocephaly may occasionally be seen
• Best imaging tool: MRI to evaluate for presence of
cortical mantle

Top Differential

Diagnoses

• Schizencephaly
• Glioependymal cyst
• Aprosencephaly/atelencephaly

Pathology
• Likely encephaloclastic destruction of previously
normal cerebrum
• Scattered case reports of hemi-hydranencephaly

Clinical Issues
•
•
•
•

May be misdiagnosed as hydrocephalus
Prognosis is dismal
50% liveborn infants die in first month
85% mortality by end of first year

Diagnostic Checklist

• Hydrocephalus
• Holoprosencephaly

• Beware "bulging brainstem" may mimic fused thalami
and be confused with holoprosencephaly

Imaging Recommendations

Aprosencephaly / atelencephaly

• Best imaging tool: MRI to evaluate for presence of
cortical mantle
• Look for placental abruption as cause
• Look for signs of infection
• Complete anatomic survey

• Primary malformation
o No development of structures derived form
prosencephalon
• Usually associated with abnormal facies
o Anophthalmia/microphthalmia
o Abnormal nose
• Limb positioning abnormal

I

DIFFERENTIAL DIAGNOSIS

Hydrocephalus
• Cortical mantle present
• Posterior fossa often abnormal
o Dandy-Walker continuum: Posterior fossa cyst
o Chiari II malformation: Obliteration of cisterna
magna
• Aqueductal stenosis
o Dilated third ventricle
o Head often large
o In severe cases, cortical mantle may be difficult to
discern

Holoprosencephaly
•
•
•
•
•

Cortical mantle
Absent falx/monoventricle
Fused thalami
Microcephaly
Frequently associated with abnormal face
o Midline facial cleft
o Cyclopia
o Proboscis
o Cebocephaly

Schizencephaly
• Bilateral giant open lip may mimic hydranencephaly
• Frontal and parieto-occipital cortex present
• Large symmetric cortical defects lined by grey matter

Glioependymal

cyst

• Large cysts can displace/compress

• Centered on midline

normal brain

Subdural hemorrhage
• Would have to be large/bilateral
• Cerebral hemispheres compressed

I PATHOLOGY
General Features
• Genetics
o Usually sporadic and isolated
o Autosomal recessive
• Consanguineous family with defect mapped to
chromosome 16p13.3-12.1
• Fowler type
• Etiology
o Likely encephaloclastic destruction of previously
normal cerebrum
• Vascular occlusion
• Hemorrhage
• Fetal/maternal hypotension
• Infection
o Vascular occlusion
• Absent internal carotid system
• Carotid intraluminal webs
• Bilateral supraclinoid carotid occlusion
o Hemorrhage
• Coagulation disorders
• Thrombocytopenia
o Fetal/maternal hypotension
• Maternal trauma
• Placental abruption
• Monochorionic co-twin demise
• Cocaine abuse

HYDRANENCEPHALY
o Intrauterine infection
• Herpes simplex/varicella
• Multiple other agents cited as causative in isolated
case reports
o Miscellaneous reported causes
• Irradiation
• Aggressive tumor '* brain destruction
• Vascular malformation
• Epidemiology
o 1:4-10,000 live births
• 0.6% of CNS malformations in perinatal/neonatal
autopsy series
o Scattered case reports of hemi-hydranencephaly
o Increased risk
• Smoking
• Decreased maternal age

o Developmental delay "mild" in 4 of 6 reported cases
• No recurrence risk unless Fowler type (autosomal
recessive)

Treatment
•
•
•
•
•

Infection screen
Coagulation screen
Consider karyotype
Offer termination
If pregnancy progresses
o No monitoring in labor
o No resuscitation attempts
• If macrocephaly
o Offer cephalocentesis to allow vaginal delivery
o No impact on fetal prognosis
o Avoids maternal morbidity, especially for future
deliveries

Gross Pathologic & Surgical Features
• Cerebral hemispheres replaced by thin sacs containing
CSF and necrotic debris
• Sacs lined by translucent double layer membrane
o Outer layer = leptomeningeal tissue
o Inner layer = glial tissue without ependyma (cortical
and white matter remnants)
• Postmortem pathologic examination of carotid arteries
rarely shows abnormalities
o Suggests that primary carotid pathology not
common cause
o More likely hypotension/destruction
o Postnatal imaging has shown intraluminal carotid
webs in liveborn cases
• Fowler type
o Characteristic proliferative "glomeruloid"
vasculopathy
o Impairs vascular invasion of cerebral mantle in first
trimester
o Possible mitochondrial dysfunction
• Careful examination of membranes/placenta
may
reveal co-twin demise

IClINICAllSSUES
Presentation
• Most common signs/symptoms
o Has been diagnosed by US as early as 11 weeks
gestational age
• Failure to identify normal lateral ventricles and
choroid plexus
o Usually detected in second trimester
• May be misdiagnosed as hydrocephalus

Natural History & Prognosis
• Prognosis is dismal
o 50% liveborn infants die in first month
o Sy}'t! mortality by end of first year
o Occasional long term survivors
• No cognitive function, require institutional care
• Management issues may include control of
macrocephaly
• May require shunt or choroid plexectomy
• Longest living survivor 20 yrs
• Hemihydranencephaly
o Better prognosis

I DIAGNOSTIC

CHECKLIST

Consider
• Fetal MRI for clarification of anatomy
o Hydranencephaly
almost invariably lethal
o Hydrocephalic infants may do well with shunt
placement

Image Interpretation

Pearls

• Beware "bulging brain stem" may mimic fused thalami
and be confused with holoprosencephaly

I SELECTED

REFERENCES

Jordan Let al: CT angiography in a newborn child with
hydranencephaly. J Perinatol. 24(9):565-7, 2004
2. Covington C et al: Prolonged survival in hydranencephaly:
a case report. Tenn Med. 96(9):423-4, 2003
3.
Hahn JS et al: Hydranencephaly owing to twin-twin
transfusion: serial fetal ultrasonography and magnetic
resonance imaging findings. J Child Neurol. 18(5):367-70,
2003
Laurichesse-Delmas H et al: First trimester features of
4.
Fowler syndrome (hydrocephaly-hydranencephaly
proliferative vasculopathy). Ultrasound Obstet Gynecol
20:612-15,2002
5. Wellons JC 3rd et al: Choroid plexectomy reduces
neurosurgical intervention in patients with
hydranencephaly. Pediatr Neurosurg. 36(3):148-52, 2002
6.
de Laveaucoupet J et al: Fetal magnetic resonance imaging
(MRI) of ischemic brain injury. Prenat Diagn. 21(9):729-36,
2001
7.
Greco F et al: Hemihydranencephaly: Case report and
literature review.] Child NeuroI16:218-21, 2001
8. Stevenson DA et al: Hydranencephaly in an infant with
vascular malformations. Am] Med Genet. 104(4):295-8,
2001
9.
Kavaslar GN et al: The novel genetic disorder
microhydranencephaly
maps to chromosome
16p13.3-12.1. Am] Hum Genet 66:1705-9, 2000
10. Lam YH et al: Serial sonographic features of a fetus with
hydranencephaly from 11 weeks to term. Ultrasound
Obstet Gynecol. 16(1):77-9,2000
1.

HYDRANENCEPHALY
I

IMAGE GAllERY
(Left) Coronal ultrasound

in

a 74 week fetus with
hydranencephaly
shows a
falx (arrow) with complete
absence of cerebral tissue.
(Right) Sagittal T2WI MR in a
different case shows a
normal posterior fossa
(arrow) but complete lack of
cerebral tissue. In this case
there is macrocrania, which
can occasionally be seen in
hydranencephaly,
and is felt
to be secondary to
decreased CSF resorption.

(Left) Axial ultrasound shows
absence of cerebral
hemispheres
with the falx
preserved (open arrow). The
brainstem extends into the
supratentorial space (curved
arrow). (Right) Axial T2WI
MR shows a similar
appearance of absent
cerebral hemispheres
(falx arrow). The brainstem is
bulging into the
supratentorial space (open
arrow). This appearance can
be confused with fused
thalami seen in
holoprosencephaly.

(Left) Axial ultrasound shows
a small amount of remaining
parenchyma
in the occipital
lobes (arrows) in an
otherwise completely
fluid-filled supratentorial
space (falx - open arrow).
(Right) Coronal Tl WI MR in
a neonate shows similar
findings, with preservation of
a portion of the occipital
lobes (arrows) and the
cerebellum. These structures
are supplied by the posterior
circulation and are preserved
in hydranencephaly.

ENCEPHALOMALACIA

Axial ultrasound shows mild ventriculomegaly
and
subtle lucencies in the periventricular white matter
(arrows) in a patient with prior trauma and placental
abruption. This is concerning for ischemic damage.

Axial T2WI MR in the same case shows obviously
abnormal high signal within the periventricular white
matter (arrows). PVL confirmed at autopsy. MRI is very
helpful in evaluating cases of suspected ischemic injury

ITERMINOLOGY

IIMAGING

Abbreviations

General Features

•
•
•
•

and Synonyms

Encephalomalacia
Periventricular leukomalacia
Porencephaly
Porencephalic cyst

FINDINGS

• Best diagnostic clue
o Porencephalic cyst: Intraaxial, avascular, fluid-filled
structure without mass effect
o Encephalomalacia: Findings often subtle
• Ventriculomegaly may be first clue

(PVL)

Definitions
• Destructive lesions of brain parenchyma with several
manifestations
• Encephalomalacia
o Regional brain parenchymal damage
o Associated astrocytic proliferation, glial septations
o May see multiple small parenchymal defects
o Defects not in communication
with cerebral spinal
fluid (CSF) spaces
• Porencephaly
o Cavitary lesion due to focal brain destruction
o Minimal glial reaction
o Usually communicates with CSF space
o Some authors consider 2 types of porencephaly
• Type 1: Parenchymal damage followed by
Iiq uefacti 0 n / resorption
• Type 2: Defect in generation or migration of
neurons (e.g. schizencephaly)
• Type 2 best considered separately as a primary
developmental abnormality

Ultrasonographic

Findings

• Encephalomalacia.
o Affected periventricular white matter tracts have
variable echogenicity
• May be normal, especially early
• Often subtle increased echogenicity
• May be decreased due to parenchymal edema
o Periventricular lucencies
• Focal areas of cystic degeneration
• Occurs later
• Porencephalic cysts
o Round or irregular shape
o Ex-vacuo, no mass effect
o No flow on Doppler
o If secondary to bleed
• Hyperechoic focus evolving into anechoic
CSF-filled cyst
• Hydrocephalus
o Two potential causes

DDx: Focal Cystic Brain lesions

Schizencephaly

Vein Of Galen

Arachnoid Cyst

Arachnoid Cyst

ENCEPHALOMALACIA
Key Facts
• Hydrocephalus

Terminology
• Destructive lesions of brain parenchyma
manifestations

with several

Imaging Findings
• Porencephalic cyst: Intraaxial, avascular, fluid-filled
structure without mass effect
• Encephalomalacia: Findings often subtle
• Ventriculomegaly may be first clue
• Abnormally high T2 signal in adjacent brain
parenchyma ~ destruction
• Affected periventricular white matter tracts have
variable echogenicity

Top Differential

Diagnoses

• Schizencephaly
• Arachnoid cyst

• Parenchymal destruction
• Intracranial bleed ~ obstruction

to CSF flow

MR Findings
• TlWI
o Increased signal in areas of ischemic injury =
reactive astrocytosis
o Focal areas of high signal may represent hemorrhage
• Hemorrhage and ischemia often seen together
• T2WI
o Encephalomalacia
• Abnormally high T2 signal in adjacent brain
parenchyma ~ destruction
• Reactive astrocytosis
• Glial septa better visualized on ultrasound
• Foci of low T2 signal may represent areas of
hemorrhage or calcification
o Porencephaly
• Cyst fluid follows CSF signal
• Space not lined with gray matter
• Communication
with ventricles
• OWl
o Diffusion-weighted imaging
o Not routinely used in fetal MRI
o Preliminary reports suggest increased sensitivity for
ischemia

Imaging Recommendations
• Best imaging tool
o Consider MRI in at-risk pregnancy
• Better demonstration
of blood products
• Better demonstration
parenchymal destruction
• OWl may prove to be most sensitive method to
detect acute ischemia
• Lesions develop over time
o Normal ultrasound scan at time of an acute "event"
does not exclude brain injury
oRe-image at 10 to 14 days
o Examine periventricular white matter carefully for
altered echogenicity (encephalomalacia)
• Check for placental abruption
• Look for vascular malformations: Important cause of
ischemic brain injury

Clinical Issues
• Important potential complication of fetal
in terven tion
• Monochorionic twins at risk if co-twin demise
• Apparently mild maternal trauma may cause
devastating fetal cerebral injury
• Neurodevelopmental
outcome poor
• Emergency delivery at time of acute event does not
alter outcome

Diagnostic Checklist
• Fetal MRI in all suspicious cases and at-risk patients
• US findings can be subtle despite severe damage
• Normal US at time of acute event does not exclude
brain injury

o Vascular "steal" +/- venous hypertension ~
parenchymal destruction
o Vein of Galen malformation
• Located in quadrigeminal plate cistern,
postero-superior to thalami
o Dural arteriovenous fistula
• Extraaxial
• Enlarged feeding and draining vessels
• Careful survey for other defects
o Vascular compromise ~ ischemic lesions elsewhere
• Kidneys
• Extremities
o Signs of infection
• Liver calcifications
• Intracranial calcifications
• Hydrops
• Monitor amniotic fluid volume
o Renal ischemia ~ oligohydramnios
o CNS injury ~ impaired swallowing ~
polyhydramnios

I DIFFERENTIAL DIAGNOSIS
Schizencephaly
• Cortical cleft, lined with gray matter
• Wedge shaped rather than round or irregular

Arachnoid cyst
• Extraaxial
• Displaces normal brain
• Not associated with destructive

Hydrocephalus
• Look for structural cause
o Dandy-Walker continuum
o Chiari II malformation
o Aqueductal stenosis

Vascular malformation
• Flow on Doppler interrogation

process

ENCEPHALOMALACIA
o Placental abruption

I PATHOLOGY

Natural History & Prognosis

General Features
• General path comments
o Fetal inflammatory response to infection or
hypoxic/ischemic event
• Cytokine release
• Research focussing on control of inflammation to
prevent ongoing damage
• Etiology
o Infection
• Cytomegalovirus
• Toxoplasmosis
• Varicella/Zoster
o Vascular: Hypoperfusion
• Intracranial hemorrhage
• Monochorionic twin demise/twin-twin
transfusion syndrome
• Fetal intervention: Intrauterine transfusion, twin
vessel laser coagulation
• Maternal drug use: Cocaine
• Maternal trauma/placental abruption
o Syndromic
• Encephalocraniocutaneous
lipomatosis
• Familial orofaciodigital syndrome type I
• Oculocerebrocutaneous syndrome
• DK-phocomelia
o Teratogen exposure
• Vitamin A
o Fetal surgery
• 21% incidence central nervous system (CNS)
injury in 33 patients with fetal surgery
• Epidemiology: Rare

Gross Pathologic & Surgical Features
• Encephaloclastic porencephaly
o Focal destruction of normal parenchyma
o Usually unilateral
o Smooth-walled cavity
o Surrounding brain structural normal
• Encephalomalacia
o More diffuse brain insult ~ multicystic
o Provokes astrogliotic response with glial reaction
o Gysts may have shaggy walls
o Can have calcifications

I CLINICAL ISSUES
Presentation
• Most common signs/symptoms
o CSF-filled space in fetal cranium
o Ventriculomegaly without structural malformation
• Other signs/symptoms
o Important potential complication of fetal
intervention
• Twin-twin transfusion
• Twin reverse arterial perfusion
• Fetal surgery
o Monochorionic twins at risk if co-twin demise
o Maternal trauma
• Apparently mild maternal trauma may cause
devastating fetal cerebral injury

• Neurodevelopmental outcome poor
o Severe developmental delay
o Seizure disorder, often refractory to anticonvulsant
therapy
• Precise deficit depends on size and location
o Visual loss
o Speech impairment
o Sensory/motor deficit

Treatment
• Infection screen
• Evaluate for bleeding diathesis
• Offer termination
o Encourage autopsy for definitive diagnosis
• Ischemic changes not indication for early delivery
• Emergency delivery at time of acute event does not
alter outcome
o Adds risks of prematurity to brain injury risk
• Postnatal cyst uncapping/fenestration
may help
o Hemiparesis improved in 30%
o Intractable seizures
• Resolved in 62%
• Improved in 24%

I

DIAGNOSTIC

CHECKLIST

Consider
• Fetal MRI in all suspicious cases and at-risk patients
• US findings can be subtle despite severe damage

Image Interpretation

Pearls

• Normal US at time of acute event does not exclude
brain injury
o Lesions develop over time
o Scan at 10-14 days from acute event
• Both hemorrhage and ischemic changes commonly
are present

I SELECTED
1.

2.

3.

4.

5.

6.

REFERENCES

Garel C et al: Contribution of fetal MR imaging in the
evaluation of cerebral ischemic lesions. AJNR Am J
Neuroradiol. 25(9):1563-8, 2004
de Laveaucoupet J et al: Fetal magnetic resonance imaging
(MRI) of ischemic brain injury. Prenat Diagn. 21(9):729-36,
2001
Thauvin-Robinet C et al: Familial orofaciodigital syndrome
type I revealed by ultrasound prenatal diagnosis of
porencephaly. Prenat Diagn. 21(6):466-70, 2001
Nowaczyk MJ et al: Antenatal and postnatal findings in
encephalocraniocutaneous
lipomatosis. Am J Med Genet.
91:261-6, 2000
Koch CA et al: Fenestration of porencephalic cysts to the
lateral ventricle: Experience with a new technique for
treatment of seizures. Surg Neurol 49:524-32, 1998
Bealer JF et al: The incidence and spectrum of neurological
injury after open fetal surgery. J Pediatr Surg
30(8): 1150-4.1995

ENCEPHALOMALACIA
IIMAGE GALLERY
(Left) Corond! llWI /1'1/\
shOlvs abnormd! inUl'dsed
T2 signal surrounding the
(rontal horns (drrows).
(Right) Coronal gross
pathology at autopsy shows
confluent areas o( white
matter destruction
correlating Ivith the areas o(
abnormality on /1'1/\1.The
walls o( the cdvities dre
shaggy and irregular
(arrows).

(Left) Coronal nWI M/\
shows hydrocephalus
and a
porencephalic
cyst (arrow)
secondary to a thrombosed
dural arteriovenous (istula
(not visible on this image).
(Right) Sagittalultrd.'lJund
in
a diHerent int;mtl)('rllJ/'/l1ed
on the /Irst ddY o( Ii/I' shows
two porencl'phdlic
cysts
(arrows) communicdting
with the dildte(1 ventricle.

Typical
(Left) Coronal ultr,JS(Jund o(
the brain on day one o( Me
in a monochorionic
twin
with twin-twin transfusion
syndrome. There is profound
cystic encephalomalacia
(arrows) secondary to
intrauterine hypoxia. (Right)
Gross pathology shOll's
essentially ccJm/J/etr'
destruction o( the cl'rehral
cortex with prewrvdtion
o(
the cerebellum and
midhrain. Arl'dS o(
hemorrhage (drrow) Cdn also
he seen.

INTRACRANIAL

Axial
enduvaginal
ultrasound
of
a
massive
intraparcnchymal hemorrhage. There is liquefaction of
the parenchyma with no recognizable structures. Areas
of organized clot (arrow) appear more echogenic.

HEMORRHAGE

Axial ultrasound of intraventricular hemorrhage with clot
formation (arrow) and associated hydrocephalus.
The
clot is dependent within the ventricle and should not be
confused with a "dangling" choroid.

ITERMINOLOGY

Ultrasonographic

Abbreviations

• Hemorrhage usually extensive when diagnosed in
utera
o Normal intracranial landmarks often obscured
• Intraparenchymal
o Hyperechoic mass within parenchyma
o Porencephaly develops with time
• Subependymal
o Same appearance/grading
as neonatal GMH
• Intraventricular
o Hyperechoic intraventricular clot
o Irregular bulky choroid plexus
o Echogenic, irregular ependyma
o Hydrocephalus
• Subdural
o Hyperechoic material outlining cortex
o Separates Sylvian fissure from calvarium
• Normal distance cortex to skull vault ~ 4 mm

• Intracranial

and Synonyms

hemorrhage

(ICH)

Definitions
• Bleeding within fetal cranium

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Non-perfused, echogenic,
intracranial "mass"
• Location
o Classified by anatomic location
o Intra parenchymal
• Most are supratentorial
• Posterior fossa uncommon
o Subependymal (common)
• Germinal matrix hemorrhage (GMH)
o Intraventricular (common)
o Subdural
o Subarachnoid
o Epidural (very rare)

Findings

MR Findings
• Blood products
o T1 WI high signal (methemoglobin)
o T2WI low signal
• Confirm location of clot on multiple planes
• Do not confuse with flow artifact
o Turbulent cerebrospinal fluid (CSF) flow in a dilated
system
o Less defined signal

DDx: Hemorrhage

CP Papilloma

CP Papilloma

Tf'ratoma

Turbulenc('

i\rtifact

INTRACRANIAL

HEMORRHAGE

Key Facts
Imaging Findings
• Best diagnostic clue: Non-perfused, echogenic,
intracranial "mass"
• Classified by anatomic location
• Hemorrhage usually extensive when diagnosed in
utero
• Porencephaly develops with time
• Hyperechoic intraventricular clot
• Irregular bulky choroid plexus
• Look for vascular malformation as cause

Top Differential

Diagnoses

• Intracranial tumor
• Infection

Pathology

• Trauma
• Maternal thrombocytopenia/coagulation

disorders

Clinical Issues
• Maternal idiopathic thrombocytopenia (ITP) ~ Fetal
ICHin<l%
• Alloimmune thrombocytopenia (AITP) ~ Fetal ICH
in 10-30%
• Outcome relates to severity and extent of bleed
• Maternal testing for coagulation disorder/platelet
antibodies
• Consider delivery by cesarean section

Diagnostic Checklist
• Hemorrhage may be difficult to see on ultrasound
• Consider fetal MR in at-risk patients

• Alterations in maternal/fetal blood pressure

o "Swirl", not mass-like
o Location changes sequence-to-sequence
• Septations in CSF spaces/ventricles correlate with
hemorrhage and infection
• Blood/CSF levels
o Large flow voids on T2WI = feeding/draining vessels
from vascular malformation
• Look for periventricular leukomalacia /porencephaly

Imaging Recommendations
• Look for hydrops
o Anemia secondary to hemorrhage increases risk for
non-immune hydrops
• Pericardial/pleural effusion
• Ascites, skin edema
• Look for vascular malformation as cause
o Thrombosis of vascular malformation ~ venous
hypertension ~ bleed
• Shape/location may suggest Vein of Galen
malformation
• Tubular components suggest thrombosed
feeding/draining vessels
• Use color Doppler

I DIFFERENTIAL DIAGNOSIS
Intracranial tumor
• Large, heterogeneous, rapid growth
• Caution: Intracranial tumors may bleed
o Look for blood flow in periphery of mass with color
Doppler
o Clot is not perfused, tumor will show flow
• Macrocephaly common
• Choroid plexus (CP) papilloma is a potential mimic
for intraventricular clot

Infection
• May cause destructive brain lesions
• Intracranial/liver calcifications, hydrops

Ischemia
• Periventricular leukomalacia

o Abnormal echogenicity/signal
white matter

in periventricular

I PATHOLOGY
General Features
• General path comments
o Subependymal bleed
• Related to fragile germinal matrix capillaries and
poor autonomic control of fetal cerebral
vascularity
• Germinal matrix more susceptible < 32 weeks
• Maternal hypotension/fetal hypoxia ~ cerebral
blood vasodilatation followed by capillary rupture
• Usually extends into ventricles
o Intraparenchymal bleed
• Usually due to trauma, more common in term
infant
o Subdural/epidural bleeds
• Usually due to trauma
• Genetics
o Alloimmune thrombocytopenia (AITP):Autosomal
dominant (AD)
o Coagulation disorders: Some AD
o Hemophilia: X-linked recessive
• Etiology
o Alterations in maternal/fetal blood pressure
• Maternal seizure disorder/acute abdomen
• Drug use: Cocaine, aspirin
• Pre-eclamptic toxemia (PET)/Hemolysis-elevated
liver enzymes-low platelets (HELLP)syndrome
• Monochorionic twin demise can result in severe
fetal hypotension and subsequent bleed in
survivor
o Trauma
• Motor vehicle accident/domestic violence
• Polynesian massage for external version of breech
~ significant incidence of fetal subdural
hematoma

o Maternal thrombocytopenia/coagulation

disorders

• Factor V or X deficiency, coumadin therapy

INTRACRANIAL
o Bacterial/viral infection
o Umbilical cord abnormalities
• Thrombosis, knot, hematoma
o Placental abnormalities
• Uteroplacental insufficiency
• Abruption/placenta previa
o Fetal arteriovenous malformation/fistula
o Amniocentesis complication
• Should be avoidable with US guidance
• Epidemiology
o Uncommonly diagnosed in utero
o 6(Y(. of autopsies for stillbirth have some type of
hemorrhage
o Usually diagnosed between 26-33 weeks gestation

Staging, Grading or Classification

Criteria

• Germinal matrix hemorrhages graded same as in
neonate
o Grade 1: Limited to subependymal area
o Grade 2: Intraventricular extension without
hydrocephalus
o Grade 3: Intraventricular extension with
hydrocephalus
o Grade 4: Intraparenchymal extension
• Generally indistinguishable from primary
intra parenchymal hemorrhage

ICLINICAL

ISSUES

Presentation
• May be asymptomatic
• Decreased fetal movement
• Preterm labor especially if polyhydramnios secondary
to impaired fetal swallowing
• Non-reactive fetal heart rate tracing
• Sinusoidal fetal heart rate tracing secondary to fetal
hypoxia
o Fetal anemia ~ impaired oxygen delivery

Natural History & Prognosis
• Maternal idiopathic thrombocytopenia (ITP) ~ Fetal
ICH in < 1%
• Alloimmune thrombocytopenia (AITP) ~ Fetal ICH in
10-30%
• Long term sequelae
o Cerebral palsy/seizure disorder
o Developmental delay, mentally subnormal
o Hydrocephalus
o Fetal or neonatal death
• Outcome relates to severity and extent of bleed
• Poor outcome = demise or severe neurological
impairment
o In 92% parenchymal bleeds
o In 88% subdural/subarachnoid
bleeds
o In 45% intraventricular bleeds
• Good outcome = normal or mild neurological
impairment
o Germinal matrix bleed, good outcome
• In 100% grade 1
• In 60% grade 2
• In 0% grade 3

HEMORRHAGE
Treatment
• Maternal testing for coagulation disorder/platelet
antibodies
• Fetal transfusion may be required, platelets or whole
blood
• AITP: Consider weekly infusion immune globulin +/steroids
o Good outcome in 8/8 infants
o Prior to this therapy outcome was uniformly poor
• Consider delivery by cesarean section
o Avoids mechanical stress of vaginal delivery and
potential for repeat bleed
• May prefer to attempt vaginal delivery if severe
parenchymal damage already present
o Neurological impairment results from brain
destruction, mode of delivery does not alter
outcome
o Avoids morbidity in future pregnancies

I DIAGNOSTIC

CHECKLIST

Consider
• Hemorrhage may be difficult to see on ultrasound
o Consider fetal MR in at-risk patients
I SELECTED
1.

2.

3.
4.

5.

6.

7.

8.

9.

10.

11.
12.

REFERENCES

Ellestad SC et al: Prenatal diagnosis
of a trauma-related
fetal epidural hematoma.
Obstet Gynecol.
104(6):1298-300,2004
Ghi T et al: Outcome
of antenatally
diagnosed
intracranial
hemorrhage:
case series and review of the literature.
Ultrasound
Obstet Gynecol.
22(2):121-30,
2003
Raymond
GV: Rare neurologic
injury from amniocentesis.
Birth Defects Res A Clin Mol Teratol. 67(3):205-6,
2003
Zanders EH et al: Prenatal diagnosis
of fetal intracranial
hemorrhage
at 25 weeks of gestation.
Fetal Diagn Ther.
18(5):324-7,
2003
Emamian
SA et al: Fetal MRI evaluation
of an intracranial
mass: in utero evolution
of hemorrhage.
Pediatr Radiol.
32(8):593-7,
2002
Meagher SE et al: Mid-trimester
fetal subdural
hemorrhage:
prenatal
diagnosis.
Ultrasound
Obstet Gynecol.
20(3):296-8,
2002
Sharif U et al: Prenatal intracranial
hemorrhage
and
neurological
complications
in alloimmune
thrombocytopenia.)
Child Neurol. 16:838-42,
2001
Squier M et al: Five cases of brain injury following
amniocentesis
in mid-term
pregnancy.
Dev Med Child
Neurol. 42(8):554-60,
2000
Ranzini AC et al: Prenatal sonographic
appearance
of
hemorrhagic
cerebellar
infarction.)
Ultrasound
Med.
17(11):725-7,1998
Sherer DM et al: Antepartum
fetal intracranial
hemorrhage,
predisposing
factors and prenatal
sonography:
a review.
Am) Perinatol.
15(7):431-41,
1998
Vergani Pet al: Clinical significance
of fetal intracranial
hemorrhage.
Am) Obstet Gynecol.
176:731-2,
1996
Catanzarite
VA et al: Prenatal sonographic
diagnosis
of
intracranial
haemorrhage:
report of a case with a sinusoidal
fetal heart rate tracing, and review of the literature.
Prenat
Diagn. 15(3):229-35,
1995

INTRACRANIAL

HEMORRHAGE

I IMAGE GALLERY
Typical
(Left) Axialultrasouncl shows
hydrocephalus and
irregularity of the choroid
plexus (arrow) concerning
for hemorrhage. This is a
monochorionic pregnancy
with co-twin demise. (Right)
Coronal T2WI MR with a
large field-o/~view show, Ihe
more global picture. The
dead twin is small and ha,
skin edema (curved arroll').
The living twin has
hydrocephalus (open arro\\')
and a hypointense iocus
(arrow) in the venlricif __
con/lrming the suspicion oi
clot on ultrasound

Typical
(Left) Coronalultrasouncl
shows an abnormal area oi
increased echogenicity in the
region of the germinal matrix
(arrow) with extension of the
bleed into the ventricle.
(Right) Sagittal T2WI MR of a
fetus \vith a large,
thrombosed, dural
arteriovenous fistula (open
arrows). Ifydrocephalus is
present with a tluiel-iluiel
level (arrow) irom an
associated intravelltriculdr
bleed.

Variant
(Left) Axial obliqu<'
ultrasound ill a ."Ird trimeSler
fetus shows a "mass-like"
area of increased
echogenicity in the
cerebellum (arrows). This
Finding was not present on
previous scans. (Right) ,~xial
non-enhanced CT scall Oil
the first clay oi life shows a
large cerebellar bleed
(arrow). The posterior /()SSd
is an uncommon localioll for
fetal hemorrhages. No
underlying masses or
vascular malformalion, \Vl're
identified.

CHOROID

Axial ultrasound shows bilateral choroid plexus cysts
(arrows) in a ietus with normal chromosomes. The cysts
vary in size. The atrium oi the lateral ventricle is seen
posteriorly (curved arrow)

PLEXUS CYST

Gross pathology oi choroid plexus cysts (arrow). The
small cysts are clustered, which explains why they can
appear quite complex on ultrasound. They resolve
regardless oi etiology or morphologic appearance.

ITERMINOlOGY

Ultrasonographic

Abbreviations

• crc

and Synonyms

• Choroid plexus cyst

(crc)

Definitions
• Cysts within substance of choroid plexus

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o One or more anechoic cyst(s) in choroid plexus
• First seen in second trimester
• Disappear in third trimester
• Location
o Usually in glomus
o Most near atria
• Size
o Variable
• Should be > 2 mm to be crc
• Morphology
o Discernable wall
o Single or multiple
o Surrounded by normal choroid plexus
o Clustered small cysts mimic complex mass

Findings

easily seen on routine lateral ventricle view
o Transverse image of lateral ventricle
• Level of atria
• Fluid-filled atria should not be confused with CPC
o Normal appearance of choroid plexus in lateral
ventricle
• Echogenic
• Glomus is focal thickening posteriorly
• "Sponge-like" morphology
• < 2 mm sonolucencies are normal

• crc

o Anechoic
• Surrounded by choroid plexus
• Oblique views confirm location
o crc only when diameter> 2 mm
• < 2 mm considered normal
o Discernable echogenic wall
o No blood flow on color Doppler
o 12% with other anomalies
• Large crc
0> 10 mm
o t Association with aneuploidy
• Trisomy 18 (TI8)
o Resolve slower
o May be mistaken for ventriculomegaly
• Multiple and bilateral crc

DDx: Choroid Plexus Heterogeneity

CP Papilloma

CP Papilloma

IC Ilemorrhage

IC Hemorrhage

CHOROID

PLEXUS CYST

Key Facts
Terminology
• Choroid plexus cyst (CPC)
• Cysts within substance of choroid plexus

Imaging Findings
•
•
•
•
•
•
•
•
•
•
•
•

•

•
•

•

•

One or more anechoic cyst(s) in choroid plexus
First seen in second trimester
Disappear in third trimester
Usually in glomus
Should be > 2 mm to be crc
Oblique views confirm location
12% with other anomalies
Almost all resolve by 32 weeks
Seen in 1% of all second trimester exams
50% of TI8 fetuses have CPC
Almost all T18 have other detectable anomalies
Document open hands
o Same risk for T18 as single
o Clusters common
Transient
o Almost all resolve by 32 weeks
• Regardless of other anomalies
• Regardless of aneuploidy
o Not necessary to show resolution
crc and normal fetus
o Seen in 1% of all second trimester exams
o Benign and transient finding
CPC and TI8
o 50% of T18 fetuses have CPC
• > 10 mm more worrisome
o Almost all T18 have other detectable anomalies
o Common T18 anomalies
• Intrauterine growth restriction (IUGR)
• Cardiac defects
• Clenched hands + overlapping fingers
• Rockerbottom foot
• Dandy-Walker continuum
• Bowel-containing omphalocele
• Strawberry shaped calvarium
• Single umbilical artery
o Isolated CPC and risk for T18
• Correlate with maternal serum biochemistry
• Likelihood ratio (LR) < 2 for TI8
• < 2x more likely to have T18 than apriori risk
CPC and trisomy 21 (T21)
o No association when CPC isolated
o Higher risk for T21 when other T21 markers present
• Example: CPC + echogenic bowel (EB), greater risk
than EB alone
o Common T21 markers
• Increased nuchal fold
• Intracardiac echogenic foci
• Short femur/humerus
• Echogenic bowel
• Renal pelviectasis
• Fifth finger clinodactyly
CPC + any other anomaly
o 20x increased risk for aneuploidy

• Careful fetal heart evaluation
• No need for follow-up exam to show CPC resolution

Top Differential

Diagnoses

• Choroid plexus papilloma
• Mild ventriculomegaly
• Intraventricular hemorrhage

Pathology
• < 1:400 aneuploidy in low-risk group
• CPC + minor sonographic marker = 20% risk
• CPC + major sonographic marker = 50% risk

Diagnostic Checklist
• Amniocentesis when crc seen in high-risk patients
• crc and small for dates may indicate T18

Imaging Recommendations
• Best imaging tool: Second trimester genetic sonogram
• Protocol advice
o Determine if CPC is isolated
• No amniocentesis
o Look for markers of aneuploidy
• Document open hands
• Document normal foot
• Careful fetal heart evaluation
o Consider amniocentesis if:
• CPC not isolated
• Abnormal serum screen
• Advanced maternal age
o No need for follow-up exam to show CPC resolution
• Cysts themselves are of no consequence
• Resolve in both normal and aneuploid fetuses
• May consider follow-up for parental reassurance

I DIFFERENTIAL DIAGNOSIS
Choroid plexus papilloma
• Rare choroid plexus tumor
o Lateral ventricle most common site
o Same location as CPC
• Tumor produces cerebrospinal fluid (CSF)
o Rapid onset hydrocephalus
• Well-defined mass
o Lobular
o Hyperechoic
o Color Doppler may show flow in mass

Mild ventriculomegaly
• Atria of lateral ventricle measures 10-12 mm
o Choroid displaced from medial wall
o Usually idiopathic
o Marker for T21
• CPC may mimic distended lateral ventricle
0> 10 mm CPC

Intraventricular
• Rare

hemorrhage

CHOROID
• Usually at caudothalamic junction
o Intraventricular blood common
• Heterogeneous clot may cling to choroid
o Mimic crc or papilloma

I PATHOLOGY
General Features
• Genetics
o < 1:400 aneuploidy in low-risk group
o TI8 risk
• CPC + minor sonographic marker = 20% risk
• CPC + major sonographic marker = 50% risk
o T21 risk
• Only if other T21 markers seen
• Etiology
o Entrapped fluid
• 80-90% cerebral spinal fluid (CSF) produced by
choroid plexus
• Epidemiology
o 1% normal 2nd trimester fetuses
o 50% T18 fetuses
• Associated abnormalities
o Anomalies seen with T18
o Rarely, anomalies seen with T21
• Embryology
o Choroid plexus
• < 13 wk: Fills entire lateral ventricle
• > 13 wk: Recedes anteriorly
• Glomus becomes most prominent
• Fills body of lateral ventricle
• No choroid in frontal or occipital horns

PLEXUS CYST
I DIAGNOSTIC
Consider
• Careful evaluation of fetal heart
o Normal four chamber view
o Normal outflow tract views
o Consider formal fetal echocardiography
• Amniocentesis when crc seen in high-risk patients
o Abnormal maternal serum biochemistry
o Advanced maternal age
o Prior fetus with aneuploidy
• T18
• T21
• Amniocentesis when crc + other abnormality
• No amniocentesis when isolated finding in low-risk
patient

Image Interpretation

I SELECTED REFERENCES
1.

2.

3.

5.

Presentation
• Most common signs/symptoms
o Isolated finding in low-risk patient
• Not advanced maternal age (AMA)
• Normal maternal biochemical screen
o Major anomaly + CPC
o Minor marker + crc

6.

7.

8.

Demographics
• Age

o T18 associated with AMA
• AMA ~ 35 yrs at time of delivery

9.
10.

Natural History & Prognosis
• Transient benign finding
o Resolves by 32 weeks in both T18 and normal
fetuses
• Excellent prognosis for isolated crc
• Guarded prognosis for crc + other anomalies
o Depends on karyotype result
o Depends on severity of associated anomalies

Treatment
• None for

crc

Pearls

• Careful fetal anatomic survey
• crc and small for dates may indicate T18
o Symmetric IUGR may mimic poor menstrual data

4.

I CLINICAL ISSUES

CHECKLIST

11.
12.

13.

Bronsteen R et al: Second-trimester
sonography
and
trisomy 18: the significance
of isolated choroid plexus cysts
after an examination
that includes the fetal hands. J
Ultrasound
Med. 23(2):241-5, 2004
Doubilet PM et al: Choroid plexus cyst and echogenic
intracardiac
focus in women at low risk for chromosomal
anomalies:
the obligation
to inform the mother. J
Ultrasound
Med. 23(7):883-5, 2004
Rochon M et al: Controversial
ultrasound
findings. Obstet
Gynecol Clin North Am. 31(1):61-99, 2004
Sahinoglu Z et al: Second trimester choroid plexus cysts
and trisomy 18. Int J Gynaecol Obstet. 85(1):24-9, 2004
Souter VL et al: Correlation
of Second-Trimester
Sonography
and Biochemical
Markers. Obstet Gynecol
Surv. 59(11):758-760,
2004
Turner SR et al: Sonography
of fetal choroid plexus cysts:
detection depends on cyst size and gestational
age. J
Ultrasound
Med. 22(11):1219-27,
2003
Ghidini A et al: Isolated fetal choroid plexus cysts: Role of
ultrasonography
in establishment
of the risk of trisomy 18.
Am J Obstet Gynecol 182:972-7, 2000
Chitty LS et al: The significance
of choroid plexus cysts in
an unselected population:
results of a multicenter
study.
Ultrasound
Obstet Gynecol. 12(6):391-7, 1998
Gupta JK et al: Management
of fetal choroid plexus cysts.
Br J Obstet Gynaecol. 104(8):881-6,
1997
Gray DL et al: Is genetic amniocentesis
warranted when
isolated choroid plexus cysts are found? Prenat Diagn
16:983-90, 1996
Gupta JK et al: Clinical significance
of fetal choroid plexus
cysts. Lancet. 346(8977):724-9,
1995
Snijders RJ et al: Fetal choroid plexus cysts and trisomy 18:
Assessment of risk based on ultrasound
findings and
maternal age. Prenat Diagn 14:1119-27,1994
Nyberg DA et al: Prenatal sonographic
findings of trisomy
18: review of 47 cases. J Ultrasound
Med. 12(2):103-13,
1993

CHOROID

PLEXUS CYST

IIMAGE GALLERY
Typical
(Left) Axial ultrasounel shOl\'S
bilateral CPC (arrOlvs) in a
fetus with multiple anomdlies
and trisomy 78. (Right) Axial
ultrasound of the heart in the
same fetus shows a small left
ventricle (arrow) and
abnormal cardiac axis.
Outflow tract anomalies
were also present. The fetal
heart and extremities should
be carefully evaluated II'i)('n
choroid plexus C)'s/s ((PC)
are seen.

(Left) Coronal ultrasound of
the fetal hands in the sal11('
fetus shows bilateral
clenched hands and an
overlapping index finger
(arrow). This hand position
is classic for trisomy 78.
When CPC are seen. the
sonographer should liT to
obtain open hanel vielvs.
(Right) Clinical photograph
shows the classic hand
position of trisomy II!. The
fingers are tightly clench(>el
with an overriding Sf>conrl
finger.

Typical
(Left) Axial ultrasound shm vs
a right-sided 10 mm CPC
(arrows). Notice that the
cyst is surrounded by
choroid and is anechoic. No
other anomalies were seen in
this low-risk patient
Amniocentesis
\V<15 not
recommended
(Right) I~xi,"
ultrasound in the same I('tus
shows that the CPC resolve(/,
Follow-up ultrasound is nol
necessary but patients ofte/)
want reassurance that the
cyst is gone.

ARACHNOID

Coronal

graphic

arachnoid
interface

represents

the effect of an extra-axial

cyst. The cyst buckles
(arrow)

the grey/white

matter

and displaces and compresses normal

brain (curved arrow).

Coronal

T2WI

displacing
The

mass

MR

shows

the left cerebral
effect

hydrocephalus,

has

a

large

hemisphere

resulted

in

note dilated occipital

extra-axial
(curved

cyst

arrow).

development

of

horn (arrow).

o May exhibit rapid growth and cause obstructive
hydrocephalus

ITERMINOlOGY
Abbreviations

CYST

and Synonyms

Ultrasonographic

• Arachnoid cyst (AC)

Definitions
• Cerebrospinal fluid (CSF) collection enclosed within
layers of arachnoid

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Extra-axial cyst
• Location
o Fetal series
• Commonest over cerebral convexities
• One third of cases occur in posterior fossa
• Retrocerebellar space
• Supracollicular space
o Significant variation from postnatal series
• Over convexities only 5%
• Middle cranial fossa 50-65°;6
• Quadrigeminal cistern 5-10%
• Suprasellar cistern 5-10%
• Posterior fossa 5-10oA,
• Size
o Variable

Findings

• Grayscale Ultrasound
o Smoothly marginated, anechoic cyst
o Remaining brain sonographically normal in
majority of cases
o Agenesis of corpus callosum reported in 5% with
supratentorial AC
• It is likely many of these are actually
glioependymal cysts
o Mild ventriculomegaly/hydrocephalus
• Mass effect on Aqueduct of Sylvius
• Impaired CSF drainage
• Color Doppler
o Avascular lesion ~ no flow
o Large cyst may displace major cerebral vessels
• Pulsed Doppler
o No perfusion
o Doppler signal only from adjacent vessels
• 3D
o May help to confirm extra-axial location
o May show origin e.g. floor middle cranial fossa

MR Findings
• Simple AC displaces normal parenchyma
• Buckles gray/white matter interface
• Follows CSF signal

DDx: Arachnoid Cyst

OW Continuum

OW Continuum

Schizencephaly

Clioependymal Cyst

ARACHNOID

CYST

Key Facts
Terminology

Pathology

• Cerebrospinal fluid (CSF) collection enclosed within
layers of arachnoid

• CSF-containing cyst with thin membranous wall
• Can be seen as part of syndromes

Imaging Findings

Clinical Issues

•
•
•
•

• Prognosis good if isolated abnormality
• May require shunt or excision if significant mass
effect
• Other anomalies determine prognosis when present
• Consider amniocentesis for karyotype, even if
isolated
• Monitor for growth of cyst
• Head size may impact timing and mode of delivery

Best diagnostic clue: Extra-axial cyst
Commonest over cerebral convexities
One third of cases occur in posterior fossa
Remaining brain sonographically normal in majority
of cases

Top Differential Diagnoses
•
•
•
•
•

Glioependymal cyst (GC)
Schizencephaly
Teratoma
Dandy-Walker continuum (DWC)
Porencephalic cyst

o Low signal Tl WI
o High signal T2WI
• Look for associated findings
o Agenesis of corpus callosum
o Hydrocephalus

Imaging Recommendations
• Protocol advice
o Careful search for other anomalies
o AC may be part of multiple malformation syndrome
o Additional anomalies increase suspicion for
• Aneuploidy
• Autosomal recessive inheritance conditions
o Consider fetal MRI for associated brain anomalies

I DIFFERENTIAL DIAGNOSIS
Glioependymal cyst (GC)
• Greater association with agenesis of the corpus
callosum
• Frontal or parietotemporal
• Centered on midline
o Arachnoid cysts tend to extend to either side
• Protein content of cyst fluid higher than AC
o May alter MRI signal allowing differentiation
o Signal> CSF on T1WI
o Occasional fluid-fluid level
• Histology required to differentiate from AC
o Not generally clinically relevant
o Same treatment

Schizencephaly
•
•
•
•

Cleft in brain substance
Wedge-shaped rather than round
May be bilateral and symmetric
Lined with gray matter on MRI

Teratoma
• Can be predominately cystic
• Soft tissue component, calcification, can usually be
identified
• Rapid growth

Diagnostic Checklist
• Always check Doppler of apparent cyst

• Macrocephaly

Dandy-Walker continuum (DWC)
•
•
•
•

Differential consideration for posterior fossa AC
Torcular elevation is hallmark of DWC
4th ventricle in communication with cisterna magna
Vermian agenesis/dysgenesis
o Vermis present if AC

Intracranial hemorrhage
• May appear cystic if subacute
• Associated with destruction of normal tissue
• Blood products
o High signal on T1WI
o Low signal on T2WI

Porencephalic cyst
• Replaces damaged brain
o Arachnoid cyst displaces normal brain
• Often associated with intracranial hemorrhage
• Look for encephaloclastic changes
o Abnormal high signal cerebral cortex on T2WI
• US findings can be subtle
o Loss of normal architecture
o Mild ventriculomegaly

Vein of Galen malformation
• Elongated midline structure
• Posterior
o Quadrigeminal plate cistern toward occiput
• Flow on color Doppler
• High velocity, low resistance flow on pulse Doppler
• Porencephaly may occur if significant "steal"
phenomenon
• Intracranial hemorrhage may occur

Physiologic entities
• Differential
o Enlarged cavum septi pellucidi
o Cavum vergae
o Cyst of cavum velum interpositum
• Do not increase in size
• May regress with advancing gestational age
• Median size 10 mm (range 10-30 mm)

ARACHNOID
• Pathologic cysts often larger and may grow as
pregnancy progresses

I PATHOLOGY
General Features
• General path comments
o CSF-containing cyst with thin membranous wall
o Embryology
• Frontal, temporal embryonic meninges
(endomeninx) fail to merge as Sylvian fissure
forms (middle cranial fossa)
• Remain separate forming "duplicated" arachnoid
• Older theory: Diverticulation of developing
arachnoid
o Middle cranial fossa AC ~ hypoplasia adjacent
temporal lobe
• Genetics
o Mostly sporadic
o Can be seen as part of syndromes
• Neurofibromatosis type 1
• Multiple congenital anomaly disorders with single
gene mutation
o Trisomy 18
• Usually multiple other anomalies
• Etiology
o Possible mechanisms
• Active fluid secretion by cyst wall
• Slow distention by CSF pulsations
• CSF accumulates by one-way (ball-valve) flow
• Epidemiology
o Prenatal incidence unknown
o 1% space-occupying lesions in childhood
o 0.5% autopsies
o M>F
o Left> right

Microscopic

Features

• Walls composed of thick vascular collagenous
membrane lined by flattened arachnoid cells
• Choroid plexus-like tissue may be present in walls
o Fluid secretion ~ progressive distention of cyst

I CLINICAL

ISSUES

Presentation
• Reported cases diagnosed in first trimester on
endovaginal scans
• Most present at > 20 weeks gestational age
• Majority of postnatal cases present with macrocephaly

Natural History & Prognosis
• May cause hydrocephalus
• Hydrocephalus more likely if:
o Early gestational age at diagnosis
o Size> 15 mm
o Progressive increase in size
• Prognosis good if isolated abnormality
o May require shunt or excision if significant mass
effect
o Excision/marsupialization
favored
o Avoids complications of shunt placement

CYST

• Infection
• Blockage
• Reoperation
• Other anomalies determine prognosis when present
• Suprasellar cistern AC associated with hypothalamic
hamartoma
o Risk for precocious puberty
o Gelastic seizures

Treatment
• Consider amniocentesis for karyotype, even if isolated
• No prenatal intervention
• Monitor for growth of cyst
o Hydrocephalus
o Macrocephaly
• Head size may impact timing and mode of delivery

I DIAGNOSTIC

CHECKLIST

Consider
• Fetal MRI
o Confirm cyst
o Evaluate associated structural abnormalities

Image Interpretation

Pearls

• Always check Doppler of apparent cyst
o Arteriovenous malformation immediately apparent
o Very different prognosis

I SELECTED
1.

REFERENCES

Booth TN et al: Pre- and postnatal MR imaging of
hypothalamic hamartomas associated with arachnoid
cysts. AJNRAm J Neuroradiol. 25(7):1283-5, 2004
2.
Blaicher W et al: Magnetic resonance imaging and
ultrasound in the assessment of the fetal central nervous
system. J Perinat Med. 31(6):459-68, 2003
3.
Patel TR et al: A study of prenatal ultrasound and postnatal
magnetic imaging in the diagnosis of central nervous
system abnormalities. Eur J Pediatr Surg. 13 Suppl1:S18-22,
2003
4.
Bretelle F et al: First-trimester diagnosis of fetal arachnoid
cyst: prenatal implication. Ultrasound Obstet Gynecol.
20(4):400-2,2002
5.
Blaicher W et al: Combined prenatal ultrasound and
magnetic resonance imaging in two fetuses with suspected
arachnoid cysts. Ultrasound Obstet Gynecol. 18(2):166-8,
2001
6. Folkerth RD et al: Organizing posterior fossa hematomas
simulating developmental cysts on prenatal imaging:
report of 3 cases. J Ultrasound Med. 20(11):1233-40, 2001
7.
Golash A et al: Prenatal diagnosis of suprasellar arachnoid
cyst and postnatal endoscopic treatment. Childs Nerv Syst.
17(12):739-42, 2001
8. Bannister C et al: Fetal arachnoid cysts: Their site, progress,
prognosis, and differential diagnosis. Eur J Pediatr Surg.
9:27-8, 1999
9.
Barjot P et al: Diagnosis of arachnoid cysts on prenatal
ultrasound. Fetal Diagn Ther. 14(5):306-9, 1999
10. Pilu G et al: Differential diagnosis and outcome of fetal
intracranial hypoechoic lesions: report of 21 cases.
Ultrasound Obstet Gynecol. 9(4):229-36, 1997
11. Estroff JA et al: Posterior fossa arachnoid cyst: an in utero
mimicker of Dandy-Walker malformation. J Ultrasound
Med. 14(10):787-90, 1995

ARACHNOID

CYST

IIMAGE GALLERY
Variant
(Left) Axial color Doppler
ultrasound shows an
avascular cyst (curved
arrow). The normal vessels
are visible. Note midline shift
with displacement
of the
anterior cerebral arteries
(arrow). (Right) Axial T2WI
MR shows the large cyst
(arrow) displacing normal
brain. There had been
significant enlargement in
one month with developing
hydrocephalus.
Postnatal
cyst decompression
relieved
hydrocephalus.

(Left) Sagittal T2WI MR
shows a large simple
extra-axial cyst over the
convexity of the parietal lobe
(arrow). The lateral ventricle
(curved arrow) is displaced
and there is mild
ventriculogmegaly.
(Right)
Axial ultrasound shows an
interhemispheric
arachnoid
cyst (arrow) in a fetus with
trisomy 18. Other findings
include a "strawberry"
shaped calvarium (curved
arrow), choroid plexus cyst
(open arrow), and tetralogy
of Fallot.

Typical
(Left) Sagittal T2WI MR
shows a posterior fossa
arachnoid cyst (arrow)
displacing the cerebellar
hemisphere
(curved arrow).
The vermis was intact
excluding Dandy-Walker
continuum.
(Right) Axial
oblique ultrasound of the
posterior fossa in a neonate
with an arachnoid cyst
(arrows). The vermis is intact
(curved arrow). One third of
fetal arachnoid cysts occur in
the posterior fossa.

GLIOEPENDYMAL

Graphic shows an extra-axial cyst centered around the
falx, displacing adjacent brain. GCs are usually midline
frontoparietal but may be large enough to mimic alobar
holoprosencephaly by displacing the entire cerebrum.

•
•
•
•

and Synonyms

Glioependymal cyst (GC)
Ependymal cyst
Neuroepithelial cyst
Choroidal epithelial cyst

Definitions
• Intracranial

cyst with ependymal

lining

IIMAGING FINDINGS
Ultrasonographic

Findings

• Grayscale Ultrasound
o Smooth-walled, anechoic cyst in fetal cranium
• Multiloculated cysts described
o Typically centered on midline
• Frontal
• Parietotemporal
o Generally no communication
with ventricular
system
o May be intraventricular
o May be intra or extra-axial
o May be multiple
o May cause hydrocephalus

DDx: Glioependymal

Sagittal T2WI MR postmortem image of the fetal brain
shows a large centrally-placed frontal cyst (curved
arrow). Extra-axial location confirmed by displacement
of normal brain (black arrow).

• Compress Aqueduct of Sylvius or Foramen of
Monroe
• Obstruct cerebrospinal fluid (CSF) flow
o Associated with agenesis of corpus callosum (ACC)
• Many cysts previously called arachnoid cysts (AC)
may actually have been GC
o Other features of ACC
• Absent cavum septi pellucidi
• Parallel lateral ventricles
• Abnormal course pericallosal/callosomarginal
arteries
• "Trident-shaped" lateral ventricles on coronal view
• Colpocephaly (tear-drop shaped ventricles)
• Gyri in radial "sunray" distribution in sagittal
plain
o Not usually associated with extracranial anomalies
• Color Doppler
o No internal flow
o Vessels displaced by cyst
• 3D
o May be helpful to evaluate location of cyst
o Shows relationship of large cyst to rest of brain

ITERMINOlOGY
Abbreviations

CYST

MR Findings
• Signal intensity usually follows CSF
o Low signal TI WI
o High signal T2WI
• May be hyperintense on TI WI

Cyst
.'~'

~

.

.

.~
-·f
~

.

:.

·';-".r.~·-:
......•..
'~

~

-'<EJ

~~..

..

,"

'

--'.

~~.

"

• ..

..

-

-.;

~

-

Teratoma

A/obar

-..
-I f%pros

.

*.".

GLIOEPENDYMAL

CYST

Key Facts
• Teratoma

Terminology
• Intracranial

cyst with ep ndymallining

Clinical Issues

Imaging Findings
•
•
•
•
•
•
•

May be hyperinten e on Tl WI
Proteinac ou fluid
mooth-walled, anechoic cy t in fetal cranium
Multiloculated
y ts described
Typically centered on midline
Associated with agenesis of corpu callo um (A )
ot u ually a sociated with extracranial anomalie

Top Differential
•
•
•
•

Diagnoses

Arachnoid cy t (A )
Schizencephaly
Alobar holopro encephaly
Porencephalic cyst

o Proteinaceous fluid
o Occasional fluid-fluid level if high protein content
• If present aids differentiation from arachnoid cyst

Imaging Recommendations
• Protocol advice
o Careful search for other anomalies
o Check size/date concordance
o If anomalies or abnormal growth ~ increased
suspicion for aneuploidy/syndrome

I DIFFERENTIAL
Arachnoid
•
•
•
•

DIAGNOSIS

Schizencephaly
wall

Alobar holoprosencephaly
• Large GC may simulate a monoventricle
• Monoventricle is hallmark
o Abnormal brain tissue adjacent to monoventricle
o Cup, pancake or ball morphology
• GC displaces otherwise normal brain parenchyma
• Typically associated with abnormal facies
o Facial cleft
o Cyclopia/hypotelorism
o Cebocephaly/ethmocephaly
• If fetus has Trisomy 13
o Omphalocele
o Congenital heart disease
o Polydactyly
o Cystic renal disease

Intracranial

hemorrhage

• Associated with tissue destruction

Diagnostic Checklist
• High r signal than
SF on Tl WI support diagnosis
ofG
• Differentiation of G v. A often not po ible or
even nece sary by imaging
• I olated cy t without mas ffect has excell nt
prognosi

• Appearance evolves with time
o Echogenic mass ~ hypoechoic mass ~ cyst-like
structure
• Look for fluid-fluid levels in ventricles
o Blood-CSF
o Fluid-fluid level in cyst reflects protein content

Porencephalic

cyst

• Associated with brain destruction
o Intracranial hemorrhage
o Periventricular leukomalacia (PVL)
• Always intraparenchymal
• Cyst communicates with adjacent ventricle

Teratoma

cyst (AC)

May not be able to differentiate from GC
AC more common over convexities
AC more likely if cyst in posterior fossa
AC more likely if multiple anomalies present
o Stronger association with aneuploidy

• Wedge-shaped defect
• Extends cortical surface to ventricular
• Lined with grey matter

• Follow for hydrocephalus/macrocephaly
• Hydro phalu: Increa ed lik lihood of po tnatal
intervention
• Intellectual outcome d pendent on a ociated
structural abnormalitie
• Decompre ion preferable to urgery

• Can be predominately
• Soft tissue component,
identified
• Intraparenchymal

cystic
calcification,

can usually be

Physiologic entities
• Differential
o Enlarged cavum septi pellucidi
o Enlarged cavum vergae
o Cyst of cavum velum interpositum
• Do not increase in size
• Many regress with advancing gestational age
• Median size 10 mm (range 10-30 mm)
• Pathologic cysts like GC larger, often grow

I PATHOLOGY
General Features
• Genetics
o Isolated GC not associated with aneuploidy
o No recurrence risk
• Etiology: Leptomeningeal neuroglial heterotopia
• Epidemiology
o Isolated GC extremely rare prenatal diagnosis
o 5/145 postnatal intracranial cysts requiring surgery
at one institution
• Associated abnormalities

GLIOEPENDYMAL
o
o
o
o
o

Agenesis/dysgenesis corpus callosum
Microgyria
Heterotopia
Cerebellar hypoplasia
Elevated alpha fetoprotein levels reported

CYST

• May improve with cyst decompression
• Decompression preferable to surgery

I DIAGNOSTIC

CHECKLIST

Gross Pathologic & Surgical Features

Consider

• May occur in spine as well as brain
• GC at posterior neuropore
o Case report of GC simulating sacrococcygeal
teratoma

• Fetal MRI
o Confirm diagnosis of cyst
• Higher signal than CSF on T1WI supports
diagnosis of GC
o Shows benign physiologic entities clearly
o Evaluate associated structural abnormalities

Microscopic

Features

• Outer layer of wall
o Basement membrane
o Glial tissue
• Inner layer
o Ependymal tissue +/- cilia

ICLINICAL

ISSUES

Image Interpretation

Pearls

• Differentiation of GC vs. AC often not possible or even
necessary by imaging
o Same treatment
• Consider GC if cyst is midline and frontal
• Isolated cyst without mass effect has excellent
prognosis

Presentation
• Cystic intracranial
ultrasound

mass detected on routine obstetric

I SELECTED
1.

Natural History & Prognosis
• Depends on
o Size
o Associated abnormalities
o Location
• May obstruct CSF flow => hydrocephalus
• Hydrocephalus => shunt placement
o Shunts have associated morbidity
• Infection
• Obstruction
• Reoperation
o Mass effect on adjacent brain
• Case reports of focal hypo perfusion
• Case report of underlying brain destruction
secondary to ischemia
• Seizure disorder attributed to local hypoxemia
• Many GCs asymptomatic
o Incidental detection described in postnatal series
• Cyst decompression associated with good outcome
• No known recurrence risk

2.

3.

4.

5.

6.

7.
8.

9.

Treatment
• No documented association of GC with aneuploidy
o Amniocentesis may not be necessary if isolated
anomaly
o Often difficult to differentiate from AC, which is
associated with aneuploidy
• Follow for hydrocephalus/macrocephaly
o Either may influence timing and mode of delivery
o Hydrocephalus: Increased likelihood of postnatal
intervention
• Infant should be assessed by pediatric neurologist
• Intellectual outcome dependent on associated
structural abnormalities
• Progressive signs and symptoms require shunt
placement
o Raised intracranial pressure
o Seizure disorder reported

10.

11.
12.

13.
14.

15.

REFERENCES

Sarnat HB et al: Neuropathologic research strategies in
holoprosencephaly.
J Child Neurol. 16(12):918-31, 2001
Sundaram C et al: Cysts of the central nervous system: a
clinicopathologic
study of 145 cases. Neurollndia.
49(3):237-42,2001
Kanazawa R et al: Ependymal cyst producing
alpha-fetoprotein.
Case report. J Neurosurg. 93(4):682-5,
2000
Trummer M et al: Ependymal cyst occluding the Foramen
Magendie. Acta Neurochir (Wien). 142(5):601-2, 2000
Uematsu Y et al: Interhemispheric
neuroepithelial cyst
associated with agenesis of the corpus callosum. A case
report and review of the literature. Pediatr Neurosurg.
33(1):31-6,2000
Tillich M et al: Symptomatic neuroepithelial (ependymal)
cyst of the fourth ventricle: MR appearance. AJR Am J
Roentgenol. 172(2):553-4, 1999
Guermazi A et al: Imaging findings of central nervous
system neuroepithelial cysts. Eur Radiol. 8(4):618-23, 1998
Lustgarten Let al: Benign intracerebral cysts with
ependymal lining: pathological and radiological features.
Br J Neurosurg. 11(5):393-7, 1997
Bloechle M et al: Neuroectodermal
cyst may be a rare
differential diagnosis of fetal sacrococcygeal teratoma: first
case report of a prenatally observed neuroectodermal
cyst.
Ultrasound Obstet Gynecol. 7(1):64-7, 1996
Goh RH et al: Neuroepithelial cyst of the posterior fossa:
two case reports with radiologic-pathologic
correlation.
Can Assoc Radiol]. 47(2):126-31,1996
Ciricillo SF et al: Neuroepithelial cysts of the posterior
fossa. Case report. J Neurosurg. 72(2):302-5, 1990
Barth PG et al: Interhemispheral
neuroepithelial
(glio-ependymal) cysts, associated with agenesis of the
corpus callosum and neocortical maldevelopment.
A case
study. Childs Brain. 11(5):312-9, 1984
Gonzalez C et al: Supratentorial neuroepithelial cysts.
Report of two cases. J Neurosurg Sci. 28(2):97-102, 1984
Haddad FS et al: Ependymal brain cyst. Surg Neurol.
18(4):246-9, 1982
Solt LC et al: Interhemispheric
cyst of neuroepithelial
origin in association with partial agenesis of the corpus
callosum. Case report and review of the literature. J
Neurosurg. 52(3):399-403, 1980

GLIOEPENDYMAL

CYST

IIMAGE GALLERY
Typical
(Left) Axial oblique
ultrasound of a frontal CC
(arrows) shows posterior
displacement of the brain
(curved arrow). The thalami
are not fused and the
cerebellum (open arrow)
and cisterna magna are
normal. (Right) Axial T2WI
MR shows the mu/tiloculated
cyst (white arrows)
straddling the midline and
displacing normal brain
posteriorly (black arrow)
confirming the ultrasound
findings. The occipital horns
(curved arrows) are not
dilated

Variant
(Left) Coronal T2WI MR
shows large cyst bulging
through the anterior
fontanelle (curved arrows) in
this fetus with associated
agenesis of the corpus
callosum. Hydrocephalus
(arrows) is secondary to
mass effect (Right) Coronal
T2WI MR shows a CC cyst
(arrow) displacing brain
(curved arrow) in a different
infant with hemifacial
microsomia, unilateral
anophthalmia, ACe
heterotopia and asymmetric
brain growth.

(Left) Axial T2WI MR shows
an interhemispheric cyst
(arrow) in a fetus with ACe.
(Right) Axial T7WI MR of the
same infant in the first week
of life shows an
interhemispheric cyst The
lateral ventricles (arrows)
have a parallel orientation
due to associated callosal
agenesis. Histology would be
needed to confirm, but the
midline location and ACC
support a Ce.

SCHIZENCEPHALY

Axial ultrasound shows a unilateral cleft in the brain
parenchyma (arrows). Additional images showed the
defect extending to the underlying ventricle. No cavum
septi pellucidi could be identified.

ITERMINOLOGY
Definitions
• Gray matter lined cleft extending from brain surface to
ventricle
o Closed-lip (type 1)
• Gray matter "lips" which are in contact with each
other
o Open-lip (type 2)
• Separated gray matter "lips" with an intervening
cleft of cerebral spinal fluid (CSF)
• CSF cleft extends to underlying ventricle

IIMAGING

FINDINGS

General Features
• Best diagnostic clue
o Defect of brain parenchyma extending from inner
table of skull to underlying ventricle
o Gray matter lines cleft
• Location
o Cerebral hemispheres
• Unilateral
• Bilateral
o Uncommonly occipital
• Usually unilateral in this location
• Size: Any size possible

DDx: Schizencephaly

,-\/obdliio/opws

Axial NECT shows the cleft (arrows) and the absent
cavum septi pellucidi in the same patient after delivery,
confirming the prenatal diagnosis of open-lip
schizencephaly

• Morphology
o Wedge shaped CSF-filled defect seen in open-lip
schizencephaly
o Closed-lip defects are unlikely to be detected
prenatally on screening ultrasound

Ultrasonographic

Findings

• Most often will detect only open-lip type
o Small open-lip defects can be difficult to detect
especially in near filled
• Reverberation artifact obscures cleft
o Closed-lip type often missed
• CSF-filled cleft extending from surface of brain to
ventricle
o Ventricular wall "tented" toward defect
o Ventriculomegaly
o Roofing membrane covering cerebral defect
• Uncommonly identified
• Cavum septi pellucidi (CSP)
o Absent in 70%
o Almost always absent in bilateral schizencephaly
• Associated brain developmental abnormalities
o Heterotopia
o Polymicrogyria
o Pachygyria
o Septo-optic dysplasia
• Calvarium may be remodeled over open-lip defect

SCHIZENCEPHALY
Key Facts
Terminology

• Porencephalic cyst

• Gray matter lined cleft extending from brain surface
to ventricle
• Closed-lip (type 1)
• Open-lip (type 2)

• Most likely primary malformation from abnormal
neuronal migration
• Early prenatal injury has also been implicated

Imaging Findings

Clinical Issues

Pathology

• Defect of brain parenchyma extending from inner
table of skull to underlying ventricle
• Gray matter lines cleft
• Closed-lip type often missed

Top Differential

•
•
•
•

Diagnoses

Diagnostic

• Arachnoid cyst
• Alobar holoprosencephaly
• Agenesis of the corpus callosum with
interhemispheric cyst

Agenesis of the corpus callosum
interhemispheric
cyst

MR Findings

CT Findings
• No role in prenatal imaging
• Postnatal CT
o Can usually see open or closed-lip defects
o Grey matter lining confirms diagnosis
o Not as sensitive as MRI

I DIFFERENTIAL DIAGNOSIS
Arachnoid

cyst

• Extra-axial location
o Mass effect on adjacent brain
o Scalloping of inner table of skull
o Most over convexities

Alobar holoprosencephaly
•
•
•
•

Monoventricle
Absent cavum septi pellucidi
Fused thalami
Abnormal facial features
o Midline facial clefts
o Cyclopia
o Proboscis
o Cebocephaly

Checklist

• If diagnosis suspected, fetal MRI should be performed
• Confirms diagnosis with demonstration of gray
matter lining cleft

o Likely due to CSF pulsation originating from
ventricle
• Face and profile are normal
o Differentiates schizencephaly from
holoprosencephaly
• Higher resolution imaging of brain parenchyma
ultrasound
• Confirms grey matter lining cleft
• Detects other developmental anomalies
o Heterotopia
o Polymicrogyria
o "Mirror image" migrational abnormality in
contralateral hemisphere
• Can be seen with unilateral schizencephaly
defects

Seizures
Developmental delay
Mental retardation
Motor impairment

than

•
•
•
•
•

Absent CSP
Colpocephaly
Elevation of third ventricle
Absent cingulate gyrus
Associated interhemispheric
o Displaces normal brain

Porencephalic
•
•
•
•

with

cyst or lipoma

cyst

Round or irregular shape
CSF-filled defect in brain parenchyma
Not lined with gray matter
May be associated with hydrocephalus

Hydrocephalus
• Severe obstructive
o Head is enlarged
o Cortical mantle may be so thin it is difficult to see
• Doppler may show flow in compressed
parenchyma
• May require fetal MRI to identify cortical mantle
• Non-obstructive
o Secondary to infection, ischemia or hemorrhage
• Subsequent destruction of brain parenchyma
• Increased ventricular size
• Thinned cortical mantle

Hydranencephaly
• Complete destruction of cerebral hemispheres
o Preserved cerebellum and brain stem
• Replacement of supratentorial structures with CSF
• Falx present
• Absent Doppler flow
o Middle cerebral artery
o Anterior cerebral artery

I

PATHOLOGY

General
• Genetics

Features

SCHIZENCEPHALY
o Familial schizencephaly has been reported
o Has been associated with heterozygous mutations of
the EMX2 gene
• Normally expressed in germinal matrix
• Etiology
o Neuronal migration anomaly
• Final common pathway for several possible
etiologies
• Most likely primary malformation from abnormal
neuronal migration
o Early prenatal injury has also been implicated
• Drug abuse
• Maternal abdominal trauma
• Infection (cytomegalovirus)

I DIAGNOSTIC

Image Interpretation

I SELECTED

Gross Pathologic & Surgical Features

ICLINICALISSUES

2.
3.

4.

5.

6.

Presentation
• Prenatal
o May be incidental finding on screening second
trimester ultrasound
• Postnatal
o Seizures
• Severity of seizures not related to size or extent of
defect
o Developmental delay
• Severity correlates with extent of defect
o Mental retardation
• Severity correlates with extent of defect
o Motor impairment
• Severity correlates with extent of defect
• Symptoms usually minimal if motor cortex not
involved
o Blindness
• Optic nerve hypoplasia
• Up to 1/3 of patients with schizencephaly

Natural History & Prognosis
• Unilateral defect in 60%
o If small, neurologic deficit is milder
o Late onset seizure disorder
o Drug resistant epilepsy
o Compatible with long life span
• Bilateral defect in 40%
o Severe neurologic impairment
o Often have less tendency for seizures
o If epileptic, not drug resistant

Treatment
• Prenatal none
• Termination may be offered
• Postnatal treatment for seizures

Pearls

• If diagnosis suspected, fetal MRI should be performed
o Confirms diagnosis with demonstration of gray
matter lining cleft
• Ultrasound may miss a small defect
o Defect in near field may not be seen
• Bilateral defects have worse clinical outcome that
unilateral

1.

• Gray matter lined cleft extending from brain pial
surface to ependymal lining of ventricle
o Cleft lining is dysplastic gray matter
o Abnormal cortical lamination
• Most often found near pre-central and post-central
gyri
• Associated migrational anomalies
o Polymicrogyria
o Pachygyria

CHECKLIST

7.

8.

9.

10.

11.
12.

13.

14.

15.
16.

17.

REFERENCES

Oh et al: Fetal schizencephaly: Prenatal and postnatal
imaging with a review of the clinical manifestations.
Radiographics. 25:647-657, 2005
Barkovich AJ et al: Malformations of cortical development.
Neuroimaging Clin N Am. 14(3):401-23,2004
Barkovich AJ et al: Neuroimaging in disorders of cortical
development. Neuroimaging Clin N Am. 14(2):231-54, viii,
2004
Hayashi N et al: Morphological features and associated
anomalies of schizencephaly in the clinical population:
detailed analysis of MR images. Neuroradiology.
44(5):418-27,2002
Liang JS et al: Schizencephaly: correlation between clinical
and neuroimaging features. Acta Paediatr Taiwan.
43(4):208-13, 2002
Montenegro MA et al: Interrelationship of genetics and
prenatal injury in the genesis of malformations of cortical
development. Arch Neurol. 59(7):1147-53, 2002
Denis D et al: Prenatal diagnosis of schizencephaly by fetal
magnetic resonance imaging. Fetal Diagn Ther.
16(6):354-9, 2001
Guerrini R et al: Epileptogenic brain malformations:
clinical presentation, malformative patterns and
indications for genetic testing. Seizure. 10(7):532-43; quiz
544-7,2001
Denis D et al: Schizencephaly: clinical and imaging
features in 30 infantile cases. Brain Dev. 22(8):475-83, 2000
Iannetti P et al: Cytomegalovirus infection and
schizencephaly: case reports. Ann Neurol. 43(1):123-7,
1998
Granata T et al: Familial schizencephaly associated with
EMX2 mutation. Neurology. 48(5):1403-6, 1997
Brunelli S et al: Germline mutations in the homeobox gene
EMX2 in patients with severe schizencephaly. Nat Genet.
12(1):94-6, 1996
Barkovich A] et al: Schizencephaly: correlation of clinical
findings with MR characteristics. AJNR Am J Neuroradiol.
13(1):85-94, 1992
Aniskiewicz AS et al: Magnetic resonance imaging and
neurobehavioral correlates in schizencephaly. Arch Neurol.
47(8):911-6, 1990
Komarniski CA et al: Prenatal diagnosis of schizencephaly.
J Ultrasound Med. 9(5):305-7, 1990
Kuban KC et al: Septo-optic-dysplasia-schizencephaly.
Radiographic and clinical features. Pediatr Radiol.
19(3):145-50, 1989
Barkovich A] et al: MR imaging of schizencephaly. A]R Am
J Roentgenol. 150(6):1391-6, 1988

SCHIZENCEPHALY
I IMAGE GALLERY
Typical
(Left) Axial ultrasound shows
large bilateral open-lip
schizencephalic clefts. The
defects extend from the
underlying ventricle to the
inner table of the skull. The
falx is present (arrow).
(Right) Axial ultrasound of
the same patient shows the
thalami are not fused
(arrows). This finding, along
with the presence of a falx,
helps distinguish
schizencephaly from alobar
holoprosencephaly.

Typical
(Left) Axial T2WI MR shows
a small CSF-fi"IIcddefect.
Gray matter (arrow) can be
identified lining the cleft,
differentiating this from
porencephaly. The cavum
septi pellucidi is absent.
(Right) Coronal T2WI MR
demonstrating "tenting" of
the frontal horn of the
ventricle (arrow) towards the
schizenccphaly defect, a
diagnostic clue.

Typical
(Left) Axial ultrasound shows
giant bilateral
schizencephaly clefts
extending from the ventricles
to the undersurface of the
skull. (Right) Axial T2WI MR
confirms the diagnosis of
giant open-lip
schizencephaly. Note the
gray matter (arrows) lining
the very small amount of
remaining brain
parenchyma.

MICROCEPHALY

Sagittal ultrasound shows severe microcephaly in an 78
week fetus. Head measurements are more than 4 SO
smaller than expected. The forehead is sloped (arrow)
as is typically seen with frontal atrophy.

ITERMINOLOGY
Abbreviations

and Synonyms

• Microencephaly

Definitions
• Mild
o Fetal head circumference (HC) 2-3 standard
deviations (SO) below mean for gestational age (GA)
• Severe: HC > 3 SO below mean for GA
o If GA unknown, HC compared to femur length (FL)
and abdominal circumference (AC)
• HC/AC < -3S0
• FL/HC > 3S0

IIMAGING

Lateral radiograph taken after binh in another baby with
microcephaly
once again shows a markedly sloped
forehead (arrow) and small calvarial volume. The facial
bones are normally sized.

• Ventriculomegaly
• Large subarachnoid space
o Brain may not be visible at all
• Mild microcephaly: HC 2-3 SO below mean GA
o Often normal outcome when isolated
• 67% with other brain anomalies
o Holoprosencephaly
o Agenesis of corpus callosum
o Porencephaly
• Non central nervous system anomalies common

MR Findings
• Cerebral convolution defects
o Macrogyria, pachygyria
• Parenchymal asymmetry
• Large basal ganglia

FINDINGS

Imaging Recommendations
• Protocol advice
o Amniocentesis
o Fetal MR

General Features
• Best diagnostic clue
o Markedly small HC
o Abnormal calvarial shape

Ultrasonographic

I

Findings

• Severe microcephaly: HC 4-7 SO below mean GA
o Sloping forehead
• Preferential frontal lobe atrophy
o Global cortical atrophy

DDx: Abnormal

Calvarium Morphology

Anencephaly

Anencephaly

should be offered

DIFFERENTIAL DIAGNOSIS

Craniosynostosis
• Premature fusion of cranial sutures
• Small, abnormally shaped calvarium common
o Cloverleaf skull most severe example

Atelencephaly

Strawberry

(T! 8)

MICROCEPHALY
Key Facts
Terminology

• Anencephaly

• Severe: HC > 3 SD below mean for GA

Clinical Issues

Imaging Findings

• Prognosis depends on severity of microcephaly
• False positive diagnosis common

• Sloping forehead
• Ventriculomegaly
• 67% with other brain anomalies.

Top Differential

Diagnoses

• Craniosynostosis

Anencephaly
• Open neural tube defect involving cranium
• Calvarium is absent
• Dysplastic brain tissue often seen

Diagnostic Checklist
• Fetal MR to see subtle associated brain anomalies
• Mild microcephaly is often a normal variant
• Amniocentesis warranted

• Prognosis depends on severity of microcephaly
o +/- Aneuploidy
• Minor microcephaly diagnosed in fetal life
o Often with normal outcome
o False positive diagnosis common

Atelencephaly / aprosencephaly
• Rudimentary prosencephalon
o Lack of supratentorial brain
• Dysmorphic facial features

I PATHOLOGY
General Features
• Genetics
o Chromosome abnormalities
• Trisomies 13, 18, 22; 4p-, Sp-, 18qo Single gene defects
• Fanconi, Roberts, Smith-Lemli-Opitz, etc.
• Etiology
o Teratogen exposure
• Alcohol, hydantoin, radiation
o Prenatal infection
• Cytomegalovirus (CMV), rubella, toxoplasmosis
o Part of numerous syndromes
• Cornelia de Lange, Neu-Laxova, etc.
o Often unknown etiology
• Epidemiology
o 1.6:1,000 births
o Most not diagnosed until first year of age

Microscopic

Features

• Decreased dendritic arborization

I

DIAGNOSTIC

CHECKLIST

Consider
• Fetal MR to see subtle associated brain anomalies
• Sequential ultrasound for HC growth

Image Interpretation

Pearls

• Mild microcephaly is often a normal variant
• Amniocentesis warranted
I SELECTED
1.
2.
3.
4.

5.

REFERENCES

Le Ray C et al: Late onset microcephaly:
failure of prenatal
diagnosis. Ultrasound
Obstet Gynecol. 24(4):481-3, 2004
Sztriha L et al: Microcephaly
associated with abnormal
gyral pattern. Neuropediatrics.
35(6):346-52,
2004
Persutte WH: Microcephaly--no
small deal. Ultrasound
Obstet Gynecol. 11(5):317-8, 1998
Goldstein I et al: Sonographic
assessment of the fetal
frontal lobe: a potential tool for prenatal diagnosis of
microcephaly.
Am] Obstet Gynecol. 158(5):1057-62,
1988
Chervenak
FA et al: A prospective
study of the accuracy of
ultrasound
in predicting fetal microcephaly.
Obstet
Gynecol. 69(6):908-10,
1987

IIMAGE

GAllERY

I CLINICAL ISSUES
Presentation
• Most common signs/symptoms
o Diagnosed in conjunction with other anomalies
o Isolated finding during routine exam
• Other signs/symptoms: May, not develop until third
trimester

Natural History & Prognosis
• Infants with microcephaly diagnosed in 1st year of life
o HC 2-3 SD below mean
• 330/0 moderate or severely retarded
o HC > 3 SD below mean
• 62% moderate or severely retarded

(Left) Sagittal ultrasound shows micrognathia (curved arrow) and
frontal bone flattening (arrows) in a fetus with microcephaly. Multiple
other anomalies were present. (Right) Clinical photograph of
micrognathia and sloped forehead in a syndromic baby with
microcephaly.

ATELENCEPHALY, APROSENCEPHALY

Clinical photograph shows a stillborn infant with
aprosencephaly. Note severe microcephaly. sloped
forehead (arrow), low set ears (curved arrow) and long
retrognathicchin (open arrow).

ITERMINOlOGY
Abbreviations
•
•
•
•
•

Ultrasonographic

and Synonyms

Aprosencephaly/atelencephaly
Aprosencephaly
Atelencephaly
XK aprosencephaly
Garcia-Lurie syndrome

Axial oblique ultrasound shows a mid-trimester image of
a fetus with aprosencephaly showing a hypoplastic
cerebellum (arrow) and no other recognizable
intracranialstructures.

spectrum

Definitions
• Rare lethal malformation sequence of the central
nervous system (CNS)
• Developmental arrest of formation of telencephalon
and/or prosencephalon
• Syndromal or XK aprosencephaly with associated
limb, genital defects

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Appearance similar to anencephaly with intact scalp
and calvarium
o Craniofacial anomalies, often severe
o Severe microcephaly with or without limb
abnormalities

Findings

• Brain
o Severe microcephaly
o Intact skull and scalp
o No normal cerebral structures
• Replaced with fluid
• Amorphous mass
o Cerebellum often hypoplastic
• Face
o Micrognathia
o Midline oculofacial defects including cyclopia
o May be severely dysmorphic without recognizable
features
• Absent eyes/nasal structures
o Cleft palate
• Extremities
o Hypoplastic thumbs and halluces
o Radial ray anomalies including absent thumbs
o Oligodactyly
• Missing digits, especially thumb and great toe
o Clinodactyly
• Medial or lateral deviation of one or more digits
o Camptodactyly
• Persistent finger flexion
o Clubfoot
• Urogenital anomalies
o Ambiguous genitalia

DDx: Calvarial Abnormalites

.

--~I~

~-

I- _

:-"'~,~
~...•
.
-,~~
•.••• ~"';;$:
,\"

Acrania

Anencephaly

J.

.,~,

•.
1'

Microcephaly

,

~
Spaulding

Sign

ATELENCEPHALY, APROSENCEPHALY
Key Facts
Terminology

Top Differential

• Rare lethal malformation sequence of the central
nervous system (CNS)
• Developmental arrest of formation of telencephalon
and/or prosencephalon
• Syndromal or XK aprosencephaly with associated
limb, genital defects

• Severe microcephaly
• Anencephaly
• Holoprosencephaly
(HPE)

Imaging Findings
• Craniofacial anomalies, often severe
• Severe microcephaly with or without limb
abnormalities
• No normal cerebral structures
• Cerebellum often hypoplastic
• Best imaging tool: Endovaginal ultrasound in early
gestation to confirm abnormal brain with intact skull

Diagnoses

Pathology
•
•
•
•

Generally sporadic
Autosomal recessive in some families
Partial monosomy 13q
Rudimentary prosencephalon
present in
atelencephaly
• Both prosencephalic and diencephalic structures fail
to develop in aprosencephaly

Clinical Issues
• Cranial contour may resemble that of anencephaly
but with calvarium present

• Cerebellar hypoplasia

o Hypoplastic penis
o Cryptorchidism
o Anorectal atresia
o Renal agenesis
• Cardiac
o Atrial septal defects
o Ventricular septal defects

Hydranencephaly
•
•
•
•
•

Imaging Recommendations
• Best imaging tool: Endovaginal ultrasound in early
gestation to confirm abnormal brain with intact skull
• Protocol advice: Consider MRI to evaluate CNS

I DIFFERENTIAL DIAGNOSIS
Severe microcephaly
• Sloped forehead
• Intact calvarium
• Brain may appear otherwise normal

Falx present
No visible cerebral tissue
Midbrain, hindbrain structures preserved
Craniofacial development normal
Other anomalies rare

Acalvaria/acrania
•
•
•
•

Absent calvarium above orbits
Facial appearance similar to anencephaly
Exposed, disorganized-appearing
neural tissue
Neural tissue "wears away" during gestation
o Appearance may be indistinguishable
from
anencephaly at delivery
• Amniotic fluid often very echogenic
• Other disruptions seen in cases of amniotic bands
o Orofacial clefts
o Abdominal wall defects

Anencephaly

Pseudoaprosencephaly

• No calvarium or soft tissue structures above orbits
• Associated spine abnormalities
o Cervical myelomeningocele
o Rachischisis
• Protuberant eyes due to shallow orbits
• Irregular surface due to cerebrovasculosa
• Non-CNS anomalies uncommon

• Membranous remnant of prosencephalic structures
apparent on histologic exam
• Vesicular forebrain
• May be link between alobar HPE and aprosencephaly

Holoprosencephaly

(HPE)

• Monoventricle
• Prosencephalic structures (e.g. thalamus)
malformed/fused
• Craniofacial anomalies common
o Hypotelorism
o Orofacial clefts
o Cyclopia
o Proboscis

Partial monosomy
• Brain abnormalities
aprosencephaly
• Arhinencephaly

Demise with overlapping sutures
• "Spaulding's sign"
• Obvious absent heartbeat

present but

13q
in at least half of cases including

I

PATHOLOGY

General Features
• Genetics
o Generally sporadic
o Autosomal recessive in some families
• Occurrence in siblings, twins support genetic
contribution
o Partial monosomy 13q
• Deletion 13q
• Ring chromosome 13

ATELENCEPHALY, APROSENCEPHALY
• 13q32 region involved in malformations of brain,
eyes, thumbs
o Deletion of contiguous genes possible in cytogenetic
cases
o Candidate gene(s) unknown
• OTX2 (homeodomain-containing
gene expressed
in prosencephalon)
may have role
o Rare other chromosomal aneuploidies
• Triploidy
• Trisomy 13
• Complex rearrangements
• Etiology
o Unknown but developmental arrest more likely than
encephaloclastic process
o No confirmed viral or teratogenic cause
• Epidemiology: Unknown prevalence
• Associated abnormalities
o Dysmorphic facial features
o Extremity malformations
• Especially digits
o Urogenital anomalies
o Cardiac anomalies

Gross Pathologic & Surgical Features
• Rudimentary prosencephalon
present in atelencephaly
• Both prosencephalic and diencephalic structures fail to
develop in aprosencephaly
• Absence of telencephalon and pyramidal tracts, lateral
and 3rd ventricles
• Cerebellar dysgenesis
• Normally formed spinal cord
• Craniosynostosis common

Microscopic

Features

• Clusters of premature neural cells in medulla
• Retinal dysplasia
• Perivascular mesenchymal proliferation in CNS

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Severe microcephaly on mid-trimester ultrasound
o Cranial contour may resemble that of anencephaly
but with calvarium present
• Other signs/symptoms: Limb or genital defects

Demographics
• Age: No known parental age effect
• Gender: Possibly more common in males

Natural History & Prognosis
• Prenatal or neonatal death
• One case with survival for 13 months

Treatment
•
•
•
•

No known fetal or neonatal treatment
Termination of pregnancy an option
Avoid fetal monitoring in confirmed cases
Caesarean section to be avoided

I DIAGNOSTIC

CHECKLIST

Consider
• MRI for confirmation
hydranencephaly

Image Interpretation

of diagnosis, exclusion of

Pearls

• Severe microcephaly with apparent absence of normal
intracranial anatomy and limb defects
• Differentiation from anencephaly important given
recurrence risk issues

I SELECTED REFERENCES
1.

Pasquier L et al: First occurrence
of
aprosencephaly/atelencephaly
and holoprosencephaly
in a
family with a SIX3 gene mutation
and
phenotype/genotype
correlation
in our series of SIX3
mutations.]
Med Genet. 42(1):e4, 2005
2.
McPherson
E et al: Anomalies of the forebrain with radial
limb defects: Garcia-Lurie-Steinfeld
syndrome?
Birth
Defects Res A Clin Mol Teratol. 70(8):537-44,
2004
3.
Kajantie E et al: A fetus suggesting an extension of
theXK-aprosencephaly
spectrum phenotype.
Clin
Dysmorphol.
11 (4):299-301,2002
4.
Sergi C et al: The vesicular forebrain
(pseudo-aprosencephaly):
a missing link in the
teratogenetic
spectrum of the defective brain anlage and its
discrimination
from aprosencephaly.
Acta Neuropathol
(Berl). 99(3):277-84,
2000
5.
al-Gazali LI et al: XK aprosencephaly.
Clin Dysmorphol.
7(2):143-7,1998
6.
Ippel PF et al: Atelencephalic
microcephaly:
a case report
and review of the literature.
Eur] Pediatr. 157(6):493-7,
1998
7.
Labrune Pet al: Severe brain and limb defects with possible
autosomal
recessive inheritance:
a series of six cases and
review of the literature. Am] Med Genet. 73(2):144-9, 1997
8.
Florell SR et al: Aprosencephaly
and cerebellar dysgenesis
in sibs. Am] Med Genet. 63(4):542-8,
1996
Acampora D et al: Forebrain and midbrain regions are
9.
deleted in Otx2-/- mutants due to a defective anterior
neuroectoderm
specification
during gastrulation.
Development.
121 (10):3279-90,
1995
10. Harris CP et al: Atelencephalic
aprosencephaly.
] Child
Neurol. 9(4):412-6, 1994
11. Brown S et al: Preliminary
definition
of a "critical region" of
chromosome
13 in q32: report of 14 cases with 13q
deletions and review of the literature.
Am J Med Genet.
45(1):52-9, 1993
12. Goldsmith
CL et al: Mosaic r(13) in an infant with
aprosencephaly.
Am] Med Genet. 47(4):531-3,1993
13. Norman AM et al: Hypoplastic
thumbs and
hydranencephaly:
a new syndrome?
Clin Dysmorphol.
1(2):121-3, 1992
14. Kim TS et al: Aprosencephaly:
review of the literature and
report of a case with cerebellar hypoplasia,
pigmented
epithelial cyst and Rathke's cleft cyst. Acta Neuropathol
(Berl). 79(4):424-31,1990
15. Townes PL et al: XK aprosencephaly
and anencephaly
in
sibs. Am] Med Genet. 29(3):523-8,
1988
16. Martin RA et al: A review and case report of
aprosencephaly
and the XK aprosencephaly
syndrome.
Am
] Med Genet. 11(3):369-71,
1982

ATELENCEPHALY, APROSENCEPHALY
I IMAGE GALLERY
Typical
(Left) Sagittal ultrasound
shows severe microcephaly
(open arrows). The face is
dysmorphic
with amorphus
50ft tissue (arrows) where
the mouth, nose, and orbits
should be seen. (Right)
Coronal ultrasound shows
the same fetus with
non-fused thalami (arrows)
and hypoplastic cerebellum
(curved arrows). No other
midline structures are
apparent.

Variant
(Left) Cross pathology
with
the calvarium opened shows
complete absence of the
forebrain and midbrain
structures (curved arrow).
The cerebellum is noted by
the arrows. (Right) Axial
ultrasound shows the brain
of a mid-trimester fetus with
XK aprosencephaly.
There is
severe microcephaly
(open
arrows) with disorganized
neural tissue protruding
through the orbit (arrow).
No normal cerebral
structures could be
identified

Typical
(Left) Ultrasound of the hand
shows an absent thumb
(arrow) and digital
contractures (curved arrow)
in a fetus with XK
aprosencephaly.
(Right)
Clinical photograph shows
the hand of the same infant
at term. Note the absent
thumb (arrow), ulnar
deviation of the wrist
(curved arrow) and digital
contractures (open arrow).

CRANIOSYNOSTOSIS

Coronal T2WI MR shows severe kleeblattschadel
("cloverleaf" skull) in a fetus with Pfeiffer syndrome.
The craniosynostoses (arrows) restrict normal brain
growth, resulting in marked deformity.

Frontal radiograph shows the tindings in the same intant
after birth. Craniosynostosis of the coronal sutures
(arrows) is seen, and the metopic suture is obliterated
(curved arrow).

ITERMINOlOGY

IIMAGING FINDINGS

Abbreviations

General Features

and Synonyms

• Scaphocephaly
o Sagittal synostosis
• Oxycephaly
o Bilateral coronal synostosis
• Plagiocephaly
o Unilateral coronal synostosis
• Trigonocephaly
o Metopic synostosis

Definitions
• First described by Virchow in 1851
• Premature fusion of one or more cranial sutures
• Growth of brain deforms adjacent bones, resulting in
abnormal calvarial shape
o Growth inhibited at right angles to fused suture
o Compensatory growth of cranium occurs at open
sutures
o Affects all aspects of the craniofacial complex
o Associated shallow orbits result in proptosis
• Both syndromal and non-syndromal forms of
craniosynostosis exist

DDx: Abnormal

Trisomy

18

• Best diagnostic clue
o Abnormal calvarial shape on mid-trimester
ultrasound
• Shape may be severely altered as in
kleeblattschadel ("cloverleaf") skull
o Persistent asymmetry of calvarium
o Proptosis, often severe
o Associated limb defects
• Syndactyly
• Polydactyly
o Associated skeletal abnormalities
• Short limbs
• Scoliosis

Imaging Recommendations
• Best imaging tool
o Prenatal ultrasound in mid-trimester
o Postnatal radiograph
o Postnatal CT scan
• Protocol advice
o 3D ultrasound may help distinguish between
normal molding and craniosynostosis
• Delineation of soft tissue abnormalities
o Fetal MRI best for assessment of brain

Calvarial Shape

Spau/cling

Sign

Neilier

Synclrome

CRANIOSYNOSTOSIS
Key Facts
Terminology
• Premature fusion of one or more cranial sutures
• Growth of brain deforms adjacent bones, resulting in
abnormal calvarial shape
• Both syndromal and non-syndromal forms of
craniosynostosis exist

Imaging Findings
• Abnormal calvarial shape on mid-trimester
ultrasound
• Proptosis, often severe
• Associated limb defects

Top Differential

Diagnoses

• Isolated craniosynostosis
• Apert syndrome (FGFR2)
• Crouzon syndrome (FGFR2)

I DIFFERENTIAL DIAGNOSIS
Isolated craniosynostosis
• Non-syndromal
• Affects single or multiple sutures
• Ultimate cranial shape determined by which suture(s)
fused
• Causative mutations rarely identified in isolated cases

Fibroblast growth factor receptor
(FGFR1,2,3) associated craniosynostosis
• Apert syndrome (FGFR2)
o Acrocephalosyndactyly
o Mental retardation common
o "Mitten" syndactyly of hands, feet with broad distal
phalanx of thumb, great toe
o Midface hypoplasia with malocclusion
o Autosomal dominant - most new cases sporadic
• Crouzon syndrome (FGFR2)
o Autosomal dominant with variable expressivity
o Proptosis +/- divergent strabismus
o Degree of malocclusion highly variable
o Coronal, lambdoid, sagittal synostosis with ridging
o Intellectual function variable
• Pfeiffer syndrome (FGFRl,2)
o Bilateral coronal craniosynostosis
o Midface hypoplasia
o Beaked nasal tip
o Broad and medially deviated thumbs, great toes
o 3 clinical subtypes
• Type 1: Classic with normal - near normal
intelligence, autosomal dominant or sporadic
• Type 2: Kleeblattschadel skull with extreme
proptosis, usually early lethal, sporadic
• Type 3: Severe proptosis without cloverleaf skull,
neurologic compromise, early death, sporadic
• Thanatophoric dysplasia (TD) (FGFR3)
o Lethal skeletal dysplasia
o Type II TD with kleeblattschadel ("cloverleaf" skull)
o Micromelia
o Small chest with pulmonary hypoplasia
• Jackson-Weiss syndrome (FGFR2)

• Pfeiffer syndrome (FGFRl,2)
• Thanatophoric dysplasia (TD) (FGFR3)

Pathology
• Craniosynostosis in -150 genetic disorders
• Prenatal diagnosis possible in some disorders

Clinical Issues
• Age: Syndromal forms often associated with increased
paternal age (new dominant mutations)
• Prognosis dependent upon underlying diagnosis
• Severe craniosynostosis associated with neonatal
death

Diagnostic Checklist
• Abnormal calvarial shape/asymmetry
with other
skeletal findings in syndromal craniosynostosis

• Muenke craniosynostosis (FGFR3)
• Non-classifiable disorders (FGFR2)

TWIST mutation associated craniosynostosis
• Saethre-Chotzen syndrome
o Most common heritable disorder involving coronal
suture synostosis
o Shallow orbits
o Dysplastic ears
o Partial cutaneous syndactyly of fingers, toes
o Ptosis of eyelids
o Most with normal intelligence
• Saethre-Chotzen phenotype with mental retardation
o Large deletions of 7p encompassing TWIST locus

Abnormal steroidogenesis
• Antley-Bixler syndrome
o Choanal atresia
o Radiohumeral synostosis
o Curved femora
o High postnatal mortality
o Autosomal recessive

Unknown

molecular basis

• Carpenter syndrome
o Autosomal recessive
o Kleeblattschadel skull common
o Preaxial polysyndactyly (feet)
o Cardiac defects in 30-50%
o Umbilical hernia/omphalocele
o Variable intellectual capacity
• Postnatal craniosynostosis
o Present with mid-face hypoplasia, hypertelorism
o Signs of increased intracranial pressure

Deformational

plagiocephaly

• Skull asymmetry
• Usually not associated with fusion of sutures
• Cranial molding helmet, behavioral modification

Molding of the head
• Self-limited
• Associated with vaginal birth process

CRANIOSYNOSTOSIS
Neural tube defect
• "Lemon" shaped head associated with Chiari II
malformation

Trisomy 18
• "Strawberry" shaped head

Dolichocephaly
• Associated with intrauterine constraint
o Breech, oligohydramnios
• Some due to sagittal suture synostosis

Metopic ridge without synostosis
• Prominent

ridge without fusion

Fetal demise
• Overlapping

sutures "Spaulding sign"

I PATHOLOGY
General Features
• Genetics
o Craniosynostosis in -150 genetic disorders
o Prenatal diagnosis possible in some disorders
• Molecular diagnosis possible if mutation known
o Mutations in FGFR, TWIST, MSX2 involved in
syndromic craniosynostosis
• Most autosomal dominant or sporadic

• Developmental delay including mental retardation in
50%
• Severe proptosis with corneal scarring, visual loss
• Hydrocephalus
• Hearing loss
• Orthopedic issues: Scoliosis, limb defects
• Non-syndromal cases with milder abnormalities, little
or no clinical sequelae

Treatment
• No prenatal treatment available
• Neurosurgical correction
• Early correction may prevent sequelae of corneal
exposure, increased intracranial pressure
• Cranial molding helmet therapy in milder cases
• Syndromal cases
o Extensive craniofacial surgery
o Other orthopedic or plastic surgical procedures

I DIAGNOSTIC

Image Interpretation

Microscopic

Features

• Zone of osseous obliteration in central portion of
fusion
• Nonlamellar bone across the sutural space
• Zone of partial osseous union involving non lamellar
bone and connective tissue

I SELECTED
1.

2.

3.
4.

5.

ICLINICAL

ISSUES

6.

Presentation
• Most common signs/symptoms
o Abnormal cranial shape
o Cranial asymmetry
• Other signs/symptoms
o Proptosis
o Limb, other skeletal abnormalities

Demographics
• Age: Syndromal forms often associated with increased
paternal age (new dominant mutations)

Natural History & Prognosis
• Prognosis dependent upon underlying diagnosis
• Severe craniosynostosis associated with neonatal death
o Airway obstruction in 40% with severe abnormality
• Midface hypoplasia
• Choana I atresia
• Lower airway obstruction
• Tracheostomy may be required

Pearls

• Abnormal calvarial shape/asymmetry
with other
skeletal findings in syndromal craniosynostosis

Gross Pathologic & Surgical Features
• Gross obliteration of the suture
• Sutural ridging, especially with sagittal and metopic

CHECKLIST

7.

8.

9.
10.

11.

12.
13.

REFERENCES

Adachi M et al: Compound
heterozygous
mutations
of
cytochrome
P450 oxidoreductase
gene (POR) in two
patients with Antley-Bixler
syndrome.
Am J Med Genet.
128A(4):333-9,2004
Blaumeiser
B et al: Prenatal diagnosis
of Pfeiffer syndrome
type II. Prenat Diagn. 24(8):644-6,
2004
Hansen WF et al: Prenatal diagnosis
of Apert syndrome.
Fetal Diagn Ther. 19(2):127-30,2004
Ibrahimi
OA et al: Biochemical
analysis of pathogenic
ligand-dependent
FGFR2 mutations
suggests distinct
pathophysiological
mechanisms
for craniofacial
and limb
abnormalities.
Hum Mol Genet. 13(19):2313-24,2004
Mulliken JB et al: Molecular
analysis of patients with
synostotic
frontal plagiocephaly
(unilateral
coronal
synostosis).
Plast Reconstr Surg. 113(7):1899-909,2004
Nazzaro A et al: Prenatal ultrasound
diagnosis
of a case of
Pfeiffer syndrome
without
cloverleaf skull and review of
the literature.
Prenat Diagn. 24(11):918-22,
2004
Rannan-Eliya
SV et al: Paternal origin of FGFR3 mutations
in Muenke-type
craniosynostosis.
Hum Genet.
115(3):200-7,
2004
Robson CD et al: MR imaging of fetal head and neck
anomalies.
Neuroimaging
Clin N Am. 14(2):273-91,
viii,
2004
Chun K et al: Screening
of patients with craniosynostosis:
molecular
strategy. Am J Med Genet A. 120(4):470-3,2003
Delahaye S et al: Prenatal ultrasound
diagnosis
of fetal
craniosynostosis.
Ultrasound
Obstet Gynecol. 21(4):347-53,
2003
Ghi T et al: Two-dimensional
ultrasound
is accurate in the
diagnosis
of fetal craniofacial
malformation.
Ultrasound
Obstet Gynecol.
19(6):543-51,
2002
Miller C et al: Ultrasound
diagnosis
of craniosynostosis.
Cleft Palate Craniofac].
39(1):73-80,
2002
Cohen MM and MacLean RE, Ed. Craniosynostosis
Diagnosis,
Evaluation
and Management.
Oxford University
Press, New York-Oxford,
2000

CRANIOSYNOSTOSIS
I

IMAGE GALLERY

Typical
(left) Clinical photograph
shows preterm in(ant with
Carpenter syndrome. Note
tht' severe proptosis (auo,,'),
the parietal bulge (curvecl
arrow) and 1mI' wt t'ar (opt'n
aumv) clue to
craniosynostosis.
(Right)
Coronal ultrasoun(1 shm \'5
the same I~'tus Ivith
Carpenter syndmn)(' in Ihe
mid-trimester. Nole tht'
craniosynostosis
o( the
coronal sutures associated
with ridging o( the calvarium
(arrows).

(Left) Axial ultrasound shows
trigonocephaly
(arro\v) clue
to metopic suture synostosis
in a 23 week fetus with
triploidy. (Right) I'roii/e o( a
clilierent inl;lnt with
trigonocephaly
shOll'S a very
prominent metopic ridge
(arrow).

(left) Axidl ultrasound shows
a typical klet'blallsch,'icll'i
skull (arrmvs) in ,J
mill-trim('st('r (etus with type
II thanatolJhoric clysplasid
(TO). Note the parietal bulge
due to synostosis of multiple
sutures. (Right) Clinical
photograph shows a slil/horn
pJdt'rm inl;1I1I with a
kleehlattscAidcl
skull due to
type II TO. Note the occipital
"shelf" (arrow) and frontal
bossing (curved arrow).

VEIN OF GALEN MALFORMATION

Sagittal graphic shows aneurysmal dilatation of the
MP\I, with arterial feeding vessels (arrow). The vein of
Galen malformation (VGM) drains into the straight
sinus.

ITERMINOlOGY
Abbreviations

and Synonyms

• Vein of Galen malformation (VGM)
• Vein of Galen aneurysm
• Misnomer: Actually involves median prosencephalic
vein (MPV) of Markowski

Definitions
• Arteriovenous fistula
o Aneurysmal dilatation
vein of Markowski

of median prosencephalic

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Enlarged midline vascular
structure
• Location: Cistern of velum interpositum and
quadrigeminal plate cistern
• Size
o Variable
• Depends on volume of shunt

Ultrasonographic

Findings

• Grayscale Ultrasound
o Elongated midline cystic structure

Sagittal T2WI MR shows a flow void in a dilated midline
vascular structure, the typical appearance of a VGM
(arrow). In this case, the malformation drains in/a the
straight sinus (curved arrow).

• Extends from quadrigeminal plate cistern
posteriorly toward occiput
• Drains via straight sinus or embryonic falcine
sinus
o Cardiomegaly
o Hydrocephalus
o Enlarged neck vessels
o Hydrops
o Intracranial hemorrhage
• Uncommon but important complication
• Color Doppler
o Confirms mass is vascular
o Turbulent flow
• Pulsed Doppler
o Arterialized flow in MPV
o High velocity, low resistance arterial flow
o Features of hydrops
• Pulsatile umbilical vein flow

MR Findings
• T2WI
o Flow void in arterial feeders
• May be difficult to differentiate from small foci of
hemorrhage
• Hemorrhage high signal on T1WI
o Flow void or mixed signal in MPV due to turbulent
flow

DDx: Vein Of Galen Malformation

Arachnoid

Cyst

Dural AVF

Porencephaly

Venous Congestion

VEIN OF GALEN MALFORMATION
Key Facts
Terminology

Pathology

• Misnomer: Actually involves median prosencephalic
vein (MPV) of Markowski
• Arteriovenous fistula

• Most common
malformation

Imaging Findings

•
•
•
•
•
•

•
•
•
•

Elongated midline cystic structure
Cardiomegaly
Hydrops
Turbulent flow

Top Differential

Diagnoses

• Arachnoid cyst
• Congenital dural arteriovenous
• Porencephaly

Clinical

prenatally

cerebral vascular

Issues

Most common signs/symptoms: Cardiac failure
Most cases detected in third trimester
Prognosis depends on volume of shunt
If survives to birth will need treatment
At birth vascular shunt usually increases
Postnatal cognitive impairment may be present

Diagnostic Checklist
fistula (AVF)

• Color Doppler should always be performed
cystic brain lesion

CT Findings

Choroid plexus cysts

• No role prenatally
o Postnatal imaging findings
• Venous malformation may be slightly hyperdense
• Hydrocephalus
• Parenchymal atrophy
• ± Wall calcification in older children

•
•
•
•

Imaging Recommendations

I PATHOLOGY

• Fetal MRI recommended
o Valuable for postnatal planning
o Better assessment of vascular anatomy
o Evaluate for complications
• Hemorrhage
• Ischemic changes

I DIFFERENTIAL DIAGNOSIS
Arachnoid cyst
• Extraaxial cerebral spinal fluid (CSF) filled lesion
• Displaces adjacent brain
• No Doppler flow

Congenital dural arteriovenous

fistula (AVF)

• lntraparenchymal
cerebral vessels normal in size
• Enlarged meningeal arteries
• Most involve transverse-sigmoid sinuses or torcular

Porencephaly
• CSF-filled intra parenchymal
o Irregular or round shape
• No Doppler flow
• No mass effect
• Hydrocephalus

diagnosed

lesion

Venous sinus engorgement
• Can be seen in high volume states
o Arteriovenous fistulas
• Intracranial
• Elsewhere in body
o Hydrops

on any

Located within choroid plexus
No Doppler flow
Resolves in third trimester
Present in 50% of fetuses with trisomy 18 (TI8)
o Careful search for other signs of T18 warranted

General Features
• Genetics: Sporadic
• Etiology
o Arteriovenous fistula of MPV
o Normally choroid plexus drains via temporary
midline vein (MPV)
o MPV normally regresses in fetal development
• Usually after formation of paired internal cerebral
veins
o High flow through VGM
• Inhibits involution of normal fetal venous
drainage
• MPV persists
• Joins internal cerebral veins to form VGM
• Epidemiology
o Rare
• < 1% of all cerebral vascular malformations
o Most common prenatally diagnosed cerebral
vascular malformation

Gross Pathologic & Surgical Features
• Dilated arterial vessels
• Midline engorged MPV
• Venous drainage
o Straight sinus
o Embryonic falcine sinus
• If embryonic falcine sinus present, straight sinus
usually absent
• Hydrocephalus
o Various theories on etiology

• Compression of the aqueduct
• Venous hypertension

impairing resorption

of CSF

VEIN OF GALEN MALFORMATION
• Ex-vacuo from cerebral atrophy
• Cerebral atrophy
o Secondary to vascular steal phenomenon
o Could also be from chronic venous hypertension

Microscopic

Features

• Direct arterial -+ venous connections
o No intervening capillaries
• Allows rapid, high volume flow
I CLINICAL

I DIAGNOSTIC

ISSUES

CHECKLIST

Consider

Presentation
• Most common signs/symptoms: Cardiac failure
• Most cases detected in third trimester
o Usually> 34 weeks
o Sporadic reports of detection as early as 22 weeks
• Presenting with cardiomegaly
• Cardiomegaly
o May be asymptomatic if shunt small
• Hydrocephalus
• Hydrops from high-output heart failure
o Skin edema
o Ascites
o Pleural effusions
o Pericardial effusion
• Intracranial hemorrhage
• Rarely thrombosis
o Calcifications may be seen in thrombus
• Requires close prenatal follow-up
o Spontaneous vaginal delivery possible
,,0 High perinatal
morbidity and mortality
• Often due to congestive heart failure (CHF)

i)emographiGS.
• Gender: M:F

o Reduce shunt flow
• Improve high-output CHF
o Prevent consequences of chronic cerebral venous
hypertension
o Color Doppler can be used for follow-up
• Assess flow after embolic or surgical treatment
• Emergency embolization may be necessary
o Neonates with refractory CHF

=

• Fetal MRI to assess vascular anatomy

Image Interpretation

I SELECTED
1.
2.

3.
4.

~

2:1

5.

Natural History & Prognosis
• Prognosis depends on volume of shunt
o Worse neonatal prognosis if CHF present at birth
• In utero high-output state
o High-output heart failure
o Hydrops
• If survives to birth will need treatment
• At birth vascular shunt usually increases
o Cessation of flow to low resistance placenta
o Can cause hemodynamic decompensation
• Postnatal cognitive impairment may be present
o Wide range of manifestations
• Delayed milestones
• Mental retardation
o Secondary to chronic hypoxia

6.

7.

8.

9.

10.

Treatment
• No known in utero treatment
• May lead to neonatal death if untreated
o Cardiac failure if shunt is large
• Requires aggressive management
o Medical therapy for CHF
• Usually until 5-6 months of age
• Intervention easier and safer than neonatal

• Eventually requires transcatheter embolization
o Arterial embolization

11.

12.

period

Pearls

• Color Doppler should always be performed on any
cystic brain lesion
o Evaluate for presence of vascular malformation
• Early prenatal detection imperative for aggressive
management
o Requires close sonographic follow-up
o Delivery planning essential

REFERENCES

Gupta AK et al: Vein of Galen malformations: review.
Neural India. 52(1):43-53, 2004
Hartung J et al: Detection of an aneurysm of the vein of
Galen following signs of cardiac overload in a 22-week old
fetus. Prenat Diagn. 23(11):901-3, 2003
Has R et al: Prenatal diagnosis of a vein of galen aneurysm.
Fetal Diagn Ther. 18(1):36-40, 2003
Messori A et al: Prenatal diagnosis of a vein of Galen
aneurysmal malformation with fetal MR imaging study.
AJNR Am J Neuraradiol. 24(9):1923-5; author reply 1925,
2003
Paternoster DM et al: Prenatal diagnosis of vein of Galen
aneurysmal malformations. Fetal Diagn Ther. 18(6):408-11,
2003
Sepulveda W et al: Vein of galen malformation: prenatal
evaluation with three-dimensional
power Doppler
angiography. J Ultrasound Med. 22(12):1395-8, 2003
Heling KS et al: Prenatal diagnosis of an aneurysm of the
vein of Galen with three-dimensional
color power
angiography. Ultrasound Obstet Gynecol. 15(4):333-6,
2000
Lee TH et al: Prenatal depiction of angioarchitecture
of an
aneurysm of the vein of Galen with three-dimensional
color power angiography. Ultrasound Obstet Gynecol.
15(4):337-40, 2000
Chisholm CA et al: Aneurysm of the vein of Galen:
prenatal diagnosis and perinatal management. Am J
Perinatol. 13(8):503-6, 1996
Doren M et al: Prenatal sonographic diagnosis of a vein of
Galen aneurysm: relevance of associated malformations for
timing and mode of delivery. Ultrasound Obstet Gynecol.
6(4):287-9, 1995
Sepulveda W et al: Prenatal diagnosis of cerebral
arteriovenous malformation using color Doppler
ultrasonography: case report and review of the literature.
Ultrasound Obstet Gynecol. 6(4):282-6, 1995
Tessler FN et al: Cranial arteriovenous malformations in
neonates: color Doppler imaging with angiographic
correlation. AJR Am J Roentgenol. 153(5):1027-30, 1989

VEIN OF GALEN MALFORMATION
IIMAGE

GALLERY
(Left) Axial oblique
ultrasound shows a midline
cystic structure (arrow).
Hydrocephalus (open arrow
indicates dangling choroid)
and hydrops are present with
scalp edema (curved arrow).
(Right) Axial ultrasound
through the fetal chest
confirms hydrops with
marked cardiac enlargement,
a small pericardia I effusion
(arrow), and skin edema
(curved arrow).

(Left) Color Doppler
ultrasound in the same case
demonstrates blood flow
within this cystic structure,
excluding an arachnoid cyst
and porencephaly. It is
essential to perform color
Doppler on all cystic masses
to evaluate for a vascular
malformation. (Right) Pulsed
Doppler ultrasound depicts
turbulent arterial flow within
a feeding vessel, confirming
an arteriovenous fistula.

(Left) Axial T2WI MR shows
an elongated, midline mass
with flow void (arrow).
There are areas of low signal
in the surrounding white
matter (curved arrow). II is
difficult to differentiate
arterial feeders from areas of
hemorrhage without T I WI.
(Right) Coronal gross
pathology shows the
collapsed, dilated vein
(arrow). There are diffuse
ischemic changes (R > L),
with areas of hemorrhage
(curved arrow) correlating
with the fetal MRI.

ARTERIOVENOUS

Graphic shows the effect of an intraaxial vascular
malformation on the dural veins (arrows) which can be
dramatically enlarged over the surface of the brain. This
feature is well shown on T2WI.

ITERMINOlOGY
Abbreviations
• Arteriovenous
• Arteriovenous

and Synonyms
fistula (AVF)
malformation (AVM)

Definitions
• Abnormal connection of intracranial
o Arterial to venous connection
o No intervening capillary network

vessels

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Enlarged vessels with alternating
direction of flow on color Doppler

Ultrasonographic

Findings

• Grayscale Ultrasound
o Macrocephaly
• Volume of shunt vessels
• Hydrocephalus
o Microcephaly
• Implies cortical atrophy
• May occur secondary to premature
sutures
o Ischemic changes

closure cranial

FISTULA

Coronal T2WI MR through anterior brain shows
enlarged dural veins (curved arrows) on the surface of
the brain displacing the left cerebral hemisphere
(arrows) from the skull vault.

• Ventriculomegaly
• Peri ventricular leukomalacia
• Porencephaly
o Malformation
• "Tangle" of dilated vessels
• Cyst-like structure on grayscale images
• May be intra parenchymal
• Dural AVF more commonly reported in fetus
• Enlarged meningeal arteries
• Shunt to transverse/sigmoid
sinuses or torcular
o Intracranial hemorrhage
o Enlarged neck vessels
o Cardiomegaly
o Hydrops may develop if sufficient shunt volume
• Hepatomegaly
• Ascites
• Pleural effusion
• Pericardial effusion
o Polyhydramnios
o Intrauterine growth restriction
• Color Doppler
o Alternating red and blue within vessel cross section
o Forward and backward shunt flow
• Pulsed Doppler
o High velocity, low resistance arterial flow
o Arterialized venous structures
o Features of hydrops
• Pulsatile umbilical vein flow

DDx: Extra-Axial Cystic Mass

Arachnoid Cyst

Arachnoid Cyst

Vein Of Galen

Vein Of Galen

ARTERIOVENOUS

FISTULA

Key Facts
Imaging Findings

Pathology

• Best diagnostic clue: Enlarged vessels with alternating
direction of flow on color Doppler
• Cortical atrophy
• Porencephaly
• Intracranial hemorrhage
• Periventricular leukomalacia
• "Tangle" of dilated vessels
• Enlarged neck vessels
• Hydrops may develop if sufficient shunt volume
• Polyhydramnios

•
•
•
•

Top Differential

Diagnoses

• Vein of Galen malformation
• Vascular tumor
• Intracranial cyst

(VGM)

• 3D

o May be helpful to determine
o Map feeding vessels

full extent

MR Findings
• Shunt vessels
o Plow voids on T2WI
• Ischemia
o Peri ventricular leukomalacia
• Increased signal in periventricular white matter on
T2WI
o Cortical atrophy
• Increased subarachnoid space
o Ventriculomegaly
o Porencephaly
o Successful diffusion weighted imaging (DWI) has
been performed in a fetus
• Abnormal signal on DWI in fetal study
• Correlate with severe cortical necrosis on
postnatal study
• Intracranial hemorrhage
o Blood products
• High signal T1 WI
• Low signal T2WI
o Grade as for germinal matrix hemorrhage in
neonates
• Subependymal
• Intraventricular
• Intraventricular with hydrocephalus
• Parenchymal
o Subdural hemorrhage
• May present as space occupying lesion
• MRI will confirm blood products
• Corpus callosum often abnormally thin

Imaging Recommendations
• Best imaging tool
o Petal MRI delineates vessels involved
o Ischemic damage better seen than with US
• Protocol advice
o Careful survey for other anomalies
o Pormal fetal echocardiography

Ischemic brain injury
High-output cardiac failure
Majority of fetal vascular malformations are VGM
Dural sinus malformations commonest after VGM

Clinical Issues
• No intra-uterine intervention
• Early delivery does not prevent ischemic damage

Diagnostic Checklist
• Petal MRI
• DWI may be more sensitive to ischemia than T2WI
• Careful search for AVM in fetuses with apparent
isolated cardiomegaly
• Always check Doppler of apparent intracranial cyst

• Cardiomegaly and right heart enlargement not
necessarily due to high output state
o Monitor for hydrops
• Cannot predict which fetuses will develop
hydrops
• Some high flow lesions well tolerated
• Small, relatively low flow lesions may progress
rapidly
• Doppler for tricuspid regurgitation
• Serial measurements of heart to chest
circumference (HC/CC) ratio
• Progressive cardiac enlargement precedes frank
hydrops

I DIFFERENTIAL DIAGNOSIS
Vein of Galen malformation

(VGM)

• Specific type of arteriovenous fistula
o Vein of Galen malformation actually a misnomer
o Aneurysmal dilatation of median prosencephalic
vein of Markowski
• Elongated midline cystic structure extends from
quadrigeminal plate cistern toward occiput
• Drains via straight sinus or embryonic falcine sinus

Vascular tumor
• Solid mass component even if necrotic
• Dilated draining veins unlikely
• Enlarged neck vessels unlikely

Intracranial

cyst

• Extra-axial fluid-filled lesion
• No Doppler flow
• Rarely associated with ischemic lesions

Fetal anemia
• High velocity flow in middle cerebral artery
• No associated draining veins
• No enlarged neck vessels

Venous distension
• Rare cases with diffuse cerebral venous dilatation
• No arterial shunt or venous thrombosis identified

ARTERIOVENOUS
• Good prognosis if no parenchymal

injury

I PATHOLOGY
General Features
• Genetics: Not associated with aneuploidy
• Etiology
o Ischemic brain injury
• Vascular "steal" phenomenon
• Hydrops =:> hypoperfusion, hypoxia
• Direct compression of AVM limits brain perfusion
=:> atrophy
• Venous hypertension =:> hemorrhage
• Venous thrombosis
o High-output cardiac failure
• Decreased coronary blood flow
• Myocardial ischemia +/- infarction
• Epidemiology
o Majority of fetal vascular malformations are VGM
• 92% of reported cases
o Dural sinus malformations commonest after VGM

Microscopic

Features

• Periventricular leukomalacia
• Diffuse micro infarction

I CLINICAL

o May wish to avoid caesarian section if confirmed
ischemic brain damage
• Not shown to be advantageous in VGM
• No benefit to fetus
• Additional morbidity for mother
• Early delivery does not prevent ischemic damage
o Prematurity adds to risks for infant
• For survivors consider
o Embolization
o Surgery

I DIAGNOSTIC

CHECKLIST

Consider
• Fetal MRI
o Full extent of lesion
o Hemorrhage
o Ischemic damage
• DWI may be more sensitive to ischemia than T2WI

Image Interpretation

Pearls

• Careful search for AVM in fetuses with apparent
isolated cardiomegaly
• Always check Doppler of apparent intracranial cyst
o AVM immediately apparent on color Doppler
o Prognosis very different from lesions such as
arachnoid cyst

ISSUES

Presentation
•
•
•
•

FISTULA

Hydrops
Ventriculomegaly
Polyhydramnios
Most AVFspresent late
o Typically in third trimester
o May have had a normal early scan

Natural History & Prognosis
• No recurrence risk
• Prognosis depends on associated findings
o Hydrops
o Brain injury
o Additional anomalies
• High perinatal mortality rate when fetus is
"symptomatic"
• No published outcome data available on non-VGM
cases
o Authors personal experience of two cases
• One neonatal demise
• One severe encephaloclastic changes with cerebral
palsy

Treatment
• No intra-uterine intervention
• Prenatal consultation with pediatric neurology
o Discuss potential treatment options
o Discuss risk of neurological impairment
• Prenatal consultation with pediatric cardiology
o Discuss potential additional congenital heart disease
o Discuss management of high output cardiac failure
• Deliver at tertiary center
• No consensus on mode of delivery

I SELECTED

REFERENCES

Strigini FA et al: Second-trimester diagnosis of intracranial
vascular anomalies in a fetus with subdural hemorrhage.
Prenat Diagn. 24(1):31-4, 2004
2. Hartung J et al: Detection of an aneurysm of the vein of
Galen following signs of cardiac overload in a 22-week old
fetus. Prenat Diagn. 23(11):901-3, 2003
3.
Kush ML et al: Lethal progression of a fetal intracranial
arteriovenous malformation. J Ultrasound Med.
22(6):645-8, 2003
4.
Baldoli C et al: Demonstration of acute ischemic lesions in
the fetal brain by diffusion magnetic resonance imaging.
Ann Neurol. 52(2):243-6, 2002
5. Heling KS et al: Prenatal diagnosis of an aneurysm of the
vein of Galen with three-dimensional color power
angiography. Ultrasound Obstet Gynecol. 15(4):333-6,
2000
6.
Lee TH et al: Prenatal depiction of angioarchitecture of an
aneurysm of the vein of Galen with three-dimensional
color power angiography. Ultrasound Obstet Gynecol.
15(4):337-40,2000
7.
Keck C et al: Fetal cerebral AV-malformation and
cardiomegaly, diagnostic and therapeutic problems. J
Perinat Med. 26(3):225-30, 1998
8. Sepulveda W et al: Prenatal diagnosis of cerebral
arteriovenous malformation using color Doppler
ultrasonography: case report and review of the literature.
Ultrasound Obstet Gynecol. 6(4):282-6, 1995
9. Sekhon LH et al: Syndactyly and intracranial arteriovenous
malformation: case report. Br J Neurosurg. 8(3):377-80,
1994
10. Dan U et al: Prenatal diagnosis of fetal brain arteriovenous
malformation: the use of color Doppler imaging. J Clin
Ultrasound. 20(2):149-51,1992
11. Koven MB et al: Fetal intracranial AVM presenting as
enlarged cardiac chamber. J Ultrasound Med. 11(4):177,
1992
1.

ARTERIOVENOUS

FISTULA

IIMAGE GALLERY
Typical
(Left) Axial ultrasound in a
fetus referred for possible
holoprosencephaly shows a
cystic area (arrow) mistaken
for a monoventricle. The
"cyst" was extra-axial and
two hemispheres were seen
on other scan planes. (Right)
Sagittal color Doppler
ultrasound of the same fetus
shows swirling red and blue
color secondary to turbulent
flow in this dural
arteriovenous malformation.
Always check for flow in
apparent cysts.

(Left) Axial T2WI MR in the
same case shows a large flow
void (open arrow)
correlating with the
abnormal color Doppler
findings and the grayscale
"cyst". Note
ventriculomegaly and
cortical atrophy (curved
arrows) due to vascular
"steal". (Right) Axial T2WI
MR through the markedly
dilated superior sagittal sinus
(arrow) also shows a tangle
of abnormal vessels on the
cerebral surface (curved
arrow).

Variant
(Left) Sagittal T2WI MR of

the fetal brain shows a large
mixed-signal, extra-axial mass
(arrows). Areas of
hemorrhage and
porencephaly were also
present. A thrombosed dural
AVM was confirmed at birth.
(Right) Sagittal T2WI MR in a
Down syndrome fetus shows
a hyperextended neck and
dramatically enlarged venous
sinuses (arrows) secondary
to an intracardiac shunt.
There was arterialized
venous flow on Doppler but
no AVM was present.

CNSTUMORS

Axial ultrasound of an intracranial teratoma shows a
predominately solid, echogenic, midline mass (arrow),
which is causing obstructive hydrocephalus
(curved
arrow).

ITERMINOLOGY
Definitions
• Benign or malignant

IIMAGING

intracranial

neoplasm

FINDINGS

General Features
• Best diagnostic clue: Solid intracranial mass with
Doppler flow
• Location
o Most are supratentorial
• Contrasts with pediatric tumors which are more
commonly infra tentorial
o Most common sites of origin
• Pineal gland
• Suprasellar area
• Cerebral hemispheres
o Precise point of origin can often not be determined
o May extend through skull base into oral cavity
• Size
o Often massive
o May exhibit rapid growth over short period of time
• Morphology
o Gross distortion of cerebral architecture
o Intratumoral hemorrhage may cause further
distortion

DDx: Intracranial

Hemorrhage

Gross pathology in same case shows a variegated,
lobular mass (arrows) with marked
thinning of
remaining cerebral tissue (curved arrow). Histology
confirmed a teratoma. (Shown in Radiographies, ref 7).

• Hydrocephalus
o Most often obstructive from mass
o May be from over production with choroid plexus
papillomas
• Polyhydramnios
o Decreased swallowing from hypothalamic
dysfunction
• Hydrocephalus or polyhydramnios
may present before
tumor is sonographically detectable
• Intratumoral hemorrhage not uncommon

Ultrasonographic

Findings

• Considerable overlap in appearance of tumor types
o Differentiation often not possible or even necessary
• Teratoma
o Most common tumor
o Complex masses with cystic and solid components
o Calcifications
o Typically midline
o May fill entire cranial vault
• May extend through skull base into mouth
• Astrocytoma
o Solid tumors
o Arise in cerebral hemispheres
• Marked contradistinction
to pediatric
astrocytomas, which are most common in the
cerebellum
• Craniopharyngioma

"Mass"

Intra vent Hemorrhage

Arachnoid Cyst

C/ioependymal

Cyst

CNSTUMORS
Key Facts
Imaging Findings
• Best diagnostic clue: Solid intracranial mass with
Doppler flow
• Most are supratentorial
• Contrasts with pediatric tumors which are more
commonly infratentorial
• Precise point of origin can often not be determined
• May exhibit rapid growth over short period of time
• Hydrocephalus or polyhydramnios
may present
before tumor is sonographically detectable

Top Differential

Diagnoses

• Intracranial hemorrhage
• Arachnoid cyst

Pathology

•
•
•
•
•

Astrocytoma
Lipoma
Choroid plexus papilloma
Craniopharyngioma
Primitive neuroectodermal

tumor

Clinical Issues
• Macrocephaly from hydrocephalus, tumor, or both
• Large size portends grave prognosis regardless of
histology
• Lipomas and choroid plexus papillomas have better
prognosis

Diagnostic Checklist
• Underlying neoplasm should always be considered
setting of spontaneous intracranial hemorrhage

in

• Teratoma
o Suprasellar mass
o Heterogeneous complex mass
o Frequently calcify
o Indistinguishable from teratoma
• Choroid plexus papilloma
o May occur anywhere in ventricular system
• Lateral ventricle most common
o Well-defined, lobular, hyperechoic mass
o Hydrocephalus from over production of cerebral
spinal fluid (CSF)
• Rapid onset
o Mass may also obstruct ventricle causing asymmetric
enlargement
• Lipoma
o Well-defined, echogenic mass
o Midline or lateral ventricles
o Up to SQ°;(} of midline lipomas associated with
agenesis of the corpus callosum
• Absent cavum septi pellucidi
• Colpocephaly (teardrop-shaped ventricles)
• Elevation of 3rd ventricle creating "trident" shape
in coronal plane

MR Findings
• Better for delineating anatomy
• Can confirm fat in lipoma
o Can better evaluate for associated agenesis of the
corpus callosum
• Sensitive modality for detecting hemorrhage

Imaging Recommendations
• Best imaging tool: Fetal MRI
• Protocol advice
o Color Doppler essential to look for flow
• Variable degrees of vascularity
o Important to distinguish from intracranial
hemorrhage
• Intracranial tumors have propensity to bleed
• Carefully evaluate periphery of mass
o Close surveillance if pregnancy continued
• Often very rapid growth
• Worsening hydrocephalus
• Macrocephaly

o Fetal MRI to evaluate anatomic

I DIFFERENTIAL

extent

DIAGNOSIS

Intracranial hemorrhage
• May be intra parenchymal, intraventricular
subdural/ su barach noid
• Variable echogenicity
• Disorganized appearance of brain
• No flow with Doppler
• Evolves over time
o Porencephaly

or

Arachnoid cyst
•
•
•
•

Purely cystic
Extra-axial mass
No solid component
More common over cerebral convexities
fossa

Glioependymal

and posterior

cyst

• Purely cystic
• No solid component
• More common in midline
o Associated with agenesis of the corpus callosum
• Proteinaceous fluid
o High signal on T1 WI

Choroid plexus cysts
•
•
•
•
•

May be confused with choroid plexus papilloma
Cystic, not solid
Resolve on follow-up examination
No hydrocephalus
Associated with trisomy 18
o Multiple major anomalies
o Clenched hands
o Cardiac defects
o Early, severe intrauterine growth restriction (lUGR)

CNSTUMORS

• Genetics
o Sporadic
o No recurrence risk
• Epidemiology
o Rare
o 10% of antenatal neoplasms
• In contradistinction
to pediatric population where
brain tumors are the most common solid tumor
• Extracranial teratomas, neuroblastoma and soft
tissue tumors are all more common in fetus
• Associated abnormalities
o 50% of lipomas have agenesis of corpus callosum
o 14% of other tumors have other anomalies
• Cleft lip/palate most common

o Far worse than pediatric brain tumors
• Large size portends grave prognosis regardless of
histology
o Benign tumors equally as lethal as malignant ones
o Two important exceptions
• Lipomas and choroid plexus papillomas have
better prognosis
• Choroid plexus papilloma
o Surgical resection often possible
o Survival rate 73%
o Significant neurologic deficits reported
• Psychomotor retardation
• Seizures
• Spastic quadriparesis
• Lipoma
o Best prognosis of all intracranial tumors
o Often asymptomatic

Microscopic

Treatment

I PATHOLOGY
General Features

Features

• Histologic types in order of occurrence
o Teratoma
• Contains all three germ cell layers
• Ectoderm, mesoderm, endoderm
• Approximately 50% of fetal CNS tumors
o Astrocytoma
• Neuroglial tumors
• Vary from well-differentiated to
poo rIy-d ifferen tia ted
o Lipoma
• Benign fatty tumor
• Located in subarachnoid space
• Prevalence underestimated
in pathologic series
• lO°IcJ of prenatal tumors
• Smallest intracranial tumor
• Average diameter 1.6 cm
o Choroid plexus papilloma
• Arise anywhere there is choroid plexus
• Produces CSF
• Generally benign
• Choroid plexus carcinoma has been reported
• 5-9'X)of fetal tumors
o Craniopharyngioma
• Arise from Rathke pouch, an ectodermal
diverticulum from roof of mouth
o Primitive neuroectodermal
tumor
• Highly malignant small-cell tumor
• Derive from neural crest

I CLINICAL

• Termination offered
• Supportive care
• Cephalocentesis
o At onset of labor for vaginal delivery
o Has been used therapeutically to reduce
hydrocephalus
• Improvement in survival reported
• Cesarean section may be required to prevent dystocia
• Postnatal
o Surgical resection often not possible
o Radiation contraindicated
• Severe adverse effect on normal brain growth and
development
o Chemotherapy
o Survivors left with significant psychomotor deficits

I DIAGNOSTIC

Image Interpretation

1.

2.

• Most common signs/symptoms
o Macrocephaly from hydrocephalus, tumor, or both
o Most commonly present in 3rd trimester
• Very rapid growth potential
• May have had normal scan as recently as 2 weeks
prior

5.

Natural History & Prognosis

8.

• Dismal prognosis
o In utero demise common
o 97% mortality if diagnosed

9.

before 30 weeks

in

I SELECTED REFERENCES

4.

Presentation

Pearls

• Underlying neoplasm should always be considered
setting of spontaneous intracranial hemorrhage

3.

ISSUES

CHECKLIST

6.
7.

Woodward
PJ et al: From the archives of the AFIP: a
comprehensive
review of fetal tumors with pathologic
correlation.
Radiographies.
25(1 ):215-42, 2005
Cavalheiro
5 et al: Fetal brain tumors. Childs Nerv Syst.
19(7-8):529-36,2003
Isaacs H J r: I. Perinatal brain tumors: a review of 250 cases.
Pediatr Neurol. 27(4):249-61,
2002
Isaacs H Jr: II. Perinatal brain tumors: a review of 250 cases.
Pediatr Neurol. 27(5):333-42,
2002
Mazewski CM et al: Neonatal brain tumors: a review.
Semin Perinatol. 23(4):286-98,
1999
Rickert CH: Neuropathology
and prognosis of foetal brain
tumours. Acta Neuropathol
(Berl). 98(6):567-76,
1999
Schlembach
D et al: Fetal intracranial
tumors detected by
ultrasound:
a report of two cases and review of the
literature. Ultrasound
Obstet Gynecol. 14(6):407-18,
1999
Heckel 5 et al: Prenatal diagnosis of a congenital
astrocytoma:
a case report and literature review.
Ultrasound
Obstet Gynecol. 5(1):63-6, 1995
Buetow PC et al: Congenital
brain tumors: a review of 45
cases. AJR Am J Roentgenol.
155(3):587-93,
1990

CNSTUMORS
I IMAGE GALLERY
Typical
(Left) Coronal ultrasound
shows a cystic extra-axial
mass. This could be
con/used with an arachnoid
cyst but note there is
extension 0/ the mass
through the skull base
(arrow). An echogenic solid
component
(curved arrow)
is also seen, making
arachnoid cyst unlikely.
(Right) Axial ultrasound
con/inns a solt tissue
component
with loci 0/
calcification (arrow).
Autopsy conlirmed a cystic
teratoma.

(Left) Axial ultrasound shows
a complex, midline mass
with both cystic and solid
components
(arrows) with
associated obstructive
hydrocephalus
(curved
arrow). (Right) Axial T7 WI
MR shows marked
gadolinium enhancement
01
the solid components
01 this
tumor (arrow). There has
been worsening 0/ the
hydrocephalus
since the
prenatal study. Histology
conlirmed a teratoma.

(Left) Sagittal ultrasound 0/ a
choroid plexus papilloma
shows a well-defined,
lobular, hyperechoic mass
within the atrium 0/ the
lateral ventricle (arrows).
Hydrocephalus
is the result
0/ over-production
0/ CSF.
(Right) Coronal ultrasound 0/
a lipoma within the
interhemispheric
fissure
(arrow). 50% 0/ cases have
associated agenesis 0/ the
corpus callosum, and
thorough evaluation 0/
midline structures is
essential. (Shown in
Radiographies, rei 7)

SECTION 3: Spine

Introduction
Spine Development

and Overview

& Imaging

3-2

Spine
Spina Bifida
Iniencephaly
Caudal Regression Sequence
Kyphosis, Scoliosis
Sacrococcygeal Teratoma

3-6

3-10
3-14
3-18
3-22

SPINE DEVELOPMENT & IMAGING

Sagittal ultrasound how the normalthoraci
kyphosi
(arrows) and lumbar lordosi (open arrows) of the spine
111 a mid-trimester fetus.

agittal ultrasound of the thoracic and cervical spine
how
the normal cervical lordo is (arrow) in a
mid-trime t r few .

Ilmaging Anatomy

MRI

Ultrasound

• Ultra ound typically used for characterization of f tal
o eou abnormalities
• Useful for identifying anatomy in difficult to image
patients
o Maternal obe ity
o Oligohydramnios
o Unfavorable fetal position
o hiari II brain findings by ultrasound
• Look for subtle TO not identified by onography
• an aid in identification of exact level of defect
o Level of TO has ignificant affect on progno i
• an help document extent and origin of spinal ma e
o haracterization of sacrococcygeal teratoma
• May use to visualize pinal cord
• ormal T2WI appearance
o Hypointen e vertebral bodie
Ilyperinten e disk spaces

•

agittal view
o Echogenic curvilinear structure
• ervicallordosis
• Thoracic kyphosis
• Lumbar lordosis
o Posterior elements s en ju t under skin
o V rt bral body 0 sification center deep to anechoic
pinal canal
• Later in ge tation echogenic spinal cord may be
vi ualized in spinal canal
• Axial view
3 os ification centers een in second trime ter
• Vertebral body and 2 lateral ma ses
• Lat ral ma -+ transver e process, spinous proce ,
articular proc ss
Ossification vi ible onographically by 16 weeks
o Lower lumbar 0 ification may not be seen until 19
weeks
Third trime ter di tinct bony anatomy can be
idenlifi d
• Vertebral body
• P di I

• Laminae
• Transverse proces
• pinous processes
o "Teepee" appearance of po terior vertebral body
• Inward angulation of posterior arch element
• Coronal view
o May be useful if v rtebral anomalies detected
• haracteriz extent of involvement
o Posterior element app ar as paired echog nic lines
• Flared at cervical pine
• Slight widening at lumbar spine
• Tapered at acrum
• Echogenic linear kin covering the distal spine should
be document d
o Ex lude ubtle neural tube defect ( TO)

IAnatomy-Based

Imaging Issues

Imaging Protocols
• American In titute of Ultrasound in Medicine (AlUM)
pine valuation
o Axial and longitudinal views
• ervical
• Thora i
• Lumbar
• Sacral
• Real-time evaluation important for spinal defe ts
o arefully can entire pine in axial plane
o learing lumbosacral area very important a mo t
common ite for pina bifida
• on sider performing endovaginalultra
ound
exam if fetus is breech

Imaging Pitfalls
• Oi tal pine ossification not vi ible until 19 week
ge tation
o Ma fal ely suggest TD prior to ossification
• cou tic shadowing of distal spine from iliac wing

SPINE DEVELOPMENT & IMAGING
Key Facts
Imaging Issues
• Scan entire spine in longitudinal and axial planes
• Visualization of distal spine tip and skin covering
crucial
o Can otherwise miss small NTD
• Lumbosacral area most common location NTD
o Posterior arch elements should angulate inward
o If cannot adequately visualize entire spine, normal
posterior fossa with normal MSAFP is reassuring
• 999'\1of spinal NTD have Chiari II findings
• Consider performing endovaginal ultrasound exam if
fetus is breech

Imaging Pitfalls

o Avoid incorrect diagnosis of small NTD

Serum Screening For NTD
• MSAFP screening usually performed at 16-18 weeks
• ONTD allows AFP to escape fetal circulation and enter
amniotic fluid
o Subsequent rise in MSAFP
o Larger lesions cause greatest elevation
o Skin covered defects will not be detected
• Role of sonography
o Establish dates
• Incorrect dates common cause of t MSAFP
o Rule out multiple gestations or demise
o If MSAFP is elevated and dates correct, careful
search for 0 TD and other anomalies warranted

• Lower lumbar spine may not be visibly ossified until
19 weeks

o May simulate NTD
o Axial views should clear any confusion
• Always look at posterior fossa
o 99% of spina bifida have Chiari II findings
• Cerebellar compression
• Cisterna magna obliteration

Normal Measurements
• Routine measurements not required by AlUM
• Spine length measurements
o Correlate with fetal growth parameters at 11-14
weeks gestation

I Embryology
Embryologic Events
• 3rd-4th week
• Spinal cord development
o Neural plate converted to hollow neural tube
(neurulation)
o Neural folds meet dorsally to form neural canal
• Subsequently invaginates into posterior body wall
o losure of neural tube occurs bidirectionally
• audal neuropore becomes spinal cord
o Caudal neuropore closes day 26
• Occurs in craniocaudal direction
• Finishes at level of superior sacrum
o Inferior sacrum and coccyx formed by secondary
neurulation from caudal eminence
• 4th week
• Vertebral column formation
o Sclerotome cells migrate and surround neural tube
and notochord
• Ventral portion -+ rudimentary vertebral body
• Dorsal portion -+ rudimentary vertebral arch
o Sclerotomes split into cranial and caudal segments
o Spinal nerves grow out between split segments
o Cranial segment of sclerotome recombines with
caudal segment of sclerotome above
• Forms early vertebral body
• 5th week

• Costal processes elongate in thoracic region to become
ribs

Practical Implications
• Abnormal induction
defects

of sclerotomes

causes spinal

I Clinical Implications
Clinical Importance
•

eural tube defects (NTDs)
o Abnormal induction of vertebral arch rudiments
o Failure of closure in 3rd week of development
o Milder defect results in meningocele or
myelomeningocele
o In more severe defects neural folds fail to fuse,
differentiate, invaginate, and separate from surface
ectoderm
• Cranial NTD -+ anencephaly
• Caudal NTD -+ rachischisis or myeloschisis
• Occipital/upper spinal NTD -+ inionschisis
• Entire neural tube does not close -+
craniorachischisis totalis
• Scoliosis
o Defective induction of vertebral bodies on one side
of body
o Can also be secondary to hemivertebra
• Diastematomyelia
o Longitudinal division of vertebral canal by bony,
fibrous, or cartilaginous septum
o Variable length of involvement
o May be associated with other vertebral body
anomalies
o Multiple theories of pathogenesis

Serum Screening
• Maternal serum alpha-fetoprotein
(MSAFP)
o Alpha-fetoprotein
(AFP) is a glycoprotein produced
first by yolk sac and later by fetal liver and
gastrointestinal tract
• Major serum protein in embryo
o Fetal plasma levels peak 10-13 weeks

SPINE DEVELOPMENT & IMAGING

Axial NECT of a gravid trauma patient shows the normal
ossification centers of the fetal spine, which are
composed of the vertebral body (curved arrow) and
paired lateral masses (arrows).

• A small amount accumulates in amniotic fluid
• Early: Diffusion through skin
• Later: Excreted by kidneys ~ fetal urine ~
amniotic fluid
o Peak amniotic fluid AFP (AFAFP) 12-15 weeks
o Placental permeability to fetal plasma proteins
causes increase in MSAFP
• Maternal serum levels are a small fraction of fetal
and amniotic fluid levels
• MSAFP continues to increase to 32 weeks despite
decreasing fetal plasma AFP (likely reflects
increasing placental permeability)
• Screening for neural tube defects
o Open neural tube defects (ONTO) allow AFP to
escape fetal circulation and enter amniotic fluid
• Subsequent rise in MSAFP
o Larger lesions cause greatest elevation
• Greater surface area for plasma protein to "weep"
into amniotic fluid
• Largest elevations with anencephaly
• Virtually all cases of anencephaly and open spina
bifida detectable by MSAFP
o Skin covered defects will not be detected
• 20% of spina bifida
• 80-90% of encephaloceles
o Screening usually performed at 16-18 weeks
o Results expressed as multiples of the median (MoM)
• 2.0-2.5 MoM cutoff
• 2.0 MoM; 85-90% detection rate of ONTO, 4-6%
false-positives
• 2.5 MoM; 75-80% detection rate of ONTO, 2-3%
false-positives
• Given accuracy and non-invasive nature of
ultrasound, consider using lower value to prompt
evaluation
• Median value for anencephaly 6.5 MoM
• Median value for open spina bifida 3.8 MoM
o Appropriate dating is critical
• Variation of 2 weeks may cause erroneous results
o Epidemiologic variations
• MSAFP higher in obese women and
African-Americans

Axial ultrasound shows the corresponding sonographic
appearance. The posterior elements angle inward
(arrows). The developing pedicles are obscured by
shadowing. (curved arrow - vertebral body)

• MSAFP lower in insulin dependent diabetics
• Role of sonography
o First establish dates
• Incorrect dates common cause of t MSAFP
o Rule out multiple gestations or demise
o Look for cause t MSAFP
• ONTO
• Abdominal wall defects: Gastroschisis,
omphalocele, body stalk anomaly
• Prior hemorrhage
• Role of amniocentesis
o Consider when ultrasound results are negative
o Measure amniotic fluid AFP
o Acetylcholinesterase
(AchE), neural tissue specific

I Related
1.
2.
3.
4.

5.

6.
7.
8.

9.
]0.

References

Barnewolt CE et al: Sonography of the fetal central nervous
system. Neuroimaging Clin N Am. 14(2):255-71, viii, 2004
Simon EM: MRI of the fetal spine. Pediatr Radiol.
34(9):712-9,2004
Weisz Bet aJ: Prenatal sonographic diagnosis of
hemivertebra. J Ultrasound Med. 23(6):853-7, 2004
prenatal
Aaronson as et al: Myelomeningocele:
evaluationucomparison
between transabdominal
US and
MR imaging. Radiology. 227(3):839-43, 2003
Griffiths PO et al: Postmortem MR imaging of the fetal and
stillborn central nervous system. AJ RAm J Neuroradiol.
24(1):22-7, 2003
Hubbard AM: Ultrafast fetal MRI and prenatal diagnosis.
Semin Pediatr Surg. 12(3):143-53, 2003
De Biasio Pet al: Spine length measurement in the first
trimester of pregnancy. Prenat Diagn. 22(9):818-22, 2002
Mangels KJ et al: Fetal MRI in the evaluation of
intrauterine myelomeningocele.
Pediatr Neurosurg.
32(3):124-31,2000
Larsen WJ: Human embryology.
ew York, Churchill
Livingstone. 65-91, 1993.
Haddow JE: Prenatal screening for open neural tube
defects, Down's syndrome, and other major fetal disorders.

Semin Perinatal. 14(6):488-503, 1990

SPINE DEVELOPMENT

& IMAGING

IIMAGE GAllERY
(Left) Coronal ultra ound of
the upper cervical spine and
skull base shows the typical,
gentle flare of the pedicles
(arrows). (Right) Axial
ultrasound of the cervical
spine shows the posterior
elements converging to form
a "teepee" (arrow). There is
marked posterior shadowing
from the vertebral body
(curved arrow).

(Left) Coronal ultrasound
shows the typical tapered
appearance of the distal
spine and sacrum in the
second trimester. Shadowing
from the iliac wing can
simulate an inferior NTD
(arrows). (Right) Sagittal
ultrasound shows a thin,
echogenic line of skin
overlying the tip of the spine
(arrows). Documentation of
this skin covering is essential
to exclude an open neural
lUbe defect.

(Left) Coronal 30 ultrasound
of a 76 week fetus shows the
length of spine from the
upper thoracic area through
the sacrum. (Right) Sagittal
T2WI MR performed prior to
autopsy on a 3rd trimester
fetus shows the normal
hyperintense disk spaces
(arrows) and hypointense
vertebral bodies (open
arrow). The spinous
processes are also identified
(curved arrow).

SPINA BIFIDA

Graphic of spina bifida classification. Meningoceles
(arrow) contain only fluid while myelomeningoceles
also contain neural elements (curved arrow). The defect
is uncovered in myeloschisis (open arrow).

3D
ultrasound
multiplanar
capability
allows
simultaneous views of a meningocele (arrows) in sagittal
(top) and axial (bottom) projections. The sac extends
from the canal (open arrow) and contains only fluid.

ITERMINOlOGY

Ultrasonographic

Abbreviations

• Vertebral findings
o Splayed dorsal ossification centers
• Normally lateral masses are parallel or convergent
o Transverse view best for seeing bony defect
• "V" shaped vertebra on axial view
o Coronal view best for evaluating extent of defect
• Multiple levels usually involved
• Use ribs to identify 12th thoracic level
o Sagittal view best for seeing soft tissue sac
• 80% with overlying sac
o Meningocele
• Anechoic cystic mass
• Sac contains meninges only
• Rarely covered by intact skin
o Myelomeningocele
• Complex cystic mass
• Sac contains meninges + neural elements
• 20% with no overlying sac
o Myeloschisis
• Open spinal cord is part of defect
• Calvarial findings: 99% have Chiari II malformation
o Cisterna magna obliteration
• Most common finding
• Usually fluid-filled cisterna -magna is gone or small

•
•
•
•

and Synonyms

Open neural tube defect
Myelomeningocele
Spinal dysraphism
Spina bifida aperta

Definitions
• Bony vertebral defect + neural content exposure
o Dorsal arch defect most common

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Chiari II malformation
o Splayed dorsal ossification centers
o Myelomeningocele sac
• Location
o 73% lumbar
o 17% sacral
o 9% thoracic
o 1% cervical
• Size: Variable
• Morphology: Depends on location and type of defect

«

Findings

3 mm)

o Cerebellar compression

DDx: Dysmorphic

SC Teratoma

Spine

SC Teratoma

Amniotic Bands

SPINA

BIFIDA

Key Facts
Terminology

• Almost 100% of cases are detectable

• Open neural tube defect
• Myelomeningocele
• Bony vertebral defect + neural content exposure

Top Differential

Imaging Findings

Clinical Issues

•
•
•
•
•
•
•
•

• t Maternal

Splayed dorsal ossification centers
Myelomeningocele
sac
73(rll lumbar
Transverse view best for eeing bony defect
Use ribs to identify 12th thoracic level
80% with overlying sac
Calvarial findings: 99% have hiari II malformation
Usually fluid-filled cisterna magna is gone or small «
3 mm)
• 24% clubfoot
• 40% with additional anomalies

•

•

•

•

•

• "Banana sign" = cerebellum curved around
midbrain
• Absent cerebellum rare
o Ventriculomegaly
• Atrial width ~ 10 mm
• Borderline or mild most common
• 55% at time of diagnosis
• 33% progress during pregnancy
• 90% at birth
o Frontal bone scalloping
• Lemon shaped calvarium
• Found in 1% of normal fetuses
• Usually resolves by third trimester
Lipomeningomyelocele
o Spine defect + canal lipoma
o Echogenic mass
o Chiari II signs may be absent
o Associated tethered cord common
Spina bifida occulta
o Small bony defect covered by skin
o Rarely diagnosed in utero
o Overlying soft tissue abnormalities
• Subcutaneous lipoma
• Tuft of hair
• Skin dimple
o Usually asymptomatic
Ventral spina bifida
o Extremely rare
o Splitting of vertebral body
• Lower cervical or upper thoracic
o Associated neuroenteric cyst
Common associated anomalies
o Scoliosis and kyphosis
• Seen at level of defect
o Lower extremity anomalies
• 24% clubfoot
• Rockerbottom foot
• Hip dislocation
40% with additional anomalies
o 67% aneuploid fetuses have other anomalies

MR Findings
• Not for primary diagnosis

Diagnoses

• Sacrococcygeal teratoma
• Amniotic bands

(SC teratoma)

serum alpha-fetoprotein
(AFP)
• Preventive treatment with folic acid

Diagnostic Checklist
• Genetic amniocentesis
• Presence of normal cisterna magna nearly eliminate
diagno is
• ranial markers easier to see than spine defect
• Attempt to identify level of defect

o Helpful if ultrasound visualization
• Required before fetal surgery

poor

Imaging Recommendations
• Best imaging tool
o Second trimester screening ultrasound
• Almost 100% of cases are detectable
• Cranial findings most helpful for diagnosis
• Protocol advice
o Look carefully at spine when cisterna magna is small
or absent
o Serial ultrasound when diagnosis made
• Ventriculomegaly/club
foot may develop
o Offer genetic amniocentesis for all cases
o Consider three dimensional ultrasound
• Multiplanar capacity

I DIFFERENTIAL

DIAGNOSIS

Sacrococcygeal teratoma

(SC teratoma)

• Germ cell neoplasm
• Exophytic mass extending from sacrum
o Rarely purely cystic
o May be internal or external
• No associated Chiari II malformation

Isolated scoliosis/kyphosis
• Abnormal curvature of spine
• Usually from anterior vertebral body anomaly
o Hemivertebrae
o Fused vertebrae

Amniotic bands
• Entrapment of fetal parts by disrupted amnion
• Asymmetric distribution
• Spine involvement asymmetric and bizarre
o Associated scoliosis common
• Spine finding rarely isolated

SPINA
I PATHOLOGY
General Features
• Genetics
o 14% aneuploidy rate
• Trisomy 18 (TI8)
• Trisomy 13 (TI3)
• Triploidy
• Translocation
o 4% aneuploidy rate when isolated
• Etiology
o Mostly sporadic and multifactorial
o Folate deficiency
• Folate metabolic pathway gene defect
o Teratogens
• Anticonvulsants: Carbamazepine, valproic acid
• 1% risk
o Arrhaphia theory
• Primary failure of neuropore closure
• Absent skin/muscle from failed induction
o Hydromelic theory
• Cerebrospinal fluid (CSF) imbalance
• Excess CSF accumulates in closed neural tube
• Secondary separation of dorsal wall
o Lower extremity abnormalities
• From unopposed muscle group action
• Epidemiology
o 0.4:1,000
o 3% of all spontaneous abortions
o 1-2% recurrence risk
• Associated abnormalities: 40%

Gross Pathologic & Surgical Features
• Dorsal arch defect with exposed neural elements

Staging, Grading or Classification Criteria
• Ventral defects
o Extremely rare
• Dorsal defects
oSpina bifida aperta (85%)
oSpina bifida occulta (15%)

I CLINICAL

BIFIDA
o 35% live born die within first 5 yrs
o 50% with IQ > 80
o In utero findings do not predict outcome
• Obstructive hydrocephalus
o From posterior fossa compression
• Musculoskeletal dysfunction
o 25% complete lower limb dysfunction
• Gastrointestinal/genitourinary
dysfunction
o 17% with normal continence

Treatment
• Cesarean section delivery at term
o ! Infection rate
sac rupture rate
o !Meningomyelocele
• Immediate postnatal surgery
o Cover exposed spinal cord
o Treat hydrocephalus
• 80% need ventriculoperitoneal
shunt
• In utero surgery in clinical trials
o !Shunt dependence
• 54% vs. 80%
o Paralysis and incontinence rates unchanged
o t Preterm delivery risk
• Preventive treatment with folic acid
o Preconceptual therapy best
o 4 mg/day reduces risk of recurrent neural tube defect
by 70%
o 0.4 mg/day for all women

I DIAGNOSTIC
Consider

• Genetic amniocentesis

Image Interpretation

Demographics
• Age
o Advanced maternal age (AMA) at slightly higher risk
• AMA ~ 35 yrs at time of delivery
• Secondary to association with T18 and T13
• Ethnicity
o United States data
• Hispanic> Caucasian, African-American, Asian
• Difference persists after immigration
o Highest rates in United Kingdom
o Lowest rates in Japan

Natural History & Prognosis
• Depends on level and severity of defect

REFERENCES

1.

BiggioJRJr et al: Fetal open spina bifida: a natural history
of disease progression in utero. Prenat Diagn. 24(4):287-9,

2.

Bruner JP et al: Intrauterine repair of spina bifida:
preoperative predictors of shunt-dependent hydrocephalus.
Am J Obstet Gynecol. 190(5):1305-12,2004
Mitchell LEet al: Spina bifida. Lancet. 364(9448):1885-95,

Presentation
• Most common signs/symptoms
(AFP)
o t Maternal serum alpha-fetoprotein
• > 2.5 multiples of median (MOM) detects 80%

Pearls

• Presence of normal cisterna magna nearly eliminates
diagnosis
• Cranial markers easier to see than spine defect
• Attempt to identify level of defect

I SELECTED
ISSUES

CHECKLIST

2004

3.

2004

4.
5.

Sepulveda W et al: Chromosomal abnormalities in fetuses
with open neural tube defects: prenatal identification with
ultrasound. Ultrasound Obstet Gynecol. 23(4):352-6,2004
Babcook CJ et al: Prevalence of aneuploidy and additional
anatomic abnormalities in fetuses with open spina bifida:
population based study in Utah. J Ultrasound Med.
19(9):619-23;

6.

quiz 625-6, 2000

Babcook CJ et al: Prenatally detected fetal
myelomeningocele: is karyotype analysis warranted?
Radiology. 194(2):491-4, 1995

SPINA BIFIDA
IIMAGE GALLERY
(Leh) Axial ultrasound of
myeloschisis.
The vertebra is
"V" shaped as posterior
elements (arrows) are
divergent. There is no
overlying skin (open arrows
point to intact skin) and no
overlying sac. (Right) Sagittal
T2WI MR in another
myeloschisis case shows a
large spinal defect without a
sac (curved arrow). Also,
there is cerebellar tonsil
herniation (open arrow)
indicating Chiari II
malformation.

(Left) Sagittal ultrasound
shows a cervical spine
myelomeningocele.
The sac
(arrows) contains neural
elements (curved arrows).
Communication
with the
spinal canal through the skin
and bony defect are well
seen (open arrow). The fetal
head is to the left and the
chest is to the right. (Right)
Clinical photograph in the
same case shows the large
cervical myelomeningocele.
The sac is covered by
meninges.

(Left) Axial ultrasound of the
cranium shows Chiari II
malformation.
The
cerebellum is banana-shaped
(arrows) as it wraps around
the midbrain. The cisterna
magna is obliterated. The
calvarium is lemon-shaped
(open arrows) and the
ventricles are dilated. (Right)
Coronal ultrasound in
another fetus shows bilateral
club feet (arrows). These
secondary anomalies are
commonly seen with spina
bifida.

INIENCEPHALY

Graphic shows
defect (arrow),
(open arrow).
(curved arrow)

features of iniencephaly including a skull
encephalocele
and spinal dysraphism
There are missing and fused vertebrae
causing an exaggerated cervical lordosis.

Ultrasound of a /2 week gestation shows marked
hyperextension of the head (arrow). The body appears
small secondary to the shortened neck. These are first
trimester features of iniencephaly.

ITERMINOLOGY

Ultrasonographic

Abbreviations

• First trimester
o Hyperextension of head
o Crown-rump length (CRL) less than expected
o Head appears large in relation to body
• Body shortened from absent vertebral bodies
• Cervical spine
o Fixed exaggerated lordosis
• > 150
• Face turned upward creating "stargazer"
appearance
o Large neural tube defect which may extend to
involve thoracic and lumbar spine (rachischisis)
o Short neck
• Vertebrae are missing or fused
• Causes angulation
• Face
o Orbits directed upward ("stargazer")
o "Flattened" appearance
• Mandibular skin contiguous with chest
o Cleft lip/palate in some cases
• Other brain anomalies frequently present
o Anencephaly
o Microcephaly
o Hydrocephalus
o Dandy-Walker continuum
o Holoprosencephaly

and Synonyms

• "Stargazer" malformation

Definitions
• Extensive open neural tube defect (ONTD)
characterized by
o Defect in occipital bone and inion
o Occipital encephalocele
o Spinal dysraphism
o Fixed hyperextension of head

IIMAGING

FINDINGS

General Features
• Best diagnostic clue
o Combination of findings is diagnostic
• Fixed cervical hyperextension
• Cephalocele
• Spina bifida
• Location
o Inion and cervical spine always involved
o Dysraphism often extends into thoracic and even
lumbar area

0

DDx: Iniencephaly

Cervical MMC

Cervical Teratoma

Findings

INIENCEPHALY
Key Facts
Imaging Findings
•
•
•
•
•
•
•
•
•
•
•

Crown-rump length (CRL) less than expected
Head appears large in relation to body
Body shortened from absent vertebral bodies
Fixed exaggerated lordosis
Face turned upward creating "stargazer" appearance
Large neural tube defect which may extend to involve
thoracic and lumbar spine (rachischisis)
Short neck
Vertebrae are missing or fused
Mandibular skin contiguous with chest
Polyhydramnios common
Routine views in midtrimester should detect all cases

Top Differential Diagnoses
• Cervical hyperextension
• Klippel-Feil syndrome
• Body malformations common
o Gastrointestinal
• Omphalocele
• Diaphragmatic hernia
o Genitourinary
• Hydronephrosis
• Polycystic kidneys
o Cardiac defects
o Musculoskeletal
• Caudal regression sequence
• Clubfoot
o Single umbilical artery
o Polyhydramnios common
• Depressed swallowing

MR Findings
• Not necessary for diagnosis
• Consider if ultrasound evaluation is limited
• Sagittal view can give complete picture
o Skull base defect
o Encephalocele
o Spinal defect
o Vertebral anomalies better seen

Imaging Recommendations
• Best imaging tool
o Endovaginal ultrasound in first trimester
o Routine views in mid trimester should detect all cases
• First trimester
o Look at proportion of head to body
o Persistent hyperextension of head throughout exam
o Midline sagittal plane best
• Head position
• Relative size of head to body
• Thorough evaluation of spine
o Scan in multiple planes
o Attempt to count cervical vertebrae
• Follow-up examination
o Isolated hyperextension without ONTD may resolve

• Cervical myelomeningocele
• Encephalocele

(MMC)

Pathology
• M:F=1:9

• Microcephaly and anencephaly
associations

most common

Clinical Issues
• Lethal malformation
• Hyperextension may cause dystocia
• Consider early induction

Diagnostic Checklist
• CRL < expected is not always incorrect dates
• May be diagnosed in late first trimester
• Hyperextension may be transient finding

I DIFFERENTIAL DIAGNOSIS
Cervical hyperextension
• Head held in extension throughout exam
• No structural abnormalities detected
o Resolves on follow-up exam ~ normal outcome
o Persistent finding
• 73% normal
• 27% unsuspected anomalies at delivery

Klippel-Feil syndrome
•
•
•
•
•

Cervical vertebral fusion
Short, webbed neck
Neck hyperextended
NoONTD
Some consider mildest form of iniencephaly

Cervical myelomeningocele (MMC)
• Defect involves cervical spine only
• Cranium intact

Encephalocele
• Defect involves cranium only
• Cervical spine intact

Jarcho-Levin syndrome
• Vertebral anomalies
• Rib anomalies
• Small thorax

Masses causing hyperextension of head
•
•
•
•
•
•
•
•

Cervical teratoma
Goiter
Lymphangioma
Nuchal cord
Uterine leiomyomas
Uterine malformations
Multiple gestations
Cranium and cervical spine intact in all of above

INIENCEPHALY

I PATHOLOGY

• Most stillborn
• Recurrence risk 1-4%

General Features

Treatment

• Genetics
a Sporadic inheritance pattern
a Not associated with syndromes
a Has been reported with trisomy 13
• Etiology
o Unknown
o Shares common risk factors with other ONTD
• Epidemiology
o 0.1-6:10,000 births
• Higher incidence in United Kingdom
o M:F = 1:9
• Associated abnormalities
o In up to 85%
o Marked disorganization of central nervous system
• Microcephaly and anencephaly most common
associations
• Migrational abnormalities
• Polymicrogyria
o Virtually every organ system may be involved
• Embryology
o Two proposed mechanisms
o Primary failure of anterior neuropore to close
• Occurs slightly later than in anencephaly
o Persistent embryonic cervical lordosis
• Developmental arrest in 3rd week
• Cervical spine is normally retroflexed at this time
• Persistent retroflexion results in failure of neural
tube closure

•
•
•
•

Gross Pathologic & Surgical Features
• Defect always involves foramen magnum
• Cervical dysraphism
o May extend to thoracic and lumbar spine
• Two types described
o Iniencephaly clausus
• No associated encephalocele
• May rarely be skin covered
o Iniencephaly apertus
• Encephalocele present
• Most common type

CHECKLIST

Consider
• CRL < expected is not always incorrect dates
o May be early indicator of neural tube malformation
o Transvaginal ultrasound must be performed to
evaluate embryo
• May be diagnosed in late first trimester

Image Interpretation Pearls
• Hyperextension may be transient finding
o Should alert for careful evaluation for structural
abnormalities
o Follow-up to document resolution

1.

of many neural tissues

IClINICALISSUES
Presentation
• Most common signs/symptoms
a First trimester
• CRL < expected
o Second trimester
• Obvious neural tube defect
• Other signs/symptoms
o Elevated maternal serum alpha-fetoprotein
o Polyhydramnios

I DIAGNOSTIC

I SELECTED REFERENCES

Microscopic Features
• Significant disorganization

No treatment
Termination offered
Supportive care for family
Hyperextension may cause dystocia
o Consider early induction
o Cesarian section to be avoided
• Preconceptual folic acid should be given for future
pregnancies
o 4 mg/day beginning at least 1 month prior and
continuing through first trimester
• Decreases risk of all ONTD by approximately 70%
o 0.4 mg/day recommended for all women attempting
pregnancy

(MSAFP)

Natural History & Prognosis
• Lethal malformation
o Case reports of long term survivors with mild
clausus form

Cuillier F et al: Transvaginal sonographic diagnosis of
iniencephaly apertus and craniorachischisis at 9 weeks'
gestation. Ultrasound ObstetGynecol. 22(6):657-8, 2003
2. Rousso 0 et al: Prenatal ultrasonographic diagnosis of
iniencephaly. J Obstet Gynaecol. 23(5):572-3, 2003
3. Jeanne-Pasquier C et al: [Iniencephaly: four cases and a
review of the literature] J Gynecol Obstet Bioi Reprod
(Paris). 31(3):276-82, 2002
4. Phadke SRet al: Prenatal diagnosis of iniencephaly and
alobar holoprosencephaly with trisomy 13 mosaicism: a
case report. Prenat Diagn. 22(13):1240-1, 2002
5. Bald S et al: Prenatal diagnosis in three cases of
iniencephaly with unusual postmortem findings. Prenat
Diagn. 21(7):558-62, 2001
6. Loo CK et al: CNS findings in iniencephaly: case report and
literature review. Pathology. 33(1):112-5, 2001
7. Marton T et al: Diagnosis of an unusual form of
iniencephaly in the first trimester of pregnancy.
Ultrasound Obstet Gynecol. 18(5):549-51,2001
8. Sahid S et al: Iniencephaly: Prenatal diagnosis and
management. Prenat Diagn. 20:202-5, 2000
9. Shipp TO et al: The prognostic significance of
hyperextension of the fetal head detected antenatally with
ultrasound. Ultrasound Obstet Gynecol. 15:391-6, 2000
10. Dogan MM et al: Iniencephaly: sonographic-pathologic
correlation of 19 cases. J Perinat Med. 24(5):501-11, 1996
11. Rodriguez MM et al: Cluster of iniencephaly in Miami.
Pediatr Pathol. 11(2):211-21, 1991
12. Shoham Z et al: Iniencephaly: Prenatal ultrasonographic
diagnosis--a case report. J Perinat Med. 16:139-43, 1988

INIENCEPHALY
IIMAGE GALLERY
(Left) Sagittal ultrasound
shows hyperextension of the
fetal head with discontinuity
of the occipital bone (arrow)
and an encephalocele
(curved arrow). There was
associated spinal
dysraphism. (Right) Cross
pathology in the same case
shows the typical head
positioning, with the eyes
directed upward
("stargazer"). Note the
shortened neck with the chin
contiguous with the chest. A
portion of the large open
neural tube defect is seen
(arrow).

Typical
(Left) Axial ultrasound of the
lumbar spine in the same
case shows splaying of the
posterior elements (arrows).
There is rachischisis with
exposed neural tissue
(curved arrow). (Right) Axial
ultrasound shows inferior
continuation of the spinal
defect (curved arrow) to the
level of the iliac wings
(arrow).

Typical
(Left) Cross pathology from
the case above confirms the
large ONTO extending from
the skull base to the sacrum.
(Right) Sagittal postmortem
T2WI MR in a different case
showing typical features of
iniencephaly. The spine is
markedly abnormal with
missing and fused vertebrae
(arrows) and a large cranial
and spinal defect (open
arrow). There is marked
retroflexion of the neck and
the eyes are held in the
"stargazer" position (curved
arrow).

CAUDAL REGRESSION

Graphic illustrates several features of caudal regression
sequence including abnormal lower extremity position
with muscle wasting, shortened spine (curved arrow),
and medial positioning of the iliac wings (arrows).

ITERMINOlOGY
Abbreviations
•
•
•
•
•

and Synonyms

Caudal regression sequence (CRS)
Caudal dysplasia
Caudal aplasia
Sacral agenesis
Axial mesodermal dysplasia spectrum
o Additional midline craniofacial anomalies

Definitions
• Varying degrees of distal neural tube disruption
o Spectrum includes agenesis of distal neural tube
o Severe cases may involve thoracic spine
o May have lumbar agenesis with preserved sacral and
coccygeal vertebrae

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Absent sacrum with hypoplastic
lower extremities is diagnostic

Ultrasonographic

Findings

• First trimester findings
o Short crown-rump length
o "Protuberance" of lower spine

SEQUENCE

Ultrasound shows characteristic appearance
of the
lower extremities in the "cross-legged tailor" position.
There was no lower extremity movement
during
prolonged scanning.

o Increased nuchal translucency
o Abnormal yolk sac
• Second and third trimester findings
o Abrupt termination of spine
• Seen best on sagittal section
• Looks as if spine has been "rubbed out"
o No spine visible on axial views of abdomen
o Iliac wings approximated or fused
• "Shield" appearance
• Decreased interspace between femoral heads
o Short trunk
o Clubfeet
o Lower extremity contractures: "Crossed-legged
tailor" or "Buddha" pose
o Normal to increased amniotic fluid
o Associated gastrointestinal (GI) anomalies
• Anorectal atresia
• Duodenal atresia
o Associated central nervous system (CNS) anomalies
• Chiari II malformation
o Associated genitourinary (GU) anomalies
• Cystic renal dysplasia
• Dilated bladder, hydronephrosis
• Penoscrotal inversion
• Penile agenesis
• Cryptorchidism
o Congenital heart disease (CHD)

DDx: Spine + limb Anomaly

Spina Bifida

Spina Bifida

VACTERL

Arthrogryposis

CAUDAL REGRESSION

SEQUENCE

Key Facts
Imaging Findings
• Best diagnostic clue: Ab nt sacrum with hypoplastic
lower extremitie i diagnostic
• Wedge- haped or tapered termination of cord is
classic feature
• Short crown-rump length
• Abrupt termination of pine
•
0 pine vi ible on axial views of abdomen
• Iliac wing approximat d or fused
• Lower extr mity contracture:
"Crossed-legged tailor"
or "Buddha" po e
• Cannot confidently rule out < 18 weeks
• Mild as s easily mis d

Top Differential

Diagnoses

• Myelomeningocele
• VA TERL as ociation

MR Findings
• Potential benefit for associated anomalies especially
with maternal obesity
o Confirms absent or disorganized distal ossification
centers
o Shows cord termination
• Wedge-shaped or tapered termination of cord is
classic feature
• Dorsal edge of taper longer than ventral
• Anterior and posterior roots separated at level of
cauda equina
o May demonstrate additional defects
• Myelocystocele
• Syringomyelia
• Intraspinal arachnoid cyst
• Tethered cord

Imaging Recommendations
• Protocol advice
o First trimester endovaginal scan in diabetics
• Particularly important if poor perigestational
glycemic control
• Verify dates
• Look for abnormal contour of lower spine area
o Beware "tapering" distal spine in fetus at risk for CRS
• May taper where it terminates even if not at
sacrum
• Normal sagittal spine tapers to a point at level of
fetal buttock
o Coronal section shows ribs, count down lumbar
segments to show five present
o Axial view at level iliac crests best to show sacrum
o Sacrum not well ossified until mid second trimester
• Cannot confidently rule out < 18 weeks
• Mild cases easily missed
o Fetal echocardiography
• Should be routine with maternal
insulin-dependent
diabetes
• Strong association with cardiovascular anomalies

• Sirenomelia
• rthrogryposi

-akine ia sequenc

Pathology
• 1% of infants born to diabetic mothers have caudal
regression sequence (CRS)
• 12-16% infants with CRS have diabetic mothers
• Poor glycemic control thought to be etiologic factor

Clinical Issues
• Described a early as 11 week ge tation
• lligh mortality due to associated anomalies

Diagnostic Checklist
• Fetal MRI may be helpful,
p ially in the obese
patient
• Always check for spine 0 ification centers in an axial
can lane at level of iliac win s

I DIFFERENTIAL

DIAGNOSIS

Myelomeningocele
•
•
•
•

Ossification centers present
Posterior elements splayed
Look for meningocele sac
Associated with Chiari II malformation
o Obliteration of cisterna magna
o "Banana" cerebellum
o "Lemon" sign: Bifrontal concavity

VACTERl association
• Combination

of abnormalities,

including

some or all

of

o Vertebral
o Anorectal
o Cardiac
o Tracheoesophageal fistula
o Renal
o Limbs
• Not associated with maternal

diabetes

Sirenomelia
• Renal agenesis
• Single fused lower extremity

Arthrogryposis-akinesia

sequence

• Spine normal
• May involve lower extremities only
• Not associated with maternal diabetes

Segmental spinal dysgenesis
• Probably part of same spectrum as CRS
• Thin or indiscernible cord at dysgenetic level
• Bulky cord segment caudal to abnormality

I PATHOLOGY
General Features
• General path comments
o Embryology
• Defective blastogenesis

CAUDAL REGRESSION
• Originates in primary developmental
• Internal organ derangement
• Associated axial skeleton anomalies
• Distal neural tube fails to form
• Genetics: Occasional familial cases
• Epidemiology

field

SEQUENCE

• Aim for proper seating and standing without
amputation, if possible

I DIAGNOSTIC

CHECKLIST

o M:F = 1:1

Consider

o 1-5/100,000

• Fetal MRI may be helpful, especially in the obese
patient
o Allows more accurate parental counseling

o 1% of infants born to diabetic mothers have caudal
regression sequence (CRS)
o 12-16% infants with CRS have diabetic mothers
• Poor glycemic control thought to be etiologic
factor
o Drug use in pregnancy
• Reported cases with minoxidil,
trimethoprim -sulfamethoxazole

Gross Pathologic & Surgical Features
• Spectrum
o Abnormal sacrum with normal lower extremities
o Absent sacrum
o Abnormal lower lumbar spine, occasional thoracic
spine involvement
o Clubfeet
o Flexion deformities hips/knees
o "Cross-legged tailor" or "Buddha" pose
o Decreased or absent lower extremity movement
• Sirenomelia no longer considered part of this sequence
o Fused lower extremities
o Renal agenesis
o Anhydramnios
o Vascular defect as cause
o Lethal

Image Interpretation

I SELECTED
1.

2.
3.

4.

5.
6.

I CLINICAL

ISSUES

7.

Presentation
• Described as early as 11 weeks gestation
• May affect only one of twin pair

8.

Natural History & Prognosis

9.

•
•
•
•
•

10.

Similar to high/mid lumbar myelomeningocele
Neurogenic bladder
Motor deficit> sensory
High mortality due to associated anomalies
Survivors have normal intellectual function

Treatment
• Prenatal
o Maternal diabetes testing
o No fetal intervention
• Postnatal
o Urologic consultation
• Sacral anomaly determines bladder dysfunction
• Neurogenic bladder
• Reflux nephropathy
• Aim to prevent progressive renal dysplasia
o Orthopedic surgery
• Clubfeet
• Contractures
• Spine instability
• Hip dislocation

Pearls

• Always check for spine ossification centers in an axial
scan plane at level of iliac wings
• In diabetics with poor periconceptional glycemic
control, perform endovaginal ultrasound for accurate
dating and anatomic assessment
o Shortening of torso suggestive of CRS

11.

12.

13.

14.

15.

REFERENCES

Versiani BR et al: Caudal dysplasia sequence: severe
phenotype presenting in offspring of patients with
gestational and pregestational diabetes. Clin Dysmorphol.
13(1):1-5,2004
Basu Set al: Syringomyelia in caudal dysplasia sequence. J
Assoc Physicians India. 51:820-3, 2003
De Biasio P et al: Ossification timing of sacral vertebrae by
ultrasound in the mid-second trimester of pregnancy.
Prenat Diagn. 23(13):1056-9, 2003
Martins JL et al: Anorectal anomaly associated with caudal
regression: late evaluation after posterior sagittal
anorectoplasty. Pediatr Surg Int. 19(1-2):106-8,2003
PariUa BV et al: Antenatal detection of skeletal dysplasias. J
Ultrasound Med. 22(3):255-8; quiz 259-61, 2003
Rojansky N et al: Extreme caudal agenesis. Possible
drug-related etiology? J Reprod Med. 47(3):241-5, 2002
Bohring A et al: Polytopic anomalies with agenesis of the
lower vertebral column. Am J Med Genet. 87(2):99-114,
1999
Fukada Y et al: Caudal regression syndrome detected in a
fetus with increased nuchal translucency. Acta Obstet
Gynecol Scand. 78(7):655-6, 1999
Cortes D et al: Cryptorchidism as a caudal developmental
field defect. A new description of cryptorchidism associated
with malformations and dysplasias of the kidneys, the
ureters and the spine from T10 to S5. APMIS.
106(10):953-8, 1998
Subtil D et al: Early detection of caudal regression
syndrome: Specific interest and findings in three cases. Eur
J Obstet Gynecol Reprod Bioi 80:109-12, 1998
Depraetere M et al: Severe axial mesodermal dysplasia
spectrum in an infant of a diabetic mother. Genet Couns.
6(4):303-7, 1995
Rossi R et al: Extreme hypotrophy of the lower body pole,
extensive hypoplasia of the spinal column and multiple
anomalies of abdominal organs: a maximal variant of the
caudal regression sequence? Clin Dysmorphol. 4(1):87-92,
1995
Adra A et al: Caudal regression syndrome:
Etiopathogenesis, prenatal diagnosis and perinatal
management. Obstet Gynecol Surv 49:508-16, 1994
Boemers TM et al: Urodynamic evaluation of children with
the caudal regression syndrome (caudal dysplasia
sequence). J Urol. 151(4):1038-40, 1994
Baxi L et al: Early detection of caudal regression syndrome
with transvaginal scanning. Obstet Gynecol. 75(3 Pt
2):486-9, 1990

CAUDAL REGRESSION
IIMAGE

SEQUENCE

GALLERY
(Left) Coronal ullrasound
shows apparent normal
tapering of the spine
(arrow). Maternal obesity
limited visualization,
howevel; it was clear that
the tapering occurred a very
short distance from the
lowest ribs. (Right) Sagittal
ultrasound in the same fetus
(top) shows "rubbed out"
appearance of the lumbar
spine (open arrow) at the
level of the iliac wing.
Compare this to the normal
gently tapered
sacrococcygeal curve
(bottom - curved arrow).

(Left) Sagittal T2WI MR
shows abrupt termination of
the thoracic cord with
characteristic wedge shape
(curved arrow). Dilated
spinal canal (arrow) thought
to represent an associated
terminal myelocystocele.
Infant died within hours of
birth. (Right) Axial
endovaginal ultrasound
(EVUS) shows the "shield"
appearance caused by fusion
of the iliac wings (arrows).
EVUS is particularly useful in
obese patients if the fetus is
in breech position.

(Left) Clinical photograph of
liveborn infant with caudal
regression sequence. Note
the small pelvis with the
typical" Buddha" or
"cross-legged tailor" position
of the lower extremities.
There is muscle alrophy
(arrows) from abnormal
innervation. (Right) Frontal
radiograph of a severe
caudal regression case with
no spine formed distal to T7.
Note fusion of the iliac wings
(arrow). This gives rise to the
"shield" sign on ullrasound.

KYPHOSIS, SCOLIOSIS

Coronal ultrasound shows isolated triangle-shaped
hemivertebra at T72 (arrows). The level of defect is
identified since the 72th rib (open arrow) is seen
attaching to the hemivertebra.

• Coronal for scoliosis
• Sagittal for kyphosis
o Identify level of defect
• Use ribs to identify 12th thoracic level
• Isolated vertebral body anomaly (5%)
o Hemivertebrae
• Only half of vertebral body develops
• Triangular bone acts as wedge
o Butterfly vertebrae
• Two hemivertebra side by side
• Central nonfusion
o Block vertebra
• Vertebral fusion
• Body or dorsal elements or both
• Hemivertebra may fuse
• Rectangular large vertebra
• Symmetric or asymmetric appearance
• CS more often with asymmetric fusion
o Diastematomyelia
• Posteriorly directed spur from vertebral body
• 3 dorsal bones on transverse view (2 is normal)
• Spinal cord splits around spur
• Difficult diagnosis in utero
o Vertebra anomaly without CS
• Scoliosis may develop with time
o Multiple levels
• Multiple dysmorphic vertebrae
• "Jumbled spine"

ITERMINOLOGY
Abbreviations

and Synonyms

• Congenital scoliosis (CS)
• Hemivertebra

Definitions
• Scoliosis
o Abnormal lateral spine angulation
• Kyphosis
o Abnormal anterior spine angulation
• Kyphoscoliosis
o Kyphosis + scoliosis

IIMAGING

FINDINGS

General Features
• Location: Anywhere in spine
• Size: Single or multiple levels
• Morphology
o Acute angle
o Long abnormal curve
• May be more difficult to detect

Ultrasonographic

Findings

• Abnormal spine angulation
o Longitudinal views best

DDx: Dysmorphic

Radiograph after delivery in the same case confirms the
T72 hemivertebra (arrow). This abnormal vertebra
causes only minimal scoliosis. However, spinal
curvature often progresses with time.

Spine

.
, 1
••••

;' J'"

~
Caudal Regression

Amniotic Bands

Inicncephaly

.' ~

..

KYPHOSIS, SCOLIOSIS
Key Facts
Terminology

Top Differential

•

•
•
•
•

ongenital

scoliosis (CS)

Imaging Findings
•
•
•
•
•
•
•
•
•
•
•

Longitudinal views best
Hemivertebrae
Butterfly vertebrae
Block vertebra
"Jumbled spine"
Associated anomalies (95%)
Spina bifida
VA TERL association
Amniotic band syndrome
Beware of positional curvature
Consider MR in difficult ca es

o No Chiari II malformation when isolated
• Normal calvarial posterior fossa
• Associated anomalies (95%)
oSpina bifida
• Most common cause of CS (60%)
• Abnormal curvature is at level of defect
• 80% lumbosacral
o VACTERL association
• Vertebral anomalies
• Anal atresia
• Cardiovascular anomalies
• Tracheoesophageal fistula
• Esophageal atresia
• Renal anomalies
• Limb anomalies
• Renal, cardiac and limb defects most obvious
• Atresias/fistula often missed
o Amniotic band syndrome
• Amniotic membrane rupture
• Fetus entangled in amnion
• Scoliosis + amputation
• Bizarre body wall defects
o Rib deformities
• Common with thoracic CS
• Fused ribs
• Concave hemithorax
• Difficult diagnosis in utero
• Beware of positional curvature
o Normal fetus in atypical position
• No bony defect
• Resolves with time
• Often seen in 3rd trimester
o Oligohydramnios
• Consider MR to rule out associated anomalies

MR Findings
• MR helpful when ultrasound limited
o Maternal body habitus
• MR may show associated spina bifida
o Oligohydramnios
• Often with VACTERL association

Diagnoses

Caudal regres ion equence
Iniencephaly
Sacrococcygeal teratoma (SC teratoma)
Arthrogryposis

Clinical Issues
•
•
•
•
•

M:F = 1:3
Thoracic insufficiency
Prophylactic surgery
orrective surgery
Expansion thoracopla

syndrome

ty

Diagnostic Checklist
• Amniotic fluid AFP if spina bifida suspected but not
seen
• Look at limbs

Imaging Recommendations
• Best imaging tool: Detailed orthogonal views of spine
• Protocol advice
o Consider 3D ultrasound
• Multiplanar capacity may help identify levels
• May better show vertebral dysmorphology
o Consider MR in difficult cases

I DIFFERENTIAL

DIAGNOSIS

Caudal regression sequence
• Absent sacrum
• Variable absence of lumbar spine
o Lower vertebral bodies may be dysmorphic
• Associated anomalies
o Lower limb contractures
• "Buddha pose"
o Gastrointestinal
o Genitourinary

Iniencephaly
• Extensive open neural tube defect
o From skull base to tip of sacrum
• Shortened spine
o Exaggerated lordosis
• Extended head
o "Stargazer"

Sacrococcygeal teratoma (SC teratoma)
• Germ cell tumor
o Most often solid + cystic
o Variable size
• Internal + external components
• Associated hydrops fetalis
o High output cardiac failure

Arthrogryposis
• Multiple congenital joint contractures
o Extremities more involved than spine
o Usually without bony abnormality
• Polyhydramnios common
o Abnormal swallowing

KYPHOSIS, SCOLIOSIS
o Poor fetal movement

I PATHOLOGY
General Features
• Genetics
o Isolated
• No increased risk for aneuploidy
o Associated spina bifida
• 4% with aneuploidy
o VACTERLassociation
• No increased risk for aneuploidy
• Etiology
o Anomalous development of vertebrae
• Failure of formation
• Failure of segmentation
• Abnormal fusion
• Epidemiology
o Hemivertebra
• 5-10:10,000
oSpina bifida
• 0.4:1,000
o VACTERL
• 1:1,000
• Associated abnormalities
o Spinal cord
o Heart
o Renal

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Isolated CS seen during routine exam
• Isolated vertebral anomaly
o CS + multiple other anomalies
• VACTERL
• Syndromic fetus
• Chromosome abnormality
(AFP) results
o t Maternal serum alpha-fetoprotein
• > 2.5 multiples of median (MOM)
• Spina bifida
• Amniotic band syndrome

Treatment
• Prophylactic surgery
o Avoid further curve progression
• Hemiepiphysiodesis
• In situ fusion
• Corrective surgery
o Spinal fusion
o +/- Vertebral body resection
• Expansion thoracoplasty
o For thoracic insufficiency
• Wedge thoracostomy
• Chest wall distraction

I DIAGNOSTIC
Consider

• Amniocentesis
o Amniotic fluid AFP if spina bifida suspected but not
seen

Image Interpretation

• M:F = 1:3

o Multiple vertebral defects
• M:F = 2:3

of bony

I SELECTED REFERENCES
1.

2.

3.
4.

5.

Natural History & Prognosis
• Isolated CS
o Curve progression ( > 10 degrees)
• 25% no further curve progression
• 50% slow curve progression
• 25% rapid curve progression
o 20-30% with additional intraspinal anomaly
• Often diagnosed only on postnatal MR
• Thoracic insufficiency syndrome
o Rib anomalies + concave hemithorax
• Prognosis depends on presence of other anomalies

Pearls

• CS + no Chiari II
o Probable isolated vertebral anomaly
• CS + Chiari II
o Look for spina bifida
o Defect at apex of curve
• Longitudinal views best for visualization
deformity
• Look at limbs
o VACTERL
• Radial ray anomalies
o Amniotic band syndrome
• Amputations
oSpina bifida
• Club feet

Demographics
• Gender
o Isolated hemivertebra

CHECKLIST

6.
7.
8.
9.

Belmont PJ Jr et al: Intraspinal anomalies associated with
isolated congenital hemivertebra: the role of routine
magnetic resonance imaging. J Bone Joint Surg Am.
86-A(8): 1704-10, 2004
Campbell RM Jr et al: The effect of opening wedge
thoracostomy on thoracic insufficiency syndrome
associated with fused ribs and congenital scoliosis. J Bone
Joint Surg Am. 86-A(8):1659-74, 2004
Hedequist D et al: Congenital scoliosis. J Am Acad Orthop
Surg. 12(4):266-75,2004
Kose N et al: Congenital scoliosis. Med Sci Monit.
1O(5):RA104-10, 2004
Winter RB et al: Congenital scoliosis due to unilateral
unsegmented bar: posterior spine fusion at age 12 months
with 44-year follow-up. Spine. 29(3):E52-5, 2004
Arlet V et al: Congenital scoliosis. Eur Spine J.
12(5):456-63, 2003
Dangerfield PH: The classification of spinal deformities.
Pediatr Rehabi!. 6(3-4):133-6, 2003
Goldberg CJ et al: The natural history of early onset
scoliosis. Stud Health Technol Inform. 91:68-70, 2002
Harrison LA et al: Abnormal spinal curvature in the fetus. J
Ultrasound Med. 11(9):473-9, 1992

KYPHOSIS, SCOLIOSIS
IIMAGE GALLERY
Typical
(Left) Sagittal ultrasound
shows acute kyphosis
involving the upper lumbar
spine (arrow). Careful
interrogation of this area
revealed spina bifida at the
same level as the abnormal
angulation. (Right) Axial
ultrasound in the same fetus
shows divergent posterior
elements (arrows) and a
meningomyelocele sac
(open arrow). Most
abnormal spine curves are
associated with open neural
tube defects.

(Left) 3D ultrasound shows
block vertebrae of the upper
lumbar spine (arrows). Fused
vertebrae are large and
rectangular. Mild
kyphoscoliosis drew the
sonographer's attention to
this area. (Right) Coronal
postmortem MR and
photograph of a fetus with
VACTERL association shows
a butterfly vertebra (curved
arrows). The open arrows
point to the empty renal
fossae (renal agenesis). Steel
rod follows scoliosis.

Variant
(Left) Coronal ultrasound
shows a normal fetus with
atypical positioning. No
bony nefects were seen.
Fetuses are quite flexible and
atypical spine curvature can
mimic scoliosis. (Right)
Coronal ultrasound in the
same fetus at the end of the
examination shows normal
cervical spine positioning.

SACROCOCCYGEAL TERATOMA

Sagittal ultrasound of a type 2 SCCT shows an
exophytic, complex cystic and solid mass (open arrow).
There is extension of the solid component into the pelvis
(arrows). Curved arrow marks tip of spine.

ITERMINOLOGY
Abbreviations

and Synonyms

• Sacrococcygeal teratoma

(SCGT)

Definitions
• Neoplasm derived from all three germ cell layers
o Ectoderm, mesoderm, endoderm
• 70-80% of all teratomas located in sacrococcygeal

IIMAGING

area

FINDINGS

General Features
• Best diagnostic clue: Exophytic mixed cystic/solid
mass extending from sacrum
• Size
o Variable but often large
o Size alone is not an independent factor for prognosis
• Amount of solid component far more important
• Large purely cystic mass has better prognosis than
smaller solid one
o Has potential for extremely rapid growth

Ultrasonographic

Findings

• Grayscale Ultrasound
o Heterogeneous, mixed solid/cystic mass
• Purely cystic in 15%

Clinical photograph shows an obvious external mass
(curved arrow). An intra-operative photograph (inset)
shows the internal component (arrow) being removed.
(Also shown in Radiographics, ref 7).

• May contain calcifications
o May extend into pelvis or abdomen
• Important in staging and surgical planning
o Hydrops
• Grave finding
o Placentomegaly
• Associated with hydrops
o Polyhydramnios
• Commonly present
o Oligohydramnios
• Secondary to intrapelvic portion of mass
obstructing urinary tract
• Infrequent association
o May exhibit rapid growth in short period of time
o Intratumoral hemorrhage
• Common in large solid tumors
• Very poor prognostic sign
o Associated malformations in 11-38%
• Mostly local effects secondary to tumor growth
• Hydronephrosis
• Renal dysplasia
• Urethral atresia
• Urinary ascites
• Hydrocolpos
• Undescended testes
• Imperforate anus
• Hip dislocation
• Clubbed feet

DDx: Cystic Spinal Masses

Myelomeningocele

Meningocele

SACROCOCCYGEAL TERATOMA
Key Facts
Terminology
• 70-80o/'ll of all teratomas
area

located in sacrococcygeal

Imaging Findings
• Best diagno tic clue: Exophytic mixed cystic/ olid
ma extending from sacrum
• Has potential for extremely rapid growth
• May extend into pelvi or abdomen
• Hydrop
• Placentomegaly
• Polyhydramnios
• Intratumoral hemorrhage
• A ociated malformations in ] ]-38%
• olor Doppl r essential to evaluate vascularity
• olid tumor may have ignificant arteriovenous
shunting
• Color Doppler
o Color Doppler essential to evaluate vascularity
o Solid tumors may have significant arteriovenous
shunting
• At risk for hydrops

MR Findings
• Better delineation of anatomy
o Presence and extent of internal component
• Possible involvement of spinal canal
o More accurate classification and postnatal planning
• More accurate diagnosis of intratumoral hemorrhage
• Differentiates solid tumor from microcystic one
o Both appear echogenic on ultrasound
o Solid tumors worse prognosis

Imaging Recommendations
• Protocol advice
o MRI extremely useful for evaluating intrapelvic
extent and evaluating spine
• Shadowing from iliac wings and sacrum decreases
sensitivity of ultrasound
o Large solid tumors at risk for developing hydrops
• Scan every 1-3 weeks depending on size,
vascularity, etc.
o Evaluate for signs of impending cardiovascular
compromise
• Tumor volume
• Amniotic fluid index
• Placental thickness
• Inferior cava diameter
• Cardiothoracic ratio
• Doppler evaluation of umbilical cord and ductus
venosus

I DIFFERENTIAL

DIAGNOSIS

Chiari II malformation
• Myelomeningocele
o Complex cystic mass
o Sac contains meninges + neural elements
o Splayed dorsal ossification centers

• MRI extrem ly useful for valuating intrapelvic
extent and valuating pine

Top Differential

Diagnoses

• Myelomeningocele
• Meningocele

Clinical Issues
•
•
•
•
•

Described as early as 13.5 weeks
ignifi ant ob tetric complications in 81{}'ll
Prognosis significantly worse for fetus than neonate
Fetal diagnosi : 50% mortality
Hydrops almost universally fatal

Diagnostic Checklist
• In utero r ection for impending
potential option

high-output

failure

o Sac extends posteriorly in most cases
o Anterior myelomeningocele
may be more difficult to
differentiate from SCGT
• Always look at brain
• 99% of spinal defects have associated brain
findings
• Meningocele
o Anechoic cystic mass
o Sac contains meninges only
• Brain findings
o Posterior fossa compression
• Obliteration of cisterna magna
• Cerebellum wraps around brainstem ("banana"
sign)
o Ventriculomegaly
o Frontal bone concavity ("lemon" sign)
• Caution: Myelomeningocele
and SCGT may occur
together
o Always look at brain

Other solid tumors
• Multiple isolated case reports
• Generally intrapelvic with no exophytic component
• All extremely rare

I PATHOLOGY
General Features
• Etiology
o Embryology
• Primordial germ cells migrate from yolk sac to
genital ridges (weeks 4-6)
• They are then incorporated into primitive sex
cords to form gonad
• Unincorporated cells normally involute
• Continued division of unincorporated
pluripotential cells gives rise to teratoma
• Epidemiology
o 1:40,000
• Likely higher given large number of in utero
deaths and terminations, which may be
underreported

SACROCOCCYGEAL TERATOMA
o Commonest

neonatal

tumor

• Progressive maternal edema "mirroring" sick fetus
• Necessitates immediate delivery
o Preterm labor
o HELLP (hemolysis, elevated liver enzymes, low
platelets) syndrome

o M:F = 1:4

o Malignant

change M > F

Staging, Grading or Classification Criteria
• American academy of pediatrics surgery section
(AAPSS)
o Type 1
• Completely external or minimal presacral
component
o Type 2
• External and internal component extending into
presacral space
o Type 3
• External and internal component extending into
abdomen
o Type 4
• Completely internal, no external component
• Most likely to undergo malignant degeneration
(postnatal)
• Malignancy more likely in solid than cystic or
mixed tumors
o Staging system less important prognostically in fetus
• Amount of solid component and degree of
arteriovenous shunting far more important for
survival

I CLINICAL

Treatment
• Therapeutic amnioreduction
for symptomatic
polyhydramnios
• Deliver in tertiary care center at lung maturity
• Cesarean section preferred if tumor> 5 cm
o Larger masses may require classical incision
o Aspiration of cystic lesions may allow vaginal
delivery
• Fetal surgery
o Consider when fetus has signs of impending
hydrops
o Must have normal karyotype

I DIAGNOSTIC

CHECKLIST

Consider
• Fetal MRI for intrapelvic extension
• In utero resection for impending high-output
potential option

Image Interpretation

ISSUES

Presentation
• Most common signs/symptoms
o Described as early as 13.5 weeks
o Most diagnosed in 2nd trimester
o Often presents as size> dates
• Secondary to large mass
• Polyhydramnios
o Presentation at delivery
• Dystocia 6-13%
• Tumor avulsion
• Fetal exsanguination

Natural History & Prognosis
• Failure to diagnose has potentially catastrophic
consequences for fetus and mother
• Significant obstetric complications in 81 %
• Prognosis significantly worse for fetus than neonate
o Fetal diagnosis: 50% mortality
• Hydrops from high-output state
• Intratumoral hemorrhage
o Newborn diagnosis: .:5 5% mortality generally
related to malignancy
• Poor prognostic factors
o Hydrops almost universally fatal
o Maternal indication for scan (e.g. large for dates)
o Diagnosis < 30 weeks
o Large solid component
• Better outcome if cystic
o Less vascular ~ decreased risk hemorrhage, hydrops
• Maternal complications
o Hyperemesis
o Preeclampsia
o "Mirror" syndrome
• Maternal fluid retention and hemodilution

failure

Pearls

• Most compelling issues for fetal/neonatal survival
o Composition
• Solid much worse prognosis than cystic
o Diagnosis < 30 weeks
o Vascularity
• Vascular masses have significant arteriovenous
shunting ~ high-out failure ~ hydrops
o Associated abnormalities
o Complicating factors
• Hydrops
• Polyhydramnios
• Intratumoral hemorrhage

I SELECTED
1.

2.

3.
4.

5.
6.

7.

8.

REFERENCES

Woodward PJ et al: From the archives of the AFIP: a
comprehensive review of fetal tumors with pathologic
correlation. Radiographies. 25(1):215-42, 2005
Hedrick HL et al: Sacrococcygeal teratoma:· prenatal
assessment, fetal intervention, and outcome. J Pediatr Surg.
39(3):430-8; discussion 430-8, 2004
.
Avni FE et al: MR imaging of fetal sacrococcygeal teratoma.
AJR. 178: 179-83, 2002
Coleman Bet al: Fetal therapy: State of the Art. J
Ultrasound Med. 21:1257-88, 2002
Chisholm CA et al: Prenatal diagnosis and perinatal
management of fetal sacrococcygeal teratoma. Am J
Perinatol. 16(1):47-50, 1999
Holterman AX et al: The natural history of sacrococcygeal
teratomas diagnosed through routine obstetric sonogram: a
single institution experience. J Pediatr Surg. 33(6):899-903,
1998
Bond SJ et al: Death due to high-output cardiac failure in
fetal sacrococcygeal teratoma. J Pediatr Surg.
25(12):1287-91, 1990
Altman RP et al: Sacrococcygeal teratoma: American
Academy of Pediatrics Surgical Section survey-1973. J
Pediatr Surg. 9:389-98, 1974

SACROCOCCYGEAL TERATOMA
IIMAGE GALLERY
(Left) Coronal ultrasound
shows an exophytic cystic
mass (curved arrow). There
appeared 10 be intrapelvic
extension (arrows) but
precise anatomic delineation
was difficult, and the spine
was incompletely
evaluated.
(Right) Sagittal T2WI MR
nicely shows the extension of
the solid component
(curved
arrow) 10 the level of the
cord insertion (arrow). MRI
is extremely valuable in
evaluating the
intra-abdominal
component
of a SCCT

Typical
(Left) Sagittal ultrasound in
the midtrimester shows a
large, predominately
solid
exophytic mass (arrows).
Teratomas may show rapid
growth and close follow-up
is warranted. (Right) Sagittal
ultrasound S weeks later
shows dramatic increase in
the size of the mass
(arrows). This fetus is at high
risk for developing hydrops
and a thorough physiologic
evaluation with possible
referral for resection is
warranted.

(Left) Coronal ultrasound in
the same fetus as above
shows dilatation of the
inferior vena cava (arrow).
Compare with the aorta
(curved arrow). This is one
sign of impending
cardiovascular compromise.
(Right) Cross pathology at
autopsy shows obvious
intra tumoral hemorrhage.
Teratomas may have
significant vascularity with
arteriovenous shunting,
putting them at risk for
hemorrhage and hydrops.
(Also shown in
Radiographics, ref 7).

SECTION 4: Face and Neck

Introduction
Facial Development

and Overview

& Imaging

4-2

Face & Neck
Cleft Lip, Palate
Absent Nasal Bone
Micrognathia
Macroglossia
Epignathus
Ear Anomalies
Midface Anomalies
Hypotelorism
Hypertelorism
Orbital Tumors
Scalp Masses
Cystic Hygroma
Goiter
Cervical Teratoma

4-6
4-10
4-14
4-18
4-22
4-26
4-30
4-34
4-38
4-42
4-44
4-48
4-52
4-56

FACIAL DEVELOPMENT & IMAGING

3D ultrasound of the fetal face at 30 wks shows
exquisite anatomic detail. Many facial anomalies are
ruled out by one volume acquisition, which can be
manipulated into many different planes.

[Terminology
Abbreviations
•
•
•
•
•
•
•

Nasal bones (NB)
Nuchal translucency (NT)
Cleft lip (CL)
Cleft palate (CP)
Cystic hygroma (CH)
Nuchal fold (NF)
Fetal medicine foundation (FMF)

I Imaging Anatomy
Critical Anatomic Structures
•
•
•
•
•
•

Orbits
Nasal bones
Upper lip and palate
Chin
Neck
Calvarial shape

IAnatomy-Based

Imaging Issues

Key Concepts or Questions
•
•
•
•
•
•
•

Is face surrounded by fluid and seen well?
Are there any facial clefts?
Is nuchal region normal?
Is NB appropriately ossified?
Are orbits appropriately spaced?
Is calvarial shape normal?
Are tongue, ears and anterior neck normal?

Imaging Approaches
• First trimester genetic screening
o NT, NB
• Second trimester screening
o Orthogonal views through face
o Genetic ultrasound
• NF, NB
• 3D ultrasound
o Problem solving tool

3D ultrasound in real time allows us to study facial
expression (furrowed brow in this case) and features. As
shown on this profile view, the fetal chin is normally
mildly receded. The foot is by the face.

o Increasingly used as primary screening tool
• MR
o Problem solving tool
• Associated brain anomalies
• Posterior soft palate assessment
• lntracranial extension of facial mass
o Helpful when ultrasound is limited
• Maternal body habitus
• Oligohydramnios

Imaging Protocols
• 1st trimester NB and NT assessment
o 11-14 wk scan to assess aneuploidy risk
• High detection rates for trisomy
• Trisomy 21 most common
o FMF certification recommended
• Didactic course
• Hands-on training
• Cases submitted for review
• Continuous audit
o Midsagittal view of head and neck
• Must be appropriately magnified
• Amnion separate from NT
o NB assessment
• Present or absent NB
o NT measurement
o Maternal serum testing
• Compared with NT/NB findings
• 2nd trimester views of fetal face
o Midsagittal profile
• Can measure NB (> 2.5 mm)
• Assess chin
o Angled coronal nose-mouth view ("snout" view)
• Show intact upper lip
• Normal round nares
o Posterior fossa view
• Measure NF
• Rule out CH
o Axial face views
• Orbital biometry
• Maxilla
o Coronal view
• Eyes

FACIAL DEVELOPMENT

& IMAGING

Key Facts
Obtain Orthogonal

Images Of Fetal Face

• Midsagittal profile view
o Level of nasal bone
o Rule out micrognathia
• Angled coronal nose-mouth view
o Normal round nares
o Intact upper lip
• Axial views as necessary
o Orbital biometry
o Intact palate
• 3D ultrasound best tool
o Orthogonal images with 1 acquisition
o Surface rendered images
o Bone rendered images
o Recognizable features for parents

• Show 2 nasal bones
o Overall calvarial shape assessment
• Orthogonal "whole head" views
• 3D ultrasound
o Multiplanar advantages
• Orthogonal planes with one acquisition
o Surface rendered images
• Recognizable facial features
o Bone rendered views
• Skeleton-like image
• Better visualization of palate
• Show 2 NB better than midsagittal views
• Cranial suture assessment
o 4D (real time 3D ultrasound) shows facial expression
and movement
• Shown to enhance parent-child bonding
• Additional observations
o Color Doppler of nasal breathing
• Helps confirm intact palate
o Tongue size
o Ear assessment
• Location and morphology
o Fetus opens and closes eyes in 3rd trimester
o Finger/hand sucking

Imaging Pitfalls
• NB

o Skin can mimic NB in 1st trimester
o 90° angle of insonation
o Measure/show both NBs
• Unilateral hypoplasia possible
o Gap between NBs can mimic absent NB
• Posterior neck (NT, NF, CH)
o Amnion can mimic NT
• Image both NT and amnion
o Overly coronal posterior fossa view
• Can mimic t NF
o Large CH can mimic amniotic fluid
• Nose/mouth assessment
o Lip folds or full lips can mimic CL
o Isolated CP often missed
• Soft tissue defect
o Extent of CP difficult to assess

Assess Nasal Bone Ossification
• Present or absent in first trimester
• Normal or small in 2nd trimester

Evaluate Nuchal Region
• Nuchal translucency in 1st trimester
• Nuchal fold in 2nd trimester

Facial Anomalies
•
•
•
•
•
•
•
•

Cleft lip/palate
Micrognathia
Hypotelorism
Hypertelorism
Cystic hygroma
Ear anomalies
Goiter
Facial mass

Normal Measurements
• NF in 2nd trimester
o < 5 mm considered normal
• NB length in 2nd trimester
o Nomograms in literature
• Orbital biometry
o Orbital diameter (OD)
o Interorbital diameter (IOD)
o Biorbital diameter (BOD)
o Normal IOD = OD
o Nomograms in literature

I Pathology-Based Imaging Issues
Key Concepts or Questions
• tNT, t NF and CH strongly associated with
aneuploidy
o t NT in first trimester
• Trisomy 21 most common
• Trisomy IS, trisomy 13
o Cystic hygroma in 2nd trimester
• Turner syndrome> trisomies
• Often with hydrops
• Type of CL/CP important for prognosis and treatment
o 80% of CL with CP
• Extent of CP difficult to assess
o Unilateral CL + CP most common (type 2)
• 20% aneuploidy rate
o Median CL/CP (types 3 and 4)
• 50% aneuploidy rate
o Trisomy 13 and 18 most common
• Delayed NB ossification is marker for aneuploidy
o Absent NB in first trimester
o Small NB in 2nd trimester
o Most often trisomy 21
• Hypotelorism associated with holoprosencephaly
o Other severe facial anomalies common
• Cyclopia with proboscis
• Ethmocephaly
• Cebocephaly
• Median CL/CP

FACIAL DEVELOPMENT & IMAGING

The angled coronal nose/mouth view ("snout" view) is
routinely obtained to rule out cleft lip and palate. The
normal nares are rounded (open arrows) and the upper
lip (arrows) is intact.

o Often with trisomy 13
• Hypertelorism rarely isolated finding
o Craniosynostosis
o Agenesis of corpus callosum
o Median facial clefts
o Teratogen exposure
• Micrognathia
o Small retracted jaw
o Associated with many different syndromes
o Often with associated ear anomalies
• Unusual diagnoses
o Macroglossia
• Trisomy 21
• Beckwith Wiedemann
o Frontal encephalocele
o Anophthalmia
o Fetal goiter
o Facial mass
• Often large and aggressive tumors
• Epignathus (teratoma)

Sagittal ultrasound shows a normal nasal bone (arrow),
intact bony maxilla (curved arrow) and normal chin.
The profile face view is desirable for parents and
contains diagnostic information.

Practical Implications
• CL/CP type 1-3
o Failure of lip/palate fusion
• CL/CP type 4
o Median maxillary agenesis
• Facial anomalies in holoprosencephaly
o Abnormal cleavage of frontonasal process
o Brain + orbit/nose anomalies
o "Face predicts the brain"

I Clinical Implications
Clinical Importance
• Fetal facial anomalies are especially difficult for
families to cope with
• Isolated findings with much better prognosis
• Genetic testing often indicated
• Prenatal visit to plastic surgeon for CL/CP
• Brain anomalies associated with facial anomalies

Ultrasound Classification Of CL/CP
•
•
•
•

Type
Type
Type
Type

1: Unilateral CL only
2: Unilateral CL + CP (most common)
3: Bilateral CL/CP
4: Midline CL/CP

I Embryology

I Related References
1.

2.

Embryologic Events
• Facial development
o Five facial prominences
• Unpaired frontonasal process
• Paired maxillary swellings
• Paired mandible swellings
o Fusion and cleavage complete by 12 wks
• Normal lip/palate embryology
o 3 primary segments
• 2 lateral + 1 medial
o Complete lip fusion by 8 wks
o Complete palate fusion by 12 wks

3.

4.

5.
6.

Benoit B et al: Three-dimensional ultrasound with maximal
mode rendering: a novel technique for the diagnosis of
bilateral or unilateral absence or hypoplasia of nasal bones
in second-trimester screening for Down syndrome.
Ultrasound Obstet Gynecol. 25(1):19-24, 2005
Hata T et al: Real-time 3-D sonographic observation of fetal
facial expression. J Obstet Gynaecol Res. 31(4):337-40,
2005
Peralta CF et al: Assessment of the gap between the fetal
nasal bones at 11 to 13 + 6 weeks of gestation by
three-dimensional ultrasound. Ultrasound Obstet Gynecol.
25(5):464-7,2005
Rotten D et al: Two- and three-dimensional sonographic
assessment of the fetal face. 1. A systematic analysis of the
normal face. Ultrasound Obstet Gynecol. 23(3):224-31,
2004
Dilmen G et al: Growth of the fetal lens and orbit. lnt J
Gynaecol Obstet. 76(3):267-71, 2002
Benacerraf BR et al: Abnormal facial features and
extremities in human trisomy syndromes: prenatal US
appearance. Radiology. 159(1):243-6, 1986

FACIAL DEVELOPMENT

& IMAGING

I IMAGE GALLERY
(Left) Axial ultrasound shows
orbital biometry
measurements. The # 1
calipers measure the BOD.
The #2 calipers measure the
100 and the 00 lies
between the #1 and #2
calipers. The eye lens can
also be seen (open arrows).
(Right) 20 US (upper) and
3D US (lower) show the
fetal eyes open (open
arrows) and close (arrows)
during the 3rd trimester as
blinking is a normal fetal
activity. The lens can be
seen on the open eye views.

(Left) Sagittal ultrasound
shows a normal first trimester
nasal bone (arrow). The NB
is the echogenic line
separate from the skin
(curved arrow) and the tip 01
the nose (open arrow).
(Right) Coronal 3D
ultrasound of an 18 wk fetus
shows bilateral nasal bone
ossification (arrows) as well
as normal sutures. Unilateral
nasal bone hypoplasia may
be easily missed with 20
ultrasound.

(Left) Sagittal power Doppler
ultrasound shows nasal
breathing. The inferior
margin of the flow (arrows)
outlines the palate. Absence
of flow into the oral cavity
suggests an intact palate.
(Right) 30 ultrasound shows
a normal fetal ear as well as
hair line (arrows) in a third
trimester fetus. Ear anomalies
are most often associated
with mandibular anomalies,
and are seen best with 30.

CLEFT LIP, PALATE

Graphic shows ultrasound classification of cleft lip and
cleft palate. Type I: Unilateral CL; type II: Unilateral CL
+ CP; type III: Bilateral CL + CP; type IV-Midline CL/CP
Type II is the most common.

ITERMINOlOGY
Abbreviations

and Synonyms

• Cleft lip (CL)
• Cleft palate (CP)
• Facial cleft

Definitions
• Failure of lip and/or palate closure

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Upper lip linear defect on nose-mouth view
• Angled coronal image ("snout" view)
o Premaxillary protuberance with bilateral CL/CP
• Profile view
• Location: L > R when unilateral
• Size: Highly variable, from thin line to large gap
• Morphology
o CL +/- CP
• 80% with cleft lip also have cleft palate
o Isolated CP rare

Ultrasonographic

Findings

• Imaging of fetal nose and lip

DDx: Cleft Lip/Cleft

Normal Philtrum

Angled coronal nose/mouth view (top) and 3D surface
rendered view (bottom) show a unilateral cleft lip
(arrow). The flattened nare (curved arrow) is seen best
with 3D. This fetus also had cleft palate.

o Angled coronal nose-mouth view
• Nares and upper lip
o Midsagittal profile view
o Axial alveolar ridge view
• Bony palate
o 3D ultrasound advantages
• Multiplanar capability
• Soft tissue rendering
• Bone detail for palate
o Color Doppler of nasal breathing
• Sagittal view + color Doppler
• Flow only above palate suggests intact palate
o MR advantages
• Multiplanar capability
• Posterior soft palate visualization
• Unilateral CL without CP (type 1)
o Upper lip defect only
• Seen best on nose-mouth view
o +/- Flattened nares
• Unilateral CL with CP (type 2)
o CL more obvious than type 1
• Almost always with flattened nares
o Variable depth of palate defect
• Alveolar ridge defect on axial view
• Fluid in nasal compartments on profile view
o Difficult to assess extension into soft palate
• MR may be helpful
• Bilateral CL/CP (type 3)

Palate

Normal Philtrum

Intact Palate

Amniotic Bands

CLEFT LIP, PALATE
Key Facts
Terminology

Top Differential

• Failure of lip and/or palate clo ure

• ormal philtrum
• Amniotic band
• Facial mass

Imaging Findings
•
•
•
•
•
•
•
•
•

Upper lip linear defect on no e-mouth view
Premaxillary protuberance with bilateral
L/ P
801}6with cleft lip also have cleft palate
Unilateral
L without
P (type 1)
Unilateral
L with P (type 2)
Bilateral L/ P (type 3)
Midline
L/ P (type 4)
P without
L (rare)
Type 3-4 L/ P often a ociated with
aneuploidy/ yndromes
• 3D ultrasound for more precise diagno i of L/CP

o Premaxillary protrusion on profile view
• Mass-like area just below nose
• "Island" of bone separate from rest of palate
• Dysplastic medial anterior palate
o Bilateral lip/palate defects on axial view
• Finding not subtle, but may be confusing
o Severe nose deformity
• Midline CL/CP (type 4)
o Anterior mid palate defect
o Large gap often seen
• Medial maxillary agenesis
o Associated with midface hypoplasia
• Flat midface on profile view
• Flattened dysplastic nose
• Small posteriorly displaced maxilla
• CP without CL (rare)
o Isolated cleft palate
o Often involves posterior soft palate only
• Rarely diagnosed in utero
o Color Doppler of nasal breathing
• Flow from nasal fossae ~ mouth
o Fetal MR may show soft palate
• Associations
o Type 3-4 CL/CP often associated with
aneuploidy /syndromes
• Holoprosencephaly
• Trisomy 13
• Trisomy 18
• Many syndromes
o Other structural anomalies
• All organ system anomalies described

Imaging Recommendations
• Best imaging tool
o 3D ultrasound for more precise diagnosis of CL/CP
• Orthogonal.views with one acquisition
• Recognizable face with surface rendered images
• Bone rendered views shows palate best
• Psychologically prepares parents
• Best images at 28-32 wks
• Protocol advice
o Obtain orthogonal planes of fetal face
• Coronal angled nose-mouth view .

Diagnoses

Pathology
• Aneuploidy rate related to type of L/
• Mo t often trisomy 13 and trisomy 18

Clinical
•
•

r

Issues

L often repaired at 2-3 months
P often repaired at 9-18 months

Diagnostic Checklist
• Referral to L/ P clinic during pr gnan y
• L/ P difficult to diagno e before 20 wks

• Midline sagittal view
• Axial view through alveolar ridge
o Look carefully for other anomalies
• Consider formal echocardiography
o Genetic counseling
• t Risk for aneuploidy
• t Risk for syndromic child
o Prenatal consultation with plastic surgery
• 3D US pictures helpful

I DIFFERENTIAL DIAGNOSIS
Normal philtrum
• Normal folds may mimic cleft
o Folds more echogenic than clefts
• Most often in late gestation
o Big baby or full lips
• Additional views helpful
o Show intact skin/palate

Amniotic bands
• Disruption of amnion with fetal entrapment
• Slash-type facial defects
o Asymmetric, random clefts
• No embryologic pattern
o Fetus may swallow disrupted bands
• Other body wall/extremity defects
o Bizarre abdominal wall defects
o Amputations

Facial mass
• Tumors tend to be large and aggressive
• Teratoma (epignathus)
o Nasal/oral origin
o Can mimic premaxillary protuberance
• Frontal encephalocele
o Bone defect + herniated brain/meninges
• Hemangioma
o Superficial and asymmetric
o Intact palate
• Rhabdomyosarcoma

CLEFT LIP, PALATE

I PATHOLOGY

Natural History & Prognosis

General Features
• Genetics
o Aneuploidy rate related to type of CL/CP
• Rare for type 1
• Type 2: 20%
• Type 3: 30%
• Type 4: 50%
o Most often trisomy 13 and trisomy 18
• CL/CP rarely isolated finding in these conditions
• Etiology
o Normal lip/palate embryology
• 3 primary lip/palate segments
• 2 lateral and 1 medial
• Complete lip fusion by 8 wks
• Complete palate fusion by 12 wks
o CL/CP embryology
• Type 1-3: Failure of fusion
• Type 4: Medial segment fails to form
o Infectious etiology
• Rubella
o Teratogen associations
• Retinoic acid
• Valproic acid
• Hydantoin
• Alcohol
• Cigarette smoking
• Epidemiology
o 80% with CL have CP
00.15% of liveborns
o 12% of first trimester loss

Staging, Grading or Classification Criteria
• Ultrasound classification system
o Type 1: CL
o Type 2: Unilateral CL/CP (most common)
o Type 3: Bilateral CL/CP
o Type 4: Midline CL/CP
o Type 5: Slash-type defect

• Excellent prognosis with surgical repair
• Associated craniofacial problems
o Feeding difficulties
o Hearing impairment
o Speech impairment
• CL/CP + other anomalies with poor prognosis

Treatment
• Treatment by CL/CP team
o Plastic surgeon
o Ear-nose-throat surgeon
o Dentist
o Speech and language specialist
o Social worker/psychiatrist
o Genetic counselor
• Surgical treatment
o CL often repaired at 2-3 months
o CP often repaired at 9-18 months
o Severe cases may need immediate repair
o Second procedures often necessary
• Possible fetal surgery in future
o Experimental fetoscope surgery with good results
o Fetal skin heals without scars
o Fetal bone heals without callus

I DIAGNOSTIC

CHECKLIST

Consider
• Referral to CL/CP clinic during pregnancy

Image Interpretation

Pearls

• CL/CP difficult to diagnose before 20 wks
• Most CL have associated CP
o Repeat scan if CP not initially seen
• Variable accuracy for predicting CP extension
o 3D ultrasound and MR often helpful

ISELECTED REFERENCES

I CLINICAL

1.

ISSUES

Presentation
• Most common signs/symptoms
o Incidentally noted at routine scan
o CL/CP + associated anomalies
• Other signs/symptoms: Polyhydramnios
swallowing difficulties

2.

3.

from
4.

Demographics
• Age
o Trisomies associated with advanced maternal age
• ~ 35 yo at time of delivery
• Gender
oM> F for CL/CP
o M < F for isolated CP
• Ethnicity
o 1:600 Asian
o 1:1,000 Caucasian'
o 1:2,500 African-American

5.

6.

7.

8.

Merritt L: Part 1. Understanding the embryology and
genetics of cleft lip and palate. Adv Neonatal Care.
5(2):64-71, 2005
Papadopulos NA et al: Foetal surgery and cleft lip and
palate: current status and new perspectives. Br) Plast Surg.
58(5):593-607, 2005
Goodacre TE et al: Does repairing a cleft lip neonatally
have any effect on the longer-term attractiveness of the
repair? Cleft Palate Craniofac). 41(6):603-8, 2004
Ghi T et al: Prenatal imaging of facial clefts by magnetic
resonance imaging with emphasis on the posterior palate.
Prenat Diagn. 23(12):970-5, 2003
Mittermayer C et al: Three-dimensional ultrasonographic
imaging of cleft lip: the winners are the parents.
Ultrasound Obstet Gynecol. 21(6):628-9, 2003
Clementi M et al: Evaluation of prenatal diagnosis of cleft
lip with or without cleft palate and cleft palate by
ultrasound. Prenat Diagn. 20:870-5, 2000
Nyberg DA et al: Fetal cleft lip with and without cleft
palate: US classification and correlation with outcome.
Radiology. 195:677-83, 1995
Aubry MC et al: Prenatal diagnosis of cleft palate:
contribution of color Doppler ultrasound. Ultrasound
Obstet Gynecol. 2(3):221-4, 1992 .

CLEFT LIP, PALATE
IIMAGE GALLERY
Typical
(Left) 3D ultrasound with
soft tissue (left) and bone
(right) rendered views shows
cleft lip and palate. The CL
(arrow), flat nare (curved
arrow) and palate defect
(open arrow) are easily
recognized. These images
were obtained from a single
volume acquisition. (Right)
Clinical photograph of the
same baby shows the
right-sided CUCP before and
after repair.

(Left) Coronal angled (top)
and axial (bottom) views
through the nose and maxilla
show a large cleft lip
(arrows) and cleft palate
(open arrows). The palate
defect is seen best on axial
views through the alveolar
ridge. (Right) Clinical
photograph of the same
baby after birth shows the
palate defect and flattened
nare. Post-repair results are
excellent.

Typical
(Left) Sagittal ultrasound
shows premaxillary
protuberance (arrow) from
bilateral CUC? Amniotic
fluid is seen extending from
the oral cavity into the nasal
cavity (open arrow) via the
palate defect. (Right)
Coronal 3D ultrasound
shows the premaxillary mass
(arrow) and the bilateral
cleft lip/palate defects (open
arrows). The island of mid
maxillary tissue is dysplastic
and mass-like when CUCP is
bilateral.

ABSENT NASAL BONE

Sagittal ultrasound in a normal first trimester fetus shows
a normal nasal bone (arrow). The tip of the nose (open
arrow) and fetal skin (curved arrow) are seen separate
from the N8.

• Morphology: Triangular when seen enface

ITERMINOlOGY
Abbreviations

Sagittal ultrasound in a first trimester fetus with trisomy
27 shows an absent nasal bone (arrow). Increased NT
was also present (open arrows). The curved arrow
points to the amnion.

Ultrasonographic

and Synonyms

Findings

• 1st trimester NB evaluation technique
o Fetal face mid sagittal view
• 90° angle of insonation
• Transducer parallel to NB long axis
o Area magnified
• Image only head and upper chest
• Normal 1st trimester NB
o NB first seen at 42 mm crown rump length (CRL)
o NB echogenicity > skin
o Correct view of NB shows 3 distinct lines
• Skin over NB
• Echogenic NB parallel to skin
• Tip of nose
o NB cartilage
• Echogenic focus near tip of nose
• Not as echogenic as NB
• 1st trimester absent NB
o NB not seen
• Only one nasal line (skin line)
o Poorly echogenic NB
• NB echogenicity ~ skin
• Considered "absent NB"
• 1st trimester absent NB significance
o Independent of other markers for aneuploidy
o Absent NB associated with t trisomy 21 (T21) risk

• Hypoplastic or absent nasal bone (! NB)

Definitions
• Absent nasal bone
o No NB ossification at 11-14 wks
• New criteria recently established
• Part of nuchal translucency (NT) screen
o Absent NB also may be noted in 2nd trimester
• Hypoplastic nasal bone
o Small NB at 2nd trimester screen
o NB length is measured
• !NB is important marker for aneuploidy

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o No NB in 1st trimester
o Short or absent NB in 2nd trimester
• Location: 2 nasal bones on either side of septum
• Size
o > 2.5 mm at 15-20 wks considered normal
o NB length nomograms in literature
• 10-20 wk percentiles

DDx: Abnormal NB

Normal (Off-Axis)

Hyperextended

Neck

Thanatophoric

Coumadin

ABSENT NASAL BONE
Key Facts
Terminology

Top Differential Diagnoses

• Hypoplastic or absent nasal bone (~ NB)
• ~ NB is important marker for aneuploidy

• Normal NB (poor technique)
• Thanatophoric dysplasia (TD)
• Warfarin (coumadin) embryopathy

Imaging Findings
• No NB in 1st trimester
• Short or absent NB in 2nd trimester
• > 2.5 mm at 15-20 wks considered normal
• NB first seen at 42 mm crown rump length (CRL)
• NB echogenicity > skin
• Correct view of NB shows 3 distinct lines
• CRL 45-64 mm + absent NB = 17x t T21 risk
• CRL 65-84 mm + absent NB = 44-48x t T21 risk
• ~ NB at 15-20 wks: 83x t T21 risk
• 3D ultrasound helpful
• Look for both NBs in 2nd trimester

•

•

•

•

• CRL 45-64 mm + absent NB = 17x t T21 risk
• CRL 65-84 mm + absent NB = 44-48x t T21 risk
o NT measurement and NB
• As NT increases, incidence of absent NB also t
2nd trimester NB evaluation technique
o Both nasal bones identified
• Axial/coronal views helpful
o Mid sagittal face view
• 2 images measuring each NB
• Example: Right NB = 3 mm and left NB = 3.5 mm
o 90° angle of insonation
o Measure maximum nasal bone length
• End to end measurement
o NB growth is linear throughout gestation
• > 2.5 mm considered normal (15-20 wk)
• May use nomogram to give percentile
~ NB diagnosis in 2nd trimester
o Hypoplastic NB
• < 2.5 mm at 15-20 wks
• < 5-10th percentile
o Absent NB
• No NB seen
• Less likely diagnosis
o Must assess both NB
• Only one may be absent/hypoplastic
Significance of finding in 2nd trimester
o ~ NB at 15-20 wks: 83x t T21 risk
o 1/3 of T21 fetuses have unilateral ~ NB
3D ultrasound helpful
o Multiplanar advantages
• Axial/coronal/sagittal on one image
o Volume acquired with maximal mode rendering
• Better visualization of bony detail
o Easier to identify unilateral ~ NB
• Hypoplasia of one bone
• Absence of one bone

Imaging Recommendations
• Best imaging tool
o 1st trimester NB evaluation
• NB present or absent
o 2nd trimester NB measurement
• Look for both NBs in 2nd trimester

Pathology
•
•
•
•

2.8% of normal fetuses have an absent NB
67% of T21 have an absent NB
1.2% of normal fetuses have a hypoplastic NB
62% of T21 have a hypoplastic NB

Diagnostic Checklist
•
•
•
•

Certified first trimester screening program
Amniocentesis when ~ NB seen in high-risk patients
Do not mistake skin for NB in 1st trimester
Finding less clinically significant in Asian and
Afro-Caribbean parents

o 3D ultrasound
• Better evaluation of both NB
• Protocol advice
o 1st trimester NB certification recommended
• Difficult technique
o Maternal fetal medicine foundation (FMF)
certification requirements
• General FMF certification in 11-14 wk scan
• FMF audit of NT measurements
• Recent FMF course with lectures on NB assessment
• Submission of NB images to FMF

I DIFFERENTIAL

DIAGNOSIS

Normal NB (poor technique)
• First trimester
o Inadequate magnification
o NB mistaken for skin (or vice versa)
• Second trimester
o > 90° angle of insonation
• Minimizes NB length
o Off-axis scanning
• Scan through cartilage
• Mimics absent NB

Thanatophoric dysplasia (TD)
• Lethal skeletal dysplasia
o Extremely short limbs
• Type II with severe calvarial findings
o Kleeblattschadel (cloverleaf) skull
o Abnormal profile
• Depressed nasal bridge + short NB
• Upturned nasal tip
• Hypoplastic midface
• Frontal bossing

Warfarin (coumadin) embryopathy
• Fetal effects of early exposure to coumadin
• Facial anomalies
o Hypoplastic midface
o Severely depressed nasal bridge
• +/- ~ NB length

ABSENT NASAL BONE
o Deep nasal grooves
• Between alae nasi and nasal tip
• Stippled epiphyses
o Punctate epiphyseal calcification

Natural History & Prognosis

I PATHOLOGY

• Depends on karyotype
• Fetuses with normal karyotype have an excellent
prognosis
• Postnatal hypoplastic nose
o Often not clinically significant

General Features

Treatment

• Genetics
o -I- NB associated with aneuploidy
• Trisomy 21 (T21) most common
• Trisomy 18 (TI8)
• Trisomy 13 (TI3)
• Turner syndrome
• Etiology
o Delayed bone maturation
• Associated with aneuploidy
• Epidemiology
o First trimester
• 2.8% of normal fetuses have an absent NB
• 67% of T21 have an absent NB
• 57% of T18 have an absent NB
• 32% of T13 have an absent NB
• 9% of Turner syndrome have an absent NB
o Second trimester
• 1.2% of normal fetuses have a hypoplastic NB
• 62% of T21 have a hypoplastic NB
• 7% of T18 have a hypoplastic NB
o Asian and Afro-Caribbean population
• More likely to have normal fetus with -I- NB
• Source of false positive diagnoses
• Associated abnormalities
o Other markers for T21
• t NT in first trimester
• t Nuchal fold in 2nd trimester
• Echogenic bowel
• Renal pelviectasis
• Short humerus/femur
• 5th finger clinodactyly
• Echogenic intracardiac focus
o Major anomalies of T21
• Atrioventricular canal
• Duodenal atresia
o Major anomalies of TI8 and T13

• Genetic counseling with risk calculation
• Consider amniocentesis based on risk assessment
• No postnatal treatment necessary

I DIAGNOSTIC
Consider

• Certified first trimester screening program
o Risk calculation software
• Compares NB, CRL, maternal age and blood test
results
• Assigns individual risk for aneuploidy
• Amniocentesis when -I- NB seen in high-risk patients

Image Interpretation

I SELECTED
1.

2.

3.

4.

6.

Presentation
• Most common signs/symptoms
o Incidentally noted
• First trimester screen
• Second trimester screen
o Seen in association with other markers/anomalies
• Higher risk for aneuploidy

7.

8.

Demographics
• Age
o Trisomies associated with advanced maternal age
(AMA)
• AMA: ~ 35 yrs at time of delivery
o Turner syndrome not associated with AMA

Pearls

• Do not mistake skin for NB in 1st trimester
o 1st trimester "=" sign is skin + NB
o Skin alone resembles "_"sign
• Finding less clinically significant in Asian and
Afro-Caribbean parents

5.

I CLINICAL ISSUES

CHECKLIST

9.

REFERENCES

Benoit B et al: Three-dimensional ultrasound with maximal
mode rendering: a novel technique for the diagnosis of
bilateral or unilateral absence or hypoplasia of nasal bones
in second-trimester screening for Down syndrome.
Ultrasound Obstet Gynecol. 25(1):19-24, 2005
Cusick W et al: Fetal nasal bone length in euploid and
aneuploid fetuses between 11 and 20 weeks' gestation: a
prospective study. J Ultrasound Med. 23(10):1327-33, 2004
Cicero S et al: Absent nasal bone at 11-14 weeks of
gestation and chromosomal defects. Ultrasound Obstet
Gynecol. 22(1):31-5, 2003
Cicero S et al: Nasal bone hypoplasia in trisomy 21 at
15-22 weeks' gestation. Ultrasound Obstet Gynecol.
21(1):15-8,2003
Lee W et al: Nasal bone evaluation in fetuses with Down
syndrome during the second and third trimesters of
pregnancy. J Ultrasound Med. 22(1):55-60, 2003
Orlandi F et al: Measurement of nasal bone length at 11-14
weeks of pregnancy and its potential role in Down
syndrome risk assessment. Ultrasound Obstet Gynecol.
22(1):36-9, 2003
Sonek JD et al: Nasal bone length throughout gestation:
normal ranges based on 3537 fetal ultrasound
measurements. Ultrasound Obstet Gynecol. 21(2):152-5,
2003
Bromley B et al: Fetal nose bone length: a marker for Down
syndrome in the second trimester. J Ultrasound Med.
21(12):1387-94, 2002
Guis F et al: Ultrasound evaluation of the length of the
fetal nasal bones throughout gestation. Ultrasound Obstet
Gynecol. 5(5):304-7, 1995

ABSENT NASAL BONE
IIMAGE GALLERY
Typical
(Left) Sagittal ultrasound in ,1
second trimester fetus Ivith
trisomy 21 sh()\vs
hypoplastic Nil (arrow). The
angle of insonation is 90° to
the nose yet only a tiny
echogenic focus is seen (NB
< 2.5 mm). (Right) Axial
color Doppler ultrasound
through the fetal heart in the
same fetus shows a small
atrioventricular canal defect
(arrow).

(Left) Sagittal ultrasound of
the facl' in a third trimester
fetus Ivith trisomy 21 shows
a barely ossified hypoplastic
nasal bone (arrow) and
macroglossia (open arrow
points to tongue between
upper and lower lips).
(Right) Clinical photograph
of a child \\'ith trisomy 21
shows Ihe small nasal bridgl'
associated with hypoplastic
nasal bon('.

Other
(Left) 3D ultrasound of the
NB shows the advantages of
multiplanar imaging. With
one volume acquisition, the
NBs are seen in sagittal
(arrows), coronal (open
arrows) and axial (curved
arrows) views. (Right) 3D
ultrasound with maximal
mode rendering shows the
triangular NB en{ace
(arrows) and coronal
"skeletal" view of both NBs
(open arrows). Unilateral NB
hypoplasia is identifiable
with 3D ultrasound.

MICROGNATHIA

Sagittal ultrasound shows micrognathia (curved arrow)
in a fetus with multiple anomalies (open arrow omphalocele).
The nasal bone and forehead are in
profile (arrow) indicating a true sagittal image.

ITERMINOLOGY
Definitions
• Micrognathia: Small mandible
• Retrognathia: Abnormal position of mandible -+
receding chin
o Often coexists with micrognathia
• Glossoptosis: Abnormal posterior position of tongue

IIMAGING FINDINGS

Gross pathology shows micrognathia (curved arrow) in
a fetus with multiple anomalies due to diabetic
embryopathy. There is also microtia (arrow).

• Jaw index < 21 -+ 100% positive predictive value
• Polyhydramnios seen in up to 70% of cases
o Due to impaired swallowing

MR Findings
• Used to evaluate associated central nervous system
anomalies
• May be helpful in evaluation of cleft palate, especially
with obese maternal habitus
o Hard palate is low signal intensity on T2WI
• Forms intact line between nasopharynx and
oropharynx

General Features

Imaging Recommendations

• Receding chin on true sagittal image of face

• Use 3D if available
• Beware pitfalls in diagnosis of micrognathia
o Image profile in true sagittal plane, if off axis may
"create" receding jaw
o Oligohydramnios: Obscures detail
o Agnathia
• Extremely rare, lethal malformation
• Profile abnormal but absence of mandible may
not be appreciated prenatally
• Look for associated cleft lip/palate
o Obtain axial section through toothbuds in maxilla
o Look at nose in coronal plane
• Nasal septum deviated with cleft lip
o Tongue may be unusually well seen with cleft palate
• Evaluate fetal ears
.

Ultrasonographic

Findings

• 3D US may be best method to evaluate facial structures
o Volumetric acquisition
o Ensures accurate sagittal section
• Jaw index
o Anteroposterior (AP) diameter mandible/biparietal
diameter x 100
• AP diameter taken from symphysis mentis to a
line drawn between bases of mandibular rami
o Normative data available
o Provides objective assessment of mandibular size
• Jaw index < 23 -+ 100% sensitivity, 98.7%
specificity for micrognathia

DDx: Pitfalls In Diagnosis Of Micrognathia

Off-Axis

Oligohydramnios

Agnathia

MICROGNATHIA
Key Facts
Terminology
• Micrognathia: Small mandible
• Retrognathia: Abnormal position of mandible ...•
receding chin

Imaging Findings
• Jaw index < 21 ...•100% positive predictive value
• Polyhydramnios seen in up to 70% of cases

Top Differential Diagnoses
• Pseudo-micrognathia

Clinical Issues
• Outcome depends on final diagnosis
• 54% with airway difficulties at birth requiring
intervention
• 31% with feeding problems

•

•

•

•

o Treacher Collins syndrome
• Associated with small ears, ears may not be visible
sonographically
o Nager syndrome
• Malformed ears, poorly ossified upper extremity
bones
o Goldenhar syndrome
• Malformed ears, hemifacial microsomia
o Otocephaly: Hypoplasia or absence of mandible
associated with
• Synotia: Ventromedial displacement external ears
to midline neck
• Microstomia, aglossia, nose-mouth fusion
• Can be very difficult diagnosis to make prenatally
Evaluate fetal eyes
o Neu-Laxova syndrome: Hypertelorism, protruding
eyes, absent eyelids
o Goldenhar syndrome: Microphthalmia,
anophthalmia
o Hypotelorism, cyclops suspicious for trisomy 13
Look at extremities
o Clenched fingers suspicious for trisomy 18
o Club or rockerbottom foot suspicious for trisomy 18
o Polydactyly t suspicion for trisomy 13
o "Flipper" like upper extremities with ulnar defect ~
Cornelia de Lange syndrome
Look for signs of skeletal dysplasias
o Campomelic dysplasia
o Femorofacial syndrome
Other associated abnormalities
o Congenital heart disease in 20%
o Intrauterine growth restriction

I DIFFERENTIAL

DIAGNOSIS

Pseudo-micrognathia
• Incorrect imaging plane
o Need true midline sagittal image
• Look at nose, especially nasal bone
• Chin may look small if head shape is abnormal,
especially frontal bossing

• Sleep-related airway obstruction
• 66% have abnormal chromosomes
• Consider detailed clinical genetic assessment of
family if chromosomes are normal
• Consider use of EXIT (ex utero intra partum
treatment) procedure
• Postnatal treatment requires multidisciplinary team

Diagnostic Checklist
• In at-risk fetus, normal 20 week scan does not
exclude micrognathia
• Significant mandibular growth occurs in third
trimester
• True sagittal scan plane vital for assessment of
micrognathia
• 3D ultrasound very helpful

o Thanatophoric dysplasia
o Achondroplasia

Amniotic band sequence
• Destructive "slash" defects, often multiple
• Look for band from fetus to uterine wall or placenta

I PATHOLOGY
General Features
• Genetics
o Autosomal dominant ~ recurrence risk 50%
• Treacher Collins syndrome: Mutation mapped to
TCOFI gene
• Stickler syndrome: Mutation of COL2Al gene on
chromosome 12q13
o Autosomal recessive ~ recurrence risk 25%
• Smith-Lemli-Opitz syndrome
• Neu-Laxova syndrome
o Syndromes associated with Pierre Robin sequence
• Stickler syndrome
• 22q 11 deletion
• Epidemiology
o Actual incidence of micrognathia unknown
o Micrognathia seen in heterogeneous group of
conditions
• Trisomy 18 1:3,000 live births
• Goldenhar syndrome 1:4-25,000 births
• Pierre Robin sequence 1:5-10,000 births
• Treacher Collins syndrome 1:10-25,000 births
o Incidence of Treacher Collins syndrome is increasing
as more affected infants survive to adulthood
• Associated abnormalities
o Micrognathia often associated with limb
abnormalities
• Oral-facial-digital syndromes
• Oral-mandibular-limb hypogenesis syndromes
• Teratogens
o Isotretinoin
o Penicillamine
o Valproate
o Maternal diabetes

MICROGNATHIA
• Embryology
o Defect in first and second branchial arches
o Abnormal migration or proliferation of neural crest
cells
o Mandibular hypoplasia -+ superior displacement of
tongue -+ failure of palate fusion
• Isolated cleft palate hard to detect on prenatal US
• Lip formation not affected, this is a mechanical
effect on hard palate

ICLINICAL

ISSUES

Presentation
• Abnormal findings on routine sonography
• First trimester detection of Pierre Robin sequence
reported with use of endovaginal sonography

Natural History & Prognosis
• Prenatal diagnosis
o 50% intrauterine or early neonatal demise
• In one series of 19 chromosomally normal fetuses,
only one survived
o 66% have aneuploidy
• Outcome depends on final diagnosis
• Series of sonographically "isolated" micrognathia
o 54% with airway difficulties at birth requiring
intervention
o 31 % with feeding problems
o Sleep-related airway obstruction
o 38% developmental delay, mild to severe
• Intellectual outcome
Goldenhar syndrome: 5-15% mentally subnormal
o Treacher Collins syndrome: 5% developmental
delay, may relate to undetected hearing problems
o Pierre Robin sequence: Speech and hearing
compromise but < 5% of survivors classified as
educationally subnormal
• Recurrence risk
o Aneuploidy: 1% in maternal-age-related
cases
o Syndromes often sporadic new mutations but
several have autosomal dominant or recessive
inheritance

a

• Pierre Robin sequence outcome improved with
early mandibular distraction surgery
o Ear, nose, throat surgery
o Orthodontics
o Speech therapy

I DIAGNOSTIC
Consider

• In at-risk fetus, normal 20 week scan does not exclude
micrognathia
o Significant mandibular growth occurs in third
trimester

Image Interpretation

Pearls

• True sagittal scan plane vital for assessment of
micrognathia
o 3D ultrasound very helpful
• Micrognathia rarely isolated finding in fetus
o Associated with three major disease categories
• Aneuploidy
• Skeletal dysplasias
• Primary mandibular disorders

I SELECTED
1.

2.

3.

4.

5.
6.
7.

Treatment
• Genetic counseling
o Detailed family history
o Teratogen exposure
• Offer karyotype
o 66% have abnormal chromosomes
• Consider detailed clinical genetic assessment of family
if chromosomes are normal
o Relatives may have minor features in Goldenhar
syndrome
• Prenatal consultation with neonatology
• Plan delivery at tertiary center
o Consider use of EXIT (ex utero intra partum
treatment) procedure
• Successful use reported in dysgnathia complex:
Severe micrognathia, microstomia, microglossia,
ear anomalies
• Postnatal treatment requires multidisciplinary
team
o Plastic surgery
o Maxillofacial surgery

CHECKLIST

8.

9.

10.

11.

12.

13.

REFERENCES

Baker PAet al: Airway management during an EXIT
procedure for a fetus with dysgnathia complex. Paediatr
Anaesth. 14(9):781-6, 2004
Manning MA et al: Neu-Laxova syndrome: detailed
prenatal diagnostic and post-mortem findings and
literature review. Am 1 Med Genet A. 125(3):240-9, 2004
Pinter R et al: Infant with severe penicillamine
embryopathy born to a woman with Wilson disease. Am 1
Med Genet A. 128(3):294-8, 2004
Robson CO et al: MR imaging of fetal head and neck
anomalies. Neuroimaging Clin N Am. 14(2):273-91, viii,
2004
Chapa 1B et al: Prenatal diagnosis of methotrexate
embryopathy. Obstet Gynecol. 101(5 Pt 2):1104-7, 2003
Paladini 0 et al: Prenatal ultrasound diagnosis of Nager
syndrome. Ultrasound Obstet Gynecol. 21(2):195-7, 2003
Ruangvutilert P et al: Ultrasonographic prenatal diagnosis
of Treacher Collins syndrome: a case report. 1 Med Assoc
Thai. 86(5):482-8, 2003
Vettraino 1M et al: Clinical outcome of fetuses with
sonographic diagnosis of isolated micrognathia. Obstet
Gynecol. 102(4):801-5,2003
Rotten 0 et al: The fetal mandible: a 20 and 3D
sonographic approach to the diagnosis of retrognathia and
micrognathia. Ultrasound Obstet Gynecol. 19(2):122-30,
2002
Matsumoto,M et al: Antenatal three-dimensional
sonographic features of Pierre-Robin syndrome. Case
report. Gynecol Obstet Invest. 51(2):141-2, 2001
Morin G et al: Cerebro-costo-mandibular syndrome in a
father and a female fetus: early prenatal ultrasonographic
diagnosis and autosomal dominant transmission. Prenat
Oiagn. 21(10):890-3, 2001
Erlich MS et al: Transmission of the dysgnathia complex
from mother to daughter. Am 1 Med Genet. 95(3):269-74,
2000
Paladini 0 et al: Objective diagnosis of micrognathia in the
fetus: the jaw index. Obstet Gynecol. 93(3):382-6, 1999

MICROGNATHIA
I IMAGE GALLERY
(Left) Sagittal TLWI MR
shows micrognathia (curved
arrow), glossoptosis (arrow)
and cleft palate (open
arrow) in a fetus with Pierre
Robin sequence. (Right)
Sagittal T2WI MR shows the
normal appearance of the
chin (black arrow), tongue
(curved arrow) and palate at
24 weeks gestation. The
palate (white arrows) forms
the low signal band
separating the oropharynx
from the nasopharynx.

(Left) Sagittal ultrasound
shows severe micrognathia
and retrognathia (curved
arrow) in a fetus with
Treacher Collins syndrome.
The mandible is small and
posteriorly positioned in
relation to the nose (arrow)
and forehead (open arrow).
(Right) 30 ultrasound of the
.lame case clearly shows the
dysmorphic I~Jcies with
mandibular hypoplasia
(arrow). The downward
slope of the orbits is hard to
appreciate in the felUs, even
with 30 imaging.

(Left) Axial ultrasound shows
the normal, horseshoe shape
of the fetal mandible. The AP
diameter (double-headed
arrow) is measured from the
symphysis mentis (curved
arrow) to a line joining the
bases of the rami. (Right)
Clinical photograph shows
the typical appparance of an
infant with 22q 17 deletion.
There is micrognathia
(curved arrow), a hroad
nasal root and long, slender
fingers (arrow).

MACROGLOSSIA

Coronal 3D ultrasound shows macroglossia (arrows) in
a macrosomic
fetus
with
Beckwith-Wiedemann
syndrome. The tongue persistently protruded through
the lips.

ITERMINOlOGY
Definitions
• Enlarged tongue
o True: Tongue exceeds 95th percentile for gestational
age
o Relative: Tongue appears large secondary to small
oral cavity

IIMAGING FINDINGS
General Features
• Persistent protrusion of tongue through lips
o Best seen on sagittal or coronal images
• Trisomy 21 fetuses also exhibit "tongue thrusting"
o Repetitive "in and out" motion of tongue tip
• Polyhydramnios
o Large tongue obstructs swallowing

Imaging Recommendations
• Best imaging tool
o 3D ultrasound very helpful for global view of fetal
face
• Also helpful counseling tool
• Parents may understand anatomy better with 3D
images

Coronal
ultrasound
of a different
fetus
with
Beckwith-Wiedemann
syndrome
shows
a similar
appearance on grayscale imaging. The tongue (arrows)
was protuberant throughout the scan.

o MR imaging may be useful, if quality of ultrasound
compromised (e.g. maternal obesity)
• Protocol advice
o In at-risk pregnancy, measure tongue circumference
• Normative data available
o Careful anatomic survey
• Macroglossia is rarely an isolated abnormality
o Look for signs of trisomy 21
• Atrioventricular septal defect
• Thick nuchal fold
• Absent nasal bone
• Duodenal atresia
• Rhizomelic limb shortening (humerus more
specific than femur)
• Clinodactyly
• Pelviectasis
o Look for signs of triploidy
• Multiple anomalies
• Dysmorphic face: Micrognathia, macroglossia,
broad root of nose, low-set ears
• Growth restriction
• Thick cystic placenta
o Look for signs of Beckwith-Wiedemann syndrome
• Macrosomia
• Omphalocele
• Hepatosplenomegaly
• Enlarged kidneys
• Adrenal cysts

DDx: Pitfalls In Diagnosis Of Macroglossia

Normal-Tongue Out

Facial Cleft

Facial Cleft

M icrogna thia-Clossoptosis

MACROGLOSSIA
Key Facts
Pathology

Imaging Findings
•
•
•
•
•
•
•
•

Persistent protrusion of tongue through lips
Best seen on sagittal or coronal images
Trisomy 21 fetuses also exhibit "tongue thrusting"
3D ultrasound very helpful for global view of fetal
face
In at-risk pregnancy, measure tongue circumference
Look for signs of trisomy 21
Look for signs of triploidy
Look for signs of Beckwith-Wiedemann
syndrome

Top Differential Diagnoses
• Lymphangioma
• Tongue cysts
• Epignathus

DIAGNOSIS

Lymphangioma

Tongue cysts
• Enteric duplication cyst
• Mucocele of anterior lingual salivary glands
• Ranula: Obstructed sublingual salivary glands

Epignathus
• Specific form of teratoma which protrudes through
oral cavity
.
• Complex, amorphous solid mass
• Often hypervascular
• No spontaneous movement

General Features
• Genetics
o Aneuploidy

• Genetic counseling for detailed family history
• Offer karyotype
• In one series, 77% of fetuses with macroglossia had
an abnormal karyotype, mostly trisomy 21
• Plan delivery in tertiary care facility
• Long term treatment requires multidisciplinary team
• Goal of tongue resection is to reduce size to near
normal while preserving function

Diagnostic Checklist

• Typically focal superficial mass, but may be infiltrative
-. enlargement of tongue
• Multicystic mass
• Usually isolated finding
o Macroglossia strongly associated with
aneuploidy/syndromes,
therefore seldom isolated

I PATHOLOGY

Clinical Issues

• Macroglossia is rarely an isolated finding
• Micrognathia may give false impression of
macroglossia

o Look for signs of hypothyroidism
• Goiter
• Beware pitfalls in diagnosis of macroglossia
o Normal fetal tongue activity
• Circumference is normal
• Tongue "fits" inside mouth
o Micrognathia
• Tongue may look large in relation to small
mandible
o Facial cleft
• Tongue may be unusually well seen, appears large
• Circumference is normal
• Coronal views of face show cleft

I DIFFERENTIAL

• Macroglossia strongly associated with aneuploidy

• Trisomy 21
• Triploidy
o Beckwith-Wiedemann
syndrome
• Majority sporadic
• Autosomal dominant in 10-15% of cases
o Hurler syndrome
• Autosomal recessive
o Crouzon syndrome
• Autosomal dominant craniofacial dysostosis
• Etiology
o Macroglossia strongly associated with aneuploidy
• Majority trisomy 21
• Epidemiology
o Incidence depends on underlying condition
• Beckwith-Wiedemann
syndrome 1:13,000 live
births
• Hurler syndrome 1:150,000 births
• Associated abnormalities
o May be seen with anencephaly
o CHARGE association (coloboma, heart defects,
choanal atresia, growth restriction, genitourinary
anomalies, ear anomalies)

Gross Pathologic & Surgical Features
• Beckwith-Wiedemann
syndrome -. muscular
enlargement of tongue
• Mucopolysaccharidoses
-. glycogen deposition
tongue

in

I CLINICAL ISSUES
Natural History & Prognosis
• Normal tongue growth is considerable after birth
o Tongue length, width, thickness double from birth
to adolescence
• Mechanical problems with macroglossia
o Airway obstruction
o Feeding difficulties
o Speech impediment
o Constant drooling
• Often major concern for parents
• Trisomy 21

MACROGLOSSIA
o Dawn syndr.ome infants have relative macrogl.ossia
• Small .oral cavity
• Muscular hyp.ot.onia .of t.ongue ..• exacerbates p.o.or
"fit" t.o .oral cavity
o Risk c.ongenital heart disease, especially
atri.oventricular septal defect
o Devel.opmental delay variable, mild t.o severe
• Average IQ 50-60
o Average life expectancy is 20 years, many.older
survivors
o 20-f.old risk acute leukemia
• Beckwith-Wiedemann
o Infant m.ortality 20%
o Risk.of ne.onatal hyp.oglycemia
o Risk.of pediatric tum.ors
• Hurler syndrome
o Progressive disease with mental retardati.on, heart
disease, j.oint disease
o Death by early teens in majority .of cases

• Laser caagulatian useful for superficial
malformatians
• Usually requires multiple treatments

I DIAGNOSTIC

CHECKLIST

Consider
• Mast likely diagnases in a fetus with macroglassia
o Trisamy 21
o Beckwith-Wiedemann
syndrome

Image Interpretation

Pearls

• Macroglassia is rarely an isalated finding
o L.o.okfor additianal abnormalities ta assist with
specific diagnasis
• Micrognathia may give false impressian .of
macroglassia

Treatment

I SELECTED REFERENCES

• Genetic counseling for detailed family hist.ory
• Offer kary.otype
o In .one series, 77% .of fetuses with macrogl.ossia had
an abn.ormal kary.otype, m.ostly tris.omy 21
• C.onversely.only 14%.of fetuses with tris.omy 21
had facial abnormality
o Hurler syndrome can be diagn.osed prenatally by
testing cultured amni.ocytes
• Terminati.on may be .offered far aneupl.oidy,
muc.op.olysaccharid.oses
• Plan delivery in tertiary care facility
o C.ounsel parents regarding risk .of airway
c.ompromise
o Risk for ne.onatal hyp.oglycemia In
Beckwith-Wiedemann
syndrome
• M.onitor for devel.opment .of p.olyhydramni.os
o Increases risk .of preterm lab.or
o Adds risks .of prematurity t.o airway c.ompromise
from large t.ongue
• M.onitor m.other for signs .of preeclampsia
o Increase risk with Beckwith-Wiedemann
syndr.ome
• Lang term treatment requires multidisciplinary
team
o Orth.od.ontics
o Orofacial regulati.on therapy
• Palatal plate stimulati.on improves muscle tane,
reduces tangue protrusian
o Speech therapy
o Maxillafacial surgery
• Beckwith-Wiedemann
syndrome may be
particularly difficult ta manage with same
children, requiring tracheastamy
• Gaal .of tangue resectian is ta reduce size ta near
normal while preserving functian
• Surgery generally improves casmesis and airway
functian
• Swallawing may nat be helped
• Speech impediment relates ta neurolagical
canditian
• Children with significant intellectual impairment
may nat shaw improved speech patterns
o Lymphangiamataus
macroglassia is mast likely ta
recur and daes least well with surgery

Jian xc: Surgical management of lymphangiomatous or
lymphangiohemangiomatous
macroglossia. J Oral
Maxillofac Surg. 63(1):15-9, 2005
2. Giancotti A et al: Clinical treatment of oral manifestations
of Beckwith-Wiedeman syndrome in a child. J Clin Pediatr
Dent. 27(4):377-80, 2003
3. Gasparini G et al: Surgical management of macroglossia:
discussion of 7 cases. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod. 94(5):566-71, 2002
4. Hamada H et al: Prenatal sonographic diagnosis of
Beckwith-Wiedemann syndrome in association with a
single umbilical artery. J Clin Ultrasound. 29(9):535-8,
2001
5. Kacker A et al: Tongue reduction in Beckwith-Weidemann
syndrome. Int J Pediatr OtorhinolaryngoI. 53(1):1-7, 2000
6. Sergi C et al: Analysis of the spectrum of malformations in
human fetuses of the second and third trimester of
pregnancy with human triploidy. Pathologica.
92(4):257-63,2000
7. Yoskovitch A et al: Acute airway obstruction in Hunter
syndrome. Int J Pediatr OtorhinolaryngoI. 44(3):273-8,
1998
8. Achiron R et al: Development of the fetal tongue between
14 and 26 weeks of gestation: in utero ultrasonographic
measurements. Ultrasound Obstei: GynecoI. 9(1):39-41,
1997
9. Morgan WE et al: Surgical management of macroglossia in
children. Arch Otolaryngol Head Neck Surg. 122(3):326-9,
1996
10. Weissman A et al: Macroglossia: prenatal uItrasonographic
diagnosis and proposed management. Prenat Diagn.
15(1):66-9, 1995
11. Nicolaides KH et al: Fetal facial defects: associated
malformations and chromosomal abnormalities. Fetal
Diagn Ther. 8(1):1-9, 1993
12. Siddiqui A et al: The efficacy of tongue resection in
treatment of symptomatic macroglossia in the child. Ann
Plast Surg. 25(1):14-7, 1990
1.

MACROGLOSSIA
I IMAGE GAllERY
(Left) Sagittal ultrasound
shows an extremely large
tongue (curved arrows) in a
third trimester fetus. This was
an isolated finding in this
case. Note the normal nasal
bone (arrow). (Right)
Sagittal ultrasound shows the
tongue (arrow) protruding
from the mouth in a fetus
with Beckwith-Wiedemann
syndrome. The tongue is too
large to fit inside the oral
cavity.

(Left) Sagittal ultrasound
shows an abnormal profile in
a fetus with Down
syndrome. The tongue
(curved arrows) is large and
"tongue thrusting" was
observed in real time. Note
depressed nasal bridge
(arrow). (Right) Clinical
photograph shows the
typical profile appearance of
an infant with Down
syndrome. The mouth is
often held open secondary
to the large tongue, resulting
in persistent drooling. Also
note the flattened nasal
bridge (arrow).

(Left) 30 ultrasound of a
fetus with
Beckwith-Wiedemann
syndrome shows
macroglossia, with the tip of
the tongue (curved arrow)
protruding through the lips
(arrows). (Right) Coronal
ultrasound shows the tip of
the nose (open arrow), the
lips (arrows) and the
protuberant tongue (curved
arrow) of a fetus with Down
syndrome.

EPIGNATHUS

Sagittal ultrasound of the fetal profile shows a large,
mixed cystic and solid mass (curved arrow) protruding
from the mouth. The jaw was held in a fixed open
position (arrow - mandible).

ITERMINOlOGY
Abbreviations
•
•
•
•

Epignathus
Nasopharyngeal
Oral teratoma
Facial teratoma

and Synonyms

Definitions
cavity or pharynx

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Large, fungating oral mass
o Calcifications are virtually pathognomonic
of
teratoma but are present in only half of cases and
may not be visible with ultrasound
• Location
o Most commonly arise from hard or soft palate
o Fills oral cavity and emanates from mouth and/or
nose
o Transsphenoidal intracranial extension can occur
• Produces an extra-axial mass
• Can cause marked distortion of intracranial
structures

DDx: Oral/Facial

Macroglossia

• Size
o Usually large at time of diagnosis
o Can be massive, often larger than fetal head

Ultrasonographic

teratoma

• Teratoma arising in oral/nasal

Cross pathology of the resected mass shows the
complex nature of the teratoma. The solid portion had
neuroglial elements, fat, smooth muscle and cartilage.
(Also shown in Radiographies, ref 7).

Findings

• Predominately solid or mixed cystic/solid
• Commonly distorts surrounding anatomy
o Jaw is held in a fixed open position
o Splayed mandible
o Hypertelorism
o Exophthalmos
o Cervical hyperextension
• Polyhydramnios secondary to pharyngeal obstruction
o Often severe
• Color Doppler
o Solid portions of mass often very vascular
o Arteriovenous shunting may be present
• Hydrops may develop with large masses

MR Findings
• Helpful in determining anatomic extent
o Important for intracranial involvement
• Can identify fat within lesion

CT Findings
• In utero CT with 3D reformation has been done
o Better evaluation of calcifications and boney
anatomy

Masses

Rhabdomyosarcoma

EPIGNATHUS
Key Facts
Terminology
• Teratoma arising in oral/nasal

cavity or pharynx

Clinical

Imaging Findings
•
•
•
•
•
•
•
•
•

Large, fungating oral mass
Most commonly arise from hard or soft palate
Transsphenoidal intracranial extension can occur
Predominately solid or mixed cystic/solid
Jaw is held in a fixed open position
Polyhydramnios secondary to pharyngeal obstruction
Hydrops may develop with large mass s
MRI recommended to better delineate anatomy
Evaluate brain carefully for intracranial extension

Top Differential

Issues

• May show rapid in utero growth
• Sub tantial improvement in survival achieved with ex
utero intrapartum treatment (EXIT) procedure
• Fetus is partially delivered by cesarean section while
placenta and umbilical cord remain intact
• Uteroplacental gas exchange maintained
• Fetus remain hemodynamically
stable while airway
is established

Diagnostic Checklist
• Any large, fungating oral mas
of a teratoma

Diagnoses

• Cervical teratoma
• Amniotic band yndrome

Imaging Recommendations
• Routine head and face views should detect virtually all
cases
• Color Doppler to evaluate vascularity
• MRI recommended to better delineate anatomy
o Presence of intracranial extension negatively
impacts prognosis
• Close interval scanning
o May grow rapidly to massive size
• Often larger than fetal head
o Evaluate brain carefully for intracranial extension
• Compresses and displaces normal brain
parenchyma
• Head enlargement
• Hydrocephalus
o Worsening polyhydramnios
o Mass may cause high-output cardiac failure and
hydrops
• Cardiomegaly
• Ascites
• Pleural effusion
• Skin thickening

I DIFFERENTIAL

• Frontal cephalocele
• Other rare tumors

DIAGNOSIS

Cervical teratoma

•
•
•
•

virtually diagnostic

Usually small and may be missed prenatally
Higher than typical epignathus
Hypertelorism
MRI confirms diagnosis

Other rare tumors
• Myoblastoma
o Reported in oral cavity
o Found exclusively in females
• Nasal glioma
o Collection of dysplastic brain tissue
o Located in nasal cavity or subcutaneous tissue
• Dermoid cyst
o Persistent dural projection through foramen cecum
• Dermoid or epidermoid envelops along tract
o Can have connection with intracranial contents
• Soft tissue tumors (both benign and malignant) may
cause a facial mass
o Hemangioma
o Fibromatosis, myofibromatosis
o Fibrosarcoma, rhabdomyosarcoma

Bilateral cleft lip/palate

(CL/CP)

• Premaxillary protrusion in axial plane may appear as
like soft tissue mass
• Coronal/axial views show bilateral clefts
o Clefts extend posteriorly through alveolar ridge

Macroglossia

• Point of origin of large masses may be difficult to
discern
• Look carefully at mouth and brain
o No intraoral or intracranial extension
• Neck often held in hyperextension
• May extend into mediastinum

I PATHOLOGY

Amniotic band syndrome

General Features

• May cause facial mass from "slash" defects
o Large, obliquely oriented facial clefts
• Bands may be visible
• Other body parts often affected

• Genetics
o Sporadic
o No recurrence risk
• Etiology
o Embryology
• Primordial germ cells migrate from yolk sac to
genital ridges (weeks 4-6)

Frontal cephalocele
• Frontoethmoidal

skull defect with herniation

of brain

• Mouth open, with persistent protrusion
• Seen with multiple syndromes

of fetal tongue

EPIGNATHUS
• Germ cells are then incorporated into primitive
sex cords to form gonad
• Unincorporated cells normally involute
• Continued division of unincorporated
pluripotential cells gives rise to teratoma
• Epidemiology
o Rare
o Head and neck second most common site for
teratomas after sacrococcygeal
o More common in females
• Associated abnormalities: Increased incidence of
cardiac anomalies reported

Gross Pathologic & Surgical Features
• Complex, mixed cystic and solid components
• Teeth and hair not as common as in teratomas
in life

Microscopic

latter

Features

• Unique histologic features compared to teratomas
presenting latter in life
• Composed of all three germ cell layers
o Ectodermal tissues main histologic component of
fetal teratomas
• Often contain neural tissue ("brain-like") as a
dominant component
o Mesoderm
• Fat
• Cartilage
• Smooth muscle
• Bone
o Endoderm
• Least common component
• Respiratory epithelium
• Gastrointestinal tissues

Staging, Grading or Classification Criteria
• Teratomas classified as mature or immature
o Immature teratomas do not have same poor
prognosis as those presenting latter in life
• Immaturity of tumor may reflect immaturity of
fetus rather than biologic behavior of tumor
o Size and vascularity are much more important than
histology in a fetus

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms: Obvious fungating
oral mass
• Other signs/symptoms
o Polyhydramnios
o Reported as early as 15 weeks

Natural History & Prognosis
• May show rapid in utero growth
• Polyhydramnios may cause preterm labor
• Routine resuscitation techniques
o Lethal if unable to establish airway
• Even with maximal emergency procedures,
hypoxia, acidosis and anoxic brain injuries occur
o Mortality 80-100%

• Substantial improvement in survival achieved with ex
utero intrapartum treatment (EXIT) procedure
o In large series airway established in 79%, with
overall survival of 69% for head and neck masses

Treatment
• Termination offered
• If pregnancy continued, deliver at tertiary care facility
with capability of performing EXIT procedure
• EXIT procedure provides controlled environment to
establish airway (either intubation or tracheostomy)
o Fetus is partially delivered by cesarean section while
placenta and umbilical cord remain intact
o Uteroplacental gas exchange maintained
o Fetus remains hemodynamically
stable while airway
is established
o Avoid "crash" attempt at achieving airway at birth

I DIAGNOSTIC

CHECKLIST

Consider
• MRI to better delineate anatomy and evaluate for
intracranial extension
• If pregnancy is continued refer patient to tertiary care
facility with capability of performing EXIT procedure

Image Interpretation

Pearls

• Any large, fungating oral mass is virtually diagnostic
of a teratoma

ISELECTED REFERENCES
Woodward PJ et al: From the archives of the AFIP: a
comprehensive review of fetal tumors with pathologic
correlation. Radiographies. 25(1):215-42, 2005
2.
Hirose S et al: The ex utero intrapartum treatment
procedure: Looking back at the EXIT. J Pediatr Surg.
39(3):375-80; discussion 375-80, 2004
3.
Morof 0 et al: Oropharyngeal teratoma: prenatal diagnosis
and assessment using sonography, MRI, and CT with
management by ex utero intrapartum treatment procedure.
AJR Am J Roentgenol. 183(2):493-6, 2004
4.
Bouchard S et al: The EXIT procedure: experience and
outcome in 31 cases. J Pediatr Surg. 37(3):418-26, 2002
Papageorgiou C et al: Prenatal diagnosis of epignathus in
5.
the first half of pregnancy: A case report and review of the
literature. Clin Exp Obstet Gynecol. 27:67-8, 2000
Wagner W et al: Fetal operations in the head and neck
6.
area: current state. Head Neck. 24(5):482-90, 2002
Gulli et al: Antenatal sonographic diagnosis of epignathus
7.
at 15 weeks of pregnancy. Ultrasound Obstet Gynecol.
13:271-3, 1999
8.
Stocks RM et al: Airway management of neonates with
antenatally detected head and neck anomalies. Arch
Otolaryngol Head Neck Surg. 123(6):641-5, 1997
McMahon M] et al: Perinatal management of a lingual
9.
teratoma. Obstet Gynecol. 87:848-51,1996
10. Parkes SE et al: Neonatal tumours: a thirty-year
population-based
study. Med Pediatr Oncpl. 22(5):309-17,
1994
11. Wienk MA et al: Prenatal diagnosis of fetal tumors by
ultrasonography. Obstet Gynecol Surv. 45(10):639-53,
1990
12. Isaacs H Jr: Perinatal (congenital and neonatal) neoplasms:
a report of 110 cases. Pediatr Pathol. 3(2-4):165-216, 1985
1.

EPIGNATHUS
IIMAGE GALLERY
(Left) Intra-operative
photograph of the EXIT
procedure. The fetus is
partially delivered via
cesarean section and placed
on the maternal abdomen.
The placenta and umbilical
cord remain intact and
uteroplacental gas exchange
maintained. The mass is
controlled while the
intubation is performed.
(Right) The tongue is
retracted, showing the
successful intubation. (Also
shown in Radiographies, ref

1).

(Left) Coronal (left) and
sagittal (right) views of the
fetal head show a complex
cystic mass centered at the
skull base, with intracranial
growth (arrow) and
extension out the mouth
(curved arrow). (Right)
Postmortem T2WI (left) and
photograph (right) show the
oral component of the mass
(white arrows), with splaying
of the mandible and
deviation of the tongue
(open arrows). The black
arrow shows intracranial
extension.

(Left) Sagittal T2WI MR of a
nasopharyngeal teratoma
shows a predominately solid
mass (arrow) involving the
midface. There was no
intracranial extension and
the brain was normal. (Right)
Sagittal gadolinium
enhanced scan after delivery
shows areas of enhancement
within this large solid mass,
which involved both the oroand nasopharynx. The inset
shows the resected mass.

EAR ANOMALIES

Second trimester ultrasound in a fetus with Treacher
Collins syndrome shows small low-set ears (open
arrow) on the coronal view. The fetal profile shows
severe micrognathia (arrow).

ITERMINOLOGY
Abbreviations
• Congenital

and Synonyms

auricular anomalies

Definitions
• Abnormal external ear formation
o Heterogeneous group of disorders
• Malformation anomalies
o Embryologic maldevelopment
• Deformation anomalies
o 2° to in utero physical forces

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Abnormal ears seen best with 3D ultrasound
• Isolated or with other anomalies
• Often with other craniofacial defects
• Location: Unilateral or bilateral
• Size: Unusually small or large ears
• Morphology: Highly variable

Ultrasonographic

Findings

• Fetal ear evaluation
o Determine ear position

30 ultrasound In the same fetus shows micrognathia
(arrow), low-set ears + microtia (open arrows) and
proptosis (curved arrow). The findings are all classic
features of Treacher Collins syndrome.

• Identify eyes
• Inner canthi line (join 2 inner canthi)
• Top of helix should be at level of inner canthi line
• Identify top and bottom of ears
• Measure ear length
o Evaluate ear morphology
• Enface ear view
o 3D Ultrasound
• Multiplanar capability
• Soft tissue rendering
• Look for other fetal face anomalies
• Normal ear size
o Normal length
• Ear growth is linear through gestation
• Ear length = 1/3 biparietal diameter (BPD)
• May use nomograms for percentiles
o Ear width more difficult to assess
• Nomograms for 18-22 weeks most accurate
• Measurement unreliable with t fetal age
• Normal auricular topography
o Helix
• Most external curve of auricle
o Antihelix
• V-shaped internal auricle
o Tragus
• Inferior to root of helix, over external acoustic
meatus
o Antitragus

DDx: Craniofacial Anomalies (3D Ultrasound)

Cleft Palate

Micrognathia

Anencephaly

EAR ANOMALIES
Key Facts
Terminology

• Offer genetic counseling

• Abnormal external ear formation
• Heterogeneous group of disorders

Top Differential

Imaging Findings
•
•
•
•
•
•
•
•

Abnormal ears seen best with 3D ultrasound
Determine ear position
Evaluate ear morphology
Ear length = 1/3 biparietal diameter (BPD)
Anotia
Microtia
Absent auricular components
Low- et ears: Top of helix lower than inner canthi
line
• Protruding ear often isolated idiopathic finding
• Auricular tags
• Look at ears when other facial anomalies seen

•

•

•

• Superior to lobe and faces tragus
o Lobule (ear lobe)
• Non-cartilaginous
(fibrofatty tissue)
o Concha fossa
• Inner fossa near root of helix
• Contiguous with external auditory canal
Deficient ear
o Anotia
• Absent ear
o Microtia
• Small ear
• Cephalo-caudad ear length < 1/3 of BPD
• < 10th percentile for gestational age
o Absent auricular components
• Partial or complete helix absent
• Antihelix absent
• Absent lobe (lobule)
Malpositioned ears
o Low-set ears: Top of helix lower than inner canthi
line
o Malrotated ears
• Often also dysplastic, may be large or small
o Protruding ears often isolated idiopathic finding
• > 2 cm from mastoid skin (at birth)
Supernumerary parts
o Duplication of embryologic components
o Auricular tags
• Found at embryologic junctions
• Pre-auricular tag most common
o Mirror image auricular duplication
• Polyotia
• Partial or complete duplication
• Mirror image orientation to 1 ear
• Appears as long dysplastic ear
Deformation of ear cartilage
o Lop ear
• Top of ear is curled downward
o Crinkled ear
• Crinkled helix
Ear anomaly associations
o Trisomy 21 (T21)
• 60% of T21 fetuses have short ears
0

•

•

Diagnoses

• ormal ear
• Facial clefts
• Severe facial anomalies

Pathology
• T21, T18, T13, Turner syndrome
• Often with other craniofacial anomalies

Clinical Issues
• Surgical treatment for malformation
• on-surgical treatment for deformations
• Auricular cartilage malleable first 3 months of life

Diagnostic Checklist
• Ear anomalies often missed prenatally

o

o

o

o

o

o

o

• Sensitivity 80%
• Positive predictive value 73%
• Rarely an isolated finding
Trisomy 18 (TI8)
• Short malformed ear
• + Multiple other anomalies
Trisomy 13 (TI3)
• Microtia/anotia
• Holoprosencephaly
is hallmark finding
Turner syndrome
• Short ear length
• Cystic hygroma is hallmark finding
Treacher Collins syndrome
• Microtia/anotia common
• Micrognathia
• Abnormal eyes with ocular fissures
Anencephaly
• Low-set/lop ear
• Open neural tube defect
• Absent calvarium superior to face
Potter syndrome
• Deformation from severe oligohydramnios
• Low-set ears
Micrognathia from any cause
• Heterogeneous disorders
• Low-set dysplastic ears common

Imaging Recommendations
• Best imaging tool
o 3D ultrasound
• Assess ear location, size, morphology
• Protocol advice
o Look at ears when other facial anomalies seen
• Often associated with micrognathia
o Offer genetic counseling

I DIFFERENTIAL DIAGNOSIS
Normal ear
• False + diagnosis of low-set ears
o Difficult to judge without 3D ultrasound
• Not part of routine exam

EAR ANOMALIES
o May be difficult to see
• Complex morphology

I CLINICAL

ISSUES

Facial clefts

Presentation

• Cleft lip +/- palate
• Amniotic band syndrome
o Disruption of amnion with fetal entrapment
o Bizarre facial clefts

• Most common signs/symptoms
o Isolated ear anomaly incidentally noted
• Low detection rates (ears not routinely scanned)
o In association with other more severe anomalies
• Other signs/symptoms: Often seen with micrognathia

Severe facial anomalies
• Ears mayor may not be normal
• Holoprosencephaly
o Hypotelorism
o Proboscis
o Midline/bilateral cleft lip & palate
• Midface anomalies
• Mandibular hypoplasia

I PATHOLOGY
General Features
• Genetics
o Aneuploidy
• T21, T18, T13, Turner syndrome
o Hereditary
• Single gene mutation
• Sex-linked traits
o Many syndromes
• Often with other craniofacial anomalies
• Etiology
o Embryology of normal ear
• Ears arise from 1st and 2nd branchial arches
• 6 hillocks from branchial arches form ear
• Ears migrate dorsal and lateral
• Migration as mandible/maxilla develop
• Folding of auricular cartilage
• Fully developed auricle by 9th wk
o Abnormal ear
• Abnormal genetic information
• Ischemia (stapedial artery hemorrhage)
• Chondrogenesis interference
o Toxin exposure
• Thalidomide
• Retinoic acid
• Epidemiology
o Microtia/anotia
• 0.8 to 2.4:10,000 live births
• 8.3:10,000 live births in Navajo
• Associated abnormalities
o Craniofacial sequence
o Cardiac, renal, eye anomalies
• Same embryologic timeline

Demographics
• Age
o Trisomies associated with advanced maternal age
• ~ 3S yo at time of delivery

Natural History & Prognosis
• Depends on severity of anomaly
• Presence of other anomalies

Treatment
• Surgical treatment for malformations
o Multiple procedures over time, with growth of child
• Non-surgical treatment for deformations
o All ear components present
o Auricular cartilage malleable first 3 months of life
• 2° to maternal estrogen effect
o Molding and splinting
• Surgery + molding often necessary

I DIAGNOSTIC
Consider

• Ear anomalies often missed prenatally
• Perform 3D ultrasound when anomalies suspected

Image Interpretation

Failure of formation
Failure of differentiation
Duplication
Overgrowth
Undergrowth
Part of craniofacial sequence

Pearls

• Early referral to plastic surgery
o Nonsurgical treatment works best in first 3 months
o Prenatal consultation possible (3D pictures helpful)
• Look carefully at ears when mandible anomalies seen

I SELECTED
1.

2.

3.

4.

Staging, Grading or Classification Criteria
•
•
•
•
•
•

CHECKLIST

5.

6.

REFERENCES

Johnson JM et al: Early prenatal diagnosis of
oculoauriculofrontonasal syndrome by three-dimensional
ultrasound. Ultrasound Obstet Gyneco!. 25(2):184-6, 2005
Porter CJ et al: Congenital auricular anomalies:
topographic anatomy, embryology, classification, and
treatment strategies. Plast Reconstr Surg. 115(6):1701-12,
2005
Shaw GM et al: Epidemiologic characteristics of anotia and
microtia in California, 1989-1997. Birth Defects Res A Clin
Mol Terato!. 70(7):472-5, 2004
Shih JC et al: Antenatal depiction of the fetal ear with
three-dimensional ultrasonography. Obstet Gyneco!.
91(4):500-5, 1998
Shimizu T et al: The role of reduced ear size in the prenatal
detection of chromosomal abnormalities. Prenat Diagn.
17(6):545-9,1997
Shimizu T et al: Ultrasonographic measurements of fetal
ear. Obstet Gyneco!. 80(3 Pt 1):381-4, 1992

EAR ANOMALIES
IIMAGE

GALLERY
(Left) Coronal oblique
ultrasound shows a low-set
dysplastic ear (arrow) in a
fetus with multiple other
anomalies, including
micrognathia. (Right) Clinical
photograph of another fetus
with agnathia (absent
mandible) shows elongated,
low-set ears, with some
mirror image duplication.
Mandible and ear anomalies
are often seen together.

(Left) Sagittal oblique 30
ultrasound shows a
deformed ear (arrows) in a
fetus with anencephaly. The
mass effect of the herniated
brain (open arrows) may be
the cause of the lop ear.
(Right) Clinical photograph
of anencephaly shows a
low-set, deformed ear. Ear
anomalies often occur in
conjunction with craniofacial
defects, including
anencephaly.

(Left) 30 ultrasound of a
fetus with Pierre Robin
syndrome shows
micrognathia (curved arrow)
and low-set ears (open
arrows). The arrow points to
the expected location of the
top of the helix, based on the
inner canthi line. (Right) 30
ultrasound of normal 2nd
trimester (left) and 3rd
trimester (right) ears shows
exquisite morphologic detail.

MIDFACE ANOMALIES

Sagittal ultrasound shows subUe midface hypoplasia in a
2nd trimester fetus with T21. The midface (arrows) is
flat. The nasal bone (open arrow) is small and flattened
and the maxilla (curved arrow) is posteriorly displaced.

ITERMINOlOGY
Definitions
• Abnormalities of fetal midface
• 2 major categories
o Midface hypoplasia
• Depressed nasal bridge
• Maxillary hypoplasia
o Holoprosencephaly
spectrum

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Abnormal fetal profile
• Hypoplastic flat midface
• Dysplastic midface
• Location: Maxilla + nose +/- orbit involvement
• Morphology
o Highly variable
o Midface hypoplasia
• Findings may be subtle
o Holoprosencephaly
• Nose, mouth, eyes may be unrecognizable

Ultrasonographic

Findings

• Midface hypoplasia

Sagittal TZWI MR in a syndromic fetus shows a small
nose (open arrow) and maxilla (curved arrow). The
mandible (arrow) ends at the same level as the maxilla.
instead a/slightly posterior to it.

o Profile view shows flat face
o Abnormal fronto-nasal bone angle
• Flat nasal bridge
• Short nose
o Hypoplastic maxilla
• Maxilla displaced posteriorly
o Reverse overbite, if severe
• Mandible anterior to maxilla
o Cleft lip (CL) +/- cleft palate(CP) may be seen
• Isolated CL often with only flattened nares
• Midface hypoplasia associated with skeletal dysplasia
o Thanatophoric dysplasia
• Most common fatal skeletal dysplasia
• Severe limb shortening
• Small chest
o Achondroplasia
• Autosomal dominant
• Homozygous form is fatal
• Rhizomelic limb shortening
• Heterozygous: Mild midface hypoplasia
o Craniosynostosis syndromes
• Apert syndrome
• Carpenter syndrome
• 11q deletion Qacobsen syndrome)
• Midface hypoplasia associated with aneuploidy
o Trisomy 21 (T21)
• Frontal bossing
• Midface findings often subtle

DDx: Midface Anomalies

Teratoma

Cleft Palate

MIDFACE ANOMALIES
Key Facts
Terminology

Top Differential Diagnoses

• 2 major categories
• Midface hypoplasia
• Holopro encephaly

• ormal face
• Unilateral cleft lip and palate
• Midfa e mass

pectrum

Imaging Findings

Pathology

•
•
•
•
•
•
•
•
•
•
•

• Holoprosencephaly
• Holoprosencephaly

Flat nasal bridge
Hypoplastic maxilla
Rever e overbite, if severe
Midface hypoplasia associat d with keletal dyspla ia
Spectrum of holoprosencephaly
face anomalies
yclopia with proboscis
Ethmocephaly
ebocephaly
Spectrum of median cleft lip/palate
3D help delineate midface anomalies
MR helpful for brain anomalies

• Most obvious later in gestation
o Trisomy 13 (T13)
• Median CL/CP + midface hypoplasia
• More often with holoprosencephaly
• Holoprosencephaly
o Midline brain anomalies +/- face anomalies
• Complete or partial fused thalami
• Monoventricle or fused ventricles
• Abnormal brain mantle
o Spectrum of brain findings
• Alobar (most severe)
• Semilobar
• Lobar
• Septo-optic dysplasia (most mild)
o "Face predicts the brain"
• Brain is abnormal if face is abnormal
o Brain does not always predict the face
• 28% with normal face
• Spectrum of holoprosencephaly
face anomalies
o Normal face
• Holoprosencephaly
brain
o Cyclopia with proboscis
• Single eye globe +/- some doubling
• Blind-ending tube instead of nose
• Proboscis located superior to orbit
o Ethmocephaly
• Severe hypotelorism
• Arrhinia (no nose) or proboscis
• Proboscis often at orbit level
o Cebocephaly
• Hypotelorism
• Nose with single nostril
o Spectrum of median cleft lip/palate
• Midline CL/CP
• Bilateral CL/CP
• Median maxillary agenesis
• Isolated midline CP
• 3D helps delineate midface anomalies
o Multiplanar advantages
• Sagittal, coronal, axial images with single volume
acquisition
o Soft tissue rendering

(50-60°/6 with aneuploidy)
associated with diabete

Clinical Issues
• TI8, T13, T2I association
• Alcohol (fetal alcohol effects)

Diagnostic Checklist
• Look at fr fHo-nasal bon angle on profil
• Recommend genetic coun ling

views

• Recognizable fetal face
o Bone rendering
• Visualization of sutures, bone detail
• MR helpful for brain anomalies
o Holoprosencephaly
spectrum
o Can detect subtle anomalies missed with ultrasound

Imaging Recommendations
• Best imaging tool
o We routinely look at face for "take home" pictures
• Look carefully at nasal bone
• Orbit/nose/maxilla/mandible
relationships
• Protocol advice
o Look for other anomalies
• Markers for aneuploidy/syndromes
o Consider fetal MR
• Anytime midline facial defects seen
• Mild holoprosencephaly
can be missed

I DIFFERENTIAL

DIAGNOSIS

Normal face
• Mid-sagittal plane
o Assess fronto-nasal bone angle
o Nasal bone can be measured
o Maxilla in front of mandible
• Coronal plane snout view
o 2 nasal nares + intact upper lip
• Axial views
o 2 orbits normally spaced
• Can measure orbit biometry
o Intact alveolar ridge of palate

Unilateral cleft lip and palate
• Cleft is lateral to philtrum
• Most common is CL + CP
• Palate often dysplastic, if large CP
o Abnormal profile
• Premaxillary protrusion
• Similar to bilateral CL/CP profile
• Depressed nares with CL
o More likely than depressed nasal bridge

MIDFACE ANOMALIES
• Associated midface hypoplasia

common

o Teratogens associated with holoprosencephaly
• Alcohol
• Retinoic acid

Midface mass
• Rare
• Aggressive large tumors
• Teratoma (epignathus)
o Nasal/oral origin
o Can grow through nose (mimic proboscis)
• Frontal encephalocele
o Bone defect with herniated brain
• Rhabdomyosarcoma
• MR helpful to show extension of tumor

I PATHOLOGY
General Features
• Genetics
o Midface hypoplasia
• T21, T13, llq deletion
• Many syndromes
o Holoprosencephaly
(50-60% with aneuploidy)
• T13 (2/3)
• Trisomy 18 (TI8), triploidy, monosomy 21
• 5p+, 13q-, 18p-,
• 12 different chromosome loci identified
• Sonic hedgehog gene (SHH)
• SHH mutation in 33% of familial cases
• Etiology
o Normal facial embryology
• Five facial prominences fuse by 10 wks
• Unpaired frontonasal process contains orbits
• Paired maxillary swellings
• Paired mandibular swellings
o Midface hypoplasia
• Intermaxillary process hypoplasia
• Affects mid maxilla and nose
o Holoprosencephaly
• Prechordal mesenchyme fails to induce cleavage
• Failure of prosencephalon
cleavage
• Failure of frontonasal process cleavage
• Abnormal mid face migration and cleavage
• Epidemiology
o 1:16,000 births with holoprosencephaly
• 1:250 terminated pregnancies
• Associated abnormalities
o Holoprosencephaly
associated with diabetes
• 1% risk for fetuses of diabetic mothers

Demographics
• Age: Trisomies associated with advanced maternal age

Natural History & Prognosis
• Midface hypoplasia
o Depends on associated findings
o Mild isolated cases with good prognosis
• Holoprosencephaly
o Stillbirth common
o Liveborn infants with short lifespan
o Severe feeding difficulties
o Seizure disorder

Treatment
• Maxillary advancement surgery
o Gradual lengthening of bone
o Soft tissue maxillary expansion
o Significant relapse rates

I DIAGNOSTIC
Consider

• Fetal MR for equivocal/difficult
cases
o Fetal face often seen well
o Subtle brain anomalies detectable

Image Interpretation
•
•
•
•

1.

2.

3.

ISSUES

5.

Presentation
• Most common signs/symptoms
o Abnormal maternal serum screen result
• T18, T13, T21 association
o Incidentally identified at time of routine scan
• Other signs/symptoms
o Teratogens associated with midface hypoplasia
• Alcohol (fetal alcohol effects)
• Carbamazepine (Tegretol)
• Coumadin
• Hydantoin (Dilantin)
• Valproic acid

6.

7.
8.

Pearls

Look at fronto-nasal bone angle on profile views
Maxilla/mandible
relationship
Use 3D ultrasound if face looks atypical
Recommend genetic counseling
o Identify familial syndromes
o Amniocentesis

I SELECTED

4.

I CLINICAL

CHECKLIST

REFERENCES

Cuillier F et al: Maxillo-nasal
dysplasia (binder syndrome):
antenatal
discovery and implications.
Fetal Diagn Ther.
20(4):301-5,2005
Joo GJ et al: Prenatal diagnosis, phenotypic
and obstetric
characteristics
of holoprosencephaly.
Fetal Diagn Ther.
20(3):161-6,2005
Wang XX et al: Internal midface distraction
in correction
of severe maxillary hypoplasia
secondary to cleft lip and
palate. Plast Reconstr Surg. 116(1):51-60,2005
Thakur S et al: Spectrum of holoprosencephaly.
Indian J
Pediatr. 71(7):593-7, 2004
Lai TH et al: Prenatal diagnosis of alobar
holoprosencephaly
by two-dimensional
and
three-dimensional
ultrasound.
Prenat Diagn. 20(5):400-3,
2000
Mernagh JR et al: US assessment
of the fetal head and neck:
a state-of-the-art
pictorial review. Radiographies.
19 Spec
No:S229-41, 1999
Trout T et al: Significance
of orbital measurements
in the
fetus. J Ultrasound
Med. 13(12):937-43,
1994
McGahan JP et al: Sonography
of facial features of alobar
and semilobar holoprosencephaly.
AJR Am J Roentgenol.
154(1):143-8,
1990

MIDFACE ANOMALIES
IIMAGE

GALLERY

Typical
(Left) Sagittal ultr.Jsounc!
sho\vs midt;1C(' hypoplasia in
a fetus with achondroplasia.
Frontal bossing (arrow),
depressed nasal bridge
(open arrow) with a small
nasal bone, and maxillary
hypoplasia (curved arrow)
are classic features. (RighI)
Sagittal radiograph confirms
midface hypoplasia. ThE'
maxilla is underdeveloped
(arrows) and the ;.111' extends
anteriorly (open arrow)
resulting in a "reverse
overbite".

Typical
(Left) Sagittal ultrasound
shows a markedly abnormal
fetal profile seconc!,ny to the
presence of ,I proboscis
larrOlv), inste,1(1of ,1 nose.
This fetus with trisomy I.J
also had cYclopi,] (Right)
Clinical phologr.lph of
another fetus with trisomy 73
shows cyclopia and a
proboscis. The philtrum
larrOlv) is al)f]ormall)'
elongated anti Ih£' moulh is
small. The proboscis is a
blind ending tub£'.

Typical
(Left) Coronal ultrasound
shOlvs midline cleti palate
(arrows) in anoth£'r fetus
with trisomy' 3. /lssociated
depressed nose Jnd small
maxilla are common features
of median cleft lip/palate.
(Right) ClinicallJhotograph
of median cI£'ft lip ,md palate
from pren],]\/II,1I"Y ag£'nesis
shows a tf.Jt('n('rl
dysmorphic nuse. L.lrge
median delis are associaled
with midli1ce hypoplasia.

HYPOTELORISM

Axial ultrasound shows severe hypotelorism (calipers
measure 800 and arrows point to orbits) and an
abnormal nose with a single nostril (cebocephaly)
(open arrow) in a fetus with holoprosencephaly.

ITERMINOLOGY
Definitions
• Eyes too close together

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Decreased interocular distance
• Morphology: Variable from mild to cyclopia

Ultrasonographic

Findings

• Orbital biometry
o Ocular diameter
• Orbital width
• Measurement of bony orbit
o Interocular diameter (laD)
• Measurement between orbits
• From inner-to-inner bony margin
o Binocular diameter (BOD)
• Measurement of both orbits
• From outer-to-outer bony margin
o Axial image of orbits for biometry
• At thalamus/biparietal diameter (BPD) level
o Coronal face view helpful
• Hypotelorism often more recognizable
• Normal ocular distances

DDx: Hypotelorism

Normal Eyes

Axial ultrasound shows normal orbital biometry The
800 is measured by the # I calipers. The 100 is
measured by the #2 calipers. The orbital diameter
(arrows)measures the orbital width.

o "Rule of thirds"
• BOD divided into thirds
• Middle third is laD
• Normal laD = single orbit width
o Orbital nomograms available
• Values from 11 wks to term
• Can determine laD/BOD percentiles
• Hypotelorism diagnosis
o + laD is diagnostic
• laD < 5th percentile
o + BOD also key feature
• Unlike hypertelorism, where BOD is much less
effected
o laD < ocular diameter easiest way to make diagnosis
o Isolated hypotelorism rare
• Holoprosencephaly is major association
o Midline brain anomalies +/- face anomalies
• Fused thalamus (complete or partial)
• Fused ventricles (often monoventricle)
• Abnormal brain mantle
o Spectrum of brain morphology
• Alobar (most severe)
• Semilobar
• Lobar
• Septo-optic dysplasia (most mild)
o "Face predicts the brain"
• Brain is abnormal if face is abnormal
• Spectrum of orbital findings with holoprosencephaly

HYPOTELORISM
Key Facts
Terminology

Top Differential

• Eyes too close together

• Anophthalmia

Diagnoses

Imaging Findings

Pathology

•
•
•
•
•
•

• Trisomy 13 (TI3), trisomy 18 (TI8)
• Chromosome deletions
• Meckel-Gruber syndrome

•
•
•
•

~ IOD is diagnostic
Holoprosencephaly
is major association
"Face predicts the brain"
Cyclopia most extreme type
Proboscis (tube-like nose) superior to orbit
Ethmocephaly: Severe hypotelorism with nose or
proboscis
Cebocephaly: Severe hypotelorism, nose with single
nostril
Often with median cleft palate
Microcephaly
Trigonocephaly (craniosynostosis)

o Cyclopia most extreme type
• Single bony orbit
• Variable amounts of globe doubling
• Orbit often covered by dysplastic tissue
• Proboscis (tube-like nose) superior to orbit
• Most often with alobar holoprosencephaly
o Ethmocephaly: Severe hypotelorism with nose or
proboscis
• Orbits may touch
o Cebocephaly: Severe hypotelorism, nose with single
nostril
o Mild hypotelorism
• Less severe nasal anomalies
• Often with median cleft palate
o Normal orbits
• Brain does not always predict face
• 28% of holoprosencephaly
have normal face
• Other detectable associations with hypotelorism
o Microcephaly
• Very small head circumference (HC)
age
• He < 2 standard deviations/gestational
• Ocular biometry often symmetric but ~
• Associated facial anomalies common
• Multifactorial etiology
o Trigonocephaly (craniosynostosis)
• Metopic suture fusion
• Forehead is pointed
• Triangle appearance from top of head
o Meckel-Gruber syndrome
• Posterior encephalocele
• Cystic kidneys
• Polydactyly
• Autosomal recessive inheritance
o Myotonic dystrophy
• Absent or reduced fetal movement
• Extremity contractures
• Polyhydramnios
o Trisomy 13
• Holoprosencephaly
• Median cleft lip/palate
• Polydactyly
• Cystic kidneys

Clinical Issues
• Maternal diabetes
• Maternal phenylketonuria

(PKU)

Diagnostic Checklist
• Fetal MR for all cases
• Hypotelorism rarely seen in isolation
• Use 3D ultrasound if face looks atypical

• Cardiac anomalies
• Intrauterine growth restriction
o Trisomy 18
• Choroid plexus cysts
• Clenched hands
• Cardiac anomalies
• Omphalocele
• Intrauterine growth restriction
• 3D helps define facial features
o Cleft lip/palate
o Craniosynostoses
• Abnormal head shape
• Can see sutures best with 3D
• MR helps show brain morphology
o Holoprosencephaly
is a spectrum

Imaging Recommendations
• Best imaging tool
o Axial orbit view
• Measure IOD and BOD
• Compare with nomograms
o Coronal face views
• Facial clefts
• Identify 2 bony orbits
o Profile view
• Proboscis
• Protocol advice
o Careful evaluation of brain
• Holoprosencephaly
can be subtle
• Consider fetal MR
o Genetic counseling
• Many associated syndromes
• Aneuploidy

I DIFFERENTIAL

DIAGNOSIS

Anophthalmia
• Absent globe
o Optic vesicle fails to form
• May mimic cyclopia
• Normal globe is not midline
o Orbit in normal parasagittal

position

HYPOTELORISM
• Unilateral or bilateral

Hypertelorism
• Eyes too far apart
• t laD is best diagnostic clue
o BOD may be normal
• Often associated with other anomalies
o Craniosynostosis
o Anterior encephalocele
o Agenesis of corpus callosum
o Midline facial clefts
o Facial mass

Proptosis
• Exophytic eyes
o Forward displacement of globe
• Associated with many syndromes
o Neu-Laxova syndrome
o Anencephaly
o Apert syndrome
o Treacher-Collins syndrome
• Rare prenatal diagnosis

Dacryocystocele
• Dilatation of lacrimal drainage system
• Cyst medial to orbit
o Can be large and mimic 2nd orbit
o Unilateral or bilateral
• Most resolve spontaneously in utero

I PATHOLOGY
General Features
• Genetics
o Trisomy 13 (TI3), trisomy 18 (TI8)
o Chromosome deletions
o Meckel-Gruber syndrome
• Autosomal recessive
o Oculodentodigital syndrome
• Autosomal dominant
o Coffin-Siris syndrome
• Autosomal recessive
o Williams syndrome
• Sporadic inheritance
• Etiology
o Normal face embryology
• Five facial prominences fuse by 10 wks
• Unpaired frontonasal process contains orbits
• Paired maxillary swelling
• Paired mandible swellings
o Holoprosencephaly
• Prechordal mesenchyme fails to induce cleavage
• Failure of prosencephalon cleavage
• Failure of frontonasal process cleavage
• Abnormal midface migration
• Epidemiology
o 1:16,000 births with holoprosencephaly
• 1:250 terminated pregnancies

I CLINICAL ISSUES
Presentation
• Most common signs/symptoms
o Brain anomaly + hypotelorism
• Most often holoprosencephaly
o Abnormal maternal serum screen result
• TI3, T18
• Other signs/symptoms
o Maternal diabetes
• Holoprosencephaly in 1% fetuses
o Maternal phenylketonuria (PKU)
• Poor control associated with anomalies
• Microcephaly
• Hypotelorism
• Congenital heart disease
• Intrauterine growth restriction

Demographics
• Age

o Trisomies associated with advanced maternal age
• ~ 35 yo at time of delivery

Natural History & Prognosis
• Depends on associated anomalies
• Severe hypotelorism with worse prognosis
• Holoprosencephaly
o Stillbirth common
o Liveborn infants with short lifespan
o Severe feeding difficulties
o Seizure disorders

I DIAGNOSTIC

CHECKLIST

Consider
• Fetal MR for all cases
o Subtle brain anomalies detectable

Image Interpretation

Pearls

• Hypotelorism rarely seen in isolation
• Recommend genetic counseling
• Use 3D ultrasound if face looks atypical

I SELECTED
1.

2.
3.

4.

5.
6.
7.

REFERENCES

Joo GJ et al: Prenatal diagnosis, phenotypic
and obstetric
characteristics
of holoprosencephaly.
Fetal Diagn Ther.
20(3):161-6,2005
Thakur S et al: Spectrum of holoprosencephaly.
Indian J
Pediatr. 71(7):593-7, 2004
Rosati Pet al: Early transvaginal
fetal orbital
measurements:
a screening tool for aneuploidy?
J
Ultrasound
Med. 22(11):1201-5,
2003
Lai TH et al: Prenatal diagnosis of alobar
holoprosencephaly
by two-dimensional
and
three-dimensional
ultrasound.
Prenat Diagn. 20(5):400-3,
2000
Trout T et al: Significance
of orbital measurements
in the
fetus. J Ultrasound
Med. 13(12):937-43,
1994
Turner GM et al: The facial profile in the diagnosis of fetal
abnormalities.
Clin Radiol. 47(6):389-95,
1993
Bronshtein
M et al: First- and second-trimester
diagnosis of
fetal ocular defects and associated anomalies:
report of
eight cases. Obstet Gynecol. 77(3):443-9,
1991

HYPOTELORISM
I IMAGE GALLERY
(Left) Coronal ultrasuund of
the lace show, midline cleft
palate (open arrows) and
mild hypotelorism
(arrows).
Midline clelt lip and palate is
associated with both midlace
hypoplasia and
hypotelorism.
(Right) Clinical
photograph shows meclian
cleft palate (premaxill,ny
agenesis), a flattened
dysmorphic nose and mild
hypotelorism.
The
interocular clistance (a/TOWS)
is less than the orbital
diameter (open arrows).

(Left) Coronal ultrasound
sho\vs cyclopia (arrow,
point to partially duplicateel
globe in a single orbit) anel
proboscis (curved arrow) in
a Ictus with trisomy 73 and
holoprosencephaly.
Open
arrOlv points to a 2 vessel
umhilical cord. (Right)
Clinical photograph 01
cyclopia shOl 1'5 the hlind
ending prohoscis superior /0
the single orbit. A small
amount 01 (Ir'plastic tissue
covers the g/ohe.

(Left) Sagittal ultrasound
shows chorioamniotic
separation (curved arrows)
and diHuse anasarca (open
arrow) in a 74 wk Ictus with
trisomy 78. ;\ coronal view
01 the lace (inset) shows
severe hypotclorism
(arrows). Ifypotelorism
can
he diagnosed early in
pregnancy \I·ith transvaginal
ultrasound. (Right) Clinical
photugraph 01 a neonate
\vith semilobar
bo/oprosencephaly
anel milcl
hypotelorism.
who dieel of a
careliac anoma/r

HYPERTELORISM

Coronal
ultrasound
shows
hypertelorism.
The
interocular distance (distance measured by #1 calipers)
is markedly increased, while the binocular distance (#2
calipers) is less affected.

ITERMINOlOGY
Definitions
• Eyes too far apart

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Increased interocular distance

Ultrasonographic

Findings

• Normal orbit biometry
o Ocular diameter
• Orbital width
• Measurement of bony orbit
o Interocular diameter (100): Measurement between
orbits
o Binocular diameter (BOD): Measurement from
outer-to-outer orbit
o Measurement technique
• Often first noticed on coronal face view
• Measurement best performed in axial plane at
biparietal diameter (BPD) level
• Normal ocular distances
o "Rule of thirds"
• BOD can be divided into thirds
• Lateral thirds are orbits

DDx: Abnormal

Clinical photograph shows a child with hypertelorism
secondary to maternal Oilantin use during pregnancy.
The interocular distance (arrows) is increased. The long
philtrum and thin lips are also characteristic.

• Middle third is 100
o Normal 100 = single orbital width
o Orbital nomograms in literature
• 11 wk to term percentiles available
• Hypertelorism diagnosis
o t 100 more prominent feature than t BOD
• laD> 95th percentile
• BOD often just < 95th percentile
o laD> ocular diameter easiest way to make diagnosis
o Isolated primary hypertelorism rare
o Many associations
• Craniosynostosis
o Premature fusion of skull sutures
• Deformed skull and face
• +/- Other skeletal dysplasia
o Craniofrontonasal dysplasia
• Tall narrow skull (acrocephaly)
• Coronal suture synostosis
• Hypertelorism + midline facial clefting
o Apert syndrome
• Acrocephalosyndactyly type 1
• Flat face with hypertelorism
• Coronal suture synostosis
• Acrocephaly (high forehead)
• Brachycephaly (flat occiput)
• Syndactyly is key feature
• Autosomal dominant
o Carpenter syndrome

Orbits

~"~-"
•••

!~

•..".--:~~~

. ;'

~

• =-....•..
- ,

-

-

.,

.

~

.

-

Anophthalmia

f

It\
Anophthalmia

~11

Hypotelorism

Proptosis

HYPERTELORISM
Key Facts
Imaging Findings
• Interocular diameter (100): Measurement between
orbits
• Binocular diameter (BOD): Measurement from
outer-to-outer orbit
• "Rule of thirds"
• BOD can be divided into thirds
• Lateral thirds are orbits
• Middle third is 100
• Normal 100 = single orbital width
• t 100 more prominent feature than t BOD
• Isolated primary hypertelorism rare
• Many associations
• Craniosynostosis
• Anterior encephalocele
• Midline facial mass (displaces orbit laterally)

•

•

•

•

•

• Acrocephalosyndactyly type 2
• Similar to Apert
• + Polydactyly
• + Cardiac defects
• + Omphalocele
• Autosomal recessive
o Crouzon syndrome
• Craniofacial dysostosis type 1
• Coronal suture synostosis
• Midface hypoplasia
• Ocular proptosis
• Hypertelorism > hypotelorism
o Thanatophoric dysplasia
• Severe skeletal dysplasia with craniosynostosis
• Cloverleaf skull
• Displaced eyes
Anterior encephalocele
o Herniation of intracranial contents via bony defect
• May contain brain or fluid/meninges
• MR helpful to show involved tissue
o Bony defect best seen on axial views
• Frontal, ethmoid, sphenoid
o Variable size
• Small encephaloceles can be subtle and missed
Midline facial mass (displaces orbit laterally)
o Extremely rare
• Often aggressive and grow very large
o Rhabdomyosarcoma
o Retinoblastoma
o Epignathus
• Oral teratoma
Agenesis of corpus callosum
o Ventricle findings
• Colpocephaly with splayed frontal horns
o Hypertelorism often mild finding
o Variable prognosis
• Associated with other syndromes
Median cleft syndrome
o Median facial clefts
o Eyes displaced laterally
Chromosome aberrations
o Turner syndrome

•
•
•
•

Agenesis of corpus callosum
Median cleft syndrome
Chromosome aberrations
3D US helpful to show associated face anomalies

Top Differential

Diagnoses

• Proptosis

Clinical Issues
• Antiepileptic drugs can cause hypertelorism
• Prognosis grim if other severe anomalies present

Diagnostic Checklist
•
•
•
•
•

Orbital biometry when facial defects seen
1/2 of all isolated facial defects are missed
t BOD is not best determinant of hypertelorism
100 > 95th percentile is best definition
Offer 2enetic counselin~ and amniocentesis

• Cystic hygroma is hallmark finding
o Trisomy 13
• Holoprosencephaly is hallmark finding
• Hypotelorism > hypertelorism
• Midline cleft palate associated with hypertelorism
• MR
o Helpful in delineating other cranial anomalies
• Agenesis of corpus callosum
• Brain involvement with frontal encephalocele
o Facial features often seen well
• 3D US helpful to show associated face anomalies
o Cleft lip/palate
o Mandibular anomalies

Imaging Recommendations
• Best imaging tool
o Axial view through fetal orbits
• Most accurate measurements
o Coronal face view
• Can still compare 100 with BOD
o 3D ultrasound
• Recognizable facial features
• Protocol advice
o Careful evaluation of fetal brain when facial
anomalies seen
• "The face predicts the brain"
o Compare orbital measurements with nomograms
• Can detect subtle hypertelorism
o 3D helpful
• Craniosynostosis
• Other facial anomalies
o Consider fetal MR to rule out subtle frontal
encephalocele, if no other obvious cause
o Measure long bones
• Associated skeletal dysplasia
o Genetic counseling
• Amniocentesis
• Chorionic villus sampling

HYPERTELORISM
I DIFFERENTIAL

o Skeletal dysplasia
o Hydrocephalus
o Aneuploidy

DIAGNOSIS

Proptosis
• Exophytic orbits
• Often associated with hypertelorism
• Associations
o Treacher-Collins syndrome
o Craniosynostosis
o Orbital cyst or mass

Anophthalmia
• Absent globe
o Optic vesicle fails to form
o Unilateral or bilateral
• Associations
o Goldenhar-Gorlin syndrome
• Hemifacial microsomia
o Trisomy 13
• Microphthalmia more common
o Lenz syndrome
• X-linked microphthalmia

ICLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Rarely seen in isolation
• Isolated cases often missed
• Orbits are not part of routine exam
o In association with other anomalies
• Often severe craniofacial anomalies
• Other signs/symptoms
o Antiepileptic drugs can cause hypertelorism
• Hydantoin (Dilantin)
• Carbamazepine (Tegretol)
• Valproic acid
• Phenantoin

Natural History & Prognosis

Hypotelorism

• Prognosis grim if other severe anomalies present

• Eyes too close together

Treatment

o ~ 100

o More often with ~ BOD
• Associations
o Holoprosencephaly
o Trisomy 13
o Microcephaly
o Meckel-Gruber syndrome

• Lamella osteotomy + rigid fixation
o Orbital rim and wall reconstruction
• Intracranial osteotomy may be necessary

I DIAGNOSTIC

CHECKLIST

Consider

I PATHOLOGY
General Features
• Genetics
o Turner syndrome
o Trisomies
o Translocations
o Gene deletions
• Etiology
o Normal eye embryology
• Diverticula of forebrain
• Optic cup migrates to surface
• Ectoderm thickens to form lens
• Eyes initially laterally displaced
o Normal face embryology
• Five facial prominences fuse by 10 wks
• Unpaired frontonasal process (contains orbit)
• Paired maxillary swellings
• Paired mandibular swellings
o Hypertelorism
• Disrupted eye migration
• Abnormal fusion of facial prominences
• Epidemiology
o Children born with craniofacial anomalies
• Hypertelorism in 33%
• Craniosynostosis in 74%
• 50% with identifiable syndrome
• Associated abnormalities
o Facial clefting
o Craniosynostosis

• Orbital biometry when facial defects seen
• Routine evaluation of eyes at 2nd trimester screen
o 1/2 of all isolated facial defects are missed

Image Interpretation

Pearls

• Distance between orbits approximates orbit diameter
o Only enough room for a "3rd eye between eyes"
• t BOD is not best determinant of hypertelorism
o 100 > 95th percentile is best definition
• Use transvaginal ultrasound (TVUS) for early diagnosis
o Nomograms for 11-16 wks per TVUS available
• Offer genetic counseling and amniocentesis

I SELECTED
1.

2.

3.

4.

5.

6.

REFERENCES

Mu X et al: Surgical correction of orbital and periorbital
deformities using lamella and complex osteotomies in both
orbital rim and wall.] Craniofac Surg. 16(1):144-9,2005
Okkerse]M et al: Condition variables in children with
craniofacial anomalies: a descriptive study. ] Craniofac
Surg. 15(1):151-6; discussion 157,2004
Pittet B et al: Simultaneous correction of major
hypertelorism, frontal bone defect, nasal aplasia, and cleft
of the upper lip (Tessier 0-14). Plast Reconstr Surg.
113(1):299-303,2004
Rosati P et al: Early transvaginal fetal orbital
measurements: a screening tool for aneuploidy? ]
Ultrasound Med. 22(11):1201-5, 2003
Trout T et al: Significance of orbital measurements in the
fetus.] Ultrasound Med. 13(12):937-43, 1994
Bronshtein M et al: First- and second-trimester diagnosis of
fetal ocular defects and associated anomalies: report of
eight cases. Obstet Gynecol. 77(3):443-9, 1991

HYPERTELORISM
IIMAGE

GALLERY
(Left) Coronal ultrasound
shows hypertelorism
(double-headed
arrow) and
unusual frontal skull shape
(arrows) secondary to
craniosynostosis
in case of
Apert syndrome.
Hypertelorism
is often
associated with
craniosynostosis,
regardless
of cause. (Right) Clinical
photograph of a child with
Carpenter syndrome shows
hypertelorism
(arrows) as
well as a flat face,
acrocephaly
(high forehead)
and brachycephaly.

(Left) Coronal ultrasound
shows hypertelorism
secondary to frontal
encephalocele.
The distance
between the orbits (arrows)
is greater than the orbital
diameter (open arrows).
(Right) Coronal T2WI MR
shows asymmetric
hypertelorism as one globe
(arrows point to both eyes)
is displaced by a large facial
mass (open arrows). Typical
of most facial tumors, this
rhabdomyosarcoma
was
large and aggressive.

Typical
(Left) Coronal T2WI MR of a
29 week fetus with agenesis
of the corpus callosum,
shows hypertelorism
(arrows). The distance
between the eyes is greater
than the orbital diameter.
(Right) T2WI MR of the brain
in the same fetus shows
colpocephaly
(arrows),
splayed frontal horns (open
arrows) secondary to a
high-riding 3rd ventricle
(curved arrow) and
complete absence of the
corpus callosum.

ORBITAL TUMORS

Sagittal color Doppler ultrasound of the fetal face shows
a vascular 50ft tissue mass. No globe could be seen on
the involved side. An MRI was performed to better
evaluate anatomy.

Axial T2WI MR through the level of the orbits shows a
fungating 50ft tissue mass (arrow) emanating form the
left orbit. The right eye (curved arrow) is normal. A
rhabdomyosarcoma was diagnosed at autopsy.

I DIFFERENTIAL DIAGNOSIS

ITERMINOlOGY
Definitions

Dacryocystocele

• Group of rare tumors, which may involve the orbit
o Retinoblastoma
o Teratoma
o Soft tissue sarcomas

• Obstruction of nasolacrimal duct resulting in cystic
dilatation of proximal duct
• Located inferomedial to orbit, may be bilateral
• Does not displace globe
• Average size 7-13 mm
• Anechoic or with low-level echoes
• No flow seen with Doppler
• Generally presents after 30 weeks
• Benign self-limited entity, which usually resolve in
first 6 months of life

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Unilateral proptosis

Ultrasonographic

Findings

Facial hemangioma

• Globe of involved orbit may not be visible
• Boney anatomy may be distorted or destroyed
• Predominately solid masses
o Calcifications virtually pathognomonic of teratoma
• Most masses vascular by Doppler
• Polyhydramnios may be present

•
•
•
•

May occur around orbit
Globe not displaced, boney orbit normal
Homogeneous echogenicity
Flow often seen with color Doppler

Nasopharyngeal

(NP) teratoma

• Fungating masses involving mouth and nose

Imaging Recommendations
• MRI recommended to better evaluate intracranial
contents
o Rule out brain abnormality causing orbital mass
o Evaluate for extension of orbital tumor into brain

Amniotic band syndrome
• "Slash defects" of face
• Multiple body parts often involved

Frontal encephalocele
• Midline, between orbits

DDx: Orbital Mass

Frontal Enct'phaloct'/e

Dacryocystocele

ORBITAL TUMORS
Key Facts
•

Terminology

asopharyngeal

• Group of rare tumors, which may involve the orbit

Pathology

Imaging Findings

• Retinoblastoma
• Teratoma

• Be t diagnostic clue: Unilateral proptosis
• Globe of involved orbit may not be visible

Top Differential

Diagnoses

• Dacryocystocele
• Facial hemangioma

( P) teratoma

Diagnostic Checklist
• Unilateral proptosis should prompt search for
retrobulbar mass
• Always evaluate brain carefully

I DIAGNOSTIC

Proboscis
• May be confused with orbital mass
• Fleshy midline mass above orbit
o Usually single orbit (cyclopia) or severe
hypotelorism
• Occurs with alobar holoprosencephaly

I PATHOLOGY

CHECKLIST

Consider
• Prenatal testing if a parent has a history of
retinoblastoma

Image Interpretation

Pearls

• Unilateral proptosis should prompt search for
retrobulbar mass
• Always evaluate brain carefully

General Features
• Retinoblastoma
o Malignant growth of neuroepithelial cells of retina
o Deletion or mutation of chromosome 13q 14
• Prenatal testing available
o May be bilateral
o Leukokoria (white pupillary reflex) seen on physical
exam
• Teratoma
o Complex cystic/solid mass
o Calcification diagnostic but not always visible
• Other tumors
o Rhabdomyosarcoma
o Rhabdoid tumor
o Neurofibroma

I SELECTED

ICLINICAL

I IMAGE

ISSUES

1.

2.
3.

4.

5.

REFERENCES

Lee JC et al: Congenital mixed malignant germ cell tumor
involving cerebrum and orbit. J Perinat Med. 31(3):261-5,
2003
Salim A et al: Fetal retinoblastoma. J Ultrasound Med.
17(11):717-20, 1998
Shipp TD et al: The ultrasonographic appearance and
outcome for fetuses with masses distorting the fetal face. J
Ultrasound Med. 14(9):673-8, 1995
Kivela T et al: Orbital germ cell tumors revisited: a
clinicopathological approach to classification. Surv
Ophthalmol. 38(6):541-54, 1994
Maat-Kievit JA et al: A large retinoblastoma detected in a
fetus at 21 weeks of gestation. Prenat Diagn. 13(5):377-84,
1993

GALLERY

Presentation
• Most common signs/symptoms: Prenatally diagnosed
cases have all been large masses

Natural History & Prognosis
• Depends largely on size and extent of tumor
• Retinoblastoma
o Optic nerve involvement and extraorbital spread
have poor prognosis
o Bilateral neonatal tumors usually lethal
• Teratoma benign but may cause extensive damage
from large size
• Sarcomas usually lethal

Treatment
• Primary treatment enucleation
• Chemotherapy in metastatic disease

(Left) Axial NEeT of an orbital teratoma in a newborn who had an
orbital mass and unilateral proptosis diagnosed in utero. The globe
(curved arrow) is anteriorly displacr:d by a complex mass with
obvious fat and calcification. The lateral wall of the orbit is splayed by
the tumor
(arrow).
(Right) Intra-operative
photograph
shows
retraction of the globe (black arrow) and optic nerve (white arrow)
during resection of the mass.

SCALP MASSES

Axial ultrasound shows a predominately solid, soft tissue
mass (arrows) arising from the fetal skull. There was no
calvarial defect and brain anatomy
was normal.
Postnatal resection showed a hemangioma.

ITERMINOLOGY
Definitions
• Mass arising from fetal scalp

IIMAGING

FINDINGS

General Features
• Asymmetric soft tissue mass over fetal scalp
• Hemangioma
o Heterogeneous echogenicity
• Solid or mixed cystic/solid
o Color Doppler shows diffuse network of vessels
o MRI Findings
• Tl WI: Heterogeneous low to intermediate signal
• T2WI: Heterogeneous high signal
• Flow voids seen due to vascular nature of tumor
• Lymphangioma
o Multilocular cystic mass
o No internal flow
• Epidermoid cyst
o Well-circumscribed cyst
• Between skull bone and scalp surface
• No bony defect
• Atretic cephalocele
o Midline
o Interparietal or occipital

Axial oblique T2WI MR shows a small scalp mass
(arrows) in a fetus with a Dandy-Walker variant. No
calvarial defect was seen. Postnatal surgery revealed an
atretic cephalocele.

o May appear cystic or solid
o May decrease in size over duration

Imaging Recommendations
• Beware pitfalls in diagnosis of scalp mass
o Scalp edema
• Uniform thickening of scalp skin
• Usually a manifestation of hydrops
• Look for fluid elsewhere; pericardial, pleural,
ascites
o Fetal hair
• Fetal hair may be long, thick in third trimester
• No internal flow
• Strands will float in amniotic fluid
o Cystic hygroma
• Septated cystic mass arising from posterior fetal
neck, rather than scalp
• Often associated with hydrops
• Strong association with Turner syndrome and
Down syndrome
• Look for other findings to confirm diagnosis
o Umbilical cord
• Coils of cord may be seen beside scalp or wrapped
around fetal neck
• Color Doppler shows umbilical vessels, clarifies
true etiology of apparent mass
• If mass confirmed, careful anatomic survey

DDx: Pitfalls In Diagnosis Of Scalp Mass

[elailiair

of pregnancy

Cyslic Hygroma

SCALP MASSES
Key Facts
Imaging Findings

Clinical Issues

• Asymmetric soft tissue mass over fetal scalp
• on ider MRI for further anatomic delineation
• Most important role of MRI is to exclude
encephalocele

• Some mas e involute over cour e f pregnancy
• Outcome depend on a sociated malformations more
than on Ie ion itself
• Karyotype not indicated if i olated finding
• Large mass may be an indication for cesarean ection

Top Differential

Diagnoses

Diagnostic Checklist

• Enc phalocele

• Alway check brain anatomy carefully when a scalp
ma s i identified
• Abnormal venous sinus anatomy trongly sugge ts
atretic cephalocele
• Scanning angle may give fal e impre ion of an
underlying calvarial defect
• calp edema and fetal hair are common pitfalls in
diagnosis

Pathology
•
•
•
•
•
•
•

auses of fetal calp masses are many and varied
Hemangioma
Lymphangioma
Epidermoid cy t
Dermoid
Fibromatosis, myofibromato i
Atretic cephalocele

o Reported association with hydrocephalus, duplex
renal system, hand and genital anomalies
• Consider MRI for further anatomic delineation
o Evaluate underlying brain
o Look for venous malformations associated with
atretic cephaloceles
• Sagittal sinus duplication
• Falcine sinus in addition to, or replacing, straight
sinus
• Falcine sinus has ascending course toward skin
lesion
o Most important role of MRI is to exclude
encephalocele

I DIFFERENTIAL

DIAGNOSIS

Encephalocele
• Neural tube defect
• Brain or meninges protrude through

calvarial defect

Bone tumor of skull vault
• May be hard to differentiate from scalp lesion in fetus
• Look for intra + extra cranial extension
o Reported case of cavernous angioma of temporal
bone with successful resection

Meningeal tumor
• Intracranial, extra-axial location
• Reported case of meningeal hemangiopericytoma
successful resection

with

I PATHOLOGY
General Features
• Genetics
o Lymphangioma may be associated with Turner
syndrome
• Usually cystic hygroma of neck, but may involve
scalp
• Etiology
o Causes of fetal scalp masses are many and varied

• Hemangioma
• Lymphangioma
• Epidermoid cyst
• Dermoid
• Mesenchymal neoplasms
• Fibromatosis, myofibromatosis
• Lipoma/hamartoma
• Atretic cephalocele
• Sequestrated meningocele
• Heterotopic neural tissue
• Metastasis
• Epidemiology
o Rare: True incidence unknown
• Most series of scalp masses in literature are
postnatal
• Only case reports of prenatal diagnosis
• Associated abnormalities
o Atretic cephaloceles associated with
• Local scalp alopecia
• Intracranial venous anomalies, if cephalocele
above torcular herophili
• Brain malformations which may be clinically
occult in neonate (e.g. Walker Warburg syndrome)
• One series: 13% hydrocephalus, 7% mild
ventriculomegaly, 3% lobar holoprosencephaly
• Another series 7S% brain "malformation"
(anomalous venous sinuses were included as
malformations)
o Encephalocraniocutaneous
lipomatosis
• Ipsilateral hamartomas scalp, eyelids and globe
• Unilateral porencephalic cysts
• Central nervous system lipomas
• Embryology
o Atretic cephaloceles are a form of posterior
dysraphism
• Anomaly of neural tube closure during 3rd-Sth
weeks of gestation
o Scalp masses can arise from any layer of embryonic
tissue
o Mesoderm
• Hemangioma, lymphangioma,
lipoma
o Ectoderm

SCALP MASSES
• Epidermoid cyst, dermoid
o Neuroectoderm
• 'With bone defect: Atretic cephalocele,
leptomeningeal cyst
• Without bony defect: Ectopic meningioma,
heterotopic brain tissue

Gross Pathologic & Surgical Features
• Dermoid cysts
o Keratinizing squamous epithelium
o Hair and glandular tissue
• Atretic cephaloceles
o May contain cerebrospinal fluid, fibrous tissue or
atretic brain tissue
• Sequestrated meningoceles
o Meningothelial cells
o Stain with vimentin, epithelial membrane antigen

ICLINICALISSUES
Presentation
• Scalp mass detected on antenatal

sonography

Natural History & Prognosis
• Depends on lesion
o Some masses involute over course of pregnancy
o Hemangioma
• lf significant flow --- high output cardiac failure --hydrops
• Tend to enlarge at birth
• Enlargement may precipitate neonatal heart
failure
• Emergency intervention required to obliterate
vascular shunt
o Atretic cephaloceles
• May become infected --- meningitis or abscess
• Outcome depends on associated malformations
more than on lesion itself
• Venous sinus anomalies of little significance
• Walker Warburg syndrome --- most infants die
within first year of life, 25% recurrence risk
o Encephalocraniocutaneous
lipomatosis
• Seizures
• Developmental delay
o Metastases
• All reported cases of metastatic maternal
adenocarcinoma to fetal scalp did well with wide
local resection
• Some instances of local recurrence requiring
re-excision
• Scalp reconstruction required skin grafts/soft
tissue flaps
• Maternal prognosis poor

Treatment
• Karyotype not indicated if isolated finding
o Consider for scalp lymphangioma,
which has been
described with Turner syndrome
• Large mass may be an indication for cesarean section
o Risk of dystocia
o Risk of injury to mass, with potential
exsanguination if vascular
• Hemangioma

o Postnatal surgical resection
• Atretic cephalocele
o Often covered by alopecic scalp
o Must be excised due to risk of infection
o Neurosurgical evaluation, not simple plastic surgery
o 75% cases in one series had associated brain
malformation
• Dermoid/epidermoid
o Elective resection
o Excellent prognosis

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Always check brain anatomy carefully when a scalp
mass is identified
• Abnormal venous sinus anatomy strongly suggests
atretic cephalocele
o Infant will require neurosurgical evaluation for
resection
o Higher likelihood of associated brain malformation
• Beware of pitfalls in diagnosing scalp mass
o Scanning angle may give false impression of an
underlying calvarial defect
o Scan in multiple planes and with color Doppler for
confirmation
o Scalp edema and fetal hair are common pitfalls in
diagnosis

ISELECTED REFERENCES
Gawel J et al: Encephalocraniocutaneous
lipomatosis. J
Cutan Med Surg. 7(1):61-5,2003
Walker JW et al: Maternal pulmonary adenocarcinoma
2.
metastatic to the fetus: first recorded case report and
literature review. Pediatr Pathol Mol Med. 21(1):57-69,
2002
3. Harpold TL et al: Maternal lung adenocarcinoma
metastatic to the scalp of a fetus. Case report. Pediatr
Neurosurg. 35(1):39-42, 2001
4.
Lau TK et al: Fetal scalp cysts: challenge in diagnosis and
counseling. J Ultrasound Med. 20(2):175-7, 2001
5. Brunelle F et al: Intracranial venous anomalies associated
with atretic cephalocoeles. Pediatr Radiol. 30(11):743-7,
2000
6. Nowaczyk MJ et al: Antenatal and postnatal findings in
encephalocraniocutaneous
lipomatosis. Am J Med Genet.
91(4):261-6,2000
7.
Mitchell CS: Vertex hemangioma mimicking an
encephalocele. J Am Osteopath Assoc. 99(12):626-7, 1999
8. Ogle RF et al: Fetal scalp cystsndilemmas in diagnosis.
Prenat Diagn. 19(12):1157-9, 1999
9.
Okaro E et al: Prenatal diagnosis of atypical cystic lesions of
the fetal scalp. Ultrasound Obstet Gynecol. 12(6):442-4,
1998
10. Haeusler MC et al: Unusual lymphangioma observed
prenatally in a 45,X fetus. Am J Med Genet. 45(4):508-10,
1993
11. Barr M Jr et al: Scalp neoplasm associated with cranium
bifidum in a 24-week human fetus. Teratology.
33(2):153-7, 1986
1.

SCALP MASSES
I IMAGE GALLERY
(Left) Axial color Doppler
ultrasound shows no internal
flow in a soft tissue mass
(curved arrow) overlying the
skull. Note the apparent
defect (open arrow) in the
skull vault echo (arrows) at
the level of the mass. (Right)
Sagittal ultrasound shows the
skull vault (arrows) is intact
deep to the mass (curved
arrow) excluding
meningocele and
encephalocele. The apparent
bone defect on the axial
view was due to beam
refraction.

Variant
(Left) Sagittal T2WI MR from
the case above shows a
subtle signal change in the
posterior occipital skin
(arrow) where the scalp
mass had been identified.
The brain was normal and
no residual scalp mass was
found at birth. Small scalp
masses may resolve in utero.
(Right) Axial ultrasound in a
fetus with complex
intracranial malformations
shows an apparent scalp or
skull mass (arrows). MRI
showed this to be focal
calvarial expansion
secondary to hydrocephalus.

Typical
(Left) Axial NECT on day
one of life shows a
hemangioma arising from the
scalp (curved arrows). The
calvarium (white arrows) is
intact but remodeled by the
large mass. Note the
calcifications (black arrows)
in the interstices of the mass.
(Right) Cross pathology of
the resected hemangioma
shows multiple vascular
spaces (arrows). Flow is well
demonstrated by color
Doppler and flow voids may
be present on MRI.

CYSTIC HYGROMA

Axial ultrasound shows a large nuchal cystic hygroma
(calipers). The CI / is larger than the fetal head and
contains multiple thin septations (arrows). The midline
septation (open arrow) is the nuchal ligament.

Postmortem
photograph
of a fetus with Turner
syndrome shows a large cystic hygroma as well as body
wall edema (arrows). Cystic hygroma, Turner syndrome
and hydrops are common associations.

ITERMINOlOGY
Abbreviations

•

and Synonyms

• Cystic hygroma (CH)
• Nuchal cystic hygromata
• Cavernous lymphangioma

•

Definitions
• Dorsal and lateral nuchal cyst
o 2° to jugular vascular-lymphatic

anomaly

•

IIMAGING FINDINGS
•

General Features
• Best diagnostic clue: Multiseptated nuchal fluid
• Location
o Posterior neck
o Lateral neck
o Often with diffuse body wall edema
• Size: Extremely variable
• Morphology
o Mass-like
o Many have thin septations

Ultrasonographic

•

Findings

• Posterior/lateral nuchal cyst
o Skin and subcutaneous fluid

DDx: Complex

•

o Best seen on axial posterior fossa view
o Sagittal views show extent of edema
Internal septations
o Multiple fine linear septations
o Thick midline septation is nuchal ligament
Size can be massive
o Larger than fetal head
o Can mimic amniotic fluid
• May be only fluid source for amniocentesis
Small CH can evolve into thick nuchal fold (t NF)
o t Nuchal skin thickness without cysts
o Often precursor to webbed neck
o Large CH almost never resolves spontaneously
Non-immune hydrops common with large hygromas
o Excess fetal fluid accumulation
• Fluid in 2 separate areas
• CH counts as 1 area
o Anasarca
• Most often seen with CH
o Pleural effusion
o Pericardial effusion
o Ascites
Cardiovascular anomalies often present
o Aortic arch defects most frequent
Aneuploidy in 2/3 fetuses with 2nd trimester CH
o Turner syndrome
• Most common
o Trisomy 21 (T21)

Exophytic Neck And Chest Masses

Cervical Teratoma

Axillary Lymphangioma

CYSTIC HYGROMA
Key Facts
Terminology

Top Differential

• Dorsal and lateral nuchal cyst

• Incr ased nuchal fold
• ervi al teratoma
• Body/trunk lymphangioma
• Occipital encephalocele

Imaging Findings
•
•
•
•
•
•
•
•
•
•
•

•

•

•

•

Best diagno tic clue: Multi eptated nuchal fluid
Multiple fine linear septation
Thick midline
ptation is nuchal ligament
ize can be massive
mall H can evolve into thick nuchal fold (t F)
on-immune hydrops common with large hygromas
ardiova cular anomalies often present
Aneuploidy in 2/3 fetuses with 2nd trimester CH
Turner yndrome
Tri omy 21 (1'21)
Large tIt trim ter nuchal translucencies seen in
Turner yndrome

• Second most common
o Trisomy 18 (1'18)
o Trisomy 13 (1'13)
Turner syndrome
o XO karyotype
• One sex chromosome is missing
o Cystic hygroma is hallmark finding
o Hydrops
• CH + anasarca most often
o Cardiovascular anomalies (60%)
• Coarctation of aorta (45%)
• Hypoplastic left heart
o Horseshoe kidney
• Kidneys fused inferiorly
• Isthmus of renal tissue anterior to aorta
o Mild short stature
• Short femur/humerus
o Occasional ambiguous genitalia
• Mixed gonadal dysgenesis
• Turner mosaic (45,XO/46,XY)
Trisomy 21 (1'21)
o t NF more common than CH
• Nuchal skin is thickened but without cysts
• Small CH more often than large
o Other markers for 1'21
• Echogenic bowel
• Intracardiac echogenic focus
• Mild pelviectasis
• Short humerus/femur
o Major anomalies of 1'21
• Cardiac anomalies
• Duodenal atresia
o Hydrops rare
T18/T13 not uncommon with CH
o Other major anomalies often seen
o Intrauterine growth restriction common
First trimester CH (11-14 wks)
o t Nuchal translucency (NT) + septations
• Measure subcutaneous fluid behind fetal neck
• > 3 mm always abnormal

• Presence of septations obligatory for diagnosis
o 1st trimester CH and aneuploidy

Clinical

Diagnoses

Issues

• Fetal demise
• Only 9(}(} survive without major morbidity
• Webbed neck from mailer re olved hygromas

Diagnostic Checklist
• en tic testing when
H een
• 1'21 > Turner with 1 t trim t r
• Turn r > 1'21 with 2nd trime ter H
• H + hydrop with grim prognosis

• 1'21 most common
• Turner syndrome
• 1'18/1'13 (t compared with 2nd trimester CH)
o Largest 1st trimester nuchal translucencies seen in
Turner syndrome
o Hydrops can be seen in 1st trimester

Imaging Recommendations
• Best imaging tool
o Second trimester
• Angled posterior fossa image
• Routine NF measurement
o First trimester NT evaluation
• Protocol advice
o First trimester CH
• Accurately measure NT
• Look carefully for septations
• Offer chorionic villus sampling
o Second trimester
• Careful exam for additional anomalies
• Formal fetal echocardiography
• Rule out hydrops
• Offer amniocentesis
o Follow-up ultrasound
• High rates of in utero demise
• May see other anomalies as fetus grows

I DIFFERENTIAL

DIAGNOSIS

Increased nuchal fold
• t Posterior fetal neck skin thickness

•
•
•
•

o Not fluid
May be byproduct of CH but should not be called CH
1'21 more likely than Turner syndrome
More likely to be idiopathic
Better prognosis

Cervical teratoma
• Germ cell tumor
o Aggressive growth common
o May be malignant
• Most often anterior neck

CYSTIC HYGROMA
o Fetal neck often hyperextended
o Associated with airway obstruction
• Solid or mixed solid-cystic mass
o +/- Calcification

Body/trunk

lymphangioma

• Non-nuchal cystic mass
o Morphology identical to CH
o 20 to lymphatic channel disruption
• Axillary most common site
o + Upper extremity lymphedema
• Not associated with aneuploidy
• Better prognosis than nuchal CH

Occipital encephalocele
• Open neural tube defect
• Posterior fossa contents herniate via cranial defect
o Must see calvarial bony defect
o Variable amounts of brain/meninges involved
• Abnormal intracranial anatomy

I PATHOLOGY
General Features
• Genetics
o Normal chromosomes in 20-40%
o Aneuploidy
• Turner syndrome
• T21
• T18
• T13
o Non-aneuploid syndromes
• Noonan syndrome
• Multiple pterygium syndrome
• Apert syndrome
• Cornelia de Lange syndrome
• Etiology
o Normal embryology
• Lymphatics from outgrowth of venous system
• Paired jugular venous buds -+ lymphatic sacs
• Communication established by 40 days
o CH
• Failed/delayed venous -+ lymphatic connection
o Hydrops
• Fluid overload from lymphatic failure
• Epidemiology
o 1:200 spontaneous abortions
o 1:600 low-risk pregnancies
o 1:1,750 live births
• Associated abnormalities
o Cardiovascular anomalies
o Large variety of other anomalies
• Mostly associated with aneuploidy/syndromes

Gross Pathologic & Surgical Features
• Cavernous lymphatic spaces with flattened endothelial
lining

I CLINICAL

• Non-immune hydrops
• Fetal demise
• Abnormal maternal serum quadruple test screen
o 53% detection rate for Turner syndrome
o 80% detection rate for Trisomy 21
• Massive CH can mimic amniotic fluid
o Can tap CH for amniocentesis if necessary

Demographics
• Age
o T21 associated with advanced maternal age (AMA)
• AMA ;:: 35 at time of delivery
o Turner syndrome not associated with AMA
• Gender: F > M

Natural History & Prognosis
• t Spontaneous pregnancy failure rate

• 12% live-birth rate
o Only 9% survive without major morbidity
o Webbed neck from smaller resolved hygromas
• Hydrops associated with grim prognosis
o 80-90% demise
• 10-20% resolve in utero
o More likely if small CH
o Often in euploid fetuses

Treatment
• Complete surgical resection
o Often difficult 2 to infiltrative nature of CH
o Post surgical recurrence (15%)
• Sclerosing agents
o Injected directly into cysts
• Most often for recurrence
o Bleomycin fat emulsion
o OK-432
• Inactivated streptococcal organism
0

I DIAGNOSTIC
Consider

• Genetic testing when CH seen

Image Interpretation

• Incidental finding on 1st or 2nd trimester ultrasound

Pearls

• T21 > Turner with 1st trimester CH
• Turner> T21 with 2nd trimester CH
• CH + hydrops with grim prognosis

I SELECTED
1.

2.

REFERENCES

Howarth ESet al: Population-based study of the outcome
following the prenatal diagnosis of cystic hygroma. Prenat
Diagn. 25(4):286-91, 2005
Ganapathy Ret al: Natural history and outcome of
prenatally diagnosed cystic hygroma. Prenat Diagn.
24(12):965-8, 2004

3.

ReyndersCSet al: Firsttrimester isolated fetal nuchal
lucency: Significanceand outcome. J Ultrasound Med.

4.

Bronshtein M et al: The differencebetween septated and
nonseptated nuchal cystic hygroma in the early second
trimester. Obstet Gynecol. 81:683-7, 1993
Thomas RL:Prenatal diagnosis of giant cystic hygroma.
Prenatal Diagn. 12:919-23, 1992

16:101-5, 1997

ISSUES

Presentation

CHECKLIST

5.

CYSTIC HYGROMA
IIMAGE

GALLERY
(Left) Axial ultrasound
through the back oi the neck
in a second trimester ietus
shows a multiseptated
cystic
mass (arrows point to thin
septations). The open arrow
points to the cervical spine.
(Right) Gross pathology oi a
cystic hygroma shows
multiple septations inside the
hygroma (arrows). Cf { are
smooth cystic masses, which
are oiten multi-lobulated
and
are lined by a single layer oi
(fattened endothelium.

(Left) Two axial images
obtained at 76 wks shows a
small, septated cystic
hygroma (calipers and
arrows) in a ietus with
trisomy 27. No other
anomalies were seen and
amniocentesis
\vas
recommended
based on this
iinding alone. (Right) Sagittal
ultrasound oi the same fetus
at 27 weeks shows increased
nuchal iold (arrows). The
CH (fuid resolved and
residual skin thickening is
seen.

Variant
(Left) Ultrasound shows
marked anasarca (arrows)
and CH (open arrows) in a
ietus with T21. The extent of
lymphedema
in this caw is
unusually severe. CII,
howevel; is oiten associated
with hydrops. (Right)
Ultrasound shows a small
septated CH (arrows) and
club foot (open arrows point
to shin, curved arrows point
to toes) in a 76 wk ietlls with
trisomy 78. CI-{ is associatecl
with Tl8, Tl3 and many
syndromes.

GOITER

Sagittal T2WI MR shows fetal goiter (curved arrow)
secondary to stimulation by maternal antibodies. The
oropharynx (arrow) is distended due to esophageal
compression, which impaired swallowing.

Clinical photograph of a neonate who was successfully
treated with intra-amniotic injections of Synthroid for
hypothyroidism and goiter. Redundant skin and mild
goiter (arrows) remain but the infant was euthyroid.

ITERMINOlOGY
Definitions

•

• Enlargement of fetal thyroid
o Fetal goiter may be due hyper- or hypothyroidism
• Fetal hyperthyroid state due to maternal thyroid
stimulating antibodies
• Fetal hypothyroid state most commonly due to
maternal anti-thyroid medication or endemic iodine
deficiency

•

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Anterior neck mass of
homogeneous echogenicity

Ultrasonographic

Findings

• Neck mass
o Maintains thyroid contour
o Normative data available for thyroid size at various
gestational ages
• Mass effect
o May obstruct swallowing -+ polyhydramnios
o May prevent normal fetal "chin tuck" -+ extended
neck -+ obstructed labor

DDx: Fetal Neck Mass

•

•

o May compress trachea -+ airway compromise at
birth
Hydrops
o Vascular shunts in enlarged gland -+ high output
state
o Shunting occurs in hyper- and hypothyroidism
Growth disturbance
o Intrauterine growth restriction (IUGR) is common
o Skeletal maturation is delayed in hypothyroidism,
accelerated in hyperthyroidism
Fetal hyperthyroidism
o Tachycardia
o Craniosynostosis
Color Doppler
o May see splaying of neck vessels by soft tissue mass
o If hypervascular carotid and jugular vessels are
increased in size
o Diffuse increased flow in gland -+ hyperthyroid
o Color at periphery of gland -+ hypothyroid

MR Findings
• TlWI
o Uniform high signal due to iodine content
• Helps differentiate from other neck masses, which
are less homogeneous
• T2WI
o Intermediate signal
o Strap/paraspinal muscles are low signal

GOITER
Key Facts
Terminology
• Fetal goiter may be due hyper- or hypothyroidi m
• Fetal hyperthyroid
tate due to maternal thyroid
timulating antibodie
• Fetal hypothyroid state most commonly due to
maternal anti-thyroid medication or endemic iodine
defici ncy

Imaging Findings
• Be t diagnostic clue: Anterior neck ma of
homogeneous cchogenicity
• May obstruct wallowing ...• polyhydramnio
• May prevent normal fetal "chin tuck" ...•extended
neck ...•obstru ted labor
• May compre
trachea ...•airway compromise at birth
• Intrauterine growth re triction (IUGR) i common

o Allows evaluation of tracheal and esophageal
compression
• Trachea normally seen as fluid-filled column
• If not visible ~ t risk airway compromise at birth

Imaging Recommendations
• Monitor
o Fetal growth
o Heart rate and rhythm
o Amniotic fluid volume
• Watch for signs of hydrops
• Consider serial measurements of fetal thyroid in at-risk
pregnancy
o Axial section mid thyroid level
o Measure maximum transverse diameter and
circumference
o Monthly, starting at 22 weeks
o Consider establishing normative data for local
population
• Regional variations in iodine availability influence
"normal" for a given population
• Use color Doppler to assess thyroid vascularity

I DIFFERENTIAL DIAGNOSIS
Cervical teratoma
•
•
•
•

Often very large, irregular shape
Mixed echogenicity +/- large irregular calcifications
May extend into mediastinum
Most teratomas exhibit rapid growth

Cervical neuroblastoma
• Heterogeneous solid mass
• Microcalcifications

Cystic neck masses
•
•
•
•
•

Lymphangioma
Cystic hygroma
Congenital laryngeal cyst
Thyroglossal duct cyst
Branchial cyst

.'

.

•

keletal maturation i delayed In hypothyroldl m,
accelerated in hyperthyroidism
• Diffu e increa ed flow in gland ...•hyperthyroid
• olor at periphery of gland ...•hypothyroid
• onsider serial m a urements of fetal thyroid in
at-ri k pregnancy

Top Differential
•
•
•

Diagnoses

ervical teratoma
rvical neuroblastoma
y tic neck masses

Clinical Issues
• Maintain high index of u picion with maternal
history of Graves disease
• Fetus may have goiter de pite maternal euthyroid
state

• Nuchal cord: Diagnosis easily confirmed with color
Doppler

I PATHOLOGY
General Features
• Genetics
o No association with aneuploidy
o Pendred syndrome
• Sensorineural deafness + goiter
• Autosomal recessive condition with deficient
thyroid hormone synthesis
• Etiology
o Hyperthyroid
• Transplacental passage of maternal
thyroid-stimulating
antibodies
o Hypothyroid
• Transplacental passage of maternal anti-thyroid
drugs
• Both iodine insufficiency and intoxication
• Inborn errors thyroid metabolism
• Maternal lithium use
• Epidemiology
o Hyperthyroidism
• 2:1,000 pregnant women
• 1:4-40,000 fetuses/neonates
o Hypothyroidism
• 1:4,000 neonates as indicated by neonatal
screening
o Pregnancy stresses maternal thyroid ...•increased risk
of fetal hypothyroidism
in iodine deficient areas
o Mothers with Graves disease (autoimmune
hyperthyroidism)
• 2-12% incidence of abnormal fetal thyroid
function
• 1.4% with Graves disease have a fetus with a
goiter

GOITER

I CLINICAL

ISSUES

Presentation
• Anterior neck mass
o May be overlooked, unless directed search
o Maintain high index of suspicion with maternal
history of Graves disease
o Fetus may have goiter despite maternal euthyroid
state

•

Natural History & Prognosis
• Graves disease patients with persistent
hyperthyroidism
in pregnancy
o Increased incidence spontaneous abortion
o 5.6% intrauterine fetal demise (IUFD) or stillbirth
• Series of 72 pregnant women with history of Graves
disease
.
o 57% antibody positive or on antithyroid medication
• 27% (11 fetuses) had goiter by 32 weeks gestation
• One IUFD due to hyperthyroidism/heart
failure
• Ten treated successfully
o 43% antibody negative, no medication
• No fetal goiter, one infant mildly hypothyroid at
birth
• Maternal hypothyroidism
associated with impaired
fertility, higher incidence of spontaneous abortion
• F.etal goiter
o Polyhydramnios
o Dystocia from abnormal head position
o Airway compromise at birth
• Associated findings with fetal hyperthyroidism
o Tachycardia -+ hydrops
o IUGR
o Craniosynostosis
o IUFD, increased perinatal mortality
• Fetal hypothyroidism
o Studies suggest deficient myelination ~ learning
difficulties
o Unlikely to result in cretinism as neonatal treatment
alone is effective in prevention
• Fetus generally responds rapidly to treatment
o Reduction in size of goiter, resolution of
polyhydramnios

Treatment
• Check maternal thyroid antibody status if not known
o If thyroid stimulating hormone (TSH) receptor
antibody levels are high, monitor pregnancy
carefully
o Repeat titers in third trimester
• If detectable titre at 36 weeks, risk for neonatal
hyperthyroidism
is increased
• Monitor maternal thyroid status with free T3, free T4
o Increased thyroxine binding globulin in pregnancy
causes spurious elevation of total T3, T4 in
euthyroid patients
• In pregnancy at risk for goiter due to maternal
hyperthyroidism
treatment, monitor fetal thyroid size
o If thyroid is large, assume fetus hypothyroid due to
maternal drugs crossing placenta
• Decrease maternal antithyroid drugs and monitor
fetal thyroid size

•

•
•

•

• If thyroid size returns to normal, no fetal
intervention required
• May need beta blocker for maternal
symptomatology when antithyroid drugs are
reduced
o If no response, or progressive increase in size, fetus
likely hyperthyroid
• Consider cordocentesis for direct measurement of
fetal thyroid hormones
Measure fetal free T3, free T4, and TSH levels in cord
blood
o Normal ranges established
o Fetal serum levels more reliable than amniotic fluid
levels
If fetal hYflerthyroidism confirmed
o Increase maternal medication until fetal response
• Propylthiouracil preferred
o Thyroxine replacement as needed to keep mother
euthyroid
If fetal hypothyroidism:
Weekly intra-amniotic
injection of thyroxine
Refer to tertiary center for delivery
o May require cesarean section for persistent head
extension
o If persistent goiter, consider EXIT procedure (ex
utero intrapartum treatment) for delivery
• Infant maintained on placental support while
airway is established
Send cord blood for antibody titer
o Better predictor of neonatal thyrotoxicosis than cord
thyroid function tests, which reflect the fetal
situation

I DIAGNOSTIC

CHECKLIST

Consider
• Fetal MRI is useful to evaluate airway compromise and
plan for surgical delivery
• Fetal goiter can occur even if maternal euthyroid state

Image Interpretation

Pearls

• Use color Doppler
o Diffuse flow -+ hyperthyroid
o Peripheral flow -+ hypothyroid

I SELECTED
1.

REFERENCES

Lazarus JH: Thyroid disorders associated with pregnancy:
etiology, diagnosis, and management. Treat Endocrinol.
4(1):31-41,2005

2.

3.

4.

5.

Polak M et al: Fetal and neonatal thyroid function in
relation to maternal Graves' disease. Best Pract ResClin
Endocrinol Metab. 18(2):289-302, 2004
Yanai N et al: Fetal hydrops, associated with maternal
propylthiouracil exposure, reversed by intrauterine
therapy. Ultrasound Obstet Gynecol. 23(2):198-201, 2004
Cohen 0 et al: Serial in utero ultrasonographic
measurements of the fetal thyroid: a new complementary
tool in the management of maternal hyperthyroidism in
pregnancy. Prenat Diagn. 23(9):740-2, 2003
Nachum Z et al: Graves' disease in pregnancy: prospective
evaluation of a selective invasive treatment protocol. Am J
Obstet GynecoJ. 189(1):159-65, 2003

GOITER
IIMAGE

GALLERY

Typical
(Left) Axial ultrasound shows
an enlarged thyroid gland
(arrows) displacing the
jugular and carotid vessels
(curved arrow) posteriorly. A
goiter displaces the vessels,
whereas tumors encase
them. (Right) Coronal
ultrasound in the same fetus
shows enlarged lobes
(arrows) on either side of the
fluid-filled trachea (curved
arrow). Airway compromise
is a major concern with a
large goiter, and the EXIT
procedure may be required
for delivery.

Typical
(Left) Axial ultrasound shows
the normal appearance of
the thyroid (arrows) in the
mid trimester (curved arrow
- spinal elements). Serial
measurements of maximum
transverse diameter and
circumference are useful in
the at-risk fetus. (Right) Axial
ultrasound shows a large
goiter delineated by calipers.
Bony elements of the
cervical vertebra (arrows)
and the paraspinal muscles
(open arrows) are also well
seen in this view.

Typical
(Left) Axial T2WI MR shows
an intermediate signal,
anterior neck mass (arrows).
The spinal cord can be seen
surrounded by high signal
cerebrospinal fluid (curved
arrow). (Right) Axial T7WI
MR shows uniform high
signal intensity throughout
the mass (arrows),
confirming that it is thyroid
tissue. Although anatomy is
poorly seen on this
sequence, it is important
diagnostically, as the high
iodine content causes
increased signal within a
goiter.

CERVICAL TERATOMA

Coronal T2WI MR of a cervical teratoma shows a large,
mixed signal intensity mass (arrow) arising within the
soft tissuesof the fetal neck. The head (curved arrow) is
deviated to the side.

Clinical photograph after delivery shows the mass
involving dJe anterior neck, with hyperextension of the
head. The neck is supported by rolled IOwels (arrow).
(Also shown in Radiographies, ref 1).

ITERMINOLOGY

Ultrasonographic

Definitions

• Predominately solid or mixed cystic/solid
• Calcifications are virtually pathognomonic
of
teratoma
o Present in only half of cases
o May not be visible by ultrasound
• Head is often held in hyperextension
o May be dramatic
o Head may be deviated to one side
• Polyhydramnios from upper esophageal obstruction
o Often severe
o Worsens as pregnancy progresses
• Color Doppler
o Solid portions of mass often very vascular
o Arteriovenous shunting may be present
• Hydrops may develop with large masses

• Teratoma: Neoplasm derived from all three germ cell
layers (ectoderm, mesoderm, endoderm)

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Mixed cystic and solid mass
involving anterior aspect of neck
• Location
o Anterior neck mass
o Frequently extends to involve surrounding
structures
o Posterior extension
• May involve trapezius
• May be nearly circumferential but bulk of mass is
anterior
o Superior extension
• Frequently up to mastoid
• May displace ear and distort jaw
o Inferiorly
• To clavicle or even into mediastinum
• Size
o Variable
o Often large and can be massive

DDx: Neck/Facial

MR Findings
• Helpful in determining anatomic extent
• Masses usually mixed signal intensity
o Cystic component
• Low signal T1 WI, high signal T2WI
o Soft tissue component
• Intermediate signal on both Tl WI, T2WI
o Fat component
• High signal T1 WI, high signal T2WI
• Signal suppresses with fat-saturation sequence

Masses

..

~,.
Goiter

Epignalhu5

Findings

Myofibromatosis

CERVICAL TERATOMA
Key Facts
• Goiter

Imaging Findings
•
•
•
•
•
•
•
•
•
•

Anterior neck mass
Frequentlyextend
to involve urrounding structures
May displace ear and distort jaw
Often large and can be massive
Predominately solid or mixed cystic/solid
Calcifications are virtually pathognomonic
of
teratoma
Head is often held in hyperextension
Polyhydramnios from upper esophageal obstruction
Hydrops may develop with large ma ses
MRI recommended to better delineate anatomy and
extent of tumor

Top Differential

Diagnoses

Pathology
• Head and neck second most common site for
teratomas after sacrococcygeal area
• Ectodermal tissues main hi tologic component of
fetal teratomas
• Often contain neural ("brain-like") tissue a dominant
component

Clinical Issues
• Hyperextension of neck re ults in malpresentation
and dystocia, precluding vaginal delivery

Diagnostic Checklist
• Referral to tertiary care facility with capability of
performing EXIT procedure

• Epignathus
• Cystic hygroma
• Could potentially confirm diagnosis of teratoma if
fat components are large enough for detection

• May occur with either increased or decreased fetal
thyroid function

Imaging Recommendations

Rare soft tissue tumors

• Routine views of chest, head and face should detect
virtuall y all cases
• Color Doppler to evaluate vascularity
• MRI recommended to better delineate anatomy and
extent of tumor
• Close interval follow-up
o May grow rapidly to massive 'size
o Worsening polyhydramnios
• Mass may cause high-output cardiac failure and
hydrops
o Cardiomegaly
o Ascites
o Pleural effusion
o Skin thickening
o Pericardial effusion

• Soft tissue tumors (both benign and malignant)
cause neck mass
o Hemangioma
o Fibromatosis
o Myofibromatosis
o Fibrosarcoma
o Rhabdomyosarcoma

I DIFFERENTIAL

DIAGNOSIS

Epignathus
•
•
•
•

Nasopharyngeal teratoma
Point of origin of large teratomas
Mouth is usually held open
May have intracranial extension

may be obscure

Cystic hygroma
• Fluid collection in posterior and lateral neck
• Internal septations
o Multiple thin septations common
o Midline thick septation is nuchal ligament
• Hydrops commonly seen
• Associated with Turner syndrome

Goiter
• Homogeneously echogenic neck mass
• Maintains normal thyroid contour
o Distinct lobes seen in coronal plane
o Prominent isthmus connects lobes in axial plane

may

I PATHOLOGY
General Features
• Genetics
o Sporadic
o No recurrence risk
• Etiology
o Embryology
• Primordial germ cells migrate from yolk sac to
genital ridges (weeks 4-6)
• Germ cells are then incorporated into primitive
sex cord to form gonads
• Unincorporated
cells normally involute
• Continued division of unincorporated
pluripotential cells gives rise to teratoma
• Epidemiology
o Rare
o Head and neck second most common site for
teratomas after sacrococcygeal area
o Equal distribution between males and females
• Different from most teratomas, which are more
common in females

Gross Pathologic & Surgical Features
• Complex, mixed cystic and solid components
• May see cartilage and bone
o Teeth and hair not as common as in teratomas latter
in life

CERVICAL TERATOMA
Microscopic

o Fetus is partially delivered by cesarean section
section while placenta and umbilical cord remain
intact
o Uteroplacental
gas exchange
maintained
o Fetus remains hemodynamically
stable while airway
is established
o Avoids "crash" attempt
at achieving
airway at birth

Features

• Frequently
involves thyroid gland
o Not thought
to directly arise from thyroid tissue
• Unique histologic
features compared
to teratomas
presenting
later in life
• Composed
of all three germ cell layers
o Ectodermal
tissues main histologic
component
of
fetal teratomas
• Often contain neural ("brain-like")
tissue as
dominant
component
o Mesoderm
• Fat
• Cartilage
• Smooth muscle
• Bone
o Endoderm
• Least common
component
• Respiratory
epithelium
• Gastrointestinal
tissues

I DIAGNOSTIC

CHECKLIST

Consider
• MRI to better delineate
anatomy
• Delivery planning
crucial, especially for large masses
o Referral to tertiary care facility with capability of
performing
EXIT procedure

Image Interpretation
• Calcifications
teratoma

within

Pearls

a neck mass are diagnostic

of a

Staging, Grading or Classification Criteria
• Teratomas
classified as mature or immature
o Immature
teratomas
do not have same poor
prognosis as those presenting
latter in life
• Immaturity
of tumor may reflect immaturity
fetus rather than biologic behavior of tumor
o Size and vascularity
are much more important
histology in a fetus

I SELECTED REFERENCES
1.
of
2.
than
3.

I CLINICAL

ISSUES

4.

Presentation
• Most common
signs/symptoms:
Obvious soft tissue
mass involving
neck
• Other signs/symptoms
o Head often held in hyperextension
or deviated to
side
o Polyhydramnios

5.

Natural History & Prognosis

8.

• Polyhydramnios
may cause preterm labor
• Hyperextension
of neck results in malpresentation
and
dystocia, precluding
vaginal delivery
• May show rapid in utero growth
• Routine resuscitation
techniques
o Lethal if unable to establish airway
o Even with maximal emergency
procedures,
hypoxia,
acidosis and anoxic brain injuries occur
o Mortality for head and neck teratomas
80-100%
• Substantial
improvement
in survival achieved with ex
utero intrapartum
treatment
(EXIT) procedure
o In large series airway established
in 79%, with
overall survival of 69% for head and neck masses

6.

7.

9.
10.

11.
12.
13.

14.

Treatment
• Termination
may be offered
• If pregnancy
continued,
deliver at tertiary care facility
with capability
of performing
EXIT procedure
• EXIT procedure
provides controlled
environment
to
establish airway

IS.
16.

Woodward P] et al: From the archives of the AFIP: a
comprehensive review of fetal tumors with pathologic
correlation. Radiographies. 25(1):215-42, 2005
Yoshino K et al: Congenital cervical rhabdomyosarcoma
arising in one fetus of a twin pregnancy. Fetal Diagn Ther.
20(4):291-5, 2005
Hirose S et al: The ex utero intrapartum treatment
procedure: Looking back at the EXIT. J Pediatr Surg.
39(3):375-80; discussion 375-80, 2004
Breysem Let al: The value of fast MR imaging as an adjunct
to ultrasound in prenatal diagnosis. Eur Radiol.
13(7):1538-48, 2003
Gorincour G et al: Prenatal presentation of cervical
congenital neuroblastoma. Prenat Diagn. 23(8):690-3, 2003
Hirose S et al: Spectrum of intrapartum management
strategies for giant fetal cervical teratoma. J Pediatr Surg.
38(3):446-50; discussion 446-50, 2003
Bouchard S et al: The EXIT procedure: experience and
outcome in 31 cases.] Pediatr Surg. 37(3):418-26, 2002
Sichel JY et al: A multidisciplinary
team approach for
management of a giant congenital cervical teratoma. Int]
Pediatr Otorhinolaryngol.
65(3):241-7, 2002
Wagner W et al: Fetal operations in the head and neck
area: current state. Head Neck. 24(5):482-90, 2002
Stocks RM et al: Airway management of neonates with
antenatally detected head and neck anomalies. Arch
Otolaryngol Head Neck Surg. 123(6):641-5, 1997
Vujanic GM: Cervical teratomas. Pediatr Pathol Lab Med.
15(1):221-2, 1995
Garmel SH et al: Prenatal diagnosis and management of
fetal tumors. Semin Perinatol. 18(4):350-65, 1994
Parkes SE et al: Neonatal tumours: a thirty-year
population-based
study. Med Pediatr Oncol. 22(5):309-17,
1994
Hitchcock A et al: Immature cervical teratoma arising in
one fetus of a twin pregnancy. Case report and review of
the literature. Acta Obstet Gynecol Scand. 66(4):377-9,
1987
Isaacs H Jr: Perinatal (congenital and neonatal) neoplasms:
a report of 110 cases. Pediatr Pathol. 3(2-4):165-216, 1985
Rempen A et al: Differential diagnosis of sonographically
detected tumours in the fetal cervical region. Eur] Obstet
Gynecol Reprod BioI. 20(2):89-105, 1985

CERVICAL TERATOMA
I IMAGE GALLERY
Typical
(Left) Coronal (upper) and
sagittal (lower) images of a
moderate-sized cervical
teratoma (calipers). It has
both cystic (arrows) and
solid components. (Right)
Sagittal T1 WI MR of a
massive cervical teratoma
(arrows) shows dramatic
hyperextension of the head
(curved arrow).

(Left) Sagittal T2WI MR
shows a mixed signal neck
mass (arrows) extending up
to the level of the skull base.
(Right) Axial T2WI MR
through the mass shows
extensive involvement of the
anterior and lateral neck.
Two cystic areas are seen
(arrows), as well as a large
soft tissue component (spinal
canal- open arrow).

(Left) Continuing from the
case above, the fetus was
delivered via the EXIT
procedure and a
tracheostomy placed.
Postnatal sagillal T2WI image
shows posterior extension of
the mass (arrows) with no
identifiable laryngeal or
pharyngeal structures.
(Right) Clinical photograph
shows the mass extending
from the ear to chest
(tracheostomy - arrow).
Histology showed an
immature teratoma.

SECTION 5: Chest

Introduction and Overview
Chest Development

& Imaging

5-2

Chest
Pulmonary Hypoplasia
Congenital Diaphragmatic Hernia
Cystic Adenomatoid Malformation
Bronchopulmonary
Sequestration
Pleural Effusion
Teratoma, Chest
Tracheal Atresia
Lymphangioma

5-6
5-10
5-14
5-18
5-22
5-26
5-28

5-30

CHEST DEVELOPMENT

Axial ultrasound at the level of the four chamber view of
heart shows a normal cardiac axis (arrow). The lungs
have a symmetric, homogeneous echotexture.

Ultrasound
• Heart most obvious finding in chest
o Should occupy 1/4 to 1/3 of thoracic cavity
o Apex directed to left
o Cardiac axis approximately 45°
o Normal axis excludes significant chest mass
• Lungs
o Homogeneous intermediate echogenicity
o Echogenicity increases with gestational age
• Can not be used to predict hypoplasia
o Right lung volume slightly greater than left
• Right lung 3 lobes, left lung 2 lobes
• Lobar anatomy can not usually be identified
• Diaphragm
o Continuous hypoechoic band between pleural and
peritoneal cavities
• Thymus
o Anterior mediastinum
o Visualization reported in 74%
o < 27 weeks hyperechoic
o > 27 weeks hypoechoic

MRI
• Excellent soft tissue contrast
• Ideally suited for evaluation of chest masses, especially
congenital diaphragmatic hernia (CDH)
• Lungs
o Intermediate-signal
intensity T1 WI
o High-intensity T2WI
• Liver
o High signal intensity T1 WI
o Low signal intensity T2WI
• Good for volumetric lung measurements

Imaging Issues

Imaging Protocols
• American Institute of Ultrasound
chest evaluation

Coronal T2WI MR shows normal, symmetric, high
signal intensity lungs. The fluid-filled trachea (black
arrow), bronchi, and stomach (white arrow) are easily
identified. The liver (curved arrow) is dark on T2WI.

o Four chamber view of heart
o Outflow tracts if technically feasible

Ilmaging Anatomy

IAnatomy-Based

& IMAGING

in Medicine (AIUM)

Imaging Pitfalls
• Oblique axis can give false appearance of CDH
o If multiple ribs are seen, image is oblique
o One continuous rib in true axial plane
• Be sure to image entire diaphragm
o Diaphragm may be intact anteriorly in Bochdalek
CDH
• Sagittal plane best for posterior defect

Normal Measurements
• Routine measurements not necessary
• Ratio of thoracic circumference to abdominal
circumference (TC/Ae) remains stable throughout
pregnancy
o Normal> 0.80

I Embryology
Embryologic Events
• Embryonic stage
o 26 days to 6 weeks
o Lung bud arises as ventral outpouching of foregut
o Penetrate surrounding mesenchyme
o Branches to form lungs and bronchopulmonary
segments
• Pseudoglandular stage
o 6-16 weeks
o Continued branching to form terminal bronchioles
• Canalicular stage
o 16-28 weeks
o Terminal bronchioles divide into respiratory
bronchioles
o Respiratory vasculature develops
o Progressive flattening of epithelial cells
• Necessary for gas exchange
• Saccular stage
o 28-36 weeks
o Respiratory bronchioles divide to produce terminal
sacs

CHEST DEVELOPMENT & IMAGING
Key Facts
Imaging Issues
• Lungs homogeneous,
• MRI ideally suited for
• Oblique axis can give
diaphragmatic hernia

intermediate echogenicity
evaluation of chest masses
false appearance of a congenital
(CDH)

Clinical Issues
• Multiple factors needed for lung development
o Normal thoracic cavity

o Occurs in a craniocaudal progression
o Process continues until 8 years of age
• 20-70 million terminal sacs at birth
• 300-400 million at maturation
• Alveolar stage
o 36 weeks to term
o Alveolar maturation
• Diaphragm development
o Composite of four embryologic structures
• Septum transversum
• Pleuroperitonea I membranes
• Paraxial mesoderm
• Esophageal mesenchyme

Requirements

For Normal Development

• Normal thoracic cavity
o Chest masses, skeletal dysplasia restrict lung growth
• ormal amniotic fluid
• Fetal breathing
• Homeostasis of fetal lung fluid
o Fluid is both secreted and absorbed
o Complex interchange of lung fluid production and
amniotic fluid exchange during breathing
o et efflux of fluid with breathing
o Fetal lung fluid functions as stent keeping
developing air spaces distended
• Decreased fetal lung fluid ~ hypoplasia
• Increased fetal lung fluid (Le. tracheal atresia
blocking efflux) ~ overgrowth and advanced
maturation

Normal amniotic fluid
Fetal breathing
• Lung development single most important factor
determining survival for many conditions
• Oligohydramnios
is an important etiologic factor for
pulmonary hypoplasia
• CDH most common chest mass to cause pulmonary
hypoplasia

I Clinical

Implications

5

Clinical Importance
• Pulmonary hypoplasia single most important factor
determining survival for many conditions
• Oligohydramnios
important etiologic component of
pulmonary hypoplasia
o Fetal compression causes decreased space for lung
growth
o Restriction of breathing movements
o Efflux of lung fluid into amniotic space
o Oligohydramnios
as short as 6 days may cause
pulmonary hypoplasia
o Oligohydramnios>
14 days at 2S wks gestational
age has 90% mortality
• Not all chest masses have same affect on developing
lungs
o CDH has more severe hypoplasia than other masses
of comparable size

I Related References
1.
2.
3.
4.

Larsen WJ: Human embryology. 3rd ed. New York,
Churchill Livingstone. 133-158,2001
Laudy JA et al: The tetallung. 1: Developmental aspects.
Ultrasound Obstet Gynecol. 16(3):284-90, 2000
Laudy JA et al: The fetal lung. 2: Pulmonary hypoplasia.
Ultrasound Obstet Gynecol. 16(5):482-94, 2000
Felker RE et al: Ultrasound ot the fetal thymus. J
Ultrasound Med. 8(12):669-73, 1989

I IMAGE GAllERY
(Left) Axial oblique ultrasound of
the chest gives the erroneous
appearance of a congenital
diaphragmatic hernia. The
stomach (open arrow) appears to
be adjacent to the heart. Note
that multiple ribs are seen
(arrows) indicating this is not a
true axial plane. (Right) Sagittal
ultrasound of the diaphragm
shows a continuous hypoechoic
band between the thoracic and
peritoneal cavities (arrow). It is
intact with the stomach (open
arrow) and heart (curved arrow)
in the correct cavities.

3

PULMONARY

Axial T2WI MR shows the technique of lung planimetry.
The lung edges are traced to derive the area. This is
multiplied by the slice thickness to obtain the volume.
All sections are added to determine total lung volume.

ITERMINOLOGY
Definitions
• Decreased number of cells, airways and alveoli
resulting in decreased size and weight of lungs
o Often result of an intrathoracic mass or small chest
circumference

IIMAGING

FINDINGS

General Features
• No universally accepted diagnostic criteria for
predicting hypoplasia
• A plethora of measurements and ratios exist
• Perplexing issue which continues to be area of
ongoing research
• Lung volumes become more variable with advancing
gestational age (GA)
o Greater correlation with fetal size than GA

Ultrasonographic

Findings

• Lung echogenicity increases with GA
o Dose not predict lung maturity
• Fetal breathing movements
o Important for lung development
o Absence over extended period poor prognostic
o No quantifiable predictive measurement

DDx: Conditions

ARPKD

sign

HYPOPLASIA

Doppler of pulmonary artery for AT/ET ratio calculation.
AT is from onset to peak systolic flow and ET is from
onset to end of systole. Diastole begins with a brief
reversal of flow (arrow).

• Direct lung measurements
o Area, length and diameter have been used
o Often difficult
• Poor soft tissue contrast
• Oligohydramnios
• Unfavorable fetal position
• Thoracic circumference (TC)
o Performed at level of four-chamber view
• Exclude soft tissues
o Compare to expected value for GA or as a ratio with
abdominal circumference (AC), femur length (FL), or
head circumference (HC)
• TCI AC ratio stable throughout pregnancy
• Normal> .80
o Useful when chest size is small
• Skeletal dysplasia
• Oligohydramnios
o Not useful for chest masses
• Lung-to-head ratio (LHR)
o Used predominately with congenital diaphragmatic
hernia (CDH)
o Lung area contralateral to CDH is calculated by
multiplying 2 orthogonal cross-section lung
measurements
• Measurements taken at level of four-chamber view
• Ipsilateral lung usually obscured by hernia
o Calculated area of contralateral lung divided by
head circumference to give LHR

Resulting In Pulmonary Hypoplasia

PUV

Renal Agenesis

PULMONARY

HYPOPLASIA

Key Facts
Imaging Findings
•

•
•
•
•

0 universally accepted diagnostic criteria for
predicting hypoplasia
A plethora of measurem nts and ratios exi t
Perplexing issue which continues to be area of
ongoing research
Lung volumes become more variable with advancing
gestational age (GA)
ot all malformations affect developing lungs to
ame degree

Top Differential

Diagnoses

• hest ma ses
• Conditions causing oligohydramnio
• Abnormal thoracic cavity

• LHR < 1.0 poor prognosis
• LHR > 1.4 favorable prognosis
• Pulsed Doppler
o Peripheral pulmonary artery resistance
• Increased with hypoplasia
• Nonspecific: Also increased in intrauterine growth
restriction (IUGR)
o Acceleration time/ejection time ratio (AT/ET)
• Performed in pulmonary arteries (PA): May only
see one PA if an intrathoracic mass is present
• Acceleration time: Time from onset of systole to
systolic peak
• Ejection time: Time from onset to end of systole
o Normal PA has a "spike and dome" pattern
• Spike: Rapid acceleration to systolic peak followed
by brief deceleration
• Dome: Slower, "rounded" waveform later in
systole
• Diastole begins with brief reversed flow from
closure of pulmonary valve
o Normal AT/ET ratio ranges
• Right PA: 0.17 ± 0.04
• Left PA: 0.15 ± 0.04
o AT/ET ratio below normal correlates with
pulmonary hypoplasia
• Reflects increased fetal pulmonary vascular
resistance
• 3D

o Currently being investigated for utility in volumetric
measurements
o Poor soft tissue contrast may limit accuracy

MR Findings
• Ideally suited for evaluation of chest masses which
may cause hypoplasia
o Excellent soft tissue contrast
o Lung more easily identified and differentiated from
liver and other chest contents
• Lung: Low signal T1WI, high signal T2WI
• Liver: High signal T1WI, low signal T2WI
• Planimetric measurements of total lung volume
o Area of lung measured and multiplied by slice
thickness

Pathology
• Oligohydramnio
mortality

> 14 days at 25 weeks GA has 90%

Clinical Issues
• Respiratory distress at birth
• Pneumothorax
• Bell-shaped chest

Diagnostic Checklist
• Single most important factor determining survival for
many conditions
• Lung volumes alone do not always correlate with
outcomes
• Persistent severe oligohydramnios
poor prognostic
sign

o Slice volumes are summed for total volume
• Lung volumes are compared with multiple biometric
indices
• Lung signal intensity may also correlate with
hypoplasia
• Disadvantages
o Labor intensive to perform calculations
o As yet, no single standard approach

Imaging Recommendations
• Protocol advice
o Thorough evaluation of chest anomalies
• Not all malformations affect developing lungs to
same degree
o Consider fetal echo
• Heart often difficult to evaluate when mass is
present
• Ability to detect cardiac defects more difficult
• Cardiac anomaly with chest malformation
worsens prognosis
o Commonly used techniques to evaluate lungs
• TC/ AC ratio
• LHR
• Doppler: AT/ET ratio
• MRI

I DIFFERENTIAL

DIAGNOSIS

Chest masses
• Congential diaphragmatic hernia (CDH)
o Most common mass to cause pulmonary hypoplasia
o Hypoplasia more severe than for other chest masses
of similar size
• Congenital cystic adenomatoid malformation (CCAM)
• Sequestration
• Teratoma
• Large pleural effusions

Conditions

causing oligohydramnios

• Bilateral renal agenesis
• Bilateral multicystic dysplastic kidneys
• Bladder outlet obstruction

PULMONARY
o Posterior urethral valves (PUV)
o Urethral atresia
o Obstructing mass
• Autosomal recessive polycystic kidney disease (ARPKD)
• Premature rupture of membranes (PROM)
o Especially before 26 weeks

Abnormal thoracic cavity
•
•
•
•
•
•

Thanatophoric dysplasia
Asphyxiating thoracic dystrophy
Achondrogenesis
Osteogenesis imperfecta
Camptomelic dysplasia
Short rib-polydactyly syndrome

Oeune syndrome)

Cardiac malformations
• Right-sided obstructive lesions decrease pulmonary
blood flow and lung growth
o Pulmonary atresia/stenosis
o Hypoplastic right heart
o Ebstein anomaly

Neuromuscular

anomalies

• May cause decreased fetal breathing and subsequent
poor lung development
o Anencephaly
o Ischemic brain injury
o Intracranial masses
o Fetal hypokinesia/akinesia
sequence

I PATHOLOGY
General Features
• Epidemiology
o 9-11:10,000 live births
o 8-22% in autopsy series
• Oligohydramnios important etiologic component
o Fetal compression causes decreased space for lung
growth
o Restriction of breathing movements
o Efflux of lung fluid into amniotic space
o Oligohydramnios as short as 6 days may cause
pulmonary hypoplasia
• Factors affecting prognosis with PROM
o GA of rupture
o Duration
o Degree of oligohydramnios
• Oligohydramnios>
14 days at 2S weeks GA has
90% mortality

Gross Pathologic & Surgical Features
• Decreased ratio of lung weight to body weight
• Decreased radial alveolar count
o Number of alveolar septa at center of respiratory
bronchiole
• Decreased lung DNA relative to body weight

ICLINICAllSSUES
Presentation
• Respiratory distress at birth
• Chest X-ray

HYPOPLASIA
o Pneumothorax
o Pneumomediastinum
o Bell-shaped chest

Natural History & Prognosis
• Pulmonary hypoplasia critical determining factor in
survival
• Major cause of death in premature infants
• Severity dependent on timing and degree of insult
• Neonatal death in severe cases

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Single most important factor determining survival for
many conditions
• Lung volumes alone do not always correlate with
outcomes
o Complex problem of multiple varying etiologies
• Persistent severe oligohydramnios
poor prognostic
sign

I SELECTED REFERENCES
1.

Tanigaki S et al: Pulmonary hypoplasia: prediction with use
of ratio of MR imaging-measured fetal lung volume to
US-estimated fetal body weight. Radiology. 232(3):767-72,
2004
2. Williams G et al: Fetal relative lung volume: quantification
by using prenatal MR imaging lung volumetry. Radiology.
233(2):457-62, 2004
3. Fuke S et al: Antenatal prediction of pulmonary hypoplasia
by acceleration time/ejection time ratio of fetal pulmonary
arteries by Doppler blood flow velocimetry. Am J Obstet
Gynecol. 188(1):228-33, 2003
4.
Paek BW et al: Congenital diaphragmatic hernia: prenatal
evaluation with MR lung volumetry--preliminary
experience. Radiology. 220(1):63-7, 2001
5.
Coakley FV et al: Normal and hypoplastic fetal lungs:
volumetric assessment with prenatal single-shot rapid
acquisition with relaxation enhancement MR imaging.
Radiology. 216(1):107-11, 2000
6. Laudy JA et al: The fetal lung. 2: Pulmonary hypoplasia.
Ultrasound Obstet Gynecol. 16(5):482-94, 2000
7.
Mitchell JM et al: Doppler waveforms from the pulmonary
arterial system in normal fetuses and those with
pulmonary hypoplasia. Ultrasound Obstet Gynecol.
11(3):167-72, 1998
8. Kilbride HW et al: Defining limits of survival: lethal
pulmonary hypoplasia after mid trimester premature
rupture of membranes. Am J Obstet Gynecol. 175(3 Pt
1):675-81, 1996
9.
Yoshimura S et al: Ultrasonographic prediction of lethal
pulmonary hypoplasia: comparison of eight different
ultrasonographic parameters. Am J Obstet Gynecol.
175(2):477-83,1996
10. D'Alton M et al: Serial thoracic versus abdominal
circumference ratios for the prediction of pulmonary
hypoplasia in premature rupture of the membranes remote
from term. Am J Obstet Gynecol. 166(2):658-63, 1992
11. Vintzileos AM et al: Comparison of six different
ultrasonographic methods for predicting lethal fetal
pulmonary hypoplasia. Am J Obstet Gynecol.
161(3):606-12, 1989

PULMONARY

HYPOPLASIA

IIMAGE GALLERY
(Left) Axial ultrasound of the
fetal chest shows a COH
with the stomach (arrow) in
the thorax and displacement
of the heart to the right
(curved arrow). (Right)
Cross pathology at autopsy
shows a small, hypoplastic
lung being retracted. The
stomach (arrow) and a
portion of the left lobe of the
liver (curved arrow) are in
the thoracic cavity. The heart
(open arrow) is displaced to
the right. Pulmonary
hypoplasia is worse for COH
than other chest masses of
comparable size.

(Left) Sagittal ultrasound
shows a very small chest
cavity (curved arrow) in this
case of thanatophoric
dysplasia. Compare to the
normal abdomen (arrow).
(Right) Clinical photograph
confirms the very small chest
size (arrows) as well as
markedly shortened limbs.
Pulmonary hypoplasia was
secondary to a small thoracic
cavity restricting lung
growth.

(Left) Frontal radiograph
shows classic features of
pulmonary hypoplasia in a
case of unsuspected
renal
agenesis. The chest is
bell-shaped, there are
bilateral pneumothoraces
with chest tubes in place,
and subcutaneous
air
(arrow). (Right) Cross
pathology from a different
case of renal agenesis shows
very small hypoplastic lungs
(arrows) in comparison to
the normal sized heart
(curved arrow).

CONGENITAL DIAPHRAGMATIC

Graphic 0( a large COH at the level of the four-chamber
view. The lung-to-head ratio is calculated by multiplying
the orthogonal lung diameters to obtain the area
(cursors) then dividing by the head circumference.

ITERMINOLOGY
Abbreviations
• Congenital

and Synonyms

diaphragmatic

hernia (CDH)

Definitions
• Herniation of abdominal contents into chest cavity
o Foramen of Bochdalek
• Posterior defect in diaphragm
o Foramen of Morgagni
• Anterior
• Right-sided
o Uncommonly herniation through esophageal hiatus
or diaphragmatic agenesis

IIMAGING

FINDINGS

General Features
• Best diagnostic clue
o Cystic chest mass and absent stomach bubble
• Peristalsis within cystic chest mass is
pathognomonic
• Location
o Left-sided 80-90%
o Right-sided lO'h,
o Bilateral < 5%

HERNIA

Axial ultrasound shows the heart displaced into the right
hemithorax (open arrow). Cursors measure the lung
(curved arrow) at the level of the 4-chamber view. The
LHR was 7.5 and this fetus had a good outcome.

• Abdominal circumference will measure less than
expected
• Most prenatally diagnosed CDHs are large
• Hydrops uncommon unless associated malformations
present
o Poor prognostic indicator
• Small CDH may be missed, especially if stomach is not
herniated
o Abnormal cardiac axis may be only clue

Ultrasonographic

Findings

• Left-sided hernia
o Four classic findings
• Cystic mass in left side of chest
• Absence of fluid-filled stomach
• Deviation of heart toward right
• Polyhydramnios
o Up to 85% contain herniated liver ("liver up")
• Often difficult to diagnose
• Typically left lobe herniates adjacent to heart
• Stomach is displaced posteriorly
• Always use Doppler to follow portal veins
• Umbilical segment of portal vein bows to left
• Right-sided more difficult
o May be confused for chest mass
o Contains liver and bowel
• Doppler will show portal veins
o Stomach is below diaphragm

DDx: Cystic lung Mass

MacroC}stic CCAM

Bronchogenic Cyst

Teratoma

CONGENITAL DIAPHRAGMATIC
Key

HERNIA

Facts

Terminology

Pathology

• Herniation of abdominal contents into chest cavity

• Pulmonary hypoplasia wor e than from other chest
masses of comparable size
• Up to 50% have an associated abnormality
• hromosomal abnormalities are common
• All fetuses hould be karyotyped

Imaging Findings
• ystic che t mass and ab ent stomach bubble
• Peristalsis within cystic chest ma s is pathognomonic
• Small DH may be missed, especially if stomach i
not herniated
• Up to 85<rh contain herniated liver ("liver up")
• alculate lung-to-head ratio (LHR)
• LHR < 1.0 poor prognosis
• LHR> 1.4 favorable progno i
• MRI best te t to evaluate anatomy and contents

Top Differential
•

Diagnoses

ongenital cystic adenomatoid
(

malformation

Clinical Issues
•
•
•
•

Factors which worsen prognosis:
Presence of other abnormalities
Liver in chest
Diagnosis before 24 weeks gestational age

Diagnostic Checklist
• Incorrect scan plane may re ult in erroneous
diagno is

AM)

• May be more midline in location
o Gallbladder often herniates
• Bilateral
o Be suspicious when stomach is in chest but little
mediastinal shift
o Use color Doppler to look for liver on right

MR Findings
• Excellent for identifying contents of hernia
• Bowel appears as tubular serpiginous structure with
variable signal intensity
o Fluid-filled small bowel
• Low signal T1WI, high signal T2WI
o Meconium
• High signal T1WI, low signal T2WI
• Accurately diagnoses presence of liver in CDH
o High signal T1WI
o Low signal T2WI
• Can perform volumetric lung measurements

CT Findings
• Used rarely in cases of maternal obesity
• Fetus will swallow contrast injected into amniotic fluid
o Confirms stomach in chest
• May be an alternative if patient can not undergo MRI

Imaging Recommendations
• Best imaging tool:' Higher frequency transducers
helpful for differentiating herniated bowel vs. liver
• Confirm that CDH findings are real
o Oblique axial image my simulate a "pseudo CDH"
• Check ribs
• If multiple ribs seen, axis is incorrect
• Cardia axis is normal
• Calculate lung-to-head ratio (LHR)
o Area of contralateral lung divided by head
circumference
• Ipsilateral lung usually obscured by hernia
o Lung area is calculated by multiplying 2 orthogonal
cross-sectional lung measurements taken at level of
four-chamber view
o Example (all calculations done in millimeters)
• Lung measurements 22 mm and 18 mm

• Lung area 396 mm2 (22 mm x 18 mm)
• Head circumference 256 mm
• LHR = 1.5 (396 divided by 256)
o LHR < 1.0 poor prognosis
o LHR > 1.4 favorable prognosis
• All fetuses with CDH need dedicated fetal echo
o CDH and cardiac defect is considered lethal
• MRI best test to evaluate anatomy and contents

I DIFFERENTIAL DIAGNOSIS
Congenital cystic adenomatoid
malformation (CCAM)
•
•
•
•
•
•

Macrocystic type
Stomach below diaphragm
Diaphragm intact
Abdominal circumference normal
No peristalsis
Doppler shows pulmonary artery supplying mass

Hybrid lesion
• Combination of CCAM + sequestration
• Consider when a cystic mass is fed by a systemic vessel

Other cystic masses
• Bronchogenic cyst
• Esophageal duplication cyst
• Neurenteric cyst
o Thoracic boney abnormality usually present
• All rare
• More often associated with mediastinum than lung

Teratoma
• Solid and cystic components
• Calcifications most specific finding
• Rare

I PATHOLOGY
General Features
• General path comments

CONGENITAL

DIAPHRAGMATIC

o Pulmonary hypoplasia worse than from other chest
masses of comparable size
• Hypoplasia always present to varying degrees
• Lungs are small and histologically immature
o Abnormal pulmonary arteries
• Muscular hypertrophy of arterial walls
• Results in pulmonary hypertension and persistent
fetal circulation
o Up to 50% have an associated abnormality
• 30% central nervous system (CNS) malformations
• 20% cardiac anomalies
• Renal
• Spinal
o Chromosomal abnormalities are common
• Reported in 16-37% of cases
• Trisomies 18, 13, 21, 9
• All fetuses should be karyotyped
o Associated syndromes
• Fryns syndrome: CDH, facial abnormalities, distal
limb hypoplasia, CNS malformations
• Genetics: Generally sporadic inheritance
• Epidemiology: 1:2,000-5,000 births
• Embryology
o Failure of fusion of posterior pleuroperitoneal
membranes

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o May be an incidental finding
• Stomach in chest
o Patient may be large-for-dates secondary to
polyhydramnios
o Respiratory distress in newborn

Natural History & Prognosis
• 65% survival if isolated
• Factors which worsen prognosis:
o Presence of other abnormalities
o Liver in chest
• Mortality "liver-up" 57%
• Mortality "liver-down" 7%
o Diagnosis before 24 weeks gestational age
o Large size
o Right-sided or bilateral
o Polyhydramnios

Treatment
• In utero repair not shown to be useful

• Tracheal occlusion
o PLUG: Plug lung until it grows
o FETO: Fetoscopic tracheal occlusion
o Causes retention of fetal lung fluid which accelerates
lung growth
o Performed before 26 weeks gestational age on fetuses
with poor prognosis
• "Liver-up"
• LHR < 1.0
o Necessitates delivery by cesarean section using ex
utero intrapartum treatment (EXIT) procedure
• Uteroplacental circulation is maintained while
tracheal occlusion is removed and fetus intubated

HERNIA

o Clinical trials ongoing
• Mixed results
• May not improve outcome over conventional
treatment in most cases
• May be limited to select group of severely affected
fetuses
• Planned delivery at tertiary care facility essential
o Antenatal steroids
o Surfactant, high-frequency oscillatory ventilation,
inhaled nitric oxide, permissive hypercapnia
o Extracorporeal membrane oxygenation (ECMO)
needed if severe
• EXIT to ECMO may be best strategy
o Uteroplacental circulation maintained while arterial
and venous lines are placed
o Avoids barotrauma
o Oxygenation and nutrition maintained
o Aggressive treatment of pulmonary hypertension

I DIAGNOSTIC

CHECKLIST

Consider
• MRI to better evaluate anatomy and contents

Image Interpretation

Pearls

• Always use Doppler to evaluate for liver
• Incorrect scan plane may result in erroneous diagnosis

I SELECTED REFERENCES
Deprest J et al: Fetoscopic tracheal occlusion (FETO)for
severe congenital diaphragmatic hernia: evolution of a
technique and preliminary results. Ultrasound Obstet
Gynecol. 24(2):121-6, 2004
2.
Hedrick HL et al: Right congenital diaphragmatic hernia:
Prenatal assessment and outcome. J Pediatr Surg.
39(3):319-23; discussion 319-23, 2004
3. Harrison MR et al: A randomized trial of fetal endoscopic
tracheal occlusion for severe fetal congenital diaphragmatic
hernia. N Engl J Med. 349(20): 1916-24, 2003
4.
Keller RL et al: The lung-to-head ratio and fetoscopic
temporary tracheal occlusion: prediction of survival in
severe left congenital diaphragmatic hernia. Ultrasound
Obstet Gynecol. 21(3):244-9, 2003
5.
Laudy JA et al: Congenital diaphragmatic hernia: an
evaluation of the prognostic value of the lung-to-head ratio
and other prenatal parameters. Prenat Diagn. 23(8):634-9,
2003
6. Paek BW et al: Congenital diaphragmatic hernia: prenatal
evaluation with MR lung volumetry--preliminary
experience. Radiology. 220(1):63-7, 2001
7.
Leung JWT et al: Prenatal MR imaging of congenital
diaphragmatic hernia. AJR 174:1607-12, 2000
8.
Hubbard AM et al: Prenatal MRI evaluation of congenital
diaphragmatic hernia. Am J Perinatol. 16(8):407-13, 1999
9.
Albanese CT et al: Fetal liver position and perinatal
outcome for congenital diaphragmatic hernia. Prenat
Diagn. 18(11):1138-42, 1998
10. Lipshutz GS et al: Prospective analysis of lung-to-head ratio
predicts survival for patients with prenatally diagnosed
congenital diaphragmatic hernia. J Pediatr Surg.
32(11):1634-6, 1997
11. Adzick NS et al: Diaphragmatic hernia in the fetus: Prenatal
diagnosis and outcome in 94 cases. J Pediatr Surg
20:357-61, 1985
1.

CONGENITAL

DIAPHRAGMATIC

HERNIA

IIMAGE GALLERY
(Left) Axial ultrasound image
of the fetal chest shows an
abnormal axis of the heart
with displacement
to the
right (open arrow). The fetal
stomach is seen within the
chest (curved arrow). The
abdominal circumference
measured less than
expected. (Right) At birth,
the infant was noted to have
a scaphoid abdomen and
significant respiratory
distress. Successful repair of
the diaphragmatic hernia
was undertaken at 2 days of
age.

(Left) Axial ultrasound
through the chest of a 76
week fetus shows the
stomach (S) within the
thorax with the heart shifted
to the right (curved arrow).
Anterior to the stomach is a
subtle area composed of
multiple small rings
representing small bowel
(arrow) and a portion of liver
(open arrow). (Right) Cross
pathology at autopsy shows
both small bowel (curved
arrow) and liver (open
arrow) in the chest.

Variant
(Left) Axial color Doppler
ultrasound of a right-sided
CDH shows shift of the heart
to the left (curved arrow).
The left portal vein is easily
identified (arrow). Color
Doppler should be
performed in every case of
CDH to evaluate for
herniated liver. (Right)
Sagittal T2W7 MR in another
case of right-sided CO! I
shows liver (arrow) filling the
right hemithorax. MRI is an
excellent modality for
determining the contents of a
CDH.

CYSTIC ADENOMATOID

Axial ultrasound shows typical features of a macrocystic
CCAM (curved arrows). It is composed of multiple cysts
of variable size. The heart is deviated to the right and
pushed against the chest wall (open arrow).

MALFORMATION

Cross pathology of a resected lower lobe in a different
case of macrocystic CCAM. Multiple irregular cysts are
seen with only a small rim of normal remaining
parenchyma (arrow).

ITERMINOlOGY

Ultrasonographic

Abbreviations

• Grayscale Ultrasound
o Macrocystic
• 1 or more cysts> 5 mm
• Often multiple cysts of varying sizes
• May have single large cyst
• Borders poorly defined
o Microcystic
• Cysts < 5 mm
• Uniformlyechogenic
• Well-defined masses
o Heart is displaced
o Stomach in normal location
o Hydrops
• Most important predictor of outcome
• Occurs in < 10%
• Dismal prognosis
o Polyhydramnios
• Compression of esophagus
• Associated with hydrops
• Color Doppler
o Vascular supply from pulmonary artery
o Venous drainage to pulmonary vein
• More difficult to see

• Congenital

and Synonyms

cystic adenomatoid

malformation

(CCAM)

Definitions
• Lung hamartoma with proliferation of terminal
bronchioles and lack of normal alveoli
• Communicates with tracheobronchial
tree

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Solid or cystic lung mass with
arterial supply from pulmonary artery
• Size
o Variable
o Usually contained within a single lobe
o Can be massive
• Morphology: Variable from solid appearing
(microcystic) to complex cystic mass (macrocystic)
• 95% are unilateral and affect only 1 lobe
• No side predilection
• May spontaneously regress
o "Disappearing CCAM"

MR Findings
• T2WI
o Microcystic

DDx: CCAM Mimics

( 1)11

Sef{lH<str,lIi,

'11

Sef{lH <str.l ti, )/)

Findings

CYSTIC ADENOMATOID

MALFORMATION

Key Facts
Terminology

Pathology

• lung hamartoma with proliferation of terminal
bronchioles and lack of normal alveoli

• Mo t common

Imaging Findings

• Majority remain stable or regress in utero
• Excellent prognosis without hydrops even if large at
diagnosis
• ear 100%, mortality with hydrop if untreated
• Postnatal workup of all Ie ion even if regressed in
utero
• Mo t feel ri k of infection and malignancy warrants
re ection in all ca e

• Morphology: Variable from olid appearing
(microcystic) to complex cy tic mass (macrocystic)
•
0 side predilection
• May have single large cyst
• Va cular supply from pulmonary artery
• Greate t growth 20-26 weeks

Top Differential

Diagnoses

• Large ize early doe not predict poor outcome
• Development of hydrops is single most important
predictor of outcome

• High signal intensity mass
o Macrocystic
• Discrete cysts discernible
• Vascular supply better seen with Doppler
• MR usually not necessary

• More commonly upper lobe
• Rare to diagnose in utero

Tracheal atresia

Imaging Recommendations
• Use color Doppler to identify feeding vessel
• Monitor closely
o Every 1-2 weeks after initial diagnosis
o Checklist
• Lesion size
• Development of hydrops
• Polyhydramnios
• Greatest growth 20-26 weeks
• If regression or no change, can increase time interval
between scans
• Calculate CCAM volume ratio (CVR)
oCCAM volume/head circumference
• > 1.6 Increased risk of developing hydrops

Bronchopulmonary
•
•
•
•
•

(BPS)

Similar appearance to microcystic CCAM
Feeding vessel from aorta
Uniformlyechogenic
90% left-sided
Ipsilateral pleural effusion highly suggestive

Hybrid lesion (CCAM + BPS)
• Consider when a systemic vessel supplies a cystic lung
mass
• Histology shows both lesions

Congenital diaphragmatic
•
•
•
•

hernia (CDH)

Absent normal fluid-filled stomach
Abdominal circumference small
Peristalsis is pathognomonic
Other anomalies common

Congenital lobar emphysema
• Uniformlyechogenic

•
•
•
•

May be confused for bilateral CCAM
Symmetric, bilateral lung enlargement
Inversion of diaphragm
Fluid-filled trachea and bronchi

Other cystic masses
• Bronchogenic cyst
• Esophageal duplication cyst
• Neurenteric cyst
o Thoracic boney abnormality usually present
• More often associated with mediastinum than lung

Teratoma
• Solid and cystic components
• Calcifications most specific finding
• Mediastinal or pericardial

I PATHOLOGY

DIAGNOSIS
sequestration

Clinical Issues

Diagnostic Checklist

• Bronchopulmonary
equestration (BP )
• Hybrid lesion ( AM + BPS)
• ongenital diaphragmatic hernia ( DH)

I DIFFERENTIAL

fetal lung mass

General Features
• Genetics
o Sporadic inheritance
o 0 recurrence risk
• Epidemiology
o Most common fetal lung mass
• 75% of all lesions
• Associated abnormalities: Seen in 3-12%

Staging, Grading or Classification

Criteria

• Pathologic staging system based on neonatal series
o Type 1
• Cysts> 2 cm
• Cysts lined by pseudostratified epithelium
• Normal alveoli between cysts
• Good prognosis
o Type II
• Cysts < 2 cm
• Cysts resemble terminal bronchioles
• Associated abnormalities

CYSTIC ADENOMATOID
• Poor prognosis
o Type III
• Cysts < 0.5 cm
• Composed of alveolus-like structures with ciliated
cuboidal epithelium
• Poor prognosis
o Not applicable to fetal masses
• In-utero sonographic classification
o Macrocystic
• 1 or more cysts ~ 5 mm
o Microcystic
• Solid echogenic masses
• Cysts < 5 mm
• New classification of lung masses proposed
o System is based on appearance of lung and vascular
supply
• Addresses issue of hybrid lesions
o Divided into five categories of fetal lung dysplasia
• Type I: Agenesis
• Type II: Normal lung with abnormal vascular
supply
• Type III: Abnormal lung with abnormal vascular
supply
• Type IV: Abnormal lung with normal vascular
supply
• Type V: Miscellaneous

I CLINICAL

• Hydrops < 32 weeks: In utero therapy
o Macroscopic CCAM
• Cyst drainage: Temporizing measure only, fluid
will recur
• Thoracoamniotic
shunt
o Microscopic CCAM
• In utero resection
• Delivery at a tertiary care facility
o At risk for neonatal complications including air
trapping and pneumothorax
o Large lesions may require extracorporeal membrane
oxygenation (ECMO)
• Postnatal workup of all lesions even if regressed in
utero
o Contrast-enhanced
CT
• Chest X-ray may not show lesion
• Postnatal resection somewhat controversial in
asymptomatic individuals
o Most feel risk of infection and malignancy warrants
resection in all cases
• Elective resection at 1 month or older
o Risk of anesthesia decreases after 4 weeks of age
o Early resection maximizes compensatory lung
growth

I DIAGNOSTIC

CHECKLIST

Image Interpretation

ISSUES

Pearls

• Large size early does not predict poor outcome
• Development of hydrops is single most important
predictor of outcome

Presentation
• Usually an incidental finding
o Cystic or echogenic lung mass
• Patient may be large-for-dates if polyhydramnios
present

MALFORMATION

is

Natural History & Prognosis
• Prenatal
o Majority remain stable or regress in utero
• Excellent prognosis without hydrops even if large
at diagnosis
o Hydrops significantly impacts prognosis
• Near 100% mortality with hydrops if untreated
o Features increasing risk of hydrops
• CVR> 1.6
• Dominant large cyst
• Postnatal
o Risk for infection
o Small risk for developing malignancy
• Infants and young children: Pleuropulmonary
blastoma, rhabdomyosarcoma,
myxosarcoma
• Older children and adults: Bronchoalveolar
carcinoma

Treatment
• None unless hydropic
• Hydrops> 32 weeks
o Maternal betamethasone
administration and early
delivery
o Immediate resection
o May be resected during delivery using ex utero
intrapartum treatment (EXIT) procedure
• Uteroplacental circulation maintained while
lesion is resected

I SELECTED REFERENCES
Achiron R et al:Fetallung lesions: a spectrum of disease.
New classification based on pathogenesis, two-dimensional
and color Doppler ultrasound. Ultrasound Obstet Gynecol.
24(2):107-14,2004
2. Achiron R et al: Fetal lung dysplasia: clinical outcome
based on a new classification system. Ultrasound Obstet
Gynecol. 24(2):127-33, 2004
Wilson RD et al: Thoracoamniotic shunts: fetal treatment
3.
of pleural effusions and congenital cystic adenomatoid
malformations. Fetal Diagn Ther. 19(5):413-20,2004
4.
Adzick NS: Management of fetal lung lesions. Clin
Perinatol. 30(3):481-92, 2003
5. Coleman BG et al: Fetal therapy: State of the art. J
Ultrasound Med. 21:1257-88, 2002
6.
Crombleholme TM et at: Cystic adenomatoid
malformation volume ratio predicts outcome in prenatally
diagnosed cystic adenomatoid malformation of the lung. J
Pediatr Surg. 37(3):331-8, 2002
7.
Hubbard AM et al: Congenital chest lesions: diagnosis and
characterization with prenatal MR imaging. Radiology.
212(1):43-8, 1999
8.
Cass DL et al: Cystic lung lesions with systemic arterial
blood supply: a hybrid of congenital cystic adenomatoid
malformation and bronchopulmonary
sequestration. J
Pediatr Surg. 32(7):986-90, 1997
9.
Thorpe-Beeston JG et al: Cystic adenomatoid malformation
of the lung: Prenatal diagnosis and outcome. Prenat Diagn.
14:677-88, 1994
10. MacGillivray TE et al: Disappearing fetal lung lesions. J
Pediatr Surg. 28(10):1321-4; discussion 1324-5, 1993
1.

CYSTIC ADENOMATOID

MALFORMATION

I IMAGE GALLERY
Typical
(Left) Coronal ultrasound
shows a large microcystic
CCAM. The mass (arrow) is
well-defined and uniformly
echogenic, with only tiny
cysts visible. The heart
(curved arrow) is displaced
against the chest wall.
(Right) Cross pathology of
the resected lesion shows
very small cysts (arrows)
within an otherwise solid
mass.

(Left) Axial color Doppler
ultrasound shows a cystic
lung mass with vascular
supply (arrow) from
pulmonary circulation
compatible with a
macrocystic CCAM. This
lesion became less obvious
on follow-up scans. The
infant had no respiratory
distress, with only a
questionable area of
abnormality on chest X-ray.
(Right) Axial NECT clearly
shows a residual area of
abnormal lung (arrows). CT
should be performed even if
chest X-ray is normal.

Variant
(Left) Axial ultrasound in a
second trimester fetus shows
an obvious echogenic lung
mass (arrows) and slight
deviation of the cardiac axis
(open arrow). Vascular
supply was from the
pulmonary circulation.
(Right) Axial ultrasound in
third trimester shows
complete resolution of the
mass. This has been termed
a "disappearing CCAM".
Despite normal appearance,
a postnatal CT should be
performed to evaluate for a
residual mass.

BRONCHOPULMONARY

Graphic shows an extra lobar sequestration at the left
lung base. The vascular supply is from the aorta. It is
covered with it's own pleural investment and there is no
communicadon
with the tracheobronchial tree.

Ultrasonographic

and Synonyms

• Bronchopulmonary
• Rokitansky lobe

Coronal power Doppler ultrasound of dJe fetal chest
shows a large feeding artery arising from the aorta
(curved arrow) supplying a wedge-shaped
echogenic
lung mass (between arrows).

• Spontaneous in utero regression common

ITERMINOlOGY
Abbreviations

SEQUESTRATION

sequestration

(BPS)

Definitions
• Bronchopulmonary tissue that does not connect to the
tracheobronchial tree or pulmonary arteries
• Extralobar sequestration type identified in fetus
o Fetal intralobar sequestration extremely rare

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Solid lung mass with arterial
supply from aorta
• Location
o 85-90% supradiaphragmatic
o 10-15% subdiaphragmatic
o 90% left-sided
• Size
o Generally small to moderate size
o Rarely can fill entire chest
• Morphology
o Pleural investment results in well marginated mass
o Triangular or lobar shape

Findings

• Intrathoracic BPS
o Homogeneously echogenic
o Typically left lung base
• Between lower lobe and diaphragm
o Unilateral pleural effusion in 6-10%
• May cause tension hydrothorax
o Cysts may be seen
• Most common in hybrid lesions
• Hybrid lesions contain histologic elements of both
BPS and congenital cystic adenomatoid
malformation (CCAM)
• Abdominal BPS
o Also typically left-sided
o Stomach is displaced anteriorly by an echogenic
mass
• May communicate with stomach
o Separate from adrenal gland
• Color Doppler
o Prominent feeding vessel from aorta
• May have more than one
• Occasionally arises from celiac axis
o Venous drainage
• Azygous or inferior vena cava
• Some may partially drain into pulmonary veins
• Often difficult to visualize

DDx: Echogenic lung Mass

Microcyslic

CCAM

Pu/m Art To CCAM

Microcystic CCAM

Pericardia/ Teratoma

BRONCHOPULMONARY

SEQUESTRATION

Key Facts
• Hybrid lesion (CCAM + BPS)

Terminology
• Bronchopulmonary tissue that does not connect to
the tracheobronchial tree or pulmonary arteries
• Extralobar sequestration type identified in fetus

Imaging Findings
• 85-90% supradiaphragmatic
• lO-l5<rh subdiaphragmatic
• 90% left- ided
• Pleural investment results in well marginated mass
• Triangular or lobar shape
• Unilateral pleural effusion in 6-10%
• Prominent feeding vessel from aorta

Top Differential
•

Diagnoses

ongenital cystic ad nomatoid malformation
(CCAM)

MR Findings
• T2WI
o Well-defined high signal mass
• Higher signal than normal lung
• Lower signal than amniotic fluid
o Feeding vessel not consistently visualized
• Not necessary in most cases
• Helpful in selected cases
o When coexistent abnormalities are present
• Especially congenital diaphragmatic hernia
o Subdiaphragmatic lesion
• Uniform high signal more suggestive of BPS rather
than neuroblastoma

Imaging Recommendations
• Use color Doppler to identify feeding vessel
• Close follow-up of lesion
o Watch for development of pleural effusion or
hydrops
o May spontaneously regress
• Careful evaluation for other anomalies
o Present in up to 50%
o Congenital diaphragmatic hernia most common
o Cardiac malformations
o Other pulmonary anomalies
• Bronchogenic cyst
• Vascular malformations
• CCAM
o Gastrointestinal
• Tracheoesophageal fistula
• Duplication cysts
• Neurenteric lesions
o Skeletal
• Vertebral anomalies
• Pectus excavatum

I DIFFERENTIAL

DIAGNOSIS

Congenital cystic adenomatoid
malformation (CCAM)
• Microcystic type

Pathology
• 23% of fetal lung ma e
• Associated abnormalities: Seen in up to 50%
• Up to 50% of BPS have hi tologic features of type II
CCAM

Clinical Issues
• Excellent prognosis when an isolated finding
• 50-7591)regre s in utero
• May be complicated by tension hydrothorax

Diagnostic Checklist
• Postnatal work-up should be performed in all cases
even if regres ed in utero
• Doppler evaluation e sential for making the diagnosis

• Feeding vessel from the pulmonary artery
• Pulmonary venous drainage
• May occur on right or left

Hybrid lesion (CCAM + BPS)
• Consider when a systemic vessel supplies a cystic lung
mass
• Histology shows both lesions
o May occur in up to 50% of cases

Teratoma
•
•
•
•

Mediastinal or pericardial
Calcifications most specific finding
Pleural or pericardial effusions
No aortic arterial feeder

Congenital
•
•
•
•

lobar emphysema

Uniformlyechogenic
More commonly upper lobe
Normal vasculature
Rare to diagnose in utero

Neuroblastoma
•
•
•
•
•

Most common differential for subdiaphragmatic
More often on right
Often cystic
No feeding vessel
Dose not present until 3rd trimester

BPS

I PATHOLOGY
General Features
• General path comments
o Embryology
• Hypothesized early insult when tracheobronchial
tree splits from primitive foregut
• Subsequent ectopic budding of tracheobronchial
tree
• Explains high association with enteric anomalies
• Genetics
o Sporadic inheritance
o No recurrence risk
• Epidemiology

BRONCHOPULMONARY
o 23% of fetal lung masses
o M:F = 4:1
• Some studies show equal sex distribution
• Associated abnormalities: Seen in up to 50%

Gross Pathologic & Surgical Features
• Pathologically two types
• Extralobar sequestration
o Type seen in fetus
o Own pleural investment
o Drains to a systemic vessel
o Histology: Dilated bronchioles, alveoli and
subpleural lymphatics
• Intralobar sequestration
o No pleural investment
o Drains to pulmonary vein
o May be acquired
• Extremely rare in utero or infancy
• > 50% present over 20 years of age
• May result from recurrent infection
• Normal blood supply may be compromised with
parasitization of systemic vessels
o Histology: Chronic inflammation and fibrosis

Microscopic

Features

• up to 50% of BPS have histologic features of type II
CCAM

Staging, Grading or Classification Criteria
• New classification system of lung masses proposed
o Addresses issue of hybrid lesions
• System is based on appearance of lung and vascular
supply
• Five categories of fetal lung dysplasia
o Type I: Agenesis
o Type II: Normal lung with abnormal vascular supply
o Type III: Abnormal lung with abnormal vascular
supply
o Type IV: Abnormal lung with normal vascular
supply
o Type V: Miscellaneous

I CLINICAL ISSUES
Presentation
• Usually an incidental finding
• Seen as early as 16 weeks
• Pleural effusion

Natural History & Prognosis
• Excellent prognosis when an isolated finding
• Poorer prognosis categories
o Largely determined by severity of associated
abnormalities
o Development of significant hydrops
• 50-75% regress in utero
• May be complicated by tension hydrothorax
o Proposed mechanisms
• Leakage from ectatic lymphatics
• Torsion of sequestered segment
o May progress to generalized hydrops from
cardiovascular compression
• Postnatal

SEQUESTRATION
o Most are asymptomatic
o May have respiratory distress or cyanosis
o May present with associated abnormality

Treatment
• Prenatal
o Usually none
o Drainage or thoracoamniotic shunt for tension
hydrothorax
• Postnatal
o Contrast enhanced CT or MRI should be done in all
cases
• Chest X-ray may miss lesion
o Embolization of feeding vessel
o Surgical ligation and resection
o Resection may not be necessary for regressed lesions
in asymptomatic individuals

I DIAGNOSTIC

CHECKLIST

Consider
• When there is a lung mass with a unilateral pleural
effusion
• Postnatal work-up should be performed in all cases
even if regressed in utero

Image Interpretation

Pearls

• Doppler evaluation essential for making the diagnosis
• May spontaneously regress

I SELECTED REFERENCES
1.

Achiron R et al:Fetallung lesions: a spectrum of disease.
New classification based on pathogenesis, two-dimensional
and color Doppler ultrasound. Ultrasound Obstet Gynecol.
24(2):107-14,2004
2.
Achiron R et al: Fetal lung dysplasia: clinical outcome
based on a new classification system. Ultrasound Obstet
Gynecol. 24(2):127-33, 2004
3. Adzick NS: Management of fetal lung lesions. Clin
Perina to I. 30(3):481-92, 2003
4.
Dhingsa R et al: Prenatal sonography and MR imaging of
pulmonary sequestration. AJRAm J Roentgenol.
180(2):433-7, 2003
5. Morville P et al: Physiology, hypothesis and treatment of
pulmonary sequestration. Am J Perinatol. 20:87-9.2003
Conran RM et al: Extralobar sequestration with frequently
6.
associated congenital cystic adenomatoid malformation,
type 2: report of 50 cases. Pediatr Dev Pathol. 2(5):454-63,
1999
7.
Lopoo JB et al: Fetal pulmonary sequestration: A favorable
congenital lung lesion. Obstet Gynecol. 94:567-71, 1999
8. Adzick NS et al: Fetal lung lesions: management and
outcome. Am J Obstet Gynecol. 179(4):884-9, 1998
9. Becmeur F et al: Pulmonary sequestrations: prenatal
ultrasound diagnosis, treatment, and outcome. J Pediatr
Surg. 33(3):492-6, 1998
10. Cass DL et al: Cystic lung lesions with systemic arterial
blood supply: a hybrid of congenital cystic adenomatoid
malformation and bronchopulmonary
sequestration. J
Pediatr Surg. 32(7):986-90, 1997
11. Curtis MR et al: Prenatal ultrasound characterization of the
suprarenal mass: distinction between neuroblastoma and

subdiaphragmatic extralobar pulmonary sequestration. J
Ultrasound Med. 16(2):75-83, 1997

BRONCHOPULMONARY

SEQUESTRATION

I IMAGE GALLERY
(Left) Coronal color Doppler
ultrasound shows a
well-defined echogenic lung
mass (arrows) being
supplied by a large artery
(curved arrow) arising from
the aorta (open arrow).
(Right) Cross pathology
shows the cut surface of the
resected sequestration.
It is a
solid mass with a pleural
covering. The dominant
feeding vessel seen on
ultrasound is easily identified
(arrow).

(Left) Sagittal ultrasound
shows an echogenic lung
mass filling the left
hemithorax. A "cyst" (arrow)
is seen but Doppler showed
arterial flow which could be
traced to the aorta. Without
Doppler this may have been
mistaken for a CCAM.
(Right) CECT with coronal
reconstructions
after delivery
shows two large systemic
vessels (arrows) arising from
the aorta and supplying the
mass.

Variant
(Left) Sagittal ultrasound of
the fetal abdomen shows an
echogenic mass arising
posteriorly (cursors) and
displacing the stomach
(arrow) anteriorly. (Right)
Sagittal ultrasound after
delivery shows cystic as well
as solid components
(arrows). The adrenal gland
(curved arrow) is clearly
separate from this mass.
Histologically, this was a
hybrid lesion with
components
of both
bronchopulmonary
sequestration and CCAM
present.

PLEURAL EFFUSION

Axial ultrasound shows a large chylothorax (arrows).
The righllung is collapsed medially (open arrow). The
hearl is shifted to the left. Mild skin edema (curved
arrow) also seen.

ITERMINOLOGY
Abbreviations

and Synonyms

• Pleural fluid
• Hydrothorax
• Chylothorax

Definitions
• Fluid accumulation in pleural space
• Chylothorax: Chylous fluid collection
• Hydrothorax: Serous fluid collection

IIMAGING FINDINGS
General

Features

• Best diagnostic clue
o Curvilinear fluid displacing lung from chest wall
• Lung appears to float in chest
• Location: Pleural space
• Size: Variable

Ultrasonographic

Findings

• Routine four chamber heart view
o Curvilinear anechoic fluid
o Echogenic lung displaced medially
• Coronal chest view
o Lung displaced superiorly and medially

Coronal ultrasound in another large chylolhorax shows
the left lung (arrows) floating in fluid (open arrows). The
gastric fundus (curved arrow) is localed benealh the
flattened diaphragm.

o "Wing-like" lungs float in fluid
• Fluid is anechoic regardless of chylothorax or
hydrothorax etiology
• Chylothorax
o Chylous fluid collection
o Unilateral
oR = L
o Mass effect common
• Mediastinal shift
• Flattened diaphragm
o May lead to hydrops when large
o 5% with aneuploidy
• Turner syndrome
• Trisomy 21
• Noonan syndrome
o 15% resolve in fetal life
• Hydrothorax
o Serous fluid collection
o Bilateral and symmetric
o Hallmark finding in hydrops fetalis
• Immune or nonimmune
• Ascites
• Skin edema
• Pericardial fluid
o Commonly occurs with abnormalities associated
with hydrops
• Cystic hygroma (Turner syndrome)
• Cardiac defects

DDx: Cystic Chest Mass
~

~ ..

~~,

.••.•.. --~

i~~
Diaphragmatic

Hernia

-..

Lymphangioma

;IJ

PLEURAL EFFUSION
Key Facts
Clinical Issues

Terminology
• Chylothorax:
• Hydrothorax:

• 759/0 mortality

Chylous fluid collection
Serous fluid collection

Imaging Findings
• "Wing-like" lungs float in fluid
• Fluid is anechoic regardless of chylothorax
hydrothorax etiology
• Hallmark finding in hydrops fetalis

Top Differential
•

or

Diagnoses

onnal chest wall mu culature

Pathology
• 591) with chylothorax have chromosome
abnormalities
• Effusion may be fir t sign of hydrop

• Cardiac arrhythmia
• Infection
• Trisomy 21 markers and anomalies
o Fetal mass
• Goiter
• Extralobar pulmonary sequestration
• Cystic adenomatoid malformation
• Lymphangioma
• Any mass causing fetal heart failure
• First trimester pleural effusion
o Can be seen as early as 7 weeks
o Associated with increased nuchal translucency
o Poor prognosis when present before 15 wks
o Aneuploidy common
• Turner syndrome most likely

Imaging Recommendations
• Best imaging tool
o Routine transverse four chamber heart view
o Coronal chest view
• Diaphragm view
• Protocol advice
o Look for hydrops
• Skin edema
• Ascites
• Pericardial effusion
o Look carefully at fetal heart
• Structural defects
• Tachycardia
o Look for signs of fetal infection
• Brain, liver, spleen calcifications
• Intracranial hemorrhage
• Intrauterine growth restriction
o Perform genetic sonogram
o Sequential ultrasound
• May resolve spontaneously
• May progress to hydrops

I DIFFERENTIAL

DIAGNOSIS

Normal chest wall musculature
• Chest wall muscles are hypoechoic

(not anechoic)

•
•
•
•
•

when hydrops present
Pulmonary hypoplasia
Worst prognosis when pre ent before 15 wks
Fetal thoracentesis
Fetal chylou fluid is clear (fasting fluid)
Thoracoamniotic
shunting

Diagnostic Checklist
• Formal fetal echocardiography
• Unlike pericardial effusion, any amount of pleural
fluid is abnormal
• When isolated, frequent follow up exam necessary to
look for developing hydrops

• Diaphragm

may mimic fluid on coronal view

Cystic adenomatoid

malformation

(CAM)

• Macrocyst type may mimic pleural effusion
o Cysts more round than curvilinear
• Microcyst more solid appearing

Congenital

diaphragmatic

hernia

• Stomach in chest when left-sided
o Curvilinear gastric fundus may mimic effusion
o Coronal views helpful

Other cystic chest masses
•
•
•
•

Bronchogenic cyst
Neurenteric cyst
Esophageal duplication cyst
Chest wall lymphangioma

I PATHOLOGY
General Features
• Genetics
o 5% with chylothorax have chromosome
abnormalities
• Turner syndrome
• Trisomy 21
• Noonan syndrome
• Etiology
o Chylothorax
• Primary congenital lymphatic defect
• Atresia fistula or absence of thoracic duct
• Thora;ic duct crosses from right to left at 5th
thoracic level
• Level of obstruction determines R vs. L
• Chylous effusion R:L ratio is 1:1
o Hydrops
• Effusion may be first sign of hydrops
• Immune vs. nonimmune
• 30% with nonimmune have anomalies
o Congenital infection
• Cytomegalovirus: Most common
• Parvovirus B19 (fifth disease)

PLEURAL EFFUSION
o Cardiac failure
• Anomalous heart
• Tachyarrhythmia
• Systemic cause
• Fetal anemia
• Epidemiology: 1:15,000
• Associated abnormalities
o Hydrops
• Polyhydramnios
o Cystic hygroma
o Cardiac anomalies
o Fetal anemia

ICLINICALISSUES
Presentation
• Most common signs/symptoms
o Abnormal screening ultrasound
o Fetus presenting with hydrops

Natural History & Prognosis
• Bilateral effusion
o More often associated with hydrops
o 75% mortality when hydrops present
o 50% mortality without hydrops
• Unilateral effusion
o Less likely associated with hydrops
o 20% resolve in utero
o Near 100% survival without hydrops and normal
chromosomes
• Pulmonary hypoplasia
o Bilateral large effusions
o Difficult to predict severity
• Isolated pleural effusion at time of diagnosis
o 15% resolve
o 5% cardiac defect seen postnatal
o 5% aneuploidy
o 36% perinatal mortality
• Most from subsequent hydrops
o Unknown etiology common
• First trimester pleural effusion
o Poor prognosis
• Worst prognosis when present before 15 wks
o 82% aneuploidy rate
• Turner most common
o 85% miscarriage rate

• Feeding neonatal chylous fluid is "milky"
• Thoracoamniotic
shunting
o Allows for continuous drainage
o Double pigtail catheter placed
o 30% catheter failure rate
o Improved survival rates
• 67% vs. 10% with hydrops
• EXIT procedure (ex utero intrapartum treatment)
o Cesarean section delivery
• Chest delivered for procedure
o Placental circulation maintained
o Thoracentesis performed
o Post delivery ventilation success improved

I DIAGNOSTIC
Consider
•
•
•
•

Amniocentesis
Fetal blood sampling for anemia
Maternal infection work-up
Formal fetal echocardiography

Image Interpretation

Pearls

• Unlike pericardial effusion, any amount of pleural
fluid is abnormal
• When isolated, frequent follow up exams necessary to
look for developing hydrops
• M-mode of fetal heart to rule out tachycardia as a
treatable cause

I SELECTED
1.

2.

3.
4.

5.

6.

Treatment
• Reasons to treat
o Pulmonary hypoplasia
• Difficult to diagnose in utero
o Hydrops
• Treat cause of hydrops when possible
o Aid with post delivery ventilation
o Small pleural effusions not treated in utero
• Fetal thoracentesis
o Ultrasound guidance for fluid aspiration
o Multiple aspirations often necessary
o Fluid sent for laboratory analysis
o Chylothorax fluid
• t Lipoprotein
• t Lymphocytes
• Fetal chylous fluid is clear (fasting fluid)

CHECKLIST

7.

8.
9.

REFERENCES

Wilson RD et al: Thoracoamniotic
shunts: fetal treatment
of pleural effusions and congenital cystic adenomatoid
malformations. Fetal Diagn Ther. 19(5):413-20,2004
Hashimoto K et al: Pregnancy outcome of embryonic/fetal
pleural effusion in the first trimester. J Ultrasound Med.
22(5):501-5, 2003
Medina 0 et al: First-trimester diagnosis of pleural effusion.
Ultrasound Obstet Gynecol. 19(4):423-4,2002
Prontera W et al: Ex utero intrapartum treatment (EXIT) of
severe fetal hydrothorax. Arch Dis Child Fetal Neonatal Ed.
86(1):F58-60, 2002
Aubard Y et al: Primary fetal hydrothorax: A literature
review and proposed antenatal clinical strategy. Fetal
Diagn Ther. 13(6):325-33, 1998
Jauniaux E: Diagnosis and management of early
non-immune hydrops fetalis. Prenat Diagn. 17(13):1261-8,
1997
Ahmad FK et al: Isolated unilateral fetal pleural effusion:
the role of sonographic surveillance and in utero therapy.
Fetal Diagn Ther. 11(6):383-9, 1996
Sohaey R et al: The fetal thorax: noncardiac chest
anomalies. Semin Ultrasound CT MR. 17(1):34-50, 1996
Hagay Z et al: Isolated fetal pleural effusion: a prenatal
management dilemma. Obstet Gynecol. 81(1):147-52, 1993

PLEURAL EFFUSION
IIMAGE GALLERY
(Left) Axial ultrasound shows
thoracentesis in a fetus with
hydrops. The tip of the
needle (arrow) is placed into
the left pleural effusion.
Curved arrows point to
bilateral hydrothorax. (Right)
Sagittal ultrasound shows
skin edema (open arrows)
and ascites (curved arrow) in
the same fetus. Although
post delivery resuscitation
was attempted, this baby
died from pulmonary
hypoplasia.

(Leh) Sagittal ultrasound

at
73 weeks shows a markedly
increased nuchal
translucency
(arrows).
(Right) Coronal ultrasound of
chest shows an associated
pleural effusion (open
arrows). Curved arrow
points to the triangular lung
surrounded by a rim of fluid.
Findings were bilateral. This
fetus was diagnosed with
Turner syndrome. Early
pleural effusion is often
associated with aneuploidy
and bad prognosis.

Other
(Left) Axial ultrasound shows
normal hypoechoic
chest
wall musculature (arrows).
This finding should not be
confused with a small rim of
pleural effusion. (Right)
Coronal ultrasound shows
normal hypoechoic
diaphragm in same patient
(arrows). Since any amount
of fluid is considered
abnormal, it is important not
to mistake these hypoechoic
structures with anechoic
pleural effusion.

TERATOMA, CHEST

Axial ultrasound shows a complex, heterogeneous mass
filling the chest and displacing the heart (open arrow).
Calcifications (curved arrow), the most specific finding
of a teratoma, and cystic areas (arrow) are present.

Coronal T2WI MR after delivery shows a mixed signal
intensity mass, which has invaded the mediastinum,
diaphragm, and chest wall (arrow). This teratoma had
malignant elements and resection was not possible.

ITERMINOLOGY
•

Definitions
• Neoplasm composed of all three germ cell!ayers
o Ectoderm, mesoderm and endoderm

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Calcifications within a chest mass
• Location
o Most originate from mediastinum or pericardium
• Most common intrapericardial mass
o Primary lung teratomas are rare
o Site of origin difficult to discern when large
• Size
o Variable
o Typically large
o May grow rapidly over short period of time

Ultrasonographic

Findings

• Heterogeneous mass
• Contains both cystic and solid components
• Calcifications most specific feature
o Not present in all cases
• Mediastinal
o Typically originate anteriorly

DDx: Complex

Lymphangioma

•
•
•

o Can cross the midline
o Difficult to differentiate from primary lung mass
Pericardia I
o Extrapericardial
• Look for attachment to pericardium
• Lung may be displaced by pleural effusion
o Intrapericardial
• Most common intra pericardia I mass
• Pericardia! effusion invariably present
• Pericardia! effusion may be massive and mistaken
for pleural effusion
• At risk for cardiac tamponade
Pleural effusions
o Isolated or with hydrops
Hydrops
Color Doppler
o Variable vascularity
o No dominate feeding vessel
• Helps differentiate from other lung masses

MR Findings
• Helpful in determining origin and extent of mass
• Not sensitive for calcifications

CT Findings
• Used in postnatal work-up
• Most sensitive modality for calcification

lung Mass

COfi, Liver

detection

TERATOMA, CHEST
Key Facts
Imaging Findings

• Sequestration

• Most originate from mediastinum or pericardium
• May grow rapidly over short period of time
• Contains both cystic and solid components
• alcifications most specific feature

Clinical Issues

Top Differential

Diagnoses

• ong nital diaphragmatic hernia (CDIl)
• Congenital cystic adenomatoid malformation
(C

AM)

I DIFFERENTIAL

DIAGNOSIS

Congenital diaphragmatic

Diagnostic Checklist
• Other chest ma ses are far more likely
• Consider when calcifications are present in che t
mass
• Most common intrapericardial mass

Natural History & Prognosis

hernia (CDH)

• Often cystic and solid components
o Stomach, small bowel, liver
• Doppler confirms portal veins
• Abdomen abnormal
o Decreased abdominal circumference
o Absent stomach bubble

• Variable based on size of mass and extent of local
involvement

Treatment
• Intrauterine pericardiocentesis has been performed for
cardiovascular compromise
• Thoracoamniotic
shunt for pleural effusion with
hydrops

Congenital cystic adenomatoid
malformation (CCAM)
• Microcystic or macrocystic
• Vascular supply from pulmonary

• May have had a normal 2nd trimester scan

I DIAGNOSTIC

CHECKLIST

Image Interpretation

artery

Pearls

• Other chest masses are far more likely
• Consider when calcifications are present in chest mass
• Most common intrapericardial mass

Sequestration
• Well-defined echogenic mass
• Systemic vascular supply
• May have associated pleural effusion

I SELECTED

lymphangioma
• Septated cystic mass
• May invade into chest and mediastinum
• Largest component will be external to chest
o Neck or axillae

Neuroblastoma

1.

2.

3.

• Arises posteriorly
• Rarely occurs in chest

I IMAGE

I PATHOLOGY

REFERENCES

Grebille AG et al: Pericardial teratoma complicated by
hydrops: successful fetal therapy by thoracoamniotic
shunting. Prenat Diagn. 23(9):735-9, 2003
Sklansky M et al: Intrapericardial teratoma in a twin fetus:
diagnosis and management. Obstet Gynecol. 89(5 Pt
2):807-9, 1997
Froberg MK et al: In utero development of a mediastinal
teratoma: a second-trimester event. Prenat Diagn.
14(9):884-7, 1994

GALLERY

General Features
• Epidemiology:

< 10% of fetal teratomas

occur in chest

Gross Pathologic & Surgical Features
• Complex masses
• May exhibit very rapid growth
o Does not correlate with malignancy
• Malignant elements are uncommon

ICLINICALISSUES
Presentation
• Most present in 3rd trimester
• May have had a normal 2nd trimester scan
o Reflects rapid growth of mass

(Left) Sagittal ultrasound of a teratoma demonstrates a mixed cystic
and solid chest mass (arrows). (Right) Axial ultrasound shows that the
mass (curved arrow) is adjacent to the heart and is surrounded by a
pleural effusion. There is also hydrops with skin edema (arrow).

TRACHEAL

Graphic shows a high tracheal atresia (arrow) with
distension of the distal trachea and bronchi. The
diaphragm is flattened. The heart is shifted towards the
midline and is dwarfed by the enlarged lungs.

ITERMINOLOGY
Abbreviations

and Synonyms

• Tracheal atresia
• Laryngeal atresia
• Congenital high airway obstruction

(CHAOS)

Definitions
• High airway obstruction
web

IIMAGING

caused by atresia, stenosis, or

FINDINGS

General Features
• Best diagnostic clue: Bilaterally enlarged, echogenic
lungs

Ultrasonographic

Findings

• Dramatic lung findings
o Symmetric, bilateral enlargement
o Uniformly hyperechoic
o Homogeneous
o Fluid-filled trachea and bronchi
• Exact point of obstruction (larynx vs. trachea) can
not usually be determined
• Heart shifted to midline
o Appears small

ATRESIA

Coronal ultrasound shows symmetrically
enlarged,
hyperechoic lungs. The trachea (curved arrow) and
bronchi (arrows) are fluid-filled. and there is inversion of
the diaphragm (open arrow).

• Compressed by enlarged lungs
• Diaphragm
o Flattened
o Inverted
• Ascites common
o May be massive
• Hydrops
o Not as common as isolated ascites
• Both polyhydramnios
and oligohydramnios
reported
• Associated anomalies in 50% of cases
o Cardiac
o Renal
o Esophageal fistula
• May decompress lungs in utero
• Diagnosis may be missed until after delivery
o May be seen with VACTERL association (vertebral
anomalies, anal atresia, tracheo-esophageal
fistula,
renal, and limb anomalies)

Imaging Recommendations
• Protocol advice
o Consider dedicated fetal echo
• Heart may be difficult to evaluate because of
compression
• Cardiac anomaly worsens prognosis

DDx: Large Echogenic Lung Mass

•
v.
. ~ ..•
-~-.-

.

~~
.....
~
..,
........•.
'~~-'
'",-.
~
c~

••

.

•0;.:11•••.••...
-

•

-

_.•••• ~_

.

.

.
-- ...

---.;;

-

Microcystic CCAM

Sequestration

TRACHEAL ATRESIA
Key Facts
Pathology

Terminology
•

ongenital high airway obstruction

(CHAOS)

• Lungs more mature than expected for gestational age

Imaging Findings

Clinical Issues

•
•
•
•

• EXIT procedure (ex utero intrapartum treatment) has
been successfully used to establish airway

Fluid-filled trachea and bronchi
Heart shifted to midline
Ascites common
A sociated anomalies in 50% of ca es

I DIFFERENTIAL

Diagnostic Checklist
• Symmetric, homogeneou
lung enlargement is
essentially pathognomonic
• Uteroplacental circulation maintained while
laryngoscopy is performed
• Airway secured before umbilical cord is clamped

DIAGNOSIS

Bilateral congential cystic adenomatoid
malformations (CCAM) or sequestrations
• Theoretically could have the same appearance
• Highly unlikely
• Trachea and bronchi would not be fluid-filled

large single hyperechoic

lung mass

• Large CCAM or sequestration can fill entire chest
o Lacks symmetry
o Heart will be shifted, not midline
o Trachea and bronchi not fluid-filled

I DIAGNOSTIC

Image Interpretation

I SELECTED
2.

General Features
• Genetics: Sporadic
• Etiology
o Mid-foregut forms esophagus only
o No endoderm for trachea
o Obstruction causes retention of fetal lung fluid and
subsequent overdevelopment
• Lungs more mature than expected for gestational
age
• Larger volumes
• Greater number of alveoli
• Associated abnormalities
o Fraser syndrome
• Tracheal atresia
• Cryptophthalmus
• Syndactyly
• Genitourinary abnormalities

Pearls

• Symmetric, homogeneous lung enlargement is
essentially pathognomonic

1.

I PATHOLOGY

CHECKLIST

3.

4.

5.

REFERENCES

Lim FY et al: Congenital high airway obstruction
syndrome: natural history and management. J Pediatr Surg.
38(6):940-5, 2003
Crombleholme TM et al: Salvage of a fetus with congenital
high airway obstruction syndrome by ex utero intrapartum
treatment (EXIT) procedure. Fetal Diagn Ther. 15(5):280-2,
2000
Scott IN et al: Tracheal atresia: ultrasonographic and
pathologic correlation. J Ultrasound Med. 18(5):375-7,
1999
Morrison PJ et al: Laryngeal atresia or stenosis presenting as
second-trimester fetal ascites--diagnosis and pathology in
three independent cases. Prenat Diagn. 18(9):963-7, 1998
Choong KKet al: Fetal laryngeal obstruction: sonographic
detection. Ultrasound Obstet Gynecol. 2(5):357-9, 1992

IIMAGE

GALLERY

I CLINICAL ISSUES
Presentation
• Reported as early as 18 weeks

Natural History & Prognosis
• Uniformly fatal if not recognized
• Better outcome if atresia is not complete
o Web or stenosis

Treatment
• Planning for delivery is essential
o EXIT procedure (ex utero intrapartum treatment)
has been successfully used to establish airway

(Left) Axial ultrasound shows markedly enlarged hyperechoic lungs.
The bronchi (arrows) are fluid-filled. The heart (curved arrow) is
shifted to the midline and appears small, being almost completely
obscured by shadowing from the vertebral body. (Right) Cross
pathology at autopsy shows enlargement of all lobes of the lung.
Note how small the heart (arrow) is in comparison. These findings
are essentially pathognomonic of tracheal atresia.

LYMPHANGIOMA

Graphic of a lymphangioma.
Multiple cysts along the
left chest, neck and arm have formed because of
congenital lymphatic obstruction. Normal lymphatic
drainage anatomy shown on fetal right.

• Size
o Variable
• Prenatal cases usually large
• Morphology
o Complex cystic mass with septations
• Septations usually thick
• No solid component
o Rarely unilocular

ITERMINOlOGY
Abbreviations
•
•
•
•

and Synonyms

Non-nuchal cystic hygroma
Cystic lymphangioma (CL)
Axillary lymphangioma
Cutaneous lymphangioma

Definitions
• Benign non-nuchal

cystic tumors of lymphatic

system

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Non-nuchal subcutaneous
complex cystic mass
• Location
o 70% of non-nuchal CL are axillary
• Often bilateral
• May extend through chest wall
• Mediastinal involvement common
o 30% other sites
• Trunk
• Limbs
o 80% of all lymphangioma are nuchal
• Cystic hygroma
• Different prognosis than non-nuchal CL

Axial ultrasound shows bilateral, large, multiloculated,
axillary cystic masses (curved arrows) in a second
trimester fetus. The masses contain thin and thick
septations (arrows).

large

Ultrasonographic

Findings

• Grayscale Ultrasound
o Complex cystic body wall mass
• Sonolucent cysts
• Septa of variable thickness
• No solid components
• May enlarge during pregnancy
• Extent of mass difficult to estimate
• Associated anomalies rare
o Axillary CL
• Cystic mass between arm and chest wall
• May extend down arm
• Secondary lymphedema common
• Abnormal arm positioning
• Arm held away from fetal trunk
• Can grow into mediastinum
• Rib deformity common
• Associated pleural effusion rare
• Associated hydrops rare

DDx: Cystic Body Wall Mass

Nuchal CH

Amniotic Bands

Amniotic Bands

LYMPHANGIOMA
Key Facts
Terminology
• on-nuchal cystic hygroma
• Cy tic lymphangioma ( L)

Imaging Findings
•
•
•
•
•
•
•
•
•

70% of non-nuchal CL are axillary
Prenatal cases usually large
Complex cystic body wall mass
Arm held away from fetal trunk
Can grow into mediastinum
Secondary lymphedema common
olor Doppler:
0 blood flow
Follow mass size with sequential exams
Consider 3D US or MR to assess volume

Top Differential
•

Diagnoses

uchal cystic hygroma (CH)

o Trunk CL
• Cystic mass involving fetal trunk
• Usually asymmetric
• May involve lower extremity
• Secondary lymphedema common
• Limb held in abnormal position
o First trimester axillary CL
• Often transient
• Non-loculated most common
• Often with chromosome abnormality
• Color Doppler: No blood flow

• Amniotic band syndrome
• Klippel Trenaunay Weber syndrome
• Hemangioma

Pathology
• Second trimester non-nuchal
chromosome abnormalities

L not a sociated with

Clinical Issues
• Outcome depends on size and location of mass
• Survival rates near 100<}6
• Surgical excision is treatment of choice

Diagnostic Checklist
• Look for bilateral masses when one is seen
• Long view of humerus identifies early axillary
• Look for blood flow in mass

o Non-septated more common
• Hydrops fetalis common

Amniotic band syndrome
• Disruption of amnion
• Entrapment of fetal parts
o Amputation is hallmark finding
• Lymphedema common
o May mimic cystic mass
• Limb body wall complex
o Complex mass of eviscerated organs

• 3D

Klippel Trenaunay Weber syndrome

MR Findings

• Large cutaneous hemangiomas
o Doppler shows blood flow in mass
o Less cystic than CL
• Hypertrophy of associated limb
o Long bone asymmetry
o Gigantism

o Extent of mass better seen
o Mass volume can be calculated

• T1WI: Low signal
• T2WI: High signal
• Extent of mass better evaluated with MR
o Mediastinum
o Chest wall
o Neurovascular structures
o Body wall musculature

Imaging Recommendations
• Protocol advice
o Follow mass size with sequential exams
• Consider 3D US or MR to assess volume
o Consider aspiration of large cysts for delivery
purposes

L

Hemangioma
• Dilated vessels deep in skin
• Solid component present
o Less cystic than lymphangioma
• Doppler shows blood flow in mass
• Scalp is a common site
• Can be infiltrative
o Chest wall involvement
o Extremity involvement

I PATHOLOGY
I DIFFERENTIAL DIAGNOSIS
Nuchal cystic hygroma (CH)
•
•
•
•

Posterior lateral neck location
Usually septated
More common than non-nuchal CL
66% associated with chromosome abnormality
o Turner most common
o Noonan syndrome
o Trisomy 21
• Commonly seen in first trimester

General Features
• Genetics
o Second trimester non-nuchal CL not associated with
chromosome abnormalities
o First trimester axillary CL
• Associated with trisomy 21
• Rare finding
• Etiology
o Axillary

LYMPHANGIOMA
• Obstruction of axillary lymph vessels at junction
with jugular venous system
o Abnormal lymphatic anlage
• Insufficient anastomoses with larger lymph
channels
• Epidemiology
o 20% of all lymphangiomas
are non-nuchal
o Axillary CL
• 5:19,200 in early second trimester
• Associated abnormalities
o Musculoskeletal dysmorphism
• Secondary to mass effect
o Hydrops fetalis

Gross Pathologic & Surgical Features
• Tumor with numerous cystic cavities
• Infiltrative features
o Skin
o Muscle
o Neurovascular structures

Microscopic

Features

• Tumor wall
o Endothelium lining
o Smooth muscle fascicles
• Small compressed capillaries
• Lymphatic spaces
o Lymphocytes
o Rare erythrocytes

I CLINICAL ISSUES
Presentation
• Most common signs/symptoms: Seen on routine
screening exam
• Other signs/symptoms
o Hydrops
• More rare than with nuchal cystic hygroma
• Skin edema
• Pleural effusion
• Ascites

Demographics
• Age
o Not associated with advanced maternal age (AMA)
• AMA ~ yrs at time of delivery
• Gender: M = F

Natural History & Prognosis
• Short term
o Obstructed labor
• Dystocia
• Cesarean section delivery preferred
o Fetal respiratory compromise
• Delivery at tertiary care center
o Birth trauma to mass
• Bleeding
• Infection
• Skin necrosis
• Long term
o Outcome depends on size and location of mass
• Functional impairment commOn
• Lymphedema

• Infection
• Hemorrhage
o Recurrence
• Microcystic components recur most commonly
• Treated with further surgery or sclerosis
• Spontaneous involution reported
o 29% partial
• Survival rates near 100%
o Much better than with nuchal cystic hygroma

Treatment
• Surgical excision is treatment of choice
o Complete excision desired
o Infiltration of vital structures common
• Makes excision difficult
o Post surgical recurrence common
• Sclerosis
o Agents injected directly into cysts
• Used most often for recurrences
o Bleomycin fat emulsion
• 40% success rate
o OK-432

• Inactivated streptococcal organisms
• Prenatal needle aspiration
o Ultrasound guided fluid aspiration of large cysts
o Reduce volume before delivery
• Prenatal sclerosis of fetal mass reported
o OK-432

I DIAGNOSTIC

CHECKLIST

Consider
• Non-nuchal CL in cases of large superficial fetal mass
• Consider fetal MR
o Better tissue characterization
o Extent of mass better shown

Image Interpretation

Pearls

• Look for bilateral masses when one is seen
• Long view of humerus identifies early axillary CL
• Look for blood flow in mass

I SELECTED
1.

2.

REFERENCES

Chiaverini C et al: Prenatal ultrasonographic detection of
an axillo-thoracic lymphangioma: an ethical dilemma.
Prenat Diagn. 23(11):946-8, 2003
Ruano R et al: Prenatal diagnosis of a large axillary cystic
lymphangioma by three-dimensional ultrasonography and
magnetic resonance imaging. J Ultrasound Med.
22(4):419-23,2003

3.

Zanotti SD et al: Prenatal sonographic diagnosis of axillary
cystic lymphangiomas. J Clin Ultrasound. 29(2): 112-5,
2001

4.

5.
6.

McCoy MC et al: Prenatal diagnosis and management of
massive bilateral axillary cystic lymphangioma. Obstet
Gynecol. 85(5 Pt 2):853-6, 1995
Reichler A et al: Early prenatal diagnosis of axillary cystic
hygroma. J Ultrasound Med. 14(8):581-4, 1995
Fonkalsrud EW: Congenital malformations of the
lymphatic system. Semin Pediatr Surg. 3(2):62-9, 1994

LYMPHANGIOMA
I IMAGE GALLERY
(Left) Coronal ultrasound
shows a fetus with a
lymphangioma
arising from
the axilla and extending
down the chest wall
(arrows). The fetal arm
(curved arrow, cross section)
was consistently held away
from chest. (Right) Clinical
photograph shows a neonate
with a large lymphangioma
which involved the chest
wall, axillae, and arm. As
often seen prenatally, the
arm is markedly abducted.

(Left) Coronal T 7 WI M R of a
newborn with bilateral
axillary lymphangiomas
diagnosed prenatally. There
are large, multiseptated,
cystic masses involving both
axilla (arrows). There was no
extension into the thoracic
cavity. (Right) Axial CECT
shows these cysts infiltrating
the chest wall and displacing
muscle (arrows). This finding
was not appreciated on the
prenatal ultrasound.

(Left) Axial ultrasound shows
a large lymphangioma
arising
from left flank (arrows).
Curved arrows point to fetal
kidneys. This extensive
lymphangioma
extended
from the lower chest to the
upper left leg. (Right) Axial
color Doppler ultrasound
shows absence of blood flow
in the mass. The
lymphangioma
did not
extend into the abdominal
cavity but secondary
lymphedema
of the leg was
severe.

I

SECTION 6: Heart

Introduction and Overview
Cardiac Development & Imaging

6-2

Heart
Echogenic Cardiac Focus
Foramen Ovale Aneurysm
Pericardial Effusion
Situs Inversus
Heterotaxy, Cardiosplenic Syndromes
Ventricular Septal Defect
Atrioventricular Septal Defect
Hypoplastic Left Heart
Coarctation of the Aorta
Aortic Stenosis
Pulmonary Valve Stenosis, Atresia
Ebstein Anomaly, Tricuspid Dysplasia
Tricuspid Atresia
Double Outlet Right Ventricle
Single Ventricle
Tetralogy of Fallot
Transposition of Great Arteries
Truncus Arteriosus
Hypertrophic Cardiomyopathy
Dilated Cardiomyopathy
Irregular Rhythm
Tachyarrhythmia
Bradyarrhythmia
Rhabdomyoma

6-6
6-8

6-10
6-14
6-16
6-20
6-22
6-26
6-30
6-34
6-38
6-42
6-44
6-46
6-48

6-50
6-54
6-58

6-62
6-66
6-70
6-72
6-76
6-80

CARDIAC DEVELOPMENT & IMAGING

M-mode ultrasound shows cardiac activity in an early
pregnancy. Cardiac activity can be seen on endovaginal
scans before the embryo can be seen well enough to be
measured.

Ilmaging Anatomy
General Anatomic Considerations
• Fetal heart axis is 30-45 degrees, apex points left
• Fetal heart lies in an axial plane in chest
• Recognition of chambers, great vessels
o Right atrium: Receives superior vena cava (SVC) and
inferior vena cava (IVC)
o Right ventricle
• Trabeculated myocardium, moderator band,
triangular shape
• Tricuspid valve leaflet attached to septum
o Left atrium: Receives pulmonary veins
• Foramen ova Ie flap seen within, flow direction
right to left
o Left ventricle
• Smooth walled, bullet shaped
• Mitral valve has no septal attachment
o Aorta gives rise to head and neck vessels at apex of
"candy cane" shaped arch
o Pulmonary artery bifurcates shortly after it exits
heart
• Gives rise to ductus arteriosus

IAnatomy-Based

Imaging Issues

Key Concepts or Questions
• Fetal circulation
o Umbilical vein brings oxygenated blood from
placenta to right atrium
• Right atrial blood is shunted to left heart through
foramen ovale
• Right atrium -. left atrium -. left ventricle (LV) -.
aorta to supply head and neck
o SVC/IVC blood -. right atrium -. right ventricle
(RV) -. pulmonary artery
o Ductus arteriosus takes majority of RV blood from
pulmonary artery to the body, bypassing lungs
o Blood returns to placenta via umbilical arteries for
oxygenation

Four chamber view shows symmetric ventricles. The
right has a moderator band (curved arrow), while the
left (open arrow) is smooth-walled. The tricuspid valve
(arrow) is lower on the septum than the mitral valve.

• Cardiac activity is seen before embryo margins can be
defined
o Absence of cardiac activity in embryos> 5 mm in
size on endovaginal scans indicates demise
• Key questions
o Is the heart size normal?
o Is the cardiac axis normal?
o Is there atrioventricular concordance?
o Is there ventriculoarterial concordance?
o Do the outflow tracts relate normally?

Imaging Approaches
• Indications for fetal echocardiography
o Family history
• Structural defect: Recurrence risk highest if mother
affected
• Syndromes: Marfan, Noonan, Holt Oram, 22q 11
deletion, Williams
• Other heritable conditions: Tuberous sclerosis
o In vitro fertilization pregnancy
o Maternal indications
• Metabolic: Diabetes mellitus, phenylketonuria
• Infections: Rubella
• Lupus: Conduction defects
o Teratogen exposure
• Phenytoin, isotretinoin, lithium
o Fetal indications
• Multiple gestations (especially twin-twin
transfusion)
• Multiple anomalies
• Abnormal nuchal translucency, even if
chromosomes normal
• Abnormality detected at routine obstetric scan
• Hydrops
• Arrhythmia

Imaging Protocols
• American Society of Echocardiography
o Establish situs
o Measure chambers, vessels and valves
o Doppler interrogation of all vessels and valves
o Examine rate and rhythm

CARDIAC

& IMAGING

DEVELOPMENT
Key Facts

Structural Survey

Embryology

• 40'Yt, of congenital heart disease (CHD) missed with
normal 4 chamber view
• 20% of CHD still missed with normal 4 chamber view
+ normal outflow tracts
o ASD, VSD, coarctation of aorta, anomalous
pulmonary venous return

• Critical period for heart development
embryonic days 20-50

Clinical Impact
• CHD is common, 8-10:1000 live births
• CIID is a leading cause of neonatal and early
childhood death
• Fetal incidence higher, given loss rate with
aneuploidy, multiple anomalies and heterotaxy
syndromes

Normal Measurements
• Atria should be abQut ~qJ,lalin siz€l
• Tricuspid valve attachmeJ;lt qn interventricular septum'
offset from mitral valve attachment
• Ventricles about equal at 20 weeks, right ventricl~ .
larger by term
• Outflow tracts should be about equal in diameter
• Heart circumference ~ 50% chest circumference
• Pericardial fluid < 2 mm

I Pathology-Based

Imaging Issues

Imaging Pitfalls
• Some lesions missed despite detailed study
o Atrial or ventricular septal defect (ASD, VSD)
o Coarctation of aorta
o Anomalous pulmonary venous return

I Embryology
Embryologic Events
• Heart and blood vessel development is controlled by
cascade of regulatory genes and signaling molecules
o Error at any point in process => structural defects
o Cardiogenic area is defined by embryonic day 15
• Experiments show that cells from this area
develop myofibrils/rhythmic contraction even if
moved
• Traditional teaching was that developing myocardium
wrapped around an endothelial tube which developed
"constrictions"
o Sinus venosus -+ atrium -+ ventricle -+ bulbus cordis
-+ truncus arteriosus
o This tube looped and septated to become
four-chambered heart
• New mechanism proposed based on myocardial
markers, research on embryonic"fields" and use of
scanning electron microscopy
o There is no single tube with linear array of all
components

is from

Pathology
• Obstructive lesions may progress
o May result in ventricular hypoplasia ± hypoplastic
great artery
• Valve regurgitation may increase
o May cause enough chamber enlargement -+
pulmonary hypoplasia

Clinical Implications
• Early detection of CHD
o Guides in utero management
o Allows for planning of delivery and prompt
institution of Dostnatal theranv
o Heart develops in modular fashion with sequential
addition of components to an initial primary
structure
• Third week of embryonic life: Angioblastic cords
canalize and fuse to form a heart tube or primary
cardiac crescent
o This primary structure forms bulk of developing LV
o Secondary (anterior) heart field gives rise to RVand
outflow tracts
o Tertiary field contributes cells which form atria and
contribute to ventricles
.
o Cardiac neural crest cells + proepicardial organ =>
aortic arches/coronary vessels
o "Sacculations" now described in primitive heart
• Sinus venosus -+ atrium -+ inlet -+ outlet -+
truncus arteriosus
• Junction of inlet/outlet portions =
bulboventricular foramen
• Primitive heart looping occurs by unknown
mechanism, complete by end 5th embryonic week
o Normal bend is to right, D-looping
o Abnormal bend to left, L-looping => dextrocardia
• Septation
o Paired hypercellular masses
(atrioventricular/endocardial
cushions) form on
dorsal and ventral walls of looping heart tube
o Approach each other and fuse separating primary
atrium from primary ventricle
o Atrial division is occurring at same time
•. Septum primum grows toward endocardial
cushions from roof of primordial atrium
• Foramen primum lies between free edge of septum
primum and endocardial cushions
• Foramen primum closes as programmed cell death
in septum primum -+ foramen secundum
• Septum secundum grows to right of septum
primum:
• Partially covers foramen secundum, residual hole
is foramen ovale
• Upper septum primum atrophies, lower portion

attached to endocardial cushions
foramen ovale

-+

flap of

..

CARDIAC

DEVELOPMENT

Four chamber view shows normal axis. A line drawn
along the septum makes an angle of 30-45 degrees with
a line drawn from spine to sternum. The latter line
passes through left atrium (LA) & right ventricle (RV).

o Apical components of ventricles "balloon" from
primary ventricle
• Rapid enlargement -+ apposition of medial walls
-+ primordial
muscular ventricular septum
• Inlet septum forms from coalescence of trabeculae
o Partitioning of truncus
• Proximal and distal parts of outflow are separated
by a bend (seen with electron microscopy)
• Outlet cushions from cardiac neural crest
mesenchyme form in proximal part and fuse
• Fusion -+ formation aortic root + subpulmonary
infundibulum
• As truncal partitioning nears completion
semilunar and atrioventricular valves develop
• Distal part ~ intrapericardial portions of great
arteries
o As ridges form and fuse they undergo 180 spiraling
~ pulmonary artery "twists" around aorta
o Fusion also occurs with primary ventricular septum,
walling aortic root into LV
o Atrioventricular and outlet cushions also fuse -+
membranous ventricular septum
• End 6th week embryonic life: Septation complete
• Arterial system
o Pharyngeal arches penetrated by arteries -+ aortic
arches
o Aortic arches -+ carotid, subclavian and pulmonary
arteries
• Venous system
o Three pairs embryonic veins drain into primordial
heart
• Vitelline system -+ portal system
• Cardinal system -+ caval system
• Umbilical system: Brings oxygenated blood from
placenta to fetus, involutes at birth

& IMAGING

Graphic shows Doppler cursor position for rhythm
assessment. Flow during an atrial contraction (arrow) is
toward the transducer, while flow during a ventricular
contraction (curved arrow) is away from the transducer.

•
•
•

•

o Atrioventricular septal defect: 46%
o Tetralogy of Fallot: 31-45%
o Double outlet right ventricle: 21-38%
Prenatal detection of CHD allows for detailed
anatomic survey and karyotype
Parents may choose termination of pregnancy if fetus
has additional malformations or aneuploidy
Prior knowledge of "duct dependent" disease through
effective use of fetal echocardiography
allows
o "Maternal" transport of infant as fetus
o Planned delivery in tertiary care facility
• Prostaglandin infusion at birth to prevent ductal
closure and cardiovascular collapse
Emerging data suggests possible survival advantage
and reduction in ICU stay for infants with prenatal
diagnosis of severe CHD

0

I Related
1.
2.

3.

4.
5.

6.

7.

IClinicallmplications
Clinical Importance
• Some forms of congenital heart disease (CHD) strongly
associated with aneuploidy

References

Cook AC et al: Normal and abnormal fetal cardiac
anatomy. Prenat Diagn. 24(13):1032-48, 2004
Rychik J et al: American Society of Echocardiography
guidelines and standards for performance of the fetal
echocardiogram. JAm Soc Echocardiogr. 17(7):803-10,
2004
Anderson RH et al: Development of the heart: (3)
formation of the ventricular outflow tracts, arterial valves,
and intrapericardial arterial trunks. Heart. 89(9):1110-8,
2003
Anderson RH et al: Development of the heart: (2) Septation
of the atriums and ventricles. Heart. 89(8):949-58, 2003
Hutson MR et al: Neural crest and cardiovascular
development: a 20-year perspective. Birth Defects Res C
Embryo Today. 69(1):2-13, 2003
Moorman A et al: Development of the heart: (1) formation
of the cardiac chambers and arterial trunks. Heart.
89(7):806-14,2003
Webb S et al: Septation and separation within the outflow
tract of the developing heart. J Anat. 202(4):327-42, 2003

CARDIAC DEVELOPMENT & IMAGING
IIMAGE GAllERY
(Left) LVOT view shows the
anterior aortic wall (arrow)
in continuity with the
ventricular septum (curved
arrow). The vessel is
followed to confirm head
and neck branches and
ventriculoarterial
concordance. (Right) RVOT
view shows the pulmonary
artery bifurcation. The
ductus arteriosus (arrow)
runs toward the spine and
descending aorta, the right
pulmonary artery (curved
arrow) wraps around the
aortic root (open arrow).

(Left) Sagittal oblique
ultrasound shows the typical
"candy cane" configuration
of the aortic arch with the
head and neck vessels
(arrows) arising from the
apex of the curve. (Right)
Sagittal ultrasound shows the
ductal arch, which has a
much flatter" hockey stick "
shape than the "candy cane"
aortic arch. The ductus
(curved arrow) bypasses the
lungs to connect with the
descending aorta (arrows).

(Left) Sagittal ultrasound
shows the superior vena
cava (SVC) and inferior vena
cava (arrow) draining into
the right atrium (RA). One of
the hepatic veins (curved
arrow) is seen entering the
inferior vena cava. (Right)
Four chamber view shows
the inferior pulmonary veins
(arrows) entering the left
atrium which connects to the
smooth-walled left ventricle
(curved arrow). This is
atrioventricular
concordance.

ECHOGENIC CARDIAC FOCUS

Axial ultrasound shows a left ventricular echogenic
cardiac focus (arrow) in a fetus with trisomy 2 7. The
patient was of advanced maternal age and had an
abnormal maternal serum quadruple test result.

ITERMINOLOGY
Abbreviations

and Synonyms

• Echogenic cardiac focus (ECF)
• lntracardiac echogenic focus (lEF)

Definitions
• Cardiac papillary muscle echogenicity

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Bright as bone echogenic focus in
cardiac ventricle
• Location: Left ventricle most common
• Size: Usually < 3 mm

Ultrasonographic

Findings

• 3-4% of all 2nd trimester fetuses
• ECF associated with trisomy 21 (T21)
o 1.8 likelihood ratio (LR)when isolated
• 1.8x higher risk for T21 than a priori risk
o Rarely turns low-risk patient into high-risk patient
o Seek other markers for T21
• Nuchal thickening
• Short femur/humerus
• Echogenic bowel
• Renal pelviectasis
o Resolution of ECF does not change risk
• ECF associated with trisomy 13 (T13)
o Associated cardiac anomaly common
• Hypoplastic left heart + ECF very suggestive of T13
o Rarely isolated finding
• Large and bilateral ECF
o t Risk for aneuploidy compared to single ECF

Imaging Recommendations

• Bright echogenic dot in ventricle of heart
o Seen best when cardiac apex pointed up towards
transducer
o Should be bright as bone to be true finding
o Often single focus in left ventricle
• 78% left ventricle
• 18% right ventricle
• 4% bilateral
o Most often an incidental finding

DDx: Intracardiac

Sagittal ultrasound of the fetal head and neck in the
same fetus with trisomy 2 7 shows nuchal fold
thickening (open arrows) and delayed fusion of the
amniotic membrane (curved arrow).

• Best imaging tool: Routine four chamber heart view
• Protocol advice
o Compare echogenicity with bone
o Look carefully for T21 markers when ECF seen
o Assess maternal a priori risk for T21 and T13
• Maternal quadruple serum test results
• Maternal age
o Considered normal when isolated in low-risk patient
• Amniocentesis not necessary

Echogenicities

.. .•.•.. \~ .

~
~

..

;~

~"
••..... ~

. ....•.

Rhabdomyoma

.if

-~._~:~
...

..
""

AV Septal Defect

.

,,-.,:

...

Papillary Muscle

ECHOGENIC CARDIAC FOCUS
Key Facts
Imaging Findings
•
•
•
•
•
•

Bright echogenic dot in ventricle of heart
Should be bright as bone to be true finding
Often single focus in left ventricle
Most often an incidental finding
ECF associated with trisomy 21 (T21)
ECF associated with trisomy 13 (T13)

Top Differential Diagnoses
• Rhabdomvoma

I DIFFERENTIAL

DIAGNOSIS

• Normal papillary muscles
• Normal moderator band muscle

Pathology
• 3-4% of normal fetuses have ECF
• 9-12% of normal Asian fetuses have ECF

Diagnostic Checklist
• Isolated ECF in low-risk patient almost always a
normal finding ,

I DIAGNOSTIC

CHECKLIST

Rhabdomyoma

Consider

• Homogeneous echogenic cardiac tumor
o Often involves ventricular septum
o Can originate from ventricular wan and atria
o Multiple tumors common
• 50-85% have tuberous sclerosis

• Isolated ECF in low-risk patient almost always a
normal finding

Normal cardiac structures
• Normal papillary muscles
o Attach to mitral and tricuspid valves
o Not as echogenic as bone
• Normal moderator band muscle
o At apex of right ventricle
o Hypoechoic structure

Image Interpretation Pearls
• Do not diagnose ECF if echogenicity is less than bone

I SELECTED REFERENCES
1.

2.

Atrioventricular (AV) septal defect
• Lack of central cardiac structures
o Variable absence of atrioventricular valves
• Remains of MV and TV can mimic ECF
• Highly associated with T21

I PATHOLOGY

3.

4.

5.

Coco C et al: An isolated echogenic heart focus is not an
indication for amniocentesis in 12,672 unselected patients.
J Ultrasound Med. 23(4):489-96, 2004
Doubilet PM et al: Choroid plexus cyst and echogenic
intracardiac focus in women at low risk for chromosomal
anomalies: the obligation to inform the mother. J
Ultrasound Med. 23(7):883-5, 2004
Filly RAet al: Choroid plexus cyst and echogenic
intracardiac focus in women at low risk for chromosomal
anomalies. J Ultrasound Med. 23(4):447-9, 2004
Souter VL et al: Correlation of second-trimester
sonographic and biochemical markers. J Ultrasound Med.
23(4):505-11,2004
Sotiriadis A et al: Diagnostic performance of intra cardiac
echo genic foci for Down syndrome: a meta-analysis. Obstet
Gynecol. 101(5 Pt 1):1009-16, 2003

General Features
• Genetics: ECF associated with T21 and T13
• Epidemiology
o 3-4% of normal fetuses have ECF
o 9-12% of normal Asian fetuses have ECF
o 18% of fetuses with T21 have ECF
o 39% of fetuses with T13 have ECF

IIMAGE GALLERY

Microscopic Features
• Mineralization of papillary muscle

ICLINICALISSUES
Presentation
• Most common signs/symptoms
o Incidental finding in low-risk patient
• High prevalence in Asian patients
o Seen with other markers of T21
o Seen with severe anomalies of T13

Natural History & Prognosis
• Excellent prognosis in low-risk patients

(Left) Axial ultrasound shows bilateral ECF (arrows) and a small left
ventricle (curved arrow) in a fetus with trisomy 13. Bilateral cleft lip
and palate was also seen. ECF is almost never an isolated finding with
T/3. (Right) Axial ultrasound shows three ECF (arrows) as bright as
bone (open arrows) in the left ventricle. The finding was isolated and
the patient was low risk based on age and serum screen so
amniocentesis was not performed despite multiplicity.

FORAMEN

OVALE ANEURYSM

Four chamber view shows the typical "ballooned"
appearance of the foramen ovale flap (arrow) in a fetus
with a foramen ovale aneurysm. There were no adverse
consequences.

Color M-mode tracing shows the typical appearance of
blocked PACs (arrows). Red reflects atrial contraction,
blue ventricular contraction. PACs can be seen in up to
36% of fetuses with foramen ovale aneurysms.

o Look for additional structural abnormality
• Mitral valve prolapse
• Mitral and tricuspid stenosis
• Pulmonary venous obstruction
o Check rhythm
• Up to 36% will have premature atrial contractions
(PACs)
• Rare case with intermittent or sustained
supraventricular tachycardia (SVT)
o Careful evaluation of mitral vale

ITERMINOlOGY
Abbreviations
•
•
•
•

and Synonyms

Foramen ovale aneurysm
Atrial septal aneurysm
Aneurysm of septum primum
Redundant septum primum flap

Definitions
• Redundant tissue in foramen ovale flap
• Definition of redundancy varies between series
o Flap extends at least half way across left atrium
o Flap excursion> 5 mm beyond plane of atrial
septum
o Flap demonstrates abnormal mobility

IIMAGING

FINDINGS

General Features

I DIFFERENTIAL

DIAGNOSIS

Normal foramen ovale flap
• Normal flap shows little motility during cardiac cycle
• Seen projecting into left atrium on four chamber view
• Linear flap
o Not enough tissue to "balloon"
• With reversed atrial shunting flap projects into right
atrium
o Seen in left heart obstruction

• "Balloon" appearance of foramen ovale flap
o May make cyclical contact with left atrial wall or
mitral valve
o Very redundant flap may even herniate through
mitral valve

I PATHOLOGY

Imaging Recommendations

General Features

• Consider formal fetal echocardiography

• Genetics: No association

with aneuploidy

DDx: Foramen Ovale Aneurysm

Normal Flap

Normal Flap

Reverse Atrial Shunt

FORAMEN

OVALE ANEURYSM
Key Facts

Terminology

Clinical Issues

• Redundant tissue in foramen ovale flap
• Flap demonstrates abnormal mobility

• No fetuses in large series (> 1,000 patients) developed
significant arrhythmia

Top Differential Diagnoses

Diagnostic Checklist

• Normal foramen ovale flap

• Isolated foramen ovale aneurysm is a benign entity
• If associated with PACs, very small risk of progression
to tachyarrhythmia

Pathology
• 5.4% of fetuses referred for arrhythmia
finding of foramen ovale aneurysm

had incidentai

• Etiology
o Unclear
• Possibly abnormally weak septum primum tissue
• Possibly secondary to abnormal flow patterns
• In neonates foramen ovale aneurysms tend to get
worse with abnormal atrial hemodynamics
• Epidemiology
o True population incidence unknown
o 5.4% of fetuses referred for arrhythmia had
incidental finding of foramen ovale aneurysm
o Seen in up to 7.6% of fetal echocardiograms done
for any indication
• Associated abnormalities
o PACs may be due to
• Cyclical contact of redundant flap with left atrial
wall
• Base of flap may irritate sinoatrial (SA) node
• Intermittent blocking SA node transmission
• Embryology
o Septum primum: Thin flap grows from top of
common atrium toward ventricular septum
• Continues until attachment to endocardial
cushion
• Separates from top of atrium leaving a hole
o Septum secundum: Thicker flap develops as true
atrial septum growing from top down, partially
covering the hole
• Residual hole is foramen ovale
o Septum primum flap normally covers foramen ovale
• Flap seen in left atrium as blood flows R -+ L in
fetus

Treatment
• Monitor for rhythm disturbance by regular
auscultation
• Scattered case reports of persistent arrhythmia in
children requiring resection of redundant tissue

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Isolated foramen ovale aneurysm is a benign entity
• If associated with PACs, very small risk of progression
to tachyarrhythmia

I SELECTED REFERENCES
1.

2.

3.
4.

Papa M et al: Prevalence and prognosis of atrial septal
aneurysm in high risk fetuses without structural heart
defects. Ital Heart J. 3(5):318-21, 2002
Haddad S et al: The antenatal diagnosis of fetal atrial septal
aneurysm. Gynecol Obstet Invest. 41(1):27-9,1996
Rice MJ et al: Fetal atrial septal aneurysm: a cause of fetal
atrial arrhythmias. J Am Call Cardia!. 12(5):1292-7, 1988
Stewart PA et al: Fetal atrial arrhythmias associated with
redundancy/aneurysm
of the foramen ovale. J Clin
Ultrasound. 16(9):643-50, 1988

IIMAGE GALLERY

!CLlNICALISSUES
Presentation
• Most common signs/symptoms
a Observed on four chamber view at routine obstetric
sonography
a May be found in fetus being evaluated for PACs or
arrhythmia

Natural History & Prognosis
• Associated with prematu're atrial contractions
• No fetuses in large series (> 1,000 patients) developed
significant arrhythmia
• All infants had normal sinus rhythm by 3 months age

(Leh) Four chamber view shows prominent "ballooning" of the
foramen ovale flap (arrow) which made cyclical contact with the left
atrial wall (curved arrow). This is thought to be a mechanical stimulus
for arrhythmia. (Right) M-mode ultrasound shows intermittent
supraventricular tachycardia. The curved arrow marks the transition
to sinus rhythm. Both intermittent and sustained SVT have been
described in fetuses with foramen ovale aneurysm.

PERICARDIAL EFFUSION

Four chamber view shows cardiomegaly and a large
pericardia I effusion (arrow) in a fetus with dilated
cardiomyopathy
secondary
to
cytomegalovirus
infection.

o If fetus not at increased risk, follow-up not necessary

ITERMINOLOGY
Abbreviations

Imaging Recommendations

and Synonyms

• Pericardial fluid
• Pericardial effusion (PE)

Definitions
• Accumulation

of fluid in pericardial space

IIMAGING

FINDINGS

General Features
• Best diagnostic clue
o Fluid collection surrounds fetal heart
• Must measure> 2 mm
• Hypoechoic rim extends over atria as well as
ventricles
• If large, heart is seen beating in a "bag of water"

Ultrasonographic

Four chamber view shows a 3 111111 rim of pericardia I
fluid (arrows) adjacent to thp right ventricular wall in
this third trimester fetus. This resolved on follow-up and
the infant was normal ,11 delivery.

Findings

• Lenticular or oval collection of fluid adjacent to, or
surrounding heart
• Seen best on standard four chamber view
• Trace of fluid along one ventricular wall is normal
o Can be up to 2 mm
o Majority of fetuses (50-80%) have trace of fluid if
careful search done

• Pericardial effusion seen in many conditions
o Complete fetal assessment required to exclude
significant pathology
• Look for other signs of hydrops
o Cardiomegaly
o Skin edema
o Pleural effusion
o Ascites
o Abnormal Doppler
• Tricuspid regurgitation
• Reversed flow in inferior vena cava
• Reversed flow in ductus venosus
• Pulsatile umbilical vein flow
• Look for signs of congenital infection
o Liver calcifications
o Brain calcifications
o Echogenic bowel
• Look for anemia
o Measure middle cerebral artery peak systolic velocity
o Plot against gestational age
o Reliable indicator of fetal anemia
• Usuallyalloimmunization
• Parvovirus
• Rare congenital anemias may present with PE
• Check growth and well-being

DDx: Pericardial Effusion

Pleural Effusion

Pleural Effusion

PERICARDIAL EFFUSION
Key Facts
Terminology

Pathology

• Accumulation of fluid in pericardial space

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•
•
•

Imaging Findings
•
•
•
•
•
•

Fluid collection surrounds fetal heart
Must measure> 2 mm
Seen best on standard four chamber vielY
Trace of fluid along one ventricular wall is normal
Pericardial effusion seen in many conditions
Complete fetal assessment required to exclude
significant pathology

Top Differential Diagnoses
• Normal pericardial fluid
• Normal peripheral myocardium
• Pleural effusion

•

•

•

•

o Severe placental insufficiency ~ intrauterine growth
restriction
o Abnormal placental resistance ~ right heart strain
o Cardiac compromise ~ pericardia I effusion
Look for shunt lesions as cause of high output state
o Placental chorioangioma
• Examine whole placental surface
o Arteriovenous malformation (AVM)
• Use color Doppler
• Vein of Galen and other brain AVMs may present
with PE/hydrops
o Fetal tumors
• Usually large and easily seen
In multiples check chorionicity and amnionicity
o Monochorionic diamniotic pairs at risk for
twin-twin transfusion syndrome (mS)
o Risk cardiac compromise in both fetuses
• High output in pump twin
• Volume overload in recipient
o Monoamniotic pairs at risk for cord accidents
• Hypoxia/ischemia ~ cardiac compromise
o Twin reverse arterial perfusion (TRAP) sequence may
cause cardiac compromise in pump twin
• Anomalous acardiac twin should be obvious
Careful search for features of aneuploidy
o One series (published in 1995) showed 30%
aneuploidy rate with apparently isolated PE
• Look for specific markers: Thick nuchal fold, short
humerus, absent nasal bone for trisomy 21
• Clenched fingers, cardiac defects for trisomy 18
Pericardial teratoma
o Effusion often very large
o May be mistaken for pleural effusion
• Lung will be compressed posteriorly by pericardial
effusion
• This appearance differs from large pleural effusion
~ circumferential pressure on lungs ~ lungs
collapse centrally ~ "angel wing" appearance
o May have tamponade physiology
o Mass arises from pericardium not myocardium
• Presentation with PE also described in fetal cardiac
hemangioma

Cardiac abnormality
Congenital infection
High-output states
Fetal endocrine abnormality

Clinical Issues
• With hydrops fetalis overall prognosis is poor
• No treatment necessary if isolated and small
• Follow-up exams necessary when fluid is > 2 mm or
in high-risk patients
• Treat underlying cause where possible

Diagnostic Checklist
• Pericardial effusion may be first sign of hydrops
especially if etiology is cardiac

• Cardiac diverticulum
o Localized protrusions of ventricle
o Thin neck
o Associated with PE which may be significant
o Color Doppler shows flow within diverticulum
• Formal fetal echocardiogram if significant effusion and
none of above etiologies
o Look for structural malformations
o Assess baseline function
o Evaluate rhythm

I DIFFERENTIAL

DIAGNOSIS

Normal pericardial fluid
• Less than 2 mm
• May be transient
• Follow-up ultrasound in high-risk patients

Normal peripheral myocardium
• Outside 1-6 mm of myocardium may be hypoechoic
and mimic fluid
• Seen encircling ventricles only, does not surround
atria
• Circular outer muscle fibers cause this effect
• Look for contraction
o Pericardial fluid creates an immobile ring

Pleural effusion
• Usually not just adjacent to heart
• Transverse section ~ fluid tracks around lungs
• Sagittal or coronal sections ~ fluid tracks under lungs

I PATHOLOGY
General Features
• Etiology
o Cardiac abnormality
• Arrhythmia
• Structural defect
• Cardiomyopathy
• Ventricular aneurysm/diverticula

PERICARDIAL EFFUSION
o Congenital infection
• CMV
• Rubella
• Toxoplasmosis
• Parvovirus B19
• Syphilis
o High-output states
• TTTSjTRAP

• AVM
• Tumors
• Anemia
o Fetal endocrine abnormality
• Fetal hypothyroidism may present as hydrops
• Epidemiology
o 0.02% of fetuses in a series of 506 routine obstetric
scans had isolated PE
• Maximum measurement 3 mm
• All normal outcome

I CLINICAL

ISSUES

o Consider fetal surgery for tumors such as
sacrococcygeal teratoma
o Intrauterine transfusion for fetal anemia
• Pericardial teratoma
o Benign neoplasm
o If no hydrops
• Follow frequently
• Postnatal resection
o If hydrops
• Pericardiocentesis may be life-saving

I DIAGNOSTIC

CHECKLIST

Consider
• Many different etiologies for pericardia I effusion
o Assessment requires thorough anatomic survey
o Evaluation for fetal anemia
o May need formal fetal echocardiogram

Image Interpretation

Pearls

Presentation

• Pericardial effusion may be first sign of hydrops
especially if etiology is cardiac

• Incidental finding on screening exam
• In association with hydrops fetalis
• In association with cardiac anomaly

ISELECTED REFERENCES

Natural History & Prognosis
• Variable depending on cause
• With hydrops fetalis overall prognosis is poor
o When PE seen early, hydrops more likely associated
with cardiac abnormality
• Some causes may be treatable (e.g.,
tachyarrhythmia)
o When PE seen late, hydrops likely from other causes
• Still potential to treat successfully (e.g.,
intrauterine transfusion for fetal anemia)
• Cardiac diverticulum
o Large associated PE may cause tamponade and
hydrops
o Single pericardiocentesis successful in number of
case reports
• No recurrence of PE
• Normal cardiac function at birth

Treatment
• No treatment necessary if isolated and small
• Follow-up exams necessary when fluid is > 2 mm or in
high-risk patients
o May progress to hydrops
o May resolve completely
• Consider karyotype
o Series of 35 isolated pericardia I effusions (no
structural cardiac defect or arrhythmia)
• 30% had some chromosomal anomaly
• 26% trisomy 21
• Infection screen
o Direct culture more reliable than maternal antibody
screening
• Treat underlying cause where possible
o Medical treatment for arrhythmias
o Treat TTTS
• Laser ablation vs. serial amnioreduction

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Woodward PJ et al: From the archives of the AFlP: a
comprehensive review of fetal tumors with pathologic
correlation. Radiographics. 25(1):215-42, 2005
Sydorak RM et al: Prenatal resection of a fetal pericardial
teratoma. Fetal Diagn Ther. 17(5):281-5, 2002
Yoo SJ et al: Normal pericardial fluid in the fetus: color and
spectral Doppler analysis. Ultrasound Obstet Gynecol.
18(3):248-52, 2001
Hirashima C et al: Isolated pericardial effusion and
transient abnormal myelopoiesis in a fetus with Down's
syndrome. J Obstet Gynaecol Res. 26(4):303-6, 2000
Kessel I et al: Congenital hypothyroidism
and nonimmune
hydrops fetalis: associated? Pediatrics. 103(1):E9, 1999
Brown DL: Borderline findings in fetal cardiac sonography.
Semin Ultrasound CT MR. 19(4):329-35, 1998
Cesko I et al: Fetal hydropericardium
associated with left
ventricular diverticulum. Prenat Diagn. 18(7):721-4, 1998
Cavalle-Garrido T et al: Evolution of fetal ventricular
aneurysms and diverticula of the heart: an
echocardiographic
study. Am J Perinatol. 14(7):393-400,
1997
Dizon-Townson OS et al: A prospective evaluation of fetal
pericardial fluid in 506 second trimester low-risk
pregnancies. Obstet Gynecol. 90:958-61, 1997
Parilla BV et al: Association of parvovirus infection with
isolated fetal effusions. AmJ Perinatol. 14(6):357-8, 1997
Johnson JA et al: Prenatal diagnosis of a fetal ventricular
diverticulum associated with pericardial effusion:
successful outcome following pericardiocentesis. Prenat
Diagn. 16(10):954-7, 1996
Sharland G et al: Isolated pericardial effusion: an
indication for fetal karyotyping? Ultrasound Obstet
Gynecol. 6(1):29-32, 1995
Di Salvo ON et al: Clinical significance of isolated fetal
pericardial effusion. J Ultrasound Med. 13(4):291-3, 1994
Rondanini GF et al: Congenital hypothyroidism and
pericardial effusion. Horm Res. 35(1):41-4,1991
Brown DL et al: The peripheral hypoechoic rim of the fetal
heart. J Ultrasound Med. 8(11):603-8, 1989
Shenker L et al: Fetal pericardial effusion. Am J Obstet
Gynecol. 160:1505-8, 1989

PERICARDIAL EFFUSION
IIMAGE GALLERY
(Left) Four chamber view
shows a small pericardia I
effusion (arrow) in a fetus
with supraventricular
tachycardia. Hydrops
developed on follow-up
scans despite digoxin
treatment. Control was
eventually achieved with
digoxin plus flecainide.
(Right) M-mode ultrasound
from the same case shows
persistent tachycardia with
heart rate of 248 beats per
minute.

(Left) Axial oblique
ultrasound of the chest
shows a 7 mm pericardial
effusion (cursors) in this fetus
with heterotaxy, hypoplastic
left heart (arrow) and critical
pulmonary stenosis. Hydrops
developed and the infant
expired within hours of
delivery. (Right) Four
chamber view shows a large
pericardial effusion (arrows)
in association with
myocardial thickening
(curved arrows) in the pump
twin of a pregnancy
complicated
by twin-twin
transfusion syndrome.

Variant
(Left) Coronal T2WI MR
shows a large intrapericardial
teratoma (arrow) adjacent to
the heart (curved arrow). It
is surrounded by a massive
high signal pericardia I
effusion. No normal lungs
are visualized. Ascites (open
arrow) is also present.
(Right) Cross pathology
shows a massively distended,
fluid-filled pericardial sac
(arrow) essentially filling the
thoracic cavity. The tumor
(curved arrow) can be seen
within the sac. (Also shown
in Radiographics, ref 7).

SITUS INVERSUS

Coronal T2WI MR shows the cardiac apex (arrow)
pointing towards the right and the liver (open arrow) on
the left side of the abdomen.

Coronal transabdominal ultrasound shows the fetal liver
and gallbladder (arrow) on the left and the cardiac apex
(curved arrow) pointing toward the right.

Definitions

o Mild ventriculomegaly reported as a fetal marker for
Kartagener syndrome
• Careful search for other anomalies

• Situs inversus (51):Heart and stomach on right
("mirror image" of normal situs)
• Situs solitus: Cardiac apex/stomach left, liver right

I DIFFERENTIAL DIAGNOSIS

ITERMINOlOGY

Heterotaxy

IIMAGING

FINDINGS

General Features
• Best diagnostic clue
o Stomach on fetal right
o Cardiac apex points to right

Imaging Recommendations
• Check fetal situs in all 2nd and 3rd trimester scans
o Never assume heart and stomach indicate fetal left
side
o Determine presenting part
o Find longitudinal orientation of spine and
relationship to maternal abdomen
• From these two, determine fetal left and right side
o Stomach and cardiac apex on same side
• Both left = situs solitus
• Both right = situs inversus
• Measure cerebral ventricles

syndromes

• Left atrial isomerism
o Complex congenital heart disease (CHD), especially
left-sided obstruction and total anomalous
pulmonary venous drainage. (TAPVR)
o Interrupted inferior vena cava with azygos
continuation
• Right atrial isomerism
o Complex CHD, especially transposition/double
outlet right ventricle, atrioventricular canal and
TAPVR
o Liver midline
o No spleen

Cardiac dextroposition
• Heart displaced into right hemithorax by mass
o Cystic adenomatoid malformation, sequestration,
congenital diaphragmatic hernia (CDH)
• May also occur with hypoplasia/aplasia right lung

Isolated dextrocardia
• Cardiac apex right, abdominal organs normal

DDx: Abnormal

CDH

Heart Position

CDH

Heterotaxy-Asplenia

Heterotaxy

SITUS INVERSUS
Key Facts
Terminology

Pathology

• 5itus inversus (51): Heart and stomach on right
("mirror image" of normal situs)

• 20% have Kartagener syndrome

Top Differential

Diagnoses

Clinical Issues
• Risk of CHD < 3%

• Heterotaxy syndromes
• Cardiac dextroposition
• Isolated dextrocardia

Diagnostic Checklist
• 51 not associated with aneuploidy
• Will be missed unless fetal left and right sides are
determined

• More likely to have congenital heart disease or other
anomalies than 51

I PATHOLOGY

Natural History & Prognosis
• Risk of CHD < 3%
• Associated bowel malrotation increases risk for
volvulus
• Prognosis excellent for isolated 51

General Features
• Genetics
o Generally sporadic
o Autosomal recessive form reported in
consanguineous family
• Associated pancreatic/renal cystic dysplasia,
skeletal anomalies and growth restriction
o In fetuses with congenital heart disease
• Normal situs => 40% aneuploidy
• Abnormal situs => think heterotaxy, chromosomes
usually normal
• Epidemiology
o 51documented in 0.3% of a series of 5539 fetal
echo cardiograms
o Of patients with dextrocardia
• 39.2% situs inversus
• 34.4% isolated dextrocardia
• 26.4% heterotaxy syndrome
• Associated abnormalities
o 20% have Kartagener syndrome
• 51,bronchiectasis and nasal polyps
o Reported in association with lethal short
rib-polydactyly syndrome
o Reported in association with renal dysplasia and
multisystem fibrosis
• Embryology
o Normal signaling cascade determines left versus
right identity in visceral organs in a concordant
fashion
o Cardiac looping controlled by same signal cascade
o In 51cardiac tube undergoes initial bend to left
• Heart displaced to right
• Ventricles "inverted" (Le., right posterior, left
anterior)
• Vessels reversed left to right as "mirror image"

I CLINICAL ISSUES
Presentation
• Most common signs/symptoms:
to right

Cardiac apex points

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• 51not associated with aneuploidy
o Karyotype not necessary
• Will be missed unless fetal left and right sides are
determined

I SELECTED
1.

2.

3.

REFERENCES

Wessels MW et al: Mild fetal cerebral ventriculomegaly as a
prenatal sonographic marker for Kartagener syndrome.
Prenat Diagn. 23(3):239-42, 2003
Balci S et al: New syndrome?: Three sibs diagnosed
prenatally with situs inversus totalis, renal and pancreatic
dysplasia, and cysts. Am] Med Genet. 90(3):185-7, 2000
Comstock CH et al: Right fetal cardiac axis: clinical
significance and associated findings. Obstet Gynecol.
91(4):495-9, 1998

I IMAGE

GAllERY

(Leh) Axial transabdominal ultrasound shows situs inversus with the
liver on the left and the stomach (arrow) on the right. This will only
be appreciated if fetal orientation is known. (Right) Axial T2WI MR
shows the fluid-filled gallbladder (arrow) and liver (curved arrow) to
the left of midline in this fetus with situs inversus. The gallbladder was
mistaken for stomach on ultrasound.

HETEROTAXY, CARDIOSPLENIC

Ultrasound of the abdomen shows midline bifurcation
of the portal vein (curved arrow) within a centrally
placed liver. No splenic tissue was seen. The heart was
on the left but the stomach (arrow) was right-sided.

and Synonyms

• Heterotaxy
• Situs ambiguous
• Terminology is confusing with multiple terms for
similar anatomic combinations
o Listed below are terms used for certain combinations
of findings, they are not necessarily synonymous
• Right atrial (RA)isomerism
o Asplenia
o Bilateral right-sidedness
o Ivemark syndrome
o Dextroisomerism
• Left atrial (LA)isomerism
o Polysplenia
o Bilateralleft-sidedness
o Levoisomerism

Definitions
• Heterotaxy is any arrangement of internal organs
other than situs solitus or complete situs inversus
• Situs solitus
o Cardiac apex left
o Dextrocardiac (D) loop
o Liver/cecum right
o Stomach left
• Situs inversus

DDx:

Abnormal location Heart/Stomach

CDH

Radiograph shows features of heterotaxy syndrome with
a left-sided cardiac apex (arrow) and right-sided
stomach
(curved arrow). This infant had bilateral
tri-Iobed lungs, central liver and asplenia.

o Complete mirror image of situs solitus

ITERMINOlOGY
Abbreviations

SYNDROMES

CDH

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Heart and stomach on opposite sides
o Abnormal relationship of abdominal aorta and
inferior vena cava (lVC)
o Complete heart block in presence of congenital
heart disease (CHD)

Ultrasonographic

Findings

• Grayscale Ultrasound
o Interrupted IVC in LA isomerism
• Hepatic veins drain directly to atrium
• Enlarged azygos vein (continuation of IVC)
posterior to aorta
o IVC anterior to aorta on same side of spine in RA
isomerism
o Bilateral superior vena cavas (SVC)
• Seen in both LA/RAisomerism
o Abnormal stomach location
• Right, left or central depending on liver position
o Midline liver
o Gallbladder may be absent in LA isomerism
• Color Doppler
o Look for splenic artery

HETEROTAXY, CARDIOSPLENIC

SYNDROMES

Key Facts
Terminology

• I olated vena cava anomalies

• Terminology is confusing with multiple term for
imilar anatomic combinations
• I leterotaxy is any arrangement of internal organs
other than situs oIitus or complete situ inversus

• Heterotaxy syndromes::::: 4(J1) of all infants with

Imaging Findings

• Depends on type and severity of associated cardiac
malformation

• II art and tomach on opposite ides
• Abnormal relationship of abdominal aorta and
inferior vena cava (lVC)
• Midline liver
• ardiac anomalies occur at every level: Atrial,
atrioventricular, ventricular, ventriculoarterial

Top Differential Diagnoses
• bnormal cardiac po ition
• Abnormal stomach bubble

• Seen with polysplenia (LA isomerism)
• Absent in asplenia (RA isomerism)
o Helpful to identify, trace course of systemic veins

Echocardiographic Findings
• Abnormal cardiac axis
• Cardiac anomalies occur at every level: Atrial,
atrioventricular, ventricular, ventriculoarterial
• Anomalies occur in any combination
• The commonest forms of CHD seen with each type of
heterotaxy are listed below
• LA isomerism/polysplenia
o Dextrocardia in 30-40%
o Bilateral SVC in 40%
o Interrupted IVC in > 70%
o Anomalous pulmonary venous return-usually partial
(PAPVR) in 20-40%
o Common atrium/atrial septal defect (ASD) in 80%
o Atrioventricular (AV) canal in 20-40%
o Single ventricle in 10%
o Left ventricular outflow tract obstruction in 40%
o Conotruncal abnormalities in 15-30%
• Pulmonary stenosis/atresia
• Transposition of great arteries
• RA isomerism/asplenia
o Dextrocardia in 30-40%
o Bilateral SVC in 50-70%
o Total anomalous pulmonary venous return (TAPVR)
in 50-70%
o Common atrium/ ASD in 90%
o AV canal in 85%
o Single ventricle> 50%
o Conotruncal abnormalities 80%
• Double outlet right ventricle (DORV)
• Pulmonary stenosis/atresia
• Transposition of great arteries

Imaging Recommendations
• Protocol advice
o Formal fetal echocardiography
o Complete anatomic survey

Pathology
liD

Clinical Issues

Diagnostic Checklist
• heck situs in all fetal ultra ound scan
• Heterotaxy yndrome have worse prognosis than
isolated
liD
• ~ 2 cardiac tructural defects strongly suggest
heterotaxy
• Interrupted IV trongly ugge ts LA i omerism
• ingle ventricle + AV canal + right outflow
ob truction = RA i merism

I DIFFERENTIAL DIAGNOSIS
Abnormal cardiac position
• Chest mass
o Congenital
o Congenital
(CCAM)

diaphragmatic hernia (CDH)
cystic adenomatoid malformation

Abnormal stomach bubble
• Malpositioned
o CDH
• Look for stomach and heart on same axial scan
plane
• Look for liver in chest

Isolated vena cava anomalies
• Azygos continuation
heart disease

of the IVC without congenital

I PATHOLOGY
General Features
• Genetics
o Majority are sporadic
o Aneuploidy rarely coexists with heterotaxy
syndromes
o A number of familial cases have been described
• X-linked (Xq26.2)
• Autosomal dominant or recessive
• All variants of situs can occur within heterotaxy
families
• Epidemiology
o M:F = 1:2 in LA isomerism
o M:F = 2:1 in RA isomerism
o Heterotaxy syndromes::::: 4% of all infants with CHD
o Heterotaxy syndromes::::: 30% cardiac malpositions
in infants
o LA isomerism more commonly diagnosed in-utero
• Associated complete heart block => hydrops =>
intrauterine fetal demise
o RA isomerism more common in post-natal series
• Associated abnormalities

HETEROTAXY, CARDIOSPLENIC
o LA isomerism
• Bilateral left atrial appendages (finger-like)
• Polysplenia in 96%
• Both lungs bilobed with hyparterial bronShus
• Malpositioned stomach
• Malrotation ofintestines with potential for
obstruction"" 85%
• Centrally-placed, abnormally-shaped liver
• Extrahepatic biliary atresia
• Absent/hypoplastic or midline gallbladder
• Absence of a sinoatrial node-often in junctional
rhythm
o RAisomerism
• Bilateral right atrial appendages (pyramidal shape)
• Asplenia in 74%
• Both lungs trilobed with eparterial bronchus
• Centrally-placed globular liver
• Stomach either midline or left in 60%
• Malrotation of intestines with potential for
obstruction"" 95%
• Presence of 2 sinoatrial nodes-often with SVT
• Broad spectrum of abnormalities fit with heterotaxy
category
o Dextrocardia + abdominal situs solitus
o Levocardia + abdominal situs inversus
o Also documented cases of isomerism with normal
spleen
• Embryology
o Midline developmental field defect
o Embryonic insult days 28-35
o Sequence of cardiac development arrested in 5th
week gestation

SYNDROMES

o 60% overall mortality for staged single ventricle
palliation
• LA isomerism
o 25% early mortality
o 60% 5 year survival
• Patients who make it to Fontan palliation have over
80% 5 year survival

Treatment
• Consider karyotype if multiple anomalies in addition
to CHD
• Detailed genetic history
• Prenatal consultation with neonatology/pediatric
cardiology
• Delivery in tertiary care facility
o Prostaglandins may be necessary for survival with
duct dependent lesions
o Emergent surgery required for obstructed TAPVR
• Surgery for outflow tract obstruction necessary in first
week of life
• Additional surgery for single ventricle palliation
within 6 months
• Surgery for complex systemic venous abnormalities
around 1 year

I DIAGNOSTIC

CHECKLIST

Consider
• Check situs in all fetal ultrasound scans
o Heterotaxy syndromes have worse prognosis than
isolated CHD

Image Interpretation

ICLINICAllSSUES
Presentation
• Most common signs/symptoms
o In fetus
• Abnormal situs
• Interrupted IVC with azygous continuation
• Two or more types of CHD
• Heart block
o At birth
• Cyanotic infant with respiratory
distress/murmur/abnormal chest X-ray
o Chest X-ray
• Cardiac malposition
• Midline liver
• Diminished or congested pulmonary vascular
markings

I SELECTED
1.

2.

3.

4.

Natural History & Prognosis
• Depends on type and severity of associated cardiac
malformation
• Biventricular repair with better long-term outcome
than single ventricle (60% vs. 30%)
• Increased mortality
o Obstructed pulmonary veins
• 95% in association with single ventricle
o Outflow tract obstruction
o Single ventricle morphology
• RAisomerism

Pearls

• ~ 2 cardiac structural defects strongly suggests
heterotaxy
• Interrupted IVC strongly suggests LA isomerism
• Single ventricle + AVcanal + right outflow obstruction
= RAisomerism

5.

6.

7.

REFERENCES

Cheung YFet al: Outcome of infants with right atrial
isomerism: is prognosis better with normal pulmonary
venous drainage? Heart. 87(2):146-52, 2002
Azakie A et al: Improving outcomes of the Fontan
operation in children with atrial isomerism and heterotaxy
syndromes. Ann Thorac Surg. 72(5):1636-40, 2001
Comstock CH et al: Right fetal cardiac axis: clinical
significance and associated findings. Obstet Gynecol.
91(4):495-9, 1998
Ming]E et al: Heterotaxia in a fetus with campomelia,
cervicallymphocele, polysplenia, and multicystic
dysplastic kidneys: expanding the phenotype of Cumming
syndrome. Am] Med Genet. 73(4):419-24, 1997
Sheley RC et al: Azygous continuation of the interrupted
inferior vena cava: a clue to prenatal diagnosis of the
cardiosplenic syndromes.] Ultrasound Med. 14(5):381-7,
1995
Shaw CT: Polysplenia in a fetus with bradycardia from 26
to 36 weeks' gestation, complex cardiac malformations,
and heart block.] Am Osteopath Assoc. 90(12):1100-2,
1990
Chitayat D et al: Prenatal diagnosis of asplenia/polysplenia
syndrome. Am] Obstet Gynecol. 158(5):1085-7, 1988

HETEROTAXY, CARDIOSPLENIC

SYNDROMES

IIMAGE GALLERY
Typical
(Left) Cross pathology of the
heart and lungs shows
bilateral superior vena cavas
(curved arrows) on either
side of the great arteries
(open arrow - pulmonary
artery, arrow - aortic arch).
(Right) Long axis ultrasound
in a fetus with heterotaxy
shows a double outlet right
ventricle with the pulmonary
artery (arrow) parallel to the
aorta (curved arrow), which
is arising from the RV (open
arrow).

(Left) Sagittal oblique
ultrasound shows a large
azygos vein posterior to the
aorta, implying an
interrupted inferior vena
cava and probable left atrial
isomerism in a fetus with
congenital heart disease.
(Right) Sagittal color
Doppler ultrasound confirms
thc' grayscale impression.
There is caudal flow within
the aorta (curved arrow) and
cephalad flow in the
prominent azygos vein
(arrow), consistent with an
interrupted inferior vena
cava.

(Leh) Four chamber view
shows a complete AVSD.
There is a common atrium.
The ventricles are symmetric
in size therefore this is a
balanced defect. The AV
valve le,l(fets (curved
arrows) are in the closed
position (arrOlv - ventricular
septum). (Right) Four
chambC'r view i/1 the same
felus shOll'S 1/](' valve lea(/e/s
(curved arrows) in the open
position. The I'en/rieular
seplUm is denoted hy the
arrow. This fetus hacl a
l]('tC'rolaxy syndrol11C'.

VENTRICULAR

SEPTAL DEFECT

Craphic shows a mid-muscular ventricular septal defect
(arrow) allowing oxygenated hlood to flow tium the leit
ventricle to the right ventricle, increasing the oxygen
saturation in the MPA (open arrow).

Color Doppler ultrasound shows flow (curved arrow)
across the ventricular septal defect from ventricle to
ventricle (arrows). Shunt flow in a fetus is hi-directional.

• Septal continuity with aortic annulus excludes
VSD in that location
• Confirm on long axis view if seen on apical four
chamber view and vice-versa
o True VSD: Visible in two scan planes
• Color Doppler
o Color Doppler used to confirm blood flow across
defect
o Right/left ventricular pressures similar in fetus '*
shunt bi-directional
o If unidirectional shunt look for other anomalies
altering balance of ventricular pressures (e.g.,
outflow tract obstruction)

ITERMINOlOGY
Abbreviations

and Synonyms

• Ventricular septal defect (VSD)

IIMAGING

FINDINGS

General Features
• Best diagnostic clue
o Defect in ventricular septum
o Small muscular VSDs may not be visible on
grayscale or with color Doppler
• Membranous 8091): Tetralogy of Fallot, truncus
arteriosus
• Muscular 10°/'<>; Trabecular, may be multiple
• Outlet 5%: Infundibular, supracristal, doubly
committed subarterial
o Often associated with aortic insufficiency
• Inlet 5%: Component of an atrioventricular septal
defect

Ultrasonographic

I DIFFERENTIAL DIAGNOSIS

Findings

• Grayscale Ultrasound
o Signal drop out in septum
• Try to image perpendicular to ventricular
• Look for echogenic edge of defect

Imaging Recommendations
• Formal fetal echocardiography
o 50% association with additional cardiac anomaly
• Complete structural survey
o Isolated VSD with extracardiac abnormality, look for
trisomy, deletion syndromes, Holt-Oram

Complete
septum

DDx: Ventricular Septal Defect

AV50-Valve Closed

atrioventricular

septal defect

• Defect involves atrial and ventricular septa
• Common AV valve straddling septal defects

VENTRICULAR

SEPTAL DEFECT

Key Facts
Imaging Findings

• 50% association with additional cardiac anomaly

• Defect in ventricular septum
• Small muscular VSDs may not be visible on grayscale
or with color Doppler
• Right/left ventricular pressures similar in fetus '*
shunt bi-directional
• If unidirectional shunt look for other anomalies
altering balance of ventricular pressures (e.g., outflow
tract obstruction)

Top Differential Diagnoses

Partial atrioventricular septal defect
• Defect involves primum atrial septum not ventricular
septum
• Often associated cleft in mitral valve with mitral
regurgitation

I PATHOLOGY
General Features
• Genetics
o Holt-Oram syndrome: Autosomal dominant
• TBX5 transcription factor gene mutation
• Septal defects, radial ray and other skeletal
malformations
• Etiology
o Teratogen exposure
• Alcohol, phenytoin, rubella, diabetes, oral
contraceptives, phenylketonuria
• Epidemiology
o VSD accounts for 30% of all congenital heart disease
(CHD) in liveborn
• Implies an incidence of 2-3:1,000 total births
o 6% of fetal CHD: Disparity due to demise of fetuses
with more complex CHD and small, missed defects

I CLINICAL

• Complete atrioventricular septal defect
• Partial atrioventricular septal defect

Clinical Issues
• Surgical repair if maximal medical therapy fails
• Large VSD '* risk early decompensation '* consider
delivery at tertiary center

• Follow for development of hydrops: Low-risk with
isolated small VSD
• Monitor growth

I DIAGNOSTIC
Consider

• Majority of VSDs missed on prenatal ultrasound
• Hemodynamically significant lesions are larger '*
more likely to be detected
• Those associated with complex heart disease less likely
to be missed

Image Interpretation

I SELECTED REFERENCES
1.

ISSUES

• Variable, depends on
o Size of defect and degree of left -+ right shunt
o Associated cardiac abnormalities (present in 50%)
• Liveborn, isolated VSD
o > 50% spontaneous closure, usually before age 5
• Surgical repair if maximal medical therapy fails
o Right atrial approach, Dacron or pericardial patch
o Operative mortality < 2%, 5% if multiple defects
o Device closure in cath lab is new technique
• Recurrence risk
o One child 3%, two 10%
o Maternal VSD 6-10%, paternal 2%

Pearls

• Look for septal continuity with aortic annulus in
LVOTview to exclude VSD
• Keep sound beam perpendicular to septum: Avoids
VSD mimic of "dropout" at membranous-muscular
junction

2.

Natural History & Prognosis

CHECKLIST

3.

Paladini D et al: The 'in-plane' view of the inter-ventricular
septum. A new approach to the characterization of
ventricular septal defects in the fetus. Prenat Diagn.
23(13):1052-5, 2003
Paladini D et al: Characterization and natural history of
ventricular septal defects in the fetus. Ultrasound Obstet
Gynecol. 16:118-22,2000
Chao RC et al: Fluctuations of interventricular shunting in
a fetus with isolated VSD. Am Heart]. 127:955-8, 1994

IIMAGE GALLERY

Treatment
• Offer karyotype if extracardiac abnormalities
• Prenatal pediatric cardiology consultation
o Large VSD '* risk early decompensation '* consider
delivery at tertiary center

(Left) Ultrasound shows a high perimembranous
VSD (arrow) in a
fetus with Tetralogy of Fal/ot. (Right) Gross pathology shows a
perimembranous VSD (arrow) in an autopsy specimen of a fetus with
truncus arteriosus (curved arrow).

ATRIOVENTRICULAR

Craphic shows a
a central defect
Vl'ntricular septa.
similar saturations

common AV valve (arrows) straddling
in the heart involving the atrial and
Mixing of blood in the heart results in
in the aorta and MPA.

SEPTAL DEFECT

Ultrasound shows a balanced /IV canal with the
common AV valve equally committed to each ventricle.
Note the inlet ventricular septal defect (arrow) and the
absence of the atrial septum.

ITERMINOlOGY

Ultrasonographic

Abbreviations

• Strong association with trisomy 21 in fetus
o Thickened nuchal fold
o Absent nasal bone
o RhizomeIic limb shortening
o Echogenic bowel
o Pyelectasis
o Clinodactyly
• Strong association with heterotaxy syndromes
o Check situs in all cases
o Look for abnormal systemic veins
• Bilateral superior venae cavae
• Interrupted inferior vena cava
o Look for outflow tract obstruction

and Synonyms

• Endocardial cushion defect
• Atrioventricular canal
• Atrioventricular septal defect (AVSD)

Definitions
• Central defect in heart involving
o Atrial septum (ASD)
o Ventricular septum (VSD)
o Atrioventricular valves
o Abnormal course of conducting system
• Defect can be balanced or unbalanced
o Balanced: Right and left ventricles are equal
o Unbalanced results in equivalent of single ventricle
physiology

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Missing "crux" of heart in four chamber view
• Atrial and ventricular septum meet
atrioventricular (AV) valves at "crux" of heart
o Usual offset of AV valves is absent
o Presence of atrial and ventricular septal defects

DDx: Atrioventricular

Primum ASD

Echocardiographic

Findings

Findings

• Single AV valve makes straight line across heart in
systole
o Tricuspid insertion normally 1-2 mm offset from
mitral insertion
o Offset increases with gestational age, may be up to 7
mm at term
• Defect in inlet ventricular septum
• Defect in primum atrial septum
• "Gooseneck" deformity of left ventricular (LV) outflow
tract
o Elongated, narrowed, somewhat horizontally
inclined LV outflow tract

Septal Defect

Heterotaxy

Heterotaxy

ATRIOVENTRICULAR

SEPTAL DEFECT

Key Facts
Imaging Findings
• Missing "crux" of heart in four chamber view
• Strong association with trisomy 21 in fetus
• Single AVvalve makes straight line across heart in
systole
• Additional cardiac malformations common
• Determine ventricular dominance (balanced or
unbalanced)
• Look for features of heterotaxy syndromes, especially
interrupted inferior vena cava
• Complete heart block (CHB) + AVSD ~ likely
heterotaxy, specifically left atrial isomerism
• Monitor for signs of hydrops

Top Differential Diagnoses
• LargeVSD
• "Partial" AV septal defect

•

•

•

•

o Aortic root is "sprung" due to lack of aortic-mitral
continuity
Additional cardiac malformations common
o Tetralogy of Fallot
o Pulmonary stenosis
o Left heart obstruction
AVvalve regurgitation
o If severe ~ high incidence of hydrops
o Hydrops ~ poor prognosis
Pulsed Doppler
o Used to evaluate presence or absence of valve
obstruction
Color Doppler
o Used to document AVvalve regurgitation
o Helpful to identify flow through VSD and ASD

Imaging Recommendations
• Full anatomic survey for other anomalies
• Formal fetal echocardiography
o Confirm diagnosis
o Determine ventricular dominance (balanced or
unbalanced)
• Impacts surgical outcome
o Evaluate associated cardiac defects
o Look for features of heterotaxy syndromes,
especially interrupted inferior vena cava
o Check rate and rhythm
• Conduction system involvement ~ bradycardia
• Complete heart block (CHB) + AVSD ~ likely
heterotaxy, specifically left atrial isomerism
• Monitor for signs of hydrops
o Pericardia I effusion
o Pleural effusion
o Ascites
o Skin edema
o Cardiomegaly
• Track ratio of heart to chest circumference
o Abnormal Doppler findings
• Reversed flow in vena cava
• Reversed flow in ductus venosus
• Pulsatile umbilical vein flow

• Heterotaxy syndromes

Pathology
Trisomy 21 found in == 40% of fetal cases
Other chromosomal anomalies or syndromes in 20%
Fetal incidence> liveborn
Loss rate reflects high association with
aneuploidy Iheterotaxy 1addi tional cardiac
malformations
• Heterotaxy found in 15-20%
•
•
•
•

Clinical Issues
• Trisomy 21 not independent
surgical outcome
• 5% operative mortality
• 70% 20 year survival rate
• Encourage amniocentesis

risk factor for adverse

I DIFFERENTIAL DIAGNOSIS
large VSD
• AVvalves normal
• Primum atrial septum intact

large ASD
• AVvalves normal
• Ventricular septum intact

"Partial" AVseptal defect
• Primum atrial septal defect
• Cleft anterior mitral leaflet

Heterotaxy syndromes
• Multiple additional cardiac defects
• Right atrial isomerism (RAI)
o Single ventricle
o Right ventricular outflow tract obstruction
• Left atrial isomerism (LAI)
o Interrupted IVC
o Complete heart block

I PATHOLOGY
General Features
• Genetics
o Trisomy 21 found in "" 40% of fetal cases
o Gene encoding alpha l/alpha 2 chains of collagen
VI is on chromosome 21
• Abnormal collagen VI expression hypothesized as
causative factor in AVSDdevelopment
o Other chromosomal anomalies or syndromes in 20%
• Trisomy 18, 13, heterotaxy syndromes
• Etiology
o Embryology
• Endocardial cushions fail to fuse normally
• Primitive AV canal persists after 6 weeks
gestational age
• Epidemiology
o 0.11-0.36/1,000 live births

ATRIOVENTRICULAR
o Partial AVSDmore common than complete in
liveborn
o Comprises 3-7% of congenital heart disease
o Fetal incidence> liveborn
• Loss rate reflects high association with
aneuploidy /heterotaxy / additional cardiac
malformations
• Associated abnormalities
o Heterotaxy found in 15-20%
o Additional cardiac malformations such as Tetralogy
of Fallot, pulmonary stenosis, left heart obstruction
• Found in 10% with trisomy 21
• Found in 33% in non-Down syndrome group

Staging, Grading or Classification Criteria
• Rastelli classification of AVSD
o Type A
• Superior bridging leaflet attached to crest of
ventricular septum
o Type B
• Superior bridging leaflet attached to right side of
ventricular septum
o Type C
• Superior bridging leaflet is free floating from LV
free wall to RV free wall
• Additional classification of right or left dominance in
unbalanced defects

ICLINICALISSUES
Presentation
• Abnormal four chamber view detected on routine
sonography
• Complete AV canal detected as early as 12-14 weeks
with endovaginal scanning

Natural History & Prognosis
• Markers for poor outcome
o Multiple congenital anomalies
o Hydrops
o Heterotaxy syndromes
o Defects which are unbalanced
• Require single ventricle palliation
• Inherent limited life expectancy due to single
ventricular pump
• Even higher risk with trisomy 21
• Trisomy 21 not independent risk factor for adverse
surgical outcome
o Outcome is often better due to redundant AVvalve
tissue
o Natural history affected by high incidence of upper
airway obstruction
• Resultant pulmonary hypertension
• Surgical repair
o 5% operative mortality
o 70% 20 year survival rate
• Recurrence risk
o One child: 3%
o Two children: 10%
o Parent with AVSDand normal chromosomes: 10%
• Higher for affected mother than father

SEPTAL DEFECT
Treatment
• Encourage amniocentesis
o Strong association with aneuploidy
• Offer termination in severe cases
o With multiple additional cardiac anomalies
o With aneuploidy
o With heterotaxy syndromes
• If pregnancy continues, refer to tertiary center for
delivery
• Prenatal consultation with pediatric
cardiology / neona tology
o Follow-up echo for valve regurgitation and function
• Not indication for early delivery or cesarean section
• Management at birth is minimal unless additional
abnormalities
o Infants tolerate oxygen saturations in 80's
• Surgical repair takes place routinely between 4-6
months

I DIAGNOSTIC

CHECKLIST

Consider
• Formal fetal echocardiography

Image Interpretation

in all cases

Pearls

• Down syndrome in"" 40% of isolated AVSD
• AVSD+ CHB = Left atrial isomerism

I SELECTED

REFERENCES

Machlitt A et al: Increased cardiac atrial-to-ventricular
length ratio in the fetal four-chamber view: a new marker
for atrioventricular septal defects. Ultrasound Obstet
Gynecol. 24(6):618-22, 2004
Bronshtein M et al: Accuracy of transvaginal sonography
2.
for diagnosis of complete atrioventricular septal defect in
early pregnancy. Am] Cardiol. 91(7):903-6, 2003
3. Gittenberger-de Groot AC et al: Collagen type VI
expression during cardiac development and in human
fetuses with trisomy 21. Anat Rec A Discov Mol Cell Evol
BioI. 275(2):1109-16, 2003
Fesslova Vet al: Spectrum and outcome of atrioventricular
4.
septal defect in fetal life. Cardiol Young. 12(1):18-26,2002
5. Digilio MC et al: Familial recurrence of nonsyndromic
interrupted aortic arch and truncus arteriosus with
atrioventricular canal. Teratology. 61(5):329-31, 2000
Pierpont ME et al: Genetic aspects of atrioventricular septal
6.
defects. Am] Med Genet. 97(4):289-96, 2000
Vaughan C] et al: Molecular determinants of atrial and
7.
ventricular septal defects and patent ductus arteriosus. Am
] Med Genet. 97(4):304-9, 2000
Allan LD: Atrioventricular septal defect in the fetus. Am]
8.
Obstet Gynecol. 181(5 Pt 1):1250-3, 1999
Park]K et al: Dilated coronary sinus in the fetus:
9.
misinterpretation as an atrioventricular canal defect.
Ultrasound Obstet Gynecol. 10(2):126-9, 1997
10. Achiron R et al: First trimester diagnosis of fetal congenital
heart diseases by transvaginal ultrasonography. Obstet
Gynecol. 84:69-72, 1994
1.

ATRIOVENTRICULAR
IIMAGE

SEPTAL DEFECT

GALLERY
(Left)

Cross pathololiY

a fetus with
atrioventricular
The plane

from

an
Sl'ptal

of section

(/e/I'Ct.
mimics

axis view and shows

a short
a single

common

atrioventricular
(curved

valve

arrows).

I here was

also pulmonary
hence

hypoplasia,

the small si/e

lungs

(open

Clinical

of the

(Right)

arrow').

photograph

show,

the characteristic
of a chilel II'ith

appearance
trisomy
4()°j"

21. Approximatel)'

of fetuses

Ivith

atrioventricular

septal

have trisomy

cle/I'ct

21.

(Left) Color

Doppler

ultrasound

in a fetus with

AVSO shows
deformity

"gooseneck"

of the left

ventricular

outflow

laminar

flow

(curved

arrow)

left-sided

tract with

in the aorta
ancl milcl

AV valve

regurgitation

(Right)

(arrow).

view shows

Four chamber

AVSO in a fetus with
atrial

isomerism

- common

atrium).

vessels behind
(arrows).
aorta

left

(open

two

the heart

The descending

is normally

location,

seen in this

the posterior

is the enlarged

view in

an unbalanced

AVSO shows

small left (LV)

and large right
ventricles.

vessel

azygos.

(Left) Four chamber
a fetus with

(RV)

Note

atrial septal

(Right)

arrow

Note

primum

clell'ct

(arrmv).

Postnatal

echocardiogram

in the same

patient

an

confirms

unbalanced

AV canal

small

left ventricle

atrial

septum

the primum

(arrow)
component

there is a VSO (curve(1
arrow).

with a

(LV). The
lacks
and

HYPOPLASTIC

Graphic shows mitral and aortic atresia. There is
asymmetry of ventricular size with the RV being apex
forming. The aortic arch is hypoplastic and fills
retrogradevia the ductus.

LEFT HEART

Four chamber view shows a thick-walled, small left
ventricle (arrow) which does not reach the apex. The
foramen ovale flap (open arrow) opens into the right
atrium indicating L to R shunting at the atriallevel.

ITERMINOLOGY
Abbreviations

and Synonyms

• Hypoplastic left ventricle
• Hypoplastic left heart syndrome (HLHS)
• Endocardial fibroelastosis

•

Definitions

•
•
•

• Hypoplasia of left ventricle associated with
o Mitral stenosis/atresia
o Aortic stenosis/atresia
o Hypoplastic ascending aorta

IIMAGING

FINDINGS

General Features

•

• Best diagnostic clue: Abnormal four chamber view
with small, non apex-forming left ventricle

Echocardiographic

Findings

Imaging Recommendations

• Left ventricle (LV)
o Small or non-existent
o Hypocontractile
o May be globular
o May see brightly echogenic LVendocardium with
endocardial fibroelastosis
• Right ventricle

DDx: Hypoplastic

o Looks large
o Good function
o Apex-forming
Atria
o Inter-atrial septum bowed left to right
• Only outlet for flow in LA
o Occasionally restrictive septum
Ascending and transverse arch very small
Ductus arteriosus (DA) large
Color Doppler
o Confirms absent or minimal flow across mitral valve
o Confirms absent or minimal flow across aortic valve
o Left to right shunt across foramen ova Ie
o Retrograde filling of arch = ductal dependence
o May see ventriculocoronary connections
o Evaluate for presence of tricuspid regurgitation
Pulsed Doppler
o Direction of flow through foramen ovale
o Direction of flow in aortic arch
o Presence of flow across mitral and aortic valves

• Formal fetal echocardiogram
o Tricuspid and mitral valve size and function
o Pulmonary and aortic valve size and function
o LVhypoplasia
• Endocardial fibroelastosis
o Coarctation of the aorta

left Heart Syndrome

.'- ...•.•.::- -,~,
i-~

l·"-/~~
/\
..
- --"

.....•.
;,..

'

I:: ~"'A'~

---~...
-~~
-

\

. \

I
.~
_.

\

~;

.

.

\

'.W'

__

~

~
-

.Coarctation Of Aorta

Aortic Stenosis

HYPOPLASTIC
Imaging Findings

Key Facts
Clinical Issues

• Best diagnostic clue: Abnormal four chamber view
with small, non apex-forming left ventricle
• May see brightly echogenic LVendocardium witH
endocardial fibroelastosis
• Inter-atrial septum bowed left to right
• Ascending and transverse arch very small
• Ductus arteriosus (DA) large'
• Left to right shunt across foramen ovale
• Retrograde filling of arch = ductal dependence
• Non-cardiac anomalies in 9% of autopsy cases

Top Differential Diagnoses
• Double inlet left ventricle
• Severe aortic stenosis
• Coarctation of aorta

• Seen in the majority if not all
o Presence of L -+ R shunting through foramen ovale
• Full anatomic survey
o Non-cardiac anomalies in 9% of autopsy cases
o Includes major central nervous system anomalies
such as holoprosencephaly
• Significant adverse impact on prognosis

IDIFFERENTIAL DIAGNOSIS
Double inlet left ventricle
• L-Iooping of heart
• Single ventricle with bulboventricular foramen
• Usually two normal atrioventricular (AV)valves
(mitral and tricuspid)
• Usually two normal semilunar valves (aorta and
pulmonary)

Severe aortic stenosis
• Antegrade flow across aortic valve
• Mitral valve may be normal in size
• LVmay be apex forming

Coarctation of aorta
•
•
•
•
•

Antegrade flow across aortic valve
Mitral valve may be normal in size
LVmay be apex forming
Flow may be R -+ L or L -+ R at atrial level
Consider association with Turner and Shone
syndromes

I PATHOLOGY
General Features
• Genetics
o Autosomal recessive transmission has been
suggested
• Multiple siblings
o Turner syndrome (4S,XO)
• 13% fetuses have HLHS
o Trisomy 18

LEFT HEART

• Most severe congenital heart lesion presenting in
neonate
• Lethal in days/weeks if untreated
• 20% intrauterine fetal demise
• Long-term survival approximately 30 years
• Chromosomal abnormality in 2-10%
• Surgical intervention ~ planned delivery at tertiary
center
• Heart transplantation ~ delivery at select institutions
nationally
• Three-stage surgical palliation most common
• Balloon valvuloplasty of fetal aortic valve in cases of
severe aortic stenosis in hopes of preventing
progression to HLHS

o Transcription factor gene mutations
• Etiology
o Multiple theories with no single unifying
explanation
• Multifactorial in most cases
o Structural defect early in cardiac development
• May be secondary to transcription factor gene
mutations
o "Form follows function"
• Aortic atresia ~ no flow out of LV ~ hypoplasia
• Mitral atresia ~ no flow into LV ~ hypoplasia
o Viral infection ~ myocarditis
o Embryology
• Abnormal partitioning of primitive conotruncus
into left and right ventricular outflow tracts
• Hypoplasia/atresia of aortic valve
• Diminished antegrade flow through aorta
• ! Flow ~ LV/aortic underdevelopment
• Epidemiology
o 9% congenital heart disease
00.16:1,000 live births
o M:F = 3:1

Gross Pathologic & Surgical Features
• LVendocardium opaque, glistening, milky white in
endocardial fibroelastosis
o Diffusely thickened to 1-2 mm
o Thickening most marked in outflow tract

IClINICAllSSUES
Presentation
• Most cases detected on routine 18-20 week scan
• Abnormal four chamber view

Natural History & Prognosis
• Most severe congenital heart lesion presenting in
neonate
• Lethal in days/weeks if untreated
• Prenatal diagnosis
o 20% intrauterine fetal demise

HYPOPLASTIC
o Termination depends on many factors but
decreasing in frequency, at least in USA
• Due to improved surgical outcomes
o Pregnancy termination rate and parental "intention
to treat" different in USA and Europe
• USA intention to treat: 67%
• Europe intention to treat: 34-36%, termination
rate ~ 50%
• Better perinatal stabilization = better surgical
candidate
o "Maternal" transport
o Prostaglandin infusion started immediately
• Improving surgical techniques = increased survival
o 80% success of first stage Norwood
o Near 100% for Glenn and Fontan (2nd and 3rd
stage)
o Long-term survival approximately 30 years
• May be improving in current era due to many
factors
• Recurrence risk
o 2% with one sibling, 6% with two
o Familial cases with autosomal recessive pattern in
some kindreds: 25% recurrence risk

Treatment
• Offer karyotype
o Chromosomal abnormality in 2-10%
• Turner syndrome most common
• Prenatal consultation with neonatology/pediatric
cardiology
• Offer termination
• If pregnancy continues
o Comfort care ~ no intrapartum monitoring, deliver
at any institution
o Surgical intervention ~ planned delivery at tertiary
center
o Heart transplantation ~ delivery at select
institutions nationally
• Three-stage surgical palliation most common
o Stage 1 (Norwood)
• First week of life
• Construction of neo-aorta from pulmonary artery,
aorta and graft
• Atrial septectomy
• Pulmonary blood flow supplied by Blalock Taussig
shunt or RV-pulmonary conduit (Sano
modification)
o Stage 2 (Glenn)
• 3-6 months
• Superior vena cava to right pulmonary artery
• Hemi-Fontan also performed in some institutions
o Stage 3 (Fontan)
• 2-3 years
• Inferior vena cava to right pulmonary artery
conduit
• Fenestration in conduit to right atrium used as a
pop-off for systemic blood flow
• Randomized controlled trial starting in 2005 to
compare Sano modification with standard
Norwood/Blalock Taussig shunt
• Balloon valvuloplasty of fetal aortic valve in cases of
severe aortic stenosis in hopes of preventing
progression to HLHS

LEFT HEART
o Selection criteria
• Prior to 20 weeks gestation if possible
• LVneeds to be large in size
• Prior to development of endocardial fibroelastosis
o Performed in only a few centers nationally
• Preliminary results improving with experience and
selection
• Majority end up with single ventricle
• Heart transplant
o 15-20% mortality on transplant list
o 70% 5 yr survival
• Most mortality within first 30 days

I DIAGNOSTIC

CHECKLIST

Consider
• Fetal echo cardiography very specific for this entity
o 95% prenatal diagnoses confirmed

Image Interpretation

Pearls

• Left ventricle non apex-forming
• Small to non-existent mitral/aortic valves

I SELECTED

REFERENCES

Ikle L et al: Developmental outcome of patients with
hypoplastic left heart syndrome treated with heart
transplantation. J Pediatr. 142(1):20-5, 2003
2. Verheijen PM et al: Prenatal diagnosis of the fetus with
hypoplastic left heart syndrome management and
outcome. Herz. 28(3):250-6, 2003
3. Meyer-Wittkopf M: Interventional fetal cardiac
therapy-possible perspectives and current shortcomings.
Ultrasound Obstet GynecoI20:527-31, 2002
4.
Nield LE et al: Endocardial fibroelastosis associated with
maternal anti-Ro and anti-La antibodies in the absence of
atrioventricular block. JAm Coll Cardio!. 40(4):796-802,
2002
5. Jenkins PC et al: Survival analysis and risk factors for
mortality in transplantation and staged surgery for
hypoplastic left heart syndrome. J Am Coll Cardio!.
36(4):1178-85,2000
6. Satomi G et al: Has fetal echocardiography improved the
prognosis of congenital heart disease? Comparison of
patients with hypoplastic left heart syndrome with and
without prenatal diagnosis. Pediatr Int. 41(6):728-32, 1999
Grobman W et al: Isolated hypoplastic left heart syndrome
7.
in three siblings. Obstet Gyneco!. 88(4 Pt 2):673-5, 1996
8.
Norwood WI: Hypoplastic left heart syndrome. Ann Thorac
Surg. 52:688-95, 1991
9.
Brenner JI et al: Cardiac malformations in relatives of
infants with hypoplastic left-heart syndrome. Am J Dis
Child. 143(12):1492-4, 1989
10. Shokeir MH: Hypoplastic left heart. Evidence for possible
autosomal recessive inheritance. Birth Defects Orig Artie
Ser. 10(4):223-7, 1974
1.

HYPOPLASTIC

LEFT HEART

I IMAGE GALLERY
Typical
(Left) Four chamber view
color Doppler ultrasound
shows no antegrade flow
into the left ventricle (LV)
and L to R shunting at the
atrial level through the
foramen ovale into the right
atrium (arrow). (Right) Four
chamber view shows a small,
non apex-forming left
ventricle (LV) in a fetus with
endocardial fibroelastosis.
Note the high echogenicity
of the left ventricular walls
(arrows).

(Left) Color Doppler
ultrasound demonstrates
absence of flow across the
mitral valve. Normal blood
flow is apparent through the
tricuspid valve into the right
ventricle (arrow). (Right)
Cross pathology shows a
hypoplastic aortic arch
(curved arrow) in
comparison to the
pulmonary artery (open
arrow) in a case of
hypoplastic left heart
syndrome.

Variant
(Left) RVOT view shows a
very large pulmonary artery
(arrow) giving rise to the
ductus arteriosus (curved
arrow) and right pulmonary
artery. (Right) LVOT view in
the same case shows a
hypoplastic aorta marked by
calipers. This fetus also had a
Dandy Walker malformation,
single umbilical artery and
abnormal situs. Hydrops
developed and the infant
died shortly after birth.

COARCTATION

Craphic shows coarctation (curved arrow) distal to the
head and neck vessels, with hypoplasia
of the
ascending aorta (arrow). Blood flow in the descending
aorta (open arrows) is mainly from the ductus.

ITERMINOlOGY
Abbreviations

and Synonyms

• Coarctation of aorta (CoA)
• Interrupted aortic arch (IAA)

Definitions
• Coarctation: Narrowing of distal aortic arch
• Interrupted arch: Occlusion of aortic lumen
• Aortic isthmus: That part of the aorta distal to left
subclavian takeoff and proximal to insertion of ductus
arteriosus

IIMAGING FINDINGS
Echocardiographic

Findings

• Asymmetry in ventricular size
o Mean right:left ventricular diameter ratio 1.69 ± 0.16
in affected fetuses
• 1.19 ± 0.08 in normal fetuses
• Pulmonary artery> aorta
• Quantitative hypoplasia, transverse arch and isthmus
o Normative data available
o Transverse arch measurements < 3rd percentile for
gestational age in fetuses with CoA
o Verify apparent areas of narrowing from several scan
planes

OF THE AORTA

Sagittal oblique
ultrasound
shows
the
normal
appearance of the fetal aortic arch, which has a "candy
cane" curve (arrows). The head and neck vessels
(curved arrows) are easily scen arising ti-om the arch.

• Color Doppler
o May show focal turbulence at narrowed area
o Left-to-right shunt across foramen ovale with left
ventricular outflow obstruction
• t Left ventricular (LV) pressure => t left atrial (LA)
pressure => flow direction at foramen ova Ie
changes, becomes left to right
• Pulsed Doppler
o May show increased velocity distal to coarctation
o Also used to assess mitral/tricuspid flow
• Flow across tricuspid may be > 2x that across
mitral valve
• Interrupted arch
o Normal "candy cane" curve not seen
o Arch gives rise to one or more head and neck vessels
which extend straight into neck
o Descending aorta reconstituted by ductus arteriosus

Imaging Recommendations
• Formal fetal echocardiogram for associated
malformations
o Bicuspid valve
• May have associated aortic stenosis
o Conotruncal malformations
o Mitral valve disease
• Supravalvar mitral ring
• Parachute mitral valve
o Ventricular septal defects in 500ill

DDx: Ventricular Asymmetry

Normal At Birth

Aortic Stenosis

EFE-HLHS

Cardiomyopathy

COARCTATION

OF THE AORTA

Key Facts
Terminology

Pathology

• Qarctation:
arrowing of distal aortic arch
• Interrupted arch: Ocelu ion of aortic lumen

• Turner syndrome (45,XO)
• 22qll deletion (Oi George syndrome)
• Fetu of diabetic moth r 3-5% ri k

Imaging Findings
Asymmetry in ventricular size
Pulmonary artery> aorta
Quantitative hypopla ia, transverse arch and isthmus
May show focal turbulence at narrowed area
Left-to-right shunt across foramen ovale with left
ventricular outflow ob truction
• Ventricular septal defect in 50lyo

Clinical Issues

Top Differential

• oarctation is extremely diffi ult diagno is in utero
• At-risk fetus with normal study still needs postnatal
evaluation
• ormallooking
arch doe not exclude coarctation

•
•
•
•
•

Diagnoses

• Sp ctrum of left heart outflow ob truction
• Other causes of ventricular a ymmetry

• Careful survey for additional extra cardiac
malformations
o Lower trunk/lower extremity malformations
• Attributed to vascular disruption
o Turner syndrome
• Cystic hygroma
• Female genitalia
• Often hydropic
• Characteristic finding is "domed" pedal edema

I DIFFERENTIAL

DIAGNOSIS

Spectrum of left heart outflow

obstruction

• Aortic stenosis (AS)
o Valve may be thickened
o Small ascending and transverse arch due to
decreased flow
o Retrograde flow around arch in severe cases
• Hypoplastic left heart syndrome (HLHS)
o Left ventricle is not apex-forming
o Severe mitral stenosis/atresia
o Severe aortic stenosis/atresia
• Endocardial fibroelastosis (EFE)
o Highly echogenic endocardium
o LV may be globular and dilated
o LV may also be normal or small in size
o Occurs as part of hypoplastic left heart syndrome

Other causes of ventricular

asymmetry

• Right heart enlargement
o Pulmonary valve stenosis/atresia
o Shunt lesions with increased venous return
• Use color Doppler to look for arteriovenous
malformations
• Fetal tumors are large at presentation, easily seen
o Incipient hydrops
• Check for rhythm disorders
• Check for signs of infection
• Check for signs of anemia
o Placental insufficiency
• Associated with growth restriction
• Oligohydramnios

• Arch hypoplasia may progress over course of
gestation
• oal at delivery is to maintain ductal patency as
y temic perfusion i duct dep ndent
• Definitive treatment is primary surgical repair

Diagnostic Checklist

I PATHOLOGY
General Features
• Genetics
o Turner syndrome (45,XO)
• 10-15% of Turner syndrome patients have CoA
• 45% Turner syndrome fetuses have CoA
o 22qll deletion (Di George syndrome)
• Present in > 50% of interrupted aortic arch cases
• Right sided aortic arch with aberrant left
subclavian more common
• Etiology
o Fetus of diabetic mother 3-5% risk
o Phenytoin
o Has been described in warfarin/Coumadin
embryopathy
• Epidemiology
o Up to 8% all congenital heart disease
o 0.2-0.6:1,000 live births
o M = F at birth
o Female more common in fetuses because of Turner
syndrome cases, which often have in utero demise
• Associated abnormalities
o Cardiac malformations in 85%
• Bicuspid aortic valve in 20%
o Non-cardiac 13%
• Embryology: Three theories
o Anomalous ductal tissue encircles arch causing local
constriction
o Failure of connection 4th and 6th branchial arches
to descending aorta
o Abnormal flow patterns in developing heart
•
.j. Aortic arch flow ~ hypoplasia

Staging, Grading or Classification

Criteria

• CoA
o Isolated coarctation
o Coarctation + ventricular septal defect
o Coarctation + complex intracardiac anomalies
• Interrupted aortic arch
o Type A: Distal to left subclavian

COARCTATION OF THE AORTA
o Type B: Between left common carotid and
subclavian arteries (most common)
o Type C: Between innominate and left common
carotid (rarest)

ICLINICAL

ISSUES

Presentation
• Abnormal nuchal thickness in first trimester
o Marker for aneuploidy and congenital heart disease
• Ventricular asymmetry RV > LV
o Nonspecific finding observed on four chamber view
• Transverse arch hypoplasia

Natural History & Prognosis
• Arch hypoplasia may progress over course of gestation
o 6/7 fetuses in one series showed progressive arch
hypoplasia
o 3/7 fetuses developed reversal of flow in ductus
arteriosus despite antegrade flow at diagnosis
• Turner syndrome in fetus carries poor prognosis
• Prognosis in CoA depends on associated anomalies
and timing of diagnosis
o Early arch repair straightforward with excellent
outcomes
• Normal life expectancy
• Restenosis 10-15%
o Delayed diagnosis in severe cases
• Cardiovascular collapse at presentation
o Delayed diagnosis in mild cases
• Develop systemic hypertension in upper
extremities
• Outcomes less favorable due primarily to added
secondary morbidity
• CoA + left heart hypoplasia, midterm follow-up =>
substantial growth of left heart structures after repair
o 55 neonates with CoA + at least one hypoplastic left
heart valve
o All alive and well at mean follow-up of 73 months
(range 3-9 yrs)
• 69% with normal LV size and function
• 16% developed LVOT obstruction by
echo cardiographic criteria
• Interrupted aortic arch
o Rarely occurs in isolation
o Common associations are truncus arteriosus,
transposition, double outlet right ventricle and
single ventricle
• Natural history will depend on associated lesions
in conjunction with arch repair
• Recurrence risk CoA
o One affected sibling 2%
o Two affected siblings 6%
o Affected mother 4%
o Affected father 2%

Treatment
• Offer karyotype
o In patients with interrupted aortic arch, fluorescent
in situ hybridization (FISH) for 22q 11 deletion
o In females with coarctation for Turner syndrome
• Prenatal consultation with pediatric
cardiology /neona tology

• Deliver at tertiary center
• Goal at delivery is to maintain ductal patency as
systemic perfusion is duct dependent
o Prostaglandin infusion
o Avoid supplemental oxygen
• Definitive treatment is primary surgical repair
o Resection with extended end-to-end anastomosis
• Operative repair < 1% mortality in experienced
hands
o Subclavian flap aortoplasty, rare
o Patch aortoplasty, rare
• Balloon angioplasty
o Associated with restenosis
o Now reserved for re-coarctation and late diagnoses
with stent implantation

I DIAGNOSTIC

CHECKLIST

Consider
• Coarctation is extremely difficult diagnosis in utero
o At-risk fetus with normal study still needs postnatal
evaluation

Image Interpretation

Pearls

• Normal looking arch does not exclude coarctation

I SELECTED REFERENCES
Puchalski MD et al: Follow-up of aortic coarctation repair
in neonates. J Am Coli Cardio!. 44(1): 188-91, 2004
2. Walhout R] et al: Comparison of surgical repair with
balloon angioplasty for native coarctation in patients from
3 months to 16 years of age. Eur J Cardiothorac Surg.
25(5):722-7, 2004
Chan KYet al: Warfarin embryopathy. Pediatr Pathol Mol
3.
Med. 22(4):277-83, 2003
4.
Rao PS et al: Severe aortic coarctation in infants less than 3
months: successful palliation by balloon angioplasty. J
Invasive Cardio!. 15(4):202-8,2003
5. Surerus E et al: Turner's syndrome in fetal life. Ultrasound
Obstet Gyneco!. 22(3):264-7, 2003
6. Zeltser I et al: Midaortic syndrome in the fetus and
premature newborn: a new etiology of nonimmune
hydrops fetalis and reversible fetal cardiomyopathy.
Pediatrics. 111(6 Pt 1):1437-42, 2003
7.
Backer CL et al: Congenital Heart Surgery Nomenclature
and Database Project: patent ductus arteriosus, coarctation
of the aorta, interrupted aortic arch. Ann Thorac Surg. 69(4
Suppl):S298-307, 2000
Towbin]A et al: Molecular determinants of left and right
8.
outflow tract obstruction. Am] Med Genet. 97(4):297-303,
2000
Hornberger LK et al: Antenatal diagnosis of coarctation of
9.
the aorta: a multicenter experience. J Am Coli Cardio!.
23(2):417-23, 1994
10. Sharland GK et al: Coarctation of the aorta: difficulties in
prenatal diagnosis. Br Heart]. 71(1):70-5, 1994
11. Lacro RV et al: Coarctation of the aorta in Turner
syndrome: a pathologic study of fetuses with nuchal cystic
hygromas, hydrops fetalis, and female genitalia. Pediatrics.
81(3):445-51, 1988
1.

COARCTATION OF THE AORTA
IIMAGE GALLERY
(Left) Sagittal
a 1('lus with
the aorta

of

marked

of the isthmus

(arrow).

The ascending

aorta

and head and neck

(H&N)

vessels are visible

but

(Right) Sd.~illdl ohlique

small.

postnatal
\vith

scan in

shows

narrowing
(Asc)

oblique
coarctation

echucdreliogram

the transducer

in the

sternal

notch

caliber

of the ascending

aorta

shows

normal

(Asc A), and head

vessels (InA,

LCC). There is

isthmus

hypoplasia

"shelf"

(arrow)

resulting

and a

posteriorly

in a coarctation.

Typical
(left)

ohliclU<' 30 MR

Sagittal

angiogram

shows

of the aorta
distal

to the origin

subclavian
arrow).

artery

Note

(open

(curved

arising

vessel
from

(Right) Cross
shows a hydropic

the arch.
fetus with

Turner syndrome.

There is a cystic
(arrows)
edema

just
of the left

collateral

arrow)

pathology

and

hygroma

"domed"

over the dorsum

the hands
arrows).
aorta

coarctation

(arrow)

Coarctation

Turner

syndrome

(Left)

Ultrasound

ventricular

of the

in 45% of

is present

(arrow)

of

and feet (curved

fetuses.

shows

septal

a

defect

in a fetus with

an

interrupted
arch. The aorta
(A) is smaller than (he
artery

Ultrasound

of an interrupted

aortic

arch shows

ascending

aorta

to the superior
(SVC).

the
(;\) parallel

vena cava

The vessel extends

craniad

without

curvature

(h(' normal

of the arlh.

Interrupted

aortic

high association
deletion

(P)

(Right)

pulmonary

arch has a
with

22q 77

and kal")'otyping

recommend('d

is

AORTIC STENOSIS

Graphic shows small aortic annulus with a thickened
valve (curved arrow), hypoplastic ascending aorta
(arrow) and thickened LV myocardium (open arrow).
The insert shows a bicuspid valve end-on.

ITERMINOLOGY
Abbreviations

and Synonyms

• Aortic stenosis (AS)
• Left ventricular outflow tract obstruction (LVOTO)

Definitions
• Obstruction to flow across aortic valve
o Valvar
o Subvalvar: Fixed or dynamic
o Supravalvar (SVAS)

IIMAGING

FINDINGS

Echocardiographic

Findings

• Left ventricle (LV)may be large, small or normal in
size
o May see concentric hypertrophy
o May see bright walls Le., endocardial fibroelastosis
(EFE)

o LVfunction usually decreased
o Right ventricle (RV) may be large to compensate
cardiac output
• Thickened valve leaflets
• Valve often bicuspid (difficult to see in fetus)
• Subvalvar aortic (subaortic) stenosis
o Muscular: Look for asymmetric septal hypertrophy

Ultrasound shows a "globular", dilated ·Ieft ventricle
(LV) with echogenic walls (arrows) in a fetus with aortic
stenosis.

o Fibrous: Membrane from septum to mitral valve
o Turbulent flow starts below valve in subvalvar AS
• Supravalvar aortic stenosis
o Turbulent flow starts above valve in supravalvar AS
• Color Doppler
o Turbulent flow in left ventricular outflow tract
(LVOT)or across valve
o Critical AS '* minimal flow in aorta
• Retrograde filling of arch via ductus arteriosus
o Mitral regurgitation from increased LVpressure
o Left-to-right shunt across foramen ovale
• Normal flow at foramen ovale is right to left
• Left heart outflow obstruction '* ~ flow left
atrium to left ventricle
• Left atrial pressure t '* flow direction at foramen
ovale changes, becomes left to right
• Pulsed Doppler
o Used to measure gradient across, above and below
the aortic valve
• Pressure drop difficult to interpret due to presence
of patent ductus arteriosus (PDA)

Imaging Recommendations
• Formal fetal echocardiogram
o 30% of fetuses have additional cardiac anomalies
• Coarctation/interrupted
aortic arch
• Ventricular septal defect (VSD)

DDx: Aortic Stenosis

EFE

HLHS

Coarctation

Cardiomyopathy

AORTIC STENOSIS
Key Facts
Pathology

Terminology

• 2-3% all congenital heart disease
• 3.5:10,000 live births

• Obstruction to flow across aortic valve

Imaging Findings
• Left ventricle (LV) may be large, small or normal it;l
size
• May see concentric hypertrophy
• LVfunction usually decreased
• Right ventricle (RV) may be large to compensate
cardiac output
• Retrograde filling of arch via ductus arteriosus '
• Left-ta-right shunt across foramen ovale
• 30% of fetuses have additional cardiac anomalies

Clinical Issues

Top Differential Diagnoses

• AS may progress to HLHS in utero
• Use color Doppler to determine origin of turbulent
flow

• Hypoplastic left heart syndrome (HLHS)
• Cardiomyopathy

•

•
•
•

•

o Pulsed Doppler interrogation of all valves required
to look for stenosis/regurgitation
Consider Shone syndrome
o Valvar/subvalvar AS
o Coarctation of aorta
o Mitral stenosis
Full fetal anatomic survey
Monitor for growth restriction: t Risk due to poor
placental perfusion
Monitor for hydrops
o Most likely to occur with severe mitral regurgitation,
LVdysfunction
Monitor for progression to hypoplastic left heart
syndrome (HLHS)
o Postnatal management more complex than isolated

AS

I DIFFERENTIAL DIAGNOSIS
Hypoplastic left heart syndrome (HlHS)
• LVnot apex-forming
• Typically associated with aortic and mitral atresia
• May occur as end result of critical AS in utero

Coarctation of aorta/interrupted

aortic arch

• Look for isthmus hypoplasia
• AS, coarctation, HLHS all part of a spectrum of left
ventricular outflow tract obstruction
o Differentiation may not be possible

• Prognosis varies with severity of obstruction
associated anomalies
• Balloon valvuloplasty of fetal aortic valve in
severe AS in hopes of preventing progression
• Prostaglandins required at birth to maintain
of ductus arteriosus
• Survivors need lifetime follow-up

and
cases of
to HLHS
patentcy

Diagnostic Checklist

I PATHOLOGY
General Features
• Genetics
o Supravalvar AS
• Autosomal dominant: William syndrome
o Turner syndrome 45,XO
• Etiology
o Valvar:
• Bicuspid valve: Thick dysplastic leaflets
o Subvalvar: Muscular
• Asymmetric septal hypertrophy
• Idiopathic hypertrophic subaortic stenosis
• Hypertrophic obstructive cardiomyopathy
o Subvalvar: Membranous
• Subaortic membrane
o Supravalvar: Narrowing in proximal ascending aorta
• William syndrome: Gene deletion for elastin ELN
on 7q11.23
• Epidemiology
o 2-3% all congenital heart disease
o 3.5:10,000 live births
o In liveborn
• 60-75% valvar
• 8-20% subvalvar
• Supravalvar: rare
o M:F up to 4:1 for valvar/subvalvar stenosis
o M:F = 1:1.2 for supravalvar stenosis

Cardiomyopathy

I CLINICAL

• Intrinsic myocardial abnormality not secondary to
valve disease
o Associated with decreased LVfunction
• Fetus of diabetic mother: t Incidence hypertrophic
cardiomyopathy
o Maximum thickening seen in interventricular
septum
o Resolves spontaneously by 6 months of age

• Has been detected at < 16 weeks gestational age on
endovaginal ultrasound
• Most common fetal presentation is abnormal four
chamber view detected on routine antenatal screen

ISSUES

Presentation

Natural History & Prognosis
• Prognosis varies with severity of obstruction and
associated anomalies

AORTIC STENOSIS

•

•

•
•

•

•

o Mild valvar stenosis « 40 mmHg) progresses slowly,
intervention more common by 4th to 6th decade
o Moderate or greater valvar stenosis (> 40 mmHg)
may require surgical or non-surgical intervention
• Untreated => pediatric sudden death
o Fetal cases tend to be more severe with progression
to HLHS described
Supravalvar AS rarely requires intervention in infancy
but progresses with time
o Coronary artery stenoses common cause of sudden
death
o William syndrome has associated mental
retardation, "elfin" facies, peripheral pulmonary
stenosis
Subvalvar AS diagnosed in childhood and usually
progresses
o May be associated with isolated VSD
o Often causes aortic regurgitation prompting earlier
treatment
Operative mortality 8% overall
o Up to 33% for neonates with critical AS
Long term outcome
o 10 yr survival> 90%
o 25 yr survival 73%
Reoperative rates
o 24% over mean 8 yr follow-up
o Actuarial curves predict 62% lifetime free of
reoperation
Recurrence risk for valvar AS
o One sibling 2%
o Two siblings 6%
o Affected mother 13-18%
o Affected father 3%

Treatment
• Prenatal consultation with pediatric
cardiology/neonatology
o Counsel parents regarding risk of progression
o Offer karyotype
• Balloon valvuloplasty of fetal aortic valve in cases of
severe AS in hopes of preventing progression to HLHS
o Prior to 20 weeks if possible
o LV needs to be large in size
o Prior to development of EFE
o Performed in only a few centers nationally
• Results improving with experience and technique
• Majority of patients still end up with single
ventricle
• Prostaglandins required at birth to maintain patentcy
of ductus arteriosus
• Balloon valvuloplasty is first line therapy if ventricle
adequate in size
o Rhodes score useful: Echocardiographic scoring
system taking into account
• Body surface area
• Mitral valve and aortic root size
• Ratio long axis of LV to long axis of heart
• Surgical aortic valve repair/replacement
common in
lifetime
o Aortic root replacement often necessary at same
time if dimension> 40 mm
• Bicuspid aortic valve may be asymptomatic
o Screen family members

• Found in first degree relatives of proband
o Increased risk of bacterial endocarditis
o Eventual significant AS development possible later
in life :::::50 years of age
• Survivors need lifetime follow-up

I DIAGNOSTIC

CHECKLIST

Consider
• Prenatal diagnosis of valvar stenosis is possible
o Sub/supravalvular stenosis very rarely diagnosed,
often not even clinically apparent in neonate
• AS may progress to HLHS in utero

Image Interpretation

Pearls

• Use color Doppler to determine origin of turbulent
flow
o SVAS:Turbulence starts above the valve
• Associated with William syndrome
o Subvalvar stenosis: Turbulent flow starts below the
valve

I SELECTED
1.

2.

3.

4.

5.
6.

7.

8.
9.

10.

11.

12.

13.

14.

REFERENCES

Brown )W et al: Surgery for aortic stenosis in children: a
40-year experience. Ann Thorac Surg. 76(5):1398-411,2003
Saxena A et al: Aortic valve balloon dilatation in a
newborn for critical aortic stenosis diagnosed during fetal
life. Indian Heart J. 53(1):95-6, 2001
Kohl T et ai: World experience of percutaneous
ultrasound-guided
balloon valvuloplasty in human fetuses
with severe aortic valve obstruction. Am) Cardio!.
85(10):1230-3,2000
Elkins RC et al: Congenital aortic valve disease. Improved
survival and quality of life. Ann Surg. 225(5):503-10;
discussion 510-1, 1997
Simpson)M et al: Natural history and outcome of aortic
stenosis diagnosed prenatally. Heart. 77(3):205-10, 1997
Berning RA et al: Reversed shunting across the ductus
arteriosus or atrial septum in utero heralds severe
congenital heart disease.) Am Coil Cardio!. 27(2):481-6,
1996
Gildein HP et al: Surgical commissurotomy
of the aortic
valve: outcome of open valvotomy in neonates with
critical aortic stenosis. Am Heart J. 131(4):754-9, 1996
Lopes LM et al: Balloon dilatation of the aortic valve in the
fetus. A case report. Fetal Diagn Ther. 11(4):296-300, 1996
Allan LD et al: Survival after fetal aortic balloon
valvoplasty. Ultrasound Obstet Gynecol. 5(2):90-1, 1995
Hornberger LK et al: Left heart obstructive lesions and left
ventricular growth in the midtrimester fetus. A
longitudinal study. Circulation. 92(6):1531-8,1995
)ouk PS et al: Prediction of outcome by prenatal Doppler
analysis in a patient with aortic stenosis. Br Heart).
65(1):53-4, 1991
Morris CD et al: 25-year mortality after surgical repair of
congenital heart defect in childhood. A population-based
cohort study. )AMA. 266(24):3447-52, 1991
Sharland GK et al: Left ventricular dysfunction in the fetus:
relation to aortic valve anomalies and endocardial
fibroelastosis. Br Heart). 66(6):419-24, 1991
Nora )) et al: Update on counseling the family with a
first-degree relative with a congenital heart defect. Am)
Med Genet. 29(1):137-42, 1988

AORTIC STENOSIS
IIMAGE

GALLERY
(Left) LVOT shOlvs a dilated
left ventricle
thick,

(arrow),

aortic

which

motion.

a

(LV) with

dysplastic

valve

had limited

RV: Right ventricle.

(Right)

Color

ultrasound

Doppler

in the same 1,'Ws

demonstrates

retrograde

in the aortic
indicates

arch

flO\v

(hlue

flow a\vay from

transducer).
supplying

the arch

veswl,

({nA - innominate

artel)",

LCC - left common
L5 -left

the

This (/O\v is

caroticl

suhclavian).

I/00v is coming

antegracle

the ascendin/{

.

Some

aorta

up

(aIIO\\'j,

(Left) Postnatal
echocardiogram
subaortic

shows

membrane

obstructing

the left

ventricular
(LVOT)

outflow

tract

immediately

the aortic

of the aorta

a normal

aortic

(open

supravalvar

narrowing

(arrOlv)

at the

Note

common

brachiocephalic

trunk

(corved

arrow).

(Left) LVOT viclv
postnatal
shows

thick

aortic

aortic

left atrium,

ventricle.
(Right)

MV

=

LV

valve.

=

le((

mitral

LVOT vit'\\'

Doppler
shows

valve

in a patient

(arrow)

a bicuspid

=

in

echocardiogram

leai/ets
LA

with

of the coronary

arteries.

with

V,l/VC'

arrO\v)

significant
takeoff

(L/~ -

(Right)

Angiogram
annulus

heleJ\\'

valve leai/ds.

left atrium).
shows

a

(arrow)

v,llve.

with

co/or

in the same caw
turbulent

(arrows)

which

i/ow
starts ,lt the

valve and continues
ascending

aorta.

into the

PULMONARY VALVE STENOSIS, ATRESIA

Graphic shows a thickened pulmonary valve (open
arrow). The RV is hypertrophied (arrow) and the
pulmonary artery is hypoplastic (curved arrow). Insert
shows an abnormal pulmonary valve.

ITERMINOlOGY
Abbreviations

and Synonyms

• Pulmonary valve stenosis (PS)
• Pulmonary valve atresia (PA)

Definitions
• Obstruction of right ventricular outflow tract (RVOT)
at level of pulmonary valve (PV)

IIMAGING FINDINGS
General

• Best diagnostic clue
o PS: Turbulent, high velocity flow across PV
o PA:No antegrade flow across pulmonary valve
• PA with intact ventricular septum (IVS) subtype
o Abnormal four chamber view: Right ventricle (RV)
small with decreased function
o RV « left ventricle (LV)with severe hypertrophy
• RV cavity obliterates over time
o Blood "must" get out ~ coronary cameral fistula
often present
• Coronary blood supply comes from high pressure
ventricle in systole
o Right atrium (RA) may be enlarged
o RVOT small or non-existent

Findings

• RA normal or large
• RV size normal, large or small
o RV hypertrophy is common
• RV function normal, increased or decreased
o Function decreased with more severe RVOT
obstruction (PS or PA)
• Pulmonary valve
o Pulmonary annulus small with thickened valve
o May see post-stenotic dilation of main pulmonary
artery
• Pulsed Doppler
o Used to characterize gradient across pulmonary
valve in PS
o Used to characterize gradient across tricuspid valve
to estimate RV pressure

Stenosis/Atresia

~r......•.
-.~\
.L.
'-

•. "

Tetralogy Of Fal/ot

o PA's usually confluent but small
• PA with ventricular septal defect (VSD) subtype
o Abnormal four chamber view due to presence of
VSD
o RV,LV symmetric in size
o "Large" aorta: Receives blood from both ventricles
o RV function usually preserved
o RVOT small or non-existent
o PA's often not confluent, rather major
aorto-pulmonary collateral arteries (MAPCA's)
supply lungs

Echocardiographic

Features

DDx: Pulmonary

Four chamber view in a fetus with pulmonary stenosis
shows concentric hypertrophy of the right ventricular
(RV) free wall and septum (arrows).

r

~vso..

Zrte .~
"P~

Tetralogy Of Fal/ot

•.,.

HLHS-Smal/ LV

Tricuspid Atresia

PULMONARY

VALVE STENOSIS, ATRESIA
Key Facts
Pathology

Terminology

• Obstruction of right ventricular outflow tract (RVOT)
at level of pulmonary valve (PV)

Imaging Findings
•
•
•
•
•
•

PS: Turbulent, high velocity flow across PV
PA: No antegrade flow across pulmonary valve
RA normal or large
RV hypertrophy is common
RV function normal, increased or decreased
If PA with intact ventricular septum, look for RV to
coronary artery fistulas
• Look for features of right atrial isomerism

Top Differential Diagnoses
• Tetralogy of Fallot (ToF)
• Hypoplastic left heart syndrome

• Deliver at tertiary care facility
• Pulmonary circulation is ductus dependent in severe
forms of PS and PA
• PS treatment involves balloon valvuloplasty
depending on gradient

Diagnostic Checklist
= duct

dependent

(HLHS),'

Imaging Recommendations
• Formal fetal echocardiography
o If PA with intact ventricular septum, look for RV to
coronary artery fistulas
• Can supply blood to RV and LV via
communications
• Course along outer wall of heart or within septum
o Look for other cardiac anomalies
• Tricuspid atresia
• Transposition of great arteries
• Double outlet right ventricle
o Look for features of right atrial isomerism
• Careful search for non cardiac anomalies

I DIFFERENTIAL DIAGNOSIS
Tetralogy of FalIot (ToF)
• Pulmonary stenosis from anterior deviation of
infundibulum is typical lesion
o Pulmonary atresia can occur (ToF with PA may also
be classified as PA with VSD)
• VSD must be present
• Aorta overrides VSD

Hypoplastic left heart syndrome (HlHS)
• LV not apex forming
• Typically associated with aortic/mitral atresia and
hypoplastic aortic arch
o Aorta looks large in PA-VSD
• Pulmonary artery branches into ductus/right
pulmonary artery shortly after exiting the heart
• RV not apex forming
• VSD usually present

heart disease

Clinical Issues

• Reverse flow in ductus arteriosus
pulmonary circulation

• Color Doppler
o Used to identify turbulent flow across pulmonary
valve in PS
o Useful for documenting tricuspid regurgitation
o Shows absent flow across pulmonary valve in PA
o Shows retrograde flow in ductus arteriosus

Tricuspid atresia

• Part of 22q 11 deletion syndrome
• PS accounts for 10% of all congenital
(CHD)
• PA accounts for 3% of CHD

• Pulmonary

valve may be atretic

I PATHOLOGY
General Features
• General path comments
o Associated with small pulmonary artery and
branches
• MAPCA's in cases of PA-VSD
o May have RV dependent coronary artery circulation
• Presence of coronary cameral fistulas
• Genetics
o Case reports of siblings '* possible autosomal
recessive inheritance with 25% recurrence risk
o Part of 22q 11 deletion syndrome
• Previously called
Di George/velocardiofacial/Sh
prin tzen syndrome
or CATCH 22
• More commonly present with PA-VSD
• Epidemiology
o All types 21.4:100,000 live births in United Kingdom
o PS accounts for 10% of all congenital heart disease
(CHD)
• "" 1% in fetus, these cases at more severe end of
spectrum
• 3-4% present in infancy
• Remainder are mild cases presenting in childhood
and later
o M=F
o PA accounts for 3% of CHD
• Incidence 8:100,000 live births
• Some cases may result from in-utero progression
of PS
• Associated abnormalities
o Ebstein anomaly of tricuspid valve
o Syndromes: Noonan, Williams and Alagille

Staging, Grading or Classification Criteria
• Congenital Heart Surgery Nomenclature and Database
Project
o PA-VSD: Classified on basis of pulmonary circulation
• Type A: Only native pulmonary arteries (NPA)

PULMONARY

VALVE STENOSIS, ATRESIA

• Type B: NPAs and MAPCAs
• Type C: MAPCAs only, no NPAs

ICLINICALISSUES
Presentation
• Abnormal four chamber view on routine sonography
• PA-IVS with RV-coronary fistula reported as early as 17
weeks

Natural History & Prognosis
• PS

o Depends on associated condition
o In isolation::::: 1/3 improve, 1/3 remain unchanged
and 1/3 increase in severity
• PA-IVS
o Severe hypoxia at birth
• Cardiomegaly ~ pulmonary hypoplasia
• Require institution of prostaglandins
o Require surgery within first week of life
o 75% survival at 1 yr
o 67% survival at 5 yr
• Increased risk with prematurity and Ebstein
anomaly
• PA-VSD
o > 50% require surgery within 1 month
o Additional 25% require surgery within 3 months
o Survival 80% at 3 yr with unifocalization (type of
surgical repair)
• Multiple catheter and surgical interventions
necessary
o Poor prognostic markers
• Low birth weight
• Male gender
• Muscular pulmonary atresia
• Discontinuous pulmonary arteries
• MAPCA's
o 22q 11 deletion
• 2Ax relative risk of surgical mortality for PA-VSD
• MAPCAs much more common with deletion
• Deletion is independent risk factor for surgical
mortality even after correction for presence of
MAPCAs

o 40-70 mmHg is moderate, intervention is
discretionary
o > 70 mm Hg is severe, intervention is necessary
• PA-IVS treatment
o Transcatheter balloon valvuloplasty or
radiofrequency perforation becoming first line
o Blalock Taussig shunt palliation ± RVOT
reconstruction often necessary
o Few patients achieve biventricular repair
• RV dependent coronary circulation (coronary
cameral fistula) precludes decompression of RV
• PA-VSD treatment
o Depends on presence of native pulmonary arteries
o Central shunt to pulmonary arteries or early
unifocalization of MAPCA's often necessary
• Unifocalization entails sewing MAPCA's together
with native PA ~ new PA on each side
• Currently standard of care
o Complete repair with VSD closure and RV to
pulmonary artery conduit is goal if possible

I DIAGNOSTIC
Consider

• Karyotype with FISH for 22q 11 deletion
o Independent risk factor for adverse outcome

Image Interpretation

I SELECTED
1.

2.

3.

o < 40 mm Hg is mild, no intervention

4.

5.

6.

7.

8.

depending on gradient
necessary

Pearls

• Reverse flow in ductus arteriosus = duct dependent
pulmonary circulation
o Prostaglandin infusion at birth to prevent ductal
closure

Treatment
• Consider karyotype with fluorescent in situ
hybridization (FISH) for 22qll microdeletion
• Prenatal consultation with pediatric
cardiology /neonatology
• Successful fetal pulmonary valvotomy has been
performed
o 28 week hydropic fetus with PA-IVS
o Postprocedural growth of RV, PVallowed
biventricular repair
• Deliver at tertiary care facility
• Pulmonary circulation is ductus dependent in severe
forms of PS and PA
o Ductal closure is life threatening
o Prostaglandin infusion necessary
• PS treatment involves balloon valvuloplasty

CHECKLIST

REFERENCES

Ashburn DA et al: Determinants of mortality and type of
repair in neonates with pulmonary atresia and intact
ventricular septum. J Thorac Cardiovasc Surg.
127(4):1000-7; discussion 1007-8, 2004
Dyamenahalli U et al: Pulmonary atresia with intact
ventricular septum: management of, and outcomes for, a
cohort of 210 consecutive patients. Cardiol Young.
14(3):299-308, 2004
Arzt W et al: Invasive intrauterine treatment of pulmonary
atresia/intact ventricular septum with heart failure.
Ultrasound Obstet Gynecol. 21(2):186-8, 2003
Favilli Set al: Pulmonary atresia or critical pulmonary
stenosis with intact interventricular septum diagnosed in
utero: echocardiographic findings and post-natal outcome.
Pediatr Med Chir. 25(4):266-8, 2003
Numata S et al: Long-term functional results of the one
and one half ventricular repair for the spectrum of patients
with pulmonary atresia/stenosis with intact ventricular
septum. Eur J Cardiothorac Surg. 24(4):516-20, 2003
Reddy VM et al: Early and intermediate outcomes after
repair of pulmonary atresia with ventricular septal defect
and major aortopulmonary collateral arteries: experience
with 85 patients. Circulation. 101(15):1826-32,2000
Tchervenkov CI et al: Congenital Heart Surgery
Nomenclature and Database Project: pulmonary
atresianventricular septal defect. Ann Thorac Surg. 69(4
Suppl):S97-105, 2000
Nishibatake M et al: Echocardiographic findings of
pulmonary atresia or critical pulmonary stenosis and intact
ventricular septum in utero. Pediatr Int 41:716-21, 1999

PULMONARY VALVE STENOSIS, ATRESIA
I IMAGE GALLERY
(Left) Four chamber view
color Doppler ultrasound
shows significant tricuspid
regurgitation (white arrow)
causing right atrial
enlargement
(black arrows)
in a fetus with pulmonary
atresia. (Right) (our chamber
view in a postnatal study
shows a hypoplastic RV with
significant wall hypertrophy
(arrows). There is a
normal-sized left ventricle
and no ventricular septal
defect in this patient with PA
with intact intraventricular
septum.

(Left) Four chamber view
shows a thick-walled right
ventricle (RV) in a fetus with
pulmonary stenosis. The
interventricular septum
(arrow) is bowed toward the
left ventricle (LV). (Right)
Pulsed Doppler ultrasound in
the same fetus shows high
grade stenosis of the
pulmonary valve with
gradient of 10].5 mm Hg.

(Left) RVOT vil'\v shO\vs a
small main (PA) and branch
pulmonary arteries (arrow)
in a fetus with pulmonary
atresia. Note the large right
atrium (RA) secondary to
tricuspid regurgitation (A aorta). (Right) Clinical
photograph ,hO\vs typical
phenotypic
/patures in a
neonate with a prenatal
diagnosis of 22q II deletion.
Note the micrognathia
(curved arrow), prominent
nose and long slim fingers
(arrow).

EBSTEIN ANOMALY, TRICUSPID

Graphic of Ebstein anomaly shows a large right atrium
(arrow), which includes the "atrialized" inlet portion of
the right ventricle (curved arrow). Note the displaced
and attached septal leaflet (open arrow).

ITERMINOLOGY
Definitions
• Ebstein anomaly and tricuspid dysplasia both have
dysplastic tricuspid valves (TV) with tricuspid
regurgitation (TR)
• Ebstein anomaly has additional findings of apical
displacement of septal and posterior TV leaflets and
"atrialization" of the right ventricle
o Displaced leaflets adhere to wall, coaptation point of
valve is lowered into right ventricle (RV), not
atrioventricular junction

IIMAGING

Ultrasound of Ebstein anomaly shows an enlarged right
atrium (RA), small functional RII, abnormal location of
the septal tricuspid valve leaflet (arrow) and long
sail-like anterior leaflet (open arrow).

o Apical displacement of septal and mural leaflet into
RY,long sail-like anterior tricuspid leaflet
o Valve dysplasia + leaflet malposition => TR
o Part of RV "atrialized" => functional RV small often
only muscular and outlet portion
'
• Pulmonary artery often small due to decreased flow
• Color Doppler helpful to demonstrate TR, measure
gradient with pulsed Doppler
• Tricuspid valve dysplasia
o Thick, nodular or irregular valve leaflets =>
incompetence => large right atrium secondary to TR
o TV in normal location
o Often associated pulmonary stenosis/atresia

Imaging Recommendations

FINDINGS

General Features
• Best diagnostic clue for Ebstein anomaly
o Right atrial enlargement with apical displacement of
tricuspid valve
• Normally lower on septum than mitral valve by
only 1-2 mm

Echocardiographic

DYSPLASIA

Findings

• Ebstein anomaly
o Cardiomegaly: Due primarily to right atrial (RA)
enlargement

• Formal fetal echocardiogram
o Tricuspid regurgitation: If severe, increased risk of
hydrops
o Pulmonary stenosis/functional pulmonary atresia
o Associated structural abnormalities in 30% of
Ebstein anomaly
• Atrial, ventricular or atrioventricular septal defect
• Tetralogy of Fallot, transposition of great arteries
• Total anomalous pulmonary venous return
• Mitral valve disease, coarctation of aorta
o Arrhythmia
• Supraventricular tachycardia or atrial flutter =>
worse prognosis

DDx: Enlarged Right Atrium

Pulmonary Atresia

Cardiomyopathy

Unbalanced AVSD

EBSTEIN ANOMALY, TRICUSPID

DYSPLASIA

Key Facts
Terminology

Imaging Findings

• Lbstein anomaly and tricuspid dy pIa ia both ha e
dysplastic tricuspid valve (TV) with tricuspid
regurgitation (TR)
• Eb tein anomaly ha additional finding of apical
di placement of septal and po terior T leaflets and
"atrialization" of the right ventricle

• Color Doppler helpful to demon trate TR, measure
gradient with pul ed Doppler
• Associated structural abnormalities in 30°;') of Eb tein
anomal}

I DIFFERENTIAL

DIAGNOSIS

Pulmonary atresia
• Tricuspid valve normally located
• RV may be hypoplastic or hypertrophied

Atrioventricular

septal defect (AVSD)

• Common atrioventricular valve
• Atrial and ventricular septal defects

I PATHOLOGY
General Features
• Etiology
o Lithium has previously been implicated
o Recent case controlled studies show no statistical
difference in heart anomalies between
lithium-exposed fetuses and control groups
• Epidemiology: 0.05:1000 live births, M = F
• Embryology: Ebstein anomaly
o Inadequate separation TV leaflets and chordae
tendineae from RV endocardium

I CLINICAL

Top Differential
• Pulmonaryatre
• trioventricular

o Valve reconstruction currently procedure of choice
with mortality < 10%
• Utilize anterior leaflet and annuloplasty to create
new coaptation point
o Valve replacement with mechanical or porcine
bioprosthesis
o Include right atrial reduction and closure of atrial
septal defect
• Tricuspid dysplasia surgery
o Tricuspid valve annuloplasty initially attempted,
valve replacement often necessary

I DIAGNOSTIC

Image Interpretation

Pearls

I SELECTED REFERENCES
1.

2.

Presentation

CHECKLIST

• Abnormal offset of tricuspid valve is key to making
diagnosis of Ebstein anomaly

ISSUES

• Enlarged right atrium noted on routine obstetric scan

Diagnoses
ia
eptal defect ( V D)

3.

Jacobson 5J et al: Prospective multicentre study of
pregnancy outcome after lithium exposure during first
trimester. Lancet. 339(8792):530-3, 1992
Hornberger LK et al: Tricuspid valve disease with
significant tricuspid insufficiency in the fetus: Diagnosis
and outcome. J Am Coil Cardio!. 17:167-73, 1991
5harland GK et al: Tricuspid valve dysplasia or
displacement in intrauterine life. J Am Coil Cardio!.
15:944-9,1991

Natural History & Prognosis
• Large heart ~ compressed lungs ~ pulmonary
hypoplasia
• Sustained arrhythmia or development of hydrops ~
poor prognosis
• Recurrence risk: One child 1%, two affected 3%

IIMAGE

GALLERY

Treatment
• Offer karyotype: Ebstein anomaly has been described
in trisomy 21,18
• Offer termination in severe cases (multiple anomalies,
aneuploidy)
• If pregnancy continues
o Prenatal consultation with pediatric
cardiology/neonatology
o Deliver at tertiary center: Early delivery does not
improve prognosis
• Monitor for arrhythmia, hydrops
• Ebstein surgery

(Left) Radiograph of a neonate with Ebstein anomaly shows
cardiomegaly with a massively enlarged right atrium (arrow) and
pulmonary oligemia. (Right) Four chamber view of a fetus shows a
thick, dysplastic tricuspid valve (arrow) which is not downwardly
displaced, thereFore this is tricuspid dysplasia, not Ebstein anomaly.
Tricuspid regurgitation was present.

TRICUSPID

Craphic shows an absent TV (arrow), a hypoplastic RV
S a ventricular septal defect (open arrow) allowing
blood to enter a hypoplastic pulmonary artery (curved
arrow). Blood admixture occurs in LA & LV

and Synonyms

Imaging Recommendations

• Tricuspid atresia (TA)

Definitions
• Absent tricuspid valve (TV)

IIMAGING

FINDINGS

Echocardiographic

Four chamber view shows tricuspid atresia (arrow).
There is a small RV (open arrow) and a large left
ventricle (LV) with a VSD (curved arrow), which allows
flow out the pulmonary artery.

o Establishes presence and degree of flow across the
pulmonary valve

ITERMINOlOGY
Abbreviations

ATRESIA

Findings

• Atria: Inter-atrial septum bows right to left (normal)
• Atrioventricular valves
o Tricuspid valve appears "plate-like" with no
movement
o Mitral valve functions normally
• Ventricular septal defect (VSD) usually present
• Right ventricle (RV): Small, non apex-forming,
function variable
• Pulmonary artery: Often small depending on amount
of flow from VSD
• Left ventricle (LV): Large, apex-forming with good
function
• Color Doppler
o Confirms direction of flow at atrial level
o Helps identify presence of a VSD

• Formal fetal echocardiography:
Additional cardiac
anomalies reported in up to 20%
o Pulmonary stenosis/atresia
o Mitral valve abnormalities
o D-transposition of great arteries
o With D-transposition look for additional aortic
obstruction
• Coarctation of aorta, subaortic stenosis common
with D-transposition and small VSD

I DIFFERENTIAL DIAGNOSIS
Pulmonary atresia-intact
(PA-IVS)

ventricular septum

• Tricuspid valve patent but usually abnormal
• RV small and hypertrophied

Double inlet left ventricle
• L-Iooping of heart
• Usually two normal atrioventricular (AV) valves but
one can be atretic
• Usually two normal semilunar valves

DDx: Tricuspid Atresia

PA-IVS

Single Ventricle

Unbalanced

AVSD

TRICUSPID

ATRESIA

Key Facts
Terminology

Top Differential

• Absent tricuspid valve (TV)

• Pulmonary atresia-intact ventricular septum (PA-IVS)
• Double inlet left ventricle
• Unbalanced left dominant atrioventricular septal
defect

Imaging Findings
• Tricuspid valve appears "plate-like" with no
movement
• Ventricular septal defect (VSD) usually pre ent
• Right ventricle (RV): Small, non apex-forming,
function variable

Clinical

Diagnoses

Issues

• Untreated, 90% mortality by 1 year
• Current surgical experience < 2% operative mortality
for children who survive to Fontan repair

• RV small, non apex-forming
• Common AV valve
• Inlet VSD with primum atrial septal defect

o Evaluate adequacy of pulmonary blood flow to
determine need for surgery
• Surgical management
o Blalock-Taussig shunt if pulmonary flow is
insufficient in first week
o Glenn at 4-6 months: Superior vena cava to right
pulmonary artery connection
o Fontan at 2-3 years of age: Inferior vena cava to
right pulmonary artery conduit
• Cardiac transplantation
in rare cases

I PATHOLOGY

I DIAGNOSTIC

Hypoplastic left heart syndrome
• LV non apex-forming (R and L often confused)
• Usually mitral and aortic atresia

Unbalanced left dominant
septal defect

atrioventricular

CHECKLIST

General Features

Image Interpretation

• Genetics: 22qll deletion in up to 8% TA
• Epidemiology
o 1:10,000 live births, M = F
o Third most common cyanotic congenital
disease

• Hypoplastic
heart

Staging, Grading or Classification Criteria
• Type 1: Great artery relationship normal 70%
(subtypes based on ± VSD)
• Type 2: D-transposition 28%
• Type 3: L-transposition 2%
• Type 4: Persistent truncus arteriosus

I SELECTED
1.
2.

3.

4.

Pearls

RV with "plate-like" tricuspid valve

REFERENCES

Sittiwangkul R et al: Outcomes of tricuspid atresia in the
Fontan era. Ann Thorac Surg. 77(3):889-94, 2004
Keating P et al: Tricuspid atresia--profile and outcome.
CardiovascJ S Mr. 12(4):202-5,2001
Mair DO et al: The Fontan procedure for tricuspid atresia:
early and late results of a 25-year experience with 216
patients. J Am Call Cardia!. 37(3):933-9, 2001
Lang 0 et al: Pathologic spectrum of malformations of the
tricuspid valve in prenatal and neonatal life. J Am Coll
Cardia!. 17(5):1161-7, 1991

ICLINICALISSUES

I IMAGE GALLERY

Presentation
• Abnormal four chamber view

Natural History & Prognosis
• Untreated, 90% mortality by 1 year
• Current surgical experience < 2% operative mortality
for children who survive to Fontan repair
o 95% survival at one month, 93% at one year
o 82% at 10 yrs
• Poor prognostic indicators
o Low birth weight
o Associated arch anomalies
o Severe RV hypoplasia

Treatment
• Prenatal consultation with pediatric
cardiology /neona tology
• Planned delivery in tertiary center
• Medical management
o Prostaglandin infusion to maintain

ductal patency

(Left) Four chamber view with color Doppler shows laminar flow into
the left ventricle (LV) (arrow) and flow into the small right ventricle
(curved arrow) via a ventricular septal defect (VSD). (Right) Postnatal
echo shows "plate-like" tricuspid valve (curved arrow), a large LV
with open mitral valve leaflets (arrows) and a VSD (open arrow)
opening to a hypoplastic RV.

DOUBLE OUTLET RIGHT VENTRICLE

Graphic shows both great arteries (curved arrows)
arising from the right ventricle. Presence of a VSD
(arrow) allows shunting of oxygenated blood to the RV
for similar saturations in the aorta and MPA.

Ultrasound shows parallel outflow tracts (arrows) arising
from the right ventricle (open arrow).

o Presence of a conusfinfundibulum
• VSD
o Subpulmonary (Taussig-Bing)
o Subaortic
o Doubly committed
o Remote from great vessels

ITERMINOLOGY
Abbreviations

and Synonyms

• Double outlet right ventricle (DORV)

Definitions
• Both great arteries arise predominantly
from right
ventricle (RV)
o Neither semilunar valve is in fibrous continuity with
an atrioventricular (AV) valve
o Ventricular septal defect (VSD) usually present
• VSD represents outlet for left ventricle (LV)

IIMAGING

FINDINGS

I DIFFERENTIAL DIAGNOSIS

General Features
• Best diagnostic clue: Outflow tracts parallel as they
exit heart

Echocardiographic

Imaging Recommendations
• Formal fetal echocardiogram
• Careful anatomic survey
o Strong association with aneuploidy if multiple
anomalies
• Look for features of heterotaxy syndromes

Tetralogy of Fallot (ToF)
• Outflow tracts relate normally (Le., not parallel)
• Right ventricular outflow tract obstruction
• Aorta overrides VSD

Findings

• Both great arteries arise predominantly from RV
o Aorta located posterior and rightward of pulmonary
artery (PA)
o Aorta located to right (side-by-side with PAl
o Aorta located to right and anterior of PA
o Aorta located to left and anterior of PA
• Aortic/mitral discontinuity

D-transposition

of great arteries (TGA)

• Outflow tracts are parallel
• Ventriculoarterial connections are key to differential
diagnosis
o Aorta arises from morphologic RV
o Pulmonary artery arises from morphologic LV

DDx: Double Outlet Right Ventricle
..~
.~
..

~~

.

'~

~

:r .
~

' .....
,..'''''6"
Se~t:riI"·

-.~~_

.

...

~
Tetralogy Of Fallot

ToF-Absent PV

.

-

..

-,,-

I

Tetralogy Of Failor

D-Transposition

DOUBLE OUTLET RIGHT VENTRICLE
Key Facts
Top Differential Diagnoses

Terminology

• Both great arteries arise predominantly
from right
ventricle (RV)
• Ventricular septal defect (VSD) usually present

• Tetralogy of Fallot (ToF)
• D-transposition of great arteries (TGA)

Imaging Findings

• Excellent early and long term outcomes if normal
chromosomes/no
heterotaxy

• Best diagnostic clue: Outflow tracts parallel as they
exit heart
• Strong association with aneuploidy if multiple
anomalies

Clinical Issues
Diagnostic Checklist
• Parallel outflow tracts

=

DORV or TGA

I PATHOLOGY

I DIAGNOSTIC

General Features

Consider

• Genetics
o Trisomy 18, 13
o Rare autosomal recessive cases: Multiple affected
siblings in consanguineous family
• Etiology: Maternal diabetes => odds ratio 21.3
• Epidemiology
o 1% of all congenital heart disease
o 0.03-0.09:1,000 live births
• Embryology
o Failure to achieve conotruncal rotation
o Failure of leftward shift of aortic/pulmonary
conus

• Formal fetal echocardiogram

Image Interpretation

I SELECTED REFERENCES
2.

Presentation
• Abnormal parallel orientation

of outflow tracts

3.

Natural History & Prognosis
• Excellent early and long term outcomes if normal
chromosomes/no
heterotaxy
o 73-88% survival at 5-8 yrs
• 95% long term survivors have no restriction on
physical activities
• 26-42% of children will need reoperation at some
point after primary repair
o More likely with outflow tract obstruction

Pearls

• Parallel outflow tracts = DORV or TGA
o Ventriculoarterial relationship is key to
differentiation
o Final diagnosis may not be possible until after
delivery

1.

I CLINICAL ISSUES

CHECKLIST

4.

Walters HL 3rd et al: Congenital Heart Surgery
Nomenclature and Database Project: double outlet right
ventricle. Ann Thorac Surg. 69(4 Suppl):S249-63, 2000
Allan LD: Sonographic detection of parallel great arteries in
the fetus. AjR Am j Roentgeno!. 168(5):1283-6, 1997
Berning RAet al: Reversed shunting across the ductus
arteriosus or atrial septum in utero heralds severe
congenital heart disease. j Am Coli Cardio!. 27(2):481-6,
1996
Ferencz C et al: Maternal diabetes and cardiovascular
malformations: predominance of double outlet right
ventricle and truncus arteriosus. Teratology. 41(3):319-26,
1990

IIMAGE GALLERY

Treatment
• Offer karyotype: 38% aneuploidy with fetal diagnosis
• Offer termination if trisomy, multiple anomalies
• Prenatal consultation with pediatric
cardiology/neonatology
• Deliver at tertiary center
• Immediate management depends on associated lesions
o Significant pulmonary stenosis => duct dependent =>
may need prostaglandins
• Corrective surgery depends on
o Great artery relationship
• VSD closure when side-by-side great arteries
o Presence and type of VSD
• Arterial switch in Taussig-Bing (subpulmonary
VSD)
o Coronary artery anatomy
• Goal of correction is to reestablish LV as systemic
ventricle and repair all associated lesions

(Leh) Angiogram shows both the aorta and MPA arising from the RV
in a patient with DORV who has undergone a PA band to limit
pulmonary blood flow. (Right) Color Doppler ultrasound shows flow
exiting the RV to the aorta (Ao) and main pulmonary artery (MPA).
MPA bifurcates into the ductus arteriosus (arrow) and right

pulmonary artery (curved arrow).

SINGLE VENTRICLE

Graphic shows the most common
single ventricle;
double-inlet leli ventricle. Both AV valves (arrows) drain
into the smooth-walled left ventricle. The aorta arises
from an outlet chamber (open arrow).

o Transposition
o One atretic great artery
• Color Doppler
o Document flow from both atria into single ventricle
o Document flow in one or both great arteries
• Turbulent flow identifies outflow tract obstruction
o Look for flow into an outlet chamber

ITERMINOLOGY
Abbreviations

and Synonyms

• Single or "common" ventricle
• Univentricular heart
• Double inlet left ventricle (OILV)

Definitions
• Heart has one functioning ventricle with inflow from
one or both atria
o Often rudimentary second outlet chamber: A
remnant of right ventricle in OILV
o VSD is present (often referred to as a
bulboventricular foramen)

IIMAGING

FINDINGS

Echocardiographic

Four chamber view shows a single ventricle (open
arrow) with LV morphology. The walls are smooth,
shape is oval, and the mitral valve leaflet (arrow) is
attached to the free wall. The other AV valve is atretic.

Imaging Recommendations
• Protocol advice
o Formal fetal echocardiography
to look for associated
lesions
• Coarctation of aorta, interrupted arch, pulmonary
stenosis/atresia
o Look for features of heterotaxy syndromes

I DIFFERENTIAL DIAGNOSIS

Findings

• Single ventricle
o Left ventricular (LV) morphology 80%, may also be
right-appearing or indeterminate
• Atrioventricular valves
o Double inlet (mitral and tricuspid), single inlet
(mitral or tricuspid) or common AV valve
• Great artery relationship is variable
o Normal relationship: Asymmetry in size ~ outflow
tract obstruction

Hypoplastic

left heart syndrome (HLHS)

• LV hypoplastic, non apex forming
• Usually mitral and aortic atresia/stenosis,
ascending aorta

Unbalanced

atrioventricular

septal defect

(AVSD)
• Common AV valve, inlet VSD and primum ASD
• Two ventricles, asymmetric in size

DDx: Single Ventricle Heart

Unbalanced

AVSD

HLHS

hypoplastic

Tricuspid Atresia

Tricuspid Atresia

SINGLE VENTRICLE
Key Facts
Top Differential

Terminology
• Heart ha on functioning
one or both atria

v ntricle with inflow from

Imaging Findings
• Left ventricular (LV) morphology 80%, may also be
right-appearing or indeterminate
• Great artery relationship is variabl
• Look for f ature of heterotaxy syndrome

Tricuspid atresia
• Absence of tricuspid valve + right ventricular
hypoplasia

I PATHOLOGY
General Features
• Epidemiology
o Rare 0.05-0.1:1000 live births
o 1.7% of fetal congenital heart disease

Diagnoses

• I lypoplastic left heart syndrome (HLH )
• Unbalanced atrioventricular
eptal defect (AV D)
• Tricuspid atresia

Clinical

Issues

• Abnormal four chamber view: Two atria, on
ventri Ie ~ three-chambered
heart
• May b ductal dependent for ystemic or pulmonary
circulation depending on a ociated outflow lesions
• Blalock-Taussig shunt necessary with diminished
or no pulmonary blood flow
• Aortic arch reconstruction necessary with left
ventricular (LV) outflow obstruction
o Glenn 4-6 months
• Superior vena cava to right pulmonary artery
connection
• Blalock-Taussig shunt taken down and/or
pulmonary artery ligated
o Fontan 2-3 years: Inferior vena cava to right
pulmonary artery conduit
• Cardiac transplantation
is last option

Staging, Grading or Classification Criteria
• Complex classification based on
o Atrioventricular connections
o Ventricular morphology
o Great artery position and relationship

I DIAGNOSTIC

ICLINICAL

I SELECTED REFERENCES

ISSUES

Presentation
• Abnormal four chamber view: Two atria, one ventricle
~ three-chambered heart

Consider
• Formal fetal echocardiography

1.

2.

Natural History & Prognosis
• Depends on morphology of ventricle and outflow
obstruction
• Current surgical experience
o 89% survival at 5 yrs, 80% at 15 yrs, 63% at 25 yrs
• Poor prognostic indicators
o Need for aortic arch reconstruction, arrhythmia or
need for pacemaker
• Recurrence risk if associated with right atrial
isomerism 3.4%

CHECKLIST

3.

in all cases

Lan YT et al: Outcome of patients with double-inlet left
ventricle or tricuspid atresia with transposed great arteries.
J Am Coli Cardio!. 43(1):113-9, 2004
Lan YT et al: Outcome of staged surgical approach to
neonates with single left ventricle and moderate size
bulboventricular foramen. Am J Cardio!. 89(8):959-63,
2002
Margossian RE et al: Septation of the single ventricle:
revisited. J Thorac Cardiovasc Surg. 124(3):442-7, 2002

IIMAGE

GALLERY

Treatment
• Karyotype not necessary if cardiac anomaly isolated
• Prenatal consultation with pediatric
cardiology / neonatology
• Deliver at tertiary center
• May be ductal dependent for systemic or pulmonary
circulation depending on associated outflow lesions
o May require prostaglandin infusion to prevent
ductal closure
• 3 stage surgical palliation
o 1st stage depends on presence of outflow tract
obstruction
• Pulmonary artery banding necessary with
excessive pulmonary flow

(Left) "Four chamber view" shows only three chambers, two atria (A)
and one ventricle (V). In real time, the AV valves (arrows) were seen
to open into the single ventricle. (Right) Color Doppler ultrasound in
the same patient shows flow from both atria (A) into a single ventricle
(V). The arrow points to the atrial septum.

TETRALOGY OF FALLOT

Graphic shows pulmonary artery hypoplasia (curved
arrow) secondary to narrowing of the pulmonary
outflow tract/infundibulum (arrow). The presence of a
VSD (open arrow) allows for mixing of blood.

Ultrasound shows a small pulmonary artery (PA) exiting
the right ventricle (RV). The aorta (Ao) is large and
overrides the ventricular septum (arrow) and ventricular
septal defect (curved arrows).

•
•
•
•

ITERMINOLOGY
Abbreviations

and Synonyms

• Tetralogy of Fallot (ToF)
• ToF with absent pulmonary

valve (ToF-APV)

•

Definitions
• Congenital heart disease with four components
o Right ventricular outflow tract obstruction (RVOTO)
o Ventricular septal defect (VSD)
.
o Overriding aorta
o Right ventricular hypertrophy

IIMAGING

•

FINDINGS

General Features
• Best diagnostic clue: Dilated aortic root overriding a
VSD

Echocardiographic

Findings

• Four chamber view normal in > 95% prenatal cases
• Outflow tract assessment key to making this diagnosis
o Large aortic outflow
• RVOTO + VSD = t flow through aorta
o Aortic root overrides perimembranous
VSD
• Extent of override variable
o RVOT obstruction

•

•

Anterior deviation of infundibulum
Pulmonary valve usually abnormal
Pulmonary annulus usually small
Turbulent flow across right ventricular outflow
tract (RVOT)
Abnormal ductus arteriosus
o Small in 70%
o Not visualized in 30%
• Autopsy confirmation of absent ductus in 50QI() of
non-visualized cases in one series
Absent pulmonary valve (APV) complex
o Back and forth flow across pulmonary valve seen
with color Doppler
o Markedly enlarged pulmonary artery (PA) and
branches
• May cause bronchial compression and affect lung
development
o Increased risk of hydrops
• ToF-APV + hydrops = 80'M) intrauterine fetal
demise in one series
Pulsed Doppler
o Used to estimate pressure in the right ventricle (RV)
and pulmonary arteries
Color Doppler
o Used to evaluate flow across and below
(insufficiency) the outflow tracts
o Used to evaluate flow across ventricular septal defect

DDx: Tetralogy Of Fallot

Double Outlet RV

Perimembranous VSD

Pulmonary Atresia

Truncus Arteriosus

TETRALOGY OF FALLOT
Key Facts
Terminology

Top Differential

•
•
•
•
•

• Pulmonary atresia with YSD
• Double outlet right ventricle (DORY)
• Peri membranous YSD

Congenital heart
Right ventricular
Ventricular septal
Overriding aorta
Right ventricular

disease with four components
outflow tract obstruction (RYOTO)
defect (YSD)

Clinical Issues

hypertrophy

Imaging Findings
• Best diagnostic clue: Dilated aortic root overriding a
YSD
• Anterior deviation of infundibulum
• Pulmonary valve usually abnormal
• Pulmonary annulu usually small
• Turbulent flow across right ventricular outflow tract
(RYOT)

• hromosomal abnormality in up to 45% of fetal cases
• Excellent short and long term outcome if normal
chromosomes and no other anomaly
• Greater than 94% urvival in liveborn
• ToF with absent pulmonary valve worse prognosis

Diagnostic Checklist
• 95% of fetuses with ToF have a normal four chamber
view
• Outflow tract assessment is key to making this
diagnosis

Imaging Recommendations
• Formal fetal echocardiogram
o Look for additional cardiac anomalies
• Absent pulmonary valve/pulmonary
atresia ~
worse prognosis
• May be associated with atrioventricular septal
defect
• Right-sided aortic arch
• Detailed anatomic survey
o Increased risk of aneuploidy/syndrome
if other
anomalies
• Trisomy 18/13
• YACTERL association

I DIFFERENTIAL

•

DIAGNOSIS

Pulmonary atresia with VSD
•
•
•
•

No antegrade flow across pulmonary valve
Retrograde flow in ductus arteriosus
Abnormal four chamber view in some: Small RY
YSD

•

•

Double outlet right ventricle (DORV)
• Outflow tracts parallel as they exit heart
• Both great arteries arise from RY
• YSD

Perimembranous

VSD

• Hole between left and right ventricles
• Absence of pulmonary or subpulmonary
• Normal relationship of great arteries

Diagnoses

stenosis

I PATHOLOGY
General Features
• Genetics
o Chromosomal anomalies
• Trisomy 21 (often more complicated with
atrioventricular septal defect rather than simple
YSD)

•

• Trisomy 18, 13
o Autosomal recessive conditions
• Phenylketonuria
o Microdeletion of chromosome 22 (22q 11deletion
syndrome)
• Previously called DiGeorge, velocardiofacial,
Shprintzen syndrome or CATCH 22
• 10% of patients with ToF have 22q 11 deletion
Etiology
o ToF also seen in developmental field defect (akin to
22qll deletion but with normal chromosomes)
• Malformation of ears/jaw/lips and palate
• Aplasia/hypoplasia of thymus/parathyroid
glands
• Cardiovascular malformations especially
conotruncal defects
• Some authorities refer to this field defect as Di
George anomaly (Di George syndrome implies
22q 11deletion)
Epidemiology
o Commonest cyanotic congenital heart disease
• 5-10% of congenital heart disease in liveborn
o 0.2-0.5:1,000 live births
Associated abnormalities
o ToF may occur in CHARGE syndrome
• Coloboma
• Heart disease
• Atresia (choanal)
• Restricted growth/development
• Genitourinary anomalies
• Ear anomalies
o YACTERL association
• Vertebral defects
• Anorectal atresia
• Cardiac disease
• Tracheoesophageal fistula
• Renal anomalies
• Limb dysplasia
o 22q 11 deletion syndrome (DiGeorge syndrome)
• Aplasia/hypoplasia of thymus
• Aplasia/hypoplasia of parathyroid glands
• Mild reduction in intelligence
Embryology

TETRALOGY OF FALLOT
o Complex process, mechanism remains uncertain
o Incomplete rotation of conotruncus
o Abnormal conotruncal septation
• Partitioning unequal '* aorta larger than
pulmonary artery
• Aortopulmonary septum does not line up with
interventricular septum '* VSD
• Larger vessel (aorta) straddles VSD

Gross Pathologic & Surgical Features
• Infundibular stenosis
o Anterior and cephalad deviation of infundibular
septum
o Hypertrophy of septum, free wall and septomarginal
trabeculations
• Pulmonary valve
o Unicuspid/bicuspid/tricuspid
o Valves thickened with poor mobility
• Pulmonary arteries
o May have focal or diffuse obstruction or hypoplasia

• Offer termination if associated aneuploidy/multiple
anomalies
• Prenatal consultation with neonatology/pediatric
cardiology
• Plan delivery at tertiary center
• Follow for progressive RVOT obstruction
o 2/25 fetuses in one series progressed to pulmonary
atresia
o Determines need for prostaglandins after birth
o Early intervention may be required if significant
RVOT obstruction/pulmonary
artery hypoplasia
• Surgical repair
o VSD closure
o Right ventricular outflow tract reconstruction
• Valve-sparing with infundibular resection
• Transannular patch
• RV-pulmonary artery conduit
o Anterior descending coronary artery may arise from
right coronary artery
• Surgeon needs to be aware

Staging, Grading or Classification Criteria
• Three major categories
o ToF with pulmonary stenosis
o ToF with pulmonary atresia
o ToF with absent pulmonary valve
• Cases with pulmonary atresia may also be categorized
as "pulmonary atresia with VSD"

I CLINICAL

ISSUES

I DIAGNOSTIC

CHECKLIST

Consider
• Formal fetal echocardiography
o Look for associated cardiac malformations
o Look for features predicting need for early
intervention/surgery
• Reversal of flow in ductus arteriosus
• Failure of growth in pulmonary trunk

Presentation

Image Interpretation

• Has been detected as early as 14 weeks on endovaginal
ultrasound

• 95% of fetuses with ToF have a normal four chamber
view
• ToF is the commonest lesion missed on the four
chamber view
• Outflow tract assessment is key to making this
diagnosis

Natural History & Prognosis
• Chromosomal abnormality in up to 45% of fetal cases
o Prognosis will be determined by
aneuploidy/syndrome
o Extremely poor in trisomy 13/18
• Excellent short and long term outcome if normal
chromosomes and no other anomaly
• Greater than 94% survival in liveborn
o Occasional palliation required prior to definitive
repair
• Balloon dilation of pulmonary valve
• Blalock Taussig shunt
• ToF with absent pulmonary valve worse prognosis
o 32% mortality at 4 yrs
o Primarily as result of significant respiratory
problems
o Associated with hydrops in fetus '* poor prognosis
• Recurrence risk
o One child 2.5%
o Two children 8%
o Mother 2.5%
o Father 1.5%

Treatment
• Encourage karyotype
o Abnormal in 45% prenatal cases
o Abnormal in 12% live born

Pearls

I SELECTED REFERENCES
1.

2.
3.

4.

5.

6.
7.

Kirshbom PM et al: Tetralogy of Fallot with absent
pulmonary valve syndrome. Semin Thorac Cardiovasc Surg
Pediatr Card Surg Annu. 7:65-71, 2004
Pepas LP et al: An echocardiographic study of tetralogy of
Fallot in the fetus and infant. Cardiol Young. 13(3):240-7,
2003
Moon-Grady AJ et al: Value of clinical and
echocardiographic features in predicting outcome in the
fetus, infant, and child with tetralogy of Fallot with absent
pulmonary valve complex. Am J Cardio!. 89(11):1280-5,
2002
Paladini D et al: Prenatal diagnosis of congenital heart
disease in the Naples area during the years 1994-1999 -- the
experience of a joint fetal-pediatric cardiology unit. Prenat
Diagn. 22(7):545-52, 2002
Jacobs ML: Congenital Heart Surgery Nomenclature and
Database Project: tetralogy of Fallot. Ann Thorac Surg. 69(4
Suppl):S77-82, 2000
Hokanson JS et al: Adults with tetralogy of Fallot:
long-term follow-up. Cardiol Rev. 7(3):149-55, 1999
Yoo SJ et al: Tetralogy of Fallot in the fetus: findings at
targeted sonography. Ultrasound Obstet Gyneco!.
14(1):29-37,1999

TETRALOGY OF FALLOT
IIMAGE GALLERY
(Left) RVOT view in a
newborn with ToF shows
laminar flow (arrow) into the
aorta from the RV via a
perimembranous ventricular
septal defect (VSD).
Turbulent flow (curved
arrow) across the RVOT is
also seen. (Right) Pulsed
Doppler ultrasound shows
right ventricular outflow
tract/pulmonary stenosis
gradient of 83 mmHg in
fetus with Tetralogy of Fallot.

(Left) Ultrasound shows
significant enlargement of
the pulmonary artery and its
branches (arrows) in a fetus
with Tetralogy of
Fallot/absent pulmonary
valve complex (ToF-APV).
(Right) Color Doppler
ultrasound in the same fetus
shows back and forth flow
(red and blue) across the
right ventricular outflow
tract. Severe pulmonary
insufficiency and PA
enlargement are prominent
features of ToF-APV

(Left) Dissection of the RV
cavity shows a small,
dysplastic pulmonary valve
(arrow) with anterior
df'viation of the conus
(muscular band separating
inflow from outflow tracts)
just below the valve. (Right)
Postnatal echocardiogram of
an infant with ToF shows a
similar appearance to those
in the pathologic specimen.
A right ventricular outflow
tract (RVOT) view shows a
small pulmonary valve (pV,
arrow) and a prominent
conus (curved arrow)
deviated anteriorly.

TRANSPOSITION

OF GREAT ARTERIES

Graphic shows the aorta (arrow) arising from the RV
and the pulmonary artery (open arrow) arising from the
LV in simple transposition without a ventricular septal
defect.

Ultrasound shows parallel orienta don of the great
arteries with absence of the normal "crossover" as the
vessels leave the heart. (P - pulmonary artery, Ao aorta, arrows - arch vessels).

ITERMINOlOGY

Echocardiographic

Abbreviations

• In TGA "normal" four chamber view
• Outflow tracts parallel as they exit heart
o Posterior artery (pulmonary) bifurcates
• Arises from left ventricle (LV)
o Anterior artery (aorta) gives rise to arch/head and
neck vessels
• Arises from right (RV)
o Associated lesions
• Ventricular septal defect (VSD) 35%
• Left ventricular outflow tract obstruction 10-20%
(with VSD)
• Coarctation of the aorta 5'Y<l
• AV valve abnormalities 5%
• In CTGA, closer inspection reveals morphologic LV
will be anterior, RV posterior
o LV smooth walled and no chordal attachments to
septum
o RV trabeculated, moderator band, chordal
attachments to septum
o PA arises from anterior, left ventricle
o Aorta arises from posterior, right ventricle
o Associated lesions
• VSD 60-70%
• Right ventricular outflow tract obstruction 30-50%
• Systemic AV valve abnormalities 90% (often
without functional significance)

and Synonyms

• Transposition of great arteries (TGA)
o D-transposition
o Dextrotransposition
• Congenitally corrected transposition of great arteries
(CTGA)
o L-transposition
o Levotransposition

Definitions
• Ventriculoarterial (VA) discordance in TGA
o Aorta arises from right ventricle
o Pulmonary artery (PA) arises from left ventricle
• Atrioventricular (AV) and VA discordance in CTGA
(ventricular inversion)
o Right atrium -+ left ventricle -+ pulmonary artery
o Left atrium -+ right ventricle -+ aorta

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Outflow tracts parallel as they
exit heart

Findings

DDx: Transposition Great Arteries

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.
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I!': '

.

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,

_

Septurif'.

-~

.

~ Ii

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;,;
-

-.-

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Tetra/ogy Of Fallot

Right Atria/Isomerism

TRANSPOSITION

OF GREAT ARTERIES
Key Facts

Terminology

Top Differential Diagnoses

• Transposition of great arteries (TGA)
• Congenitally corrected transposition of great arteries
(CTGA)
• Ventriculoarterial (VA) discordance in TGA
• Atrioventricular (AV) and VA discordance in CTGA
(ventricular inversion)

• Double outlet right ventricle
• Tetralogy of Fallot

Imaging Findings

• Excellent short and long term outcomes

• Best diagnostic clue: Outflow tracts parallel as they
exit heart
• In TGA "normal" four chamber view
• In CTGA, closer inspection reveals morphologic LV
will be anterior, RV posterior
• Differentiate TGA from CTGA by accurate
identification of AV and VA connections

• CTGA and TGA have different prognosis and
treatment
• Differentiation requires identification of
ventricles/ventriculoarterial
connections
• Normal four chamber view does not exclude
significant conotruncal malformations

• Pulsed Doppler
o Used to assess gradients across aortic/pulmonary
valves
• High velocity or turbulence seen in obstructive
lesions
• Color Doppler
o Used to identify flow turbulence across valves
o Assess flow across ventricular septal defect

Imaging Recommendations
• Protocol advice
o If parallel outflow tracts are seen
• Assess ventricular morphology
• Look for a VSD
• Assess ventriculoarterial
connections
• Differentiate aorta from PA
o Aim to classify TGA
• TGA with intact ventricular septum (IVS) or small
VSD 60% (so called "simple" TGA)
• TGA with large VSD 25%
• TGA with VSD and LV outflow tract obstruction
10%
• TGA with intact ventricular septum and LV
outflow tract obstruction 5%
o Differentiate TGA from CTGA by accurate
identification of AV and VA connections
o Check situs
• 80% of right atrial isomerism/asplenia
have
conotruncal malformations including TGA
o Full anatomic survey for other anomalies, although
rare

Pathology
• Genetics: Rarely associated with aneuploidy

Clinical Issues
Diagnostic Checklist

• PA arises from right ventricle with pulmonary or
subpulmonary stenosis
• Higher association with aneuploidy and extra cardiac
anomalies

I PATHOLOGY
General Features
• Genetics: Rarely associated with aneuploidy
• Etiology: Seen in cases of maternal diabetes
• Epidemiology
o TGA accounts for 5% fetal congenital heart disease
(CHD)
• 80% D-transposition/TGA
• 20% L-transposition/CTGA
o Fetal loss is uncommon and therefore approximates
liveborn prevalence
• 0.21/1000 live births
o M:F=2:1
o CTGA < 1% CHD in liveborn infants
• Embryology
o TGA: Abnormal division of truncus arteriosus
o CTGA: Abnormal looping of embryonic heart tube

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms:
noted on routine sonography

Parallel outflow tracts

Natural History & Prognosis

I DIFFERENTIAL

DIAGNOSIS
Double outlet right ventricle

• Normal atrioventricular connections
• Outflow tracts are parallel but both wholly or
predominantly arise from RV

Tetralogy of Fallot
• Normal atrioventricular connections
• Outflow tracts not parallel

• Excellent short and long term outcomes
o Arterial switch which is now procedure of choice for
TGA
• Midterm survival> 90%
• 89/0 incidence late coronary artery complications
• Often have branch pulmonary stenosis
• Long term (20 yr glus) survival data not yet
available
o CTGA survival past neonatal period> 75%
• Survivors into 50's without surgery

TRANSPOSITION

OF GREAT ARTERIES

• Even better outcome expected with new surgical
techniques
• TGA circulation
o Fetal connections are the only communication
between pulmonary and systemic circulations
• Ductus arteriosus
• Foramen ovale
o At birth, normal closure ~ dissociation of
circulations ~ death from hypoxia
o If present, VSD allows some admixture but also need
patent foramen ovale or ductus arteriosus
• Rashkind procedure to open atrial septum often
required to improve oxygen saturations
o Surgery required within first 2 weeks of life
• Before development pulmonary hypertension
• Before LV adapts to low pressure pulmonary
circulation
o Recurrence risk
• One sibling 1.5%
• Two siblings 5%
• CTGA circulation
o Oxygenated blood from lungs reaches systemic
circulation
o Associated lesions determine prognosis
• May require early intervention
o At risk for conduction defect before, and following
repair
• In one series 4/21 fetuses with CTGA had
complete heart block

Treatment
• TGA
o Not typically associated with aneuploidy, karyotype
may not be necessary
o Prenatal consultation with pediatric
cardiology/neonatology
o Refer to tertiary center for delivery
o After delivery
• First line of treatment is to maintain fetal shunts
• Prostaglandin infusion to prevent ductus
arteriosus closure
• Balloon atrial septostomy (Rashkind) allows L -+ R
atrial shunt
o Old surgical technique: Atrial switch
• Senning/mustard
procedure
• Significant late complications
o New surgical technique: Arterial switch, now
procedure of choice
• Great vessels transected and reconnected to
appropriate ventricles
• Coronary arteries re-implanted on transposed
aorta
o Operative mortality 3-5%
• CTGA
o Prenatal consultation with pediatric
cardiology/neonatology
o Refer to tertiary center for delivery
o No intervention necessary immediately after birth in
majority
o Without VSD: Consider no intervention
• Long term survival reported into 50's
o With VSD +/- pulmonary stenosis: Surgical options
vary

• Atrial switch with Rastelli
• Double-switch (atrial and arterial)
• Early survival data not documented

I DIAGNOSTIC

CHECKLIST

Consider
• Formal fetal echocardiography
o CTGA and TGA have different prognosis and
treatment
o Differentiation requires identification of
ventricles/ventriculoarterial
connections

Image Interpretation

Pearls

• Normal four chamber view does not exclude
significant conotruncal malformations
• Parallel outflow tracts ~ significant congenital
disease
o 64% double outlet right ventricle
o 36% transposition great arteries

I SELECTED
1.

heart

REFERENCES

Morell VO et al: The role of aortic translocation in the
management of complex transposition of the great arteries.
Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu.
7:80-4, 2004
2. Devaney EJ et al: Technical aspects of the combined arterial
switch and senning operation for congenitally corrected
transposition of the great arteries. Semin Thorac
Cardiovasc Surg Pediatr Card Surg Annu. 6:9-15, 2003
3. Jaggers JJ et al: Congenital Heart Surgery Nomenclature
and Database Project: transposition of the great arteries.
Ann Thorac Surg. 69(4 Suppl):S205-35, 2000
4.
Wilkinson JL et al: Congenital Heart Surgery Nomenclature
and Database Project: corrected (discordant) transposition
of the great arteries (and related malformations). Ann
Thorac Surg. 69(4 Suppl):S236-48, 2000
5.
Massin MM: Midterm results of the neonatal arterial switch
operation. A review. J Cardiovasc Surg (Torino).
40(4):517-22,1999
6.
Bonnet D et al: Long-term fate of the coronary arteries after
the arterial switch operation in newborns with
transposition of the great arteries. Heart. 76(3):274-9, 1996
7. Paladini D et al: Conotruncal anomalies in prenatal life.
Ultrasound Obstet Gynecol. 8(4):241-6, 1996
8. Sharland GK et al: Factors influencing the outcome of
congenital heart disease detected prenatally. Arch Dis
Child. 66(3):284-7, 1991
9.
Kirklin JW et al: Complete transposition of the great
arteries: treatment in the current era. Pediatr Clin North
Am. 37(1):171-7,1990
10. Gembruch U et al: Fetal complete heart block: antenatal
diagnosis, significance and management. Eur J Obstet
Gynecol Reprod BioI. 31(1):9-22, 1989
11. Norwood WI et al: Intermediate results of the arterial
switch repair. A 20-institution study. J Thorac Cardiovasc
Surg. 96(6):854-63, 1988

TRANSPOSITION
IIMAGE

OF GREAT ARTERIES

GALLERY
(Left) Ultrasound shows a
smooth-walled
(curved
arrow) ventricular chamber
anteriorly and moderator
band (arrow) in the posterior
ventricle. This is a case of
congenitally corrected
transposition of the great
arteries. (Right) Color
Doppler ultrasound in the
same case shows parallel
orientation of the outflow
tracts (arrows). The
pulmonary artery arose from
the anterior left ventricle and
the aorta from the posterior
right ventricle.

(Left)

Ultrasound shows the
vessel arising from the
anterior ventricle (white
arrow) has branches
supplying the head and neck
(black arrows) instead of the
expected division into
pulmonary artery and
ductus. (Right) Another
image from the same fetus
shows the typical proximal
branching (arrows) pattern
of the pulmonary artery,
arising from the posterior
ventricle (curved arrow).

(Left) Four chamber view
shows a ventricular septal
defect (arrow) in a fetus with
transposition of the great
arteries. A VSO is present in
35% of cases of TCA and up
to 70% of cases of CTCA.
(Right) Cross pathology of
TCA shows the aorta arising
from the anterior right
ventricle, note moderator
band (arrow). The
pulmonary artery (PA) arises
from the posterior left
ven tricle (LV).

TRUNCUS ARTERIOSUS

Graphic shows the truncal vessel (curved arrow) arising
over a ventricular septal defect (arrow). The pulmonary
artery (open arrow) branches from the truncus shortly
after it exits the heart.

ITERMINOLOGY
Abbreviations
•
•
•
•

and Synonyms

Truncus arteriosus
Truncus arteriosus communis
Common arterial trunk
Common aorticopulmonary
trunk

Definitions
• Single vessel (truncus) arises from heart
o Embryonic failure of separation into pulmonary
aortic trunks

and

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Single great artery (truncus) exits
heart

Echocardiographic

Findings

Outflow

• Interrupted aortic arch in 10-20%
• Ductus arteriosus
o Agenesis ~ 50%
o May be very large if arch interrupted
• Ventricular septal defect (VSD)
• Pulsed Doppler
o Useful to assess degree of truncal stenosis if present
o Persistent forward flow in truncal vessel => run-off
into low pressure system
• Pulmonary circulation is lower resistance than
systemic
• Truncal vessel gives rise to both pulmonary and
systemic vessels
• Color Doppler
o Allows visualization of truncal stenosis and
regurgitation
o Helps with detection of VSDs
o Shows flow pattern in aortic arch to aid in
diagnosing interrupted arch

Imaging Recommendations

• Single great artery (truncus) exits heart, gives rise to
o Aortic arch, head and neck vessels
o Main +/- branch pulmonary arteries
• Single truncal valve with 1-6 cusps
o Truncal valve dysplasia common
o May cause stenosis +/- regurgitation
• Right-sided aortic arch in 33%

DDx: Abnormal

Ultrasound shows early branching of the truncus into
the main pulmonary trunk (P) and ascending aorta
(Ao). Note the thickened dysplastic truncal valve
(arrow). LV = left ventricle.

Tracts

DORV

• Formal fetal echocardiography
• Careful anatomic survey
o 30% of infants with truncus are syndromic
o 10% have additional extracardiac anomalies

TRUNCUS ARTERIOSUS
Key Facts
Terminology

Pathology

• Single ves el (truncus) arises from heart

• 40% of liveborns with truncu have 22qll deletion
• Maternal diabetes: Odds ratio 12.8

Imaging Findings
•
•
•
•
•
•

Clinical Issues

Truncal valve dysplasia common
Right-sided aortic arch in 33Q'6
Interrupted aortic arch in 10-20%
Ventricular septal defect (VSD)
30% of infant with truncus are syndromic
10% have additional extracardiac anomalies

Top Differential

• Offer karyotype and fluorescent in- itu hybridization
(FISH) for 22qll deletion
• Early surgical repair now treatment of choice
• Overall operative mortality 4-5% in recent eries,
with mean age of repair at 11 days
• 97()1J of survivors very functional

Diagnoses

Diagnostic Checklist

• Pulmonary atre ia with V 0
• Tetralogy of Fallot
• Aortic atresia/hypoplastic
left heart (HLHS)

• Look for single trunk arising from heart
• Proximal branch ~ pulmonary artery is diagnostic
• Look for truncal valve with> 3 cusps

I DIFFERENTIAL DIAGNOSIS
Pulmonary atresia with VSD
• Aorta arises from left ventricle
• Pulmonary blood flow via
o Retrograde flow in ductus arteriosus or
o Collateral vessels arising from descending

aorta

Tetralogy of Fallot
• Pulmonary artery arises from right ventricle (RV),
often with small annulus
• Anterior deviation of infundibular septum
• Aorta arises from left ventricle
• VSD present

Aortic atresia/hypoplastic

left heart (HLHS)

• VSD not usually a component
• Only pulmonary artery seen leaving heart
o Aorta atresia ~ retrograde flow from ductus
arteriosus supplies the head, neck and coronary
vessels
• Left ventricle not apex-forming

I PATHOLOGY
General Features
• Genetics
o 40% of liveborns with truncus have 22q 11 deletion
o Microdeletion of chromosome 22 (22q 11 deletion
syndrome)
• Previously called DiGeorge, velocardiofacial,
Shprintzen syndrome or CATCH 22
• 10% of patients have truncus arteriosus
• Right-sided aortic arch and abnormal branching
are more common
• Etiology
o Maternal diabetes: Odds ratio 12.8
o Developmental field defect
• Malformations of ears/jaws/Iips and palate
• Aplasia/hypoplasia thymus/parathyroid
glands
• Cardiovascular malformations, especially
conotruncal defects

• Epidemiology
o 1.2% (0.7-2.5%) congenital heart disease in infancy
o 0.006:1,000 live births
o M=F
• Embryology
o Left/right signaling part of complex cascade of
events
• Cardiac neural crest cells are part of
cardiocraniofacial morphogenetic field
• Field defects explain syndromic associations of
heart and facial anomalies
o Embryonic truncus is a normal structure which lies
between the conus and the aortic arch system
o Truncal swellings divide the truncal lumen into two
channels: Aortic and pulmonary arteries
o As truncal septum fuses with conal septum, right
and left ventricular origins are established
• If truncal septum fails to fuse to conal septum a
ventricular septal defect is present
o If truncal swellings do not divide lumen ~ single
vessel leaves heart
• Embryologically this form of congenital heart
disease should be called "persistent truncus
arteriosus"
• Single vessel then gives rise to
pulmonary /systemic/ coronary circulation

Gross Pathologic & Surgical Features
• Truncal valve usually has 3 cusps
o Can be anywhere from 1-6 cusps
• Classification systems
o Collett and Edwards 1949, revised in 1976 by Calder
and Van Pragh
• Type A: Ventricular septal defect present
• Type B: Ventricular septum intact (very rare)
• Type A further divided
o Subgroup or type 1
• Short main pulmonary trunk arising from truncus,
usually left-sided
• Most common form, 50% all cases
o Subgroup or type 2
• Both pulmonary arteries arise separately from
truncus

TRUNCUS ARTERIOSUS
• 20-30% all cases
o Subgroup or type 3
• One pulmonary artery arises from ascending aorta
• Other pulmonary artery arises from ductus
(common) or a major aortopulmonary
collateral
• < 10% all cases
o Subgroup or type 4
• Underdevelopment
of the aortic arch
• Includes interrupted aortic arch, preductal
coarctation or severe hypoplasia/atresia
of aortic
arch
• 10-20% all cases

ICLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Fetus
• Abnormal outflow tracts
• Single great vessel leaves heart, overrides a
ventricular septal defect
o Infant or child
• Pulmonary overcirculation early in life
o 22q 11 deletion syndrome
• Developmental delay
• Hypocalcemia
• Immune deficiencies due to T-cell malfunction

Natural History & Prognosis
• Fetal series of 17 confirmed cases
o Termination of pregnancy 24%
o Pre-operative death 31 %
o Overall survival 42%
• 85% mortality by end first year if untreated
o Rarely, if ever, done
• At birth large L -+ R shunt as blood preferentially flows
into pulmonary arteries
o Untreated '* pulmonary
hypertension/cyanosis/heart
failure/death
o Truncal regurgitation exacerbates volume overload
• Prognosis depends on
o Pulmonary circulation
• Discontinuous pulmonary arteries or only
collateral vessels = worse prognosis
o Truncal valve function
• Stenosis or insufficiency affects morbidity and
mortality
• Current survival rates approaching 95% with complete
repair
• Recurrence risk
o 1% with one sibling affected
o 3% if two siblings affected
o Parental karyotype required for accurate recurrence
risk if ch ild has 22q 11 deletion
• Parent may have the microdeletion but not have
cardiac disease

Treatment
• Offer karyotype and fluorescent in-situ hybridization
(FISH) for 22q 11 deletion
• Offer termination
• Prenatal parental consultation with
neonatology/pediatric
cardiology

• Planned delivery in tertiary center with
multidisciplinary team
• Early surgical repair now treatment of choice
o Before development of pulmonary hypertension
o Overall operative mortality 4-5% in recent series,
with mean age of repair at 11 days
o 97% of survivors very functional
• Operative repair
o PA excised from truncus
• Pulmonary arteries connected, if not confluent
o Pulmonary outflow tract reconstructed using a
conduit
o VSD closed
o Truncal valve repaired, if necessary

I DIAGNOSTIC

CHECKLIST

Consider
• Formal fetal echocardiogram
o Evaluate for anomalies associated with 22q 11
deletion

Image Interpretation

Pearls

• Truncus is difficult diagnosis to make in utero
o Look for single trunk arising from heart
o Proximal branch '* pulmonary artery is diagnostic
o Look for truncal valve with> 3 cusps
o Look for truncal stenosis/regurgitation

I SELECTED
1.

2.

3.

4.

5.

6.

7.

8.

9.

REFERENCES

Franco D et al: The role of Pitx2 during cardiac
development. Linking left-right signaling and congenital
heart diseases. Trends Cardiovasc Med. 13(4):157-63,2003
Hutson MR et al: Neural crest and cardiovascular
development: a 20-year perspective. Birth Defects Res C
Embryo Today. 69(1):2-13, 2003
Rodefeld MD et al: Neonatal truncus arteriosus repair:
surgical techniques and clinical management. Semin
Thorac Cardiovasc Surg Pediatr Card Surg Annu. 5:212-7,
2002
Duke C et al: Echocardiographic features and outcome of
truncus arteriosus diagnosed during fetal life. Am J Cardio!.
88(12): 13 79-84, 2001
Jacobs ML: Congenital Heart Surgery Nomenclature and
Database Project: truncus arteriosus. Ann Thorac Surg. 69(4
Suppl):S50-5, 2000
Bartelings MM et al: Morphogenetic considerations on
congenital malformations of the outflow tract. Part 1:
Common arterial trunk and tetralogy of Fallot. lnt J
Cardio!. 32(2):213-30, 1991
Hong R: The DiGeorge anomaly. lmmunodefic Rev.
3(1):1-14, 1991
Ferencz C et al: Maternal diabetes and cardiovascular
malformations: predominance of double outlet right
ventricle and truncus arteriosus. Teratology. 41(3):319-26,
1990
Calder L et al: Truncus arteriosus communis. Clinical,
angiocardiographic,
and pathologic findings in 100
patients. Am Heart). 92(1):23-38, 1976

TRUNCUS ARTERIOSUS
IIMAGE GALLERY
Variant
(Left) Long axis ultrasound
shows a single OUt/lOW vessel
with a thickened valve
(arrow). The truncus
overrides a ventricular septal
defect (curved arrow).
(Right) Ultrasound shows a
single large vessel or truncus
(arrow) leaving the heart in a
77 week fetus. This fetus had
an AV septal defect and
heterotaxy as well as
posterior urethral valves with
renal parenchymal
damage.
The pregnancy \vas
tC>nllin,lted due to the dismal
prognosis.

(Left) Long axis ultrasound
shows Ihe truncus overriding
a venlricular seplal defect
(VSD). The valve (arrow) is
thickened and dysplastic.
Truncal
.I tenosisl reg urgita lion
impacts morbidily and
mortalily. (Right) Cross
pathology shows a
ventriculoseptal
defect
(curved arrow) with a single
common trunk (open
arrows) leaving the heart. A
left-sic/I'd hranch (arrO\v)
g;\'('s rise to a pulrnonary
artery.

Typical
(Left) Ultrasound shows four
cusps in the valve (arrow) of
the outflow vessel, which is
consistent with the diagnosis
of trunrus arteriosus. (Right)
Sagittal ohlique color
[)oPIJ/er ultrasound of the
truncus arteriosus (curved
ar/(J\V) shO\I'S turbulent tlOIV.
comistent wilh truncal
stenosis. This vessel gives rise
to the head and neck arteries
(arrows).

HYPERTROPHIC

CARDIOMYOPATHY

Four chamber
view shows thickened
myocardium
(arrows). The mother presented with preterm labor
attributed to polyhydramnios.

ITERMINOlOGY
Abbreviations

and Synonyms

• Cardiomyopathy
(CM)
• Hypertrophic cardiomyopathy

Definitions
• Primary disorder of cardiac muscle
o No structural malformation
o No pericardial disease
• Excludes hypertrophy and poor function secondary to
outflow obstruction
• In children CM is a diagnosis of exclusion, hard to
exclude some causative conditions in fetus
• Some hypertrophic CM cases progress to dilated CM if
underlying condition not treated

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Thickened

Ultrasonographic

myocardium

Findings

• Grayscale Ultrasound
o Thick interventricular septum
• Systolic anterior motion of the mitral valve in
systole

DDx: Thickened

Pulmonary Stenosis

Color Doppler ultrasound in the same case shows an 8
cm vascular placental mass (arrow). Chorioangioma
confirmed at delivery Shunt lesions are a cause of fetal
hypertrophic cardiomyopathy.

o Thickened free walls
o ± Cardiomegaly
• Color Doppler
o Signs of mid-cavitary obstruction
• Turbulent flow in left ventricular outflow from
subaortic stenosis
• Pulsed Doppler
o Increased gradient in left ventricular outflow tract
• Delayed upstroke suggesting dynamic obstruction

Imaging Recommendations
• Best imaging tool: Formal fetal echocardiogram
• Protocol advice
o Exclude mechanical causes
• Valvar stenoses
• Ductal constriction
• Coarctation: May not be able to exclude this in
fetus
o Measure ventricular wall thickness
• Epicardial to endocardial surface
• Measure at end-diastole for minimum thickness
• Measure just below level of closed atrioventricular
(AV) valve leaflets
o Measure chamber dimensions in 4 chamber view
• End-diastolic diameter (EDD) is longest
measurement at end-diastole
• End-systolic diameter (ESD) is shortest
measurement at end-systole

Myocardium

Idiopathic Calcification

HYPERTROPHIC

CARDIOMYOPATHY
Key Facts

Terminology

Pathology

• Primary disorder of cardiac muscle
• ome hypertrophic CM cases progress to dilated CM
if underlying condition not treated

• Hypertrophic CM reported in 30% of fetuses of
diabetic mothers
• M (all type) 0.02: 1,000 live births

Imaging Findings

Clinical Issues

• Best diagno tic clue: Thickened myocardium
• Turbulent flow in left ventricular outflow from
subaortic tenosis
• Exclude mechanical causes

• Most primary/familial ca es present in third trimester
• Fetuses of diabetic mothers may show progressive
increase in heart size/myocardial thickness from
second trimester onward
• ases due to high-output state present earlier due to
underlying condition
• Postnatal treatment options may be few

Top Differential

Diagnoses

• Outflow tract obstruction
• Rhabdomyoma
• Myocardial calcification

Diagnostic Checklist
• Formal fetal echocardiography
in all cases
• Exclude structural malformation

o Measure ventricular shortening fraction (VSF)
• VSF = EDD - ESD/EDD
• Normal right VSF 0.25
• Normal left VSF 0.3
o Look for signs of embryopathy in fetus of diabetic
mother
• Caudal regression sequence
• Central nervous system anomalies particularly
holoprosencephaly
spectrum

I DIFFERENTIAL
Outflow

DIAGNOSIS

tract obstruction

• Left ventricular outflow tract obstruction
o Aortic atresia/stenosis
o Hypoplastic left heart syndrome (HLHS)
• Pulmonary stenosis/atresia
• Ductal constriction

Rhabdomyoma
• Mimics hypertrophic CM if it involves ventricular
septum
• Usually multiple masses ~ easy differentiation
• Case reports of rhabdomyoma causing diffuse
myocardial thickening

Myocardial

calcification

• Most cases idiopathic
• Can be seen with in-utero infection
• Associated with myocardial damage
o Maternal cocaine abuse
o Viral infections

I PATHOLOGY
General Features
• Genetics
o Autosomal recessive
• Inborn errors of metabolism
o Single gene disorders
• Familial hypertrophic CM

(e.g., Pompe disease)

•
•
•
•

Neurofibromatosis
Friedrich ataxia
LEOPARD syndrome
Noonan syndrome: Only single gene disorder
likely to be diagnosed in utero
o Familial hypertrophic CM
• 50% have mutation of chromosome I, 14 or 15
• 30% missense mutation in cardiac ~ myosin heavy
chain gene on chromosome 14q 11
• 15% mutation in cardiac troponin T gene on
chromosome lq3
• 3% mutation in ()(tropomyosin gene on
chromosome 15q2
• Etiology
o Hypertrophic CM reported in 30% of fetuses of
diabetic mothers
• Higher if poor glycemic control
o Primary hypertrophic myocardium
• Noonan syndrome
• Glycogen storage disease
o Familial hypertrophic cardiomyopathy
• Case reports of fetal diagnosis with apical
hypertrophy
• Usually does not manifest until adolescence
o Non-compaction
of ventricular myocardium
• Pathologic entity characterized by abnormal
trabeculation of myocardium
• Thick-walled, non-dilated ventricles
• Atria enlarged due to atrioventricular regurgitation
o Midabdominal syndrome
• Coarctation type physiology with focal narrowing
of abdominal aorta
• Aortic narrowing ~ systemic hypertension
o Twin-twin transfusion syndrome (TITS)
• Increased work for pump twin heart, recipient has
volume overload
• Either/both may develop ventricular hypertrophy
• If untreated, ultimately progresses to dilated
end-stage heart disease
o Other high-output states
• Anemia
• Arteriovenous malformation

HYPERTROPHIC
• Twin reverse arterial perfusion (TRAP)
• Tumor: Sacrococcygeal teratoma
• Epidemiology
o CM (all types) 0.02:1,000 live births
o Series of SS cases fetal CM
• 44% dilated CM
• 66% hypertrophic CM
o Of 33 hypertrophic CM cases
• S4% TITS
• 21 % fetus of diabetic mother
• Physiology
o Ventricular walls and septum are thick
o Thick myocardium is stiff
o ! Compliance ~ ! filling ~ ! cardiac output
• Hypertrophic CM may cause diastolic dysfunction
o Myocardial perfusion occurs in diastole
o Diastolic dysfunction ~ myocardial
ischemia/myopathy
o Ischemia may ~ ventricular dilatation and
cardiomegaly

Microscopic

Features

• Pompe disease
o Muscle fibers infiltrated with glycogen
o Individual muscle fibers massively hypertrophied

CARDIOMYOPATHY
o Inborn errors of metabolism often autosomal
recessive
• May require specific treatment/dietary
measures
• Correct underlying conditions
o Laser/radiofrequency
ablation for TITS or TRAP
o Fetal surgery for tumors such as sacrococcygeal
teratoma
o Intrauterine transfusion for fetal anemia
• Monitor throughout pregnancy
o Hypertrophy may be progressive ~ secondary
outflow obstruction
• Refer to tertiary center
o Delivery plan coordinated with neonatology and
cardiology
o Careful postnatal evaluation
• Accurate diagnosis important to counsel parents
on prognosis/recurrence
risk
o Postnatal treatment options may be few
• Consider implantable cardiac defibrillator in
high-risk patients
• Cardiac transplantation
is last resort

I DIAGNOSTIC

CHECKLIST

Consider

I CLINICAL ISSUES
Presentation

• Formal fetal echocardiography
in all cases
o Exclude structural malformation
o Assess baseline function

Image Interpretation

• Most common signs/symptoms
o Most primary/familial cases present in third
trimester
o Fetuses of diabetic mothers may show progressive
increase in heart size/myocardial thickness from
second trimester onward
o Cases due to high-output state present earlier due to
underlying condition

I SELECTED

Natural History & Prognosis

1.

• Depends on underlying condition
o TITS high mortality if untreated
• Fetus of diabetic mother
o Disproportionate thickening of ventricular septum
or free wall
• Progressive throughout gestation
• Usually resolves within 6 months after birth,
prognosis excellent
• Technically not true cardiomyopathy, fetal
response to maternal hyperinsulinism
• Primary/familial forms
o Annual risk of death 1%
o Normal fetal echocardiogram does not imply
disease-free lifetime
• Familial forms may not have clinical impact until
adolescence or later

2.

3.

4.

5.

6.

7.

Treatment
• Detailed family history
o Consider echocardiography
of parents if mother not
diabetic
o Genetic testing possible for some types
• Ethical dilemma as presence of mutation does not
= presence of disease

Pearls

• Always check for mechanical obstruction
• In at-risk fetus measure ventricular shortening fraction
o Impaired systolic function may be seen before
chamber dilatation or hypertrophy

8.

9.

REFERENCES

Abu-Sulaiman RM et al: Congenital heart disease in infants
of diabetic mothers: echocardiographic study. Pediatr
Cardio!. 25(2):137-40, 2004
Barth PG et al: X-linked cardioskeletal myopathy and
neutropenia (Barth syndrome): an update. Am J Med Genet
A. 126(4):349-54,2004
Karatza AA et al: Isolated non-compaction of the
ventricular myocardium: prenatal diagnosis and natural
history. Ultrasound Obstet Gyneco!. 21(1):75-80, 2003
Zeltser I et al: Midaortic syndrome in the fetus and
premature newborn: a new etiology of nonimmune
hydrops fetalis and reversible fetal cardiomyopathy.
Pediatrics. 111(6 Pt 1):1437-42, 2003
Hajdu Jet al: Calcification of the fetal heart--four case
reports and a literature review. Prenat Diagn.
18(11):1186-90, 1998
Franzese A et al: Severe hypertrophic cardiomyopathy in an
infant of a diabetic mother. Diabetes Care. 20(4):676-7,
1997
Coates TL et al: Fetal cardiac rhabdomyomas presenting as
diffuse myocardial thickening. J Ultrasound Med.
13(10):813-6, 1994
Sonesson SE et al: Intrauterine diagnosis and evolution of a
cardiomyopathy in a fetus with Noonan's syndrome. Acta
Paediatr. 81(4):368-70, 1992
Stewart PA et al: Prenatal ultrasonic diagnosis of familial
asymmetric septal hypertrophy. Prenat Diagn. 6(4):249-56,
1986

HYPERTROPHIC

CARDIOMYOPATHY

jlMAGE GALLERY
(Left) This fetus with Barth
syndrome, an X-linked
cardiomyopathy,
has a thick
myocardium
(arrows) with
abnormal contractility. This
typically progresses to
dilated cardiomyopathy
in
infancy. (Right) Cross
pathology shows
non-compaction
of the
myocardium
with excessive
trabeculation (curved
arrows) and deep
inter-trabecular recesses
(arrow). Though rare, this
can be diagnosed in the fetus
and is associated with
systolic dysfunction.

(Left) Color Doppler
ultrasound shows significant
tricuspid regurgitation
(arrow). The regurgitant jet
during ventricular systole fills
the right atrium completely.
(LV: Left ventricle, RV: Right
ventricle). (Right) Four
chamber view shows
abnormally thick
myocardium
(arrows) in the
pump twin of a
monochorionic
twin
pregnancy, complicated by
TTTS. Note pericardial
effusion (curved arrow).

Typical
(Left) LVOT view in a
postnatal echocardiogram
shows severe asymmetric
septal hypertrophy, which
apposes the anterior leaflet
of mitral valve (MV) causing
left ventricular outflow tract
(arrow) obstruction. (LA: Left
atrium). (Right) Color
Doppler ultrasound in the
same patient with septal
hypertrophy shows turbulent
left ventricular outflow
(arrows) during systole, as
motion of the septum and
mitral valve causes
"dynamic" subaortic
stenosis.

DILATED CARDIOMYOPATHY

Thin myocardium and cardiomegaly developed after
monochorionic co-twin demise. Ischemic myocardium
and cystic encephalomalacia at autopsy were attributed
to severe hypotension at the time of twin demise.

ITERMINOLOGY
Abbreviations

and Synonyms

• Cardiomyopathy (CM)
• Dilated cardiomyopathy

Definitions
• Primary abnormality of cardiac muscle
o No structural malformation
o No pericardial disease
• In children CM is a diagnosis of exclusion, hard to
exclude some causative conditions in fetus
• Hypertrophic CM may progress to dilated CM if
underlying condition not treated

Radiograph shows a relatively normal lower body but
absent upper body in an acardiac twin. The pump twin
is at-risk for cardiomyopathy and hydrops as additional
cardiac work is required to perfuse the acardiac twin.

• Pleural effusion
• Ascites
• Skin edema
• Color Doppler
o Atrioventricular (AV)regurgitation
• Color regurgitant "jet" back into atrium during
systole
• Pulsed Doppler
o Atrioventricular regurgitation
• Retrograde flow into atrium during systole
o Signs of cardiac decompensation
• Reversed flow in inferior vena cava
• Reversed flow in ductus venosus
• Pulsatile flow in umbilical vein

Imaging Recommendations

IIMAGING

• Best imaging tool: Formal fetal echocardiogram
• Protocol advice
o Measure ventricular wall thickness
• From epicardial to endocardial surface
• Measure at end-diastole for minimum thickness
• Just below level of closed AVvalve leaflets
o Measure chamber dimensions
• Measure just below level of closed AVvalve
leaflets
• End-diastolic diameter (EDD) is largest
measurement at end-diastole

FINDINGS

General Features
• Best diagnostic clue: Cardiomegaly

Ultrasonographic

Findings

• Grayscale Ultrasound
o Large heart
o Poor myocardial contractility
o Myocardium often thin
o Signs of hydrops
• Pericardial effusion

DDx: Cardiomegaly

PseudoCM: 01

PseudoCM: TO

Ebstein Anomaly

Pulmonary Atresia

DILATED CARDIOMYOPATHY
Key Facts
Pathology

Terminology
• Primaryabn

rmality of cardiac mu cle

Imaging Findings
•
•
•
•
•

Large heart
Poor myocardial contractility
Myocardium often thin
Atrioventricular regurgitation
ome onditions cause initial myocardial
hypertrophy with a dilated heart as end- tage of
proce

Top Differential

Diagnoses

• Pseudocardiomegaly
• Outflow tract obstruction

o

o

o

o

o

o

• End-systolic diameter (ESD) is shortest
measurement at end-systole
Measure ventricular shortening fraction (VSF)
• VSF = EDD - ESD/EDD
• Normal right VSF 0.25
• Normal left VSF 0.30
Look for possible causative lesions
• Some conditions cause initial myocardial
hypertrophy with a dilated heart as end-stage of
process
Evaluate for fetal anemia
• Middle cerebral artery (MCA) Doppler
• Peak systolic velocity (PSV) of MCA plotted
against gestational age
• Determines when transfusion needed
Look for shunt lesions
• Twin-twin transfusion syndrome (TITS)
• Twin reverse arterial perfusion (TRAP)
• Arteriovenous malformation
• Fetal tumor
Look for signs of intrauterine infection
• Intracranial calcifications
• Intrahepatic calcifications
• Cerebral ventriculomegaly
• Hepatosplenomegaly
• Abnormal amniotic fluid volume
Monitor for development of hydrops

I DIFFERENTIAL

DIAGNOSIS

pseudocardiomegaly
• Heart size normal
• Chest is small
o Pulmonary hypoplasia
• Renal agenesis
• Bilateral multicystic dysplastic kidney
• Autosomal recessive polycystic kidney disease
• Posterior urethral valves
o Skeletal dysplasia
• Associated with severe limb shortening

• Familial transmi ion in 20-251}'b of cas s
• Dilated M detected in < 1% fetal echocardiograms

Clinical Issues
• Presence of hydrops i a poor progno tic sign
• Monitor for underlying arrhythmia
• urvivor may require cardiac transplantation

Diagnostic Checklist
• Formal fetal echocardiography
in all ca e
• Alway heck for shunt lesions in fetu with apparent
isolated cardiomegaly
• In at-ri k fetu , measure ventricular shortening
fraction
• Impaired ystolic function may be een before
chamber hypertrophy or dilatation

• Fractures/abnormal
mineralization seen with
osteogenesis imperfecta (01)
• Abnormal head shape in thanatophoric
dysplasia
(TD) type 2
• Characteristic "bell-shaped" chest in ]eune
asphyxiating thoracic dysplasia

Outflow

tract obstruction

• Critical aortic stenosis
• Ductal constriction
• Pulmonary atresia

Endocardial fibroelastosis
• Left ventricle may be large

Ebstein anomaly
• Marked enlargement

of right atrium

I PATHOLOGY
General Features
• Genetics
o Familial transmission in 20-25% of cases
• Autosomal recessive
• Autosomal dominant with age-related penetrance
• X-linked: Barth, Duchenne and Becker muscular
dystrophy
• Etiology
o Major causes of dilated CM
• High-output states
• Myocardial damage
• Carnitine deficiency
o High-output states
• Anemia
• Shunt
o Myocardial damage
• Infection
• Hypoxia/hypotension
• Sustained arrhythmia
• Immune complex deposition may cause
myocarditis
• Epidemiology

DILATED CARDIOMYOPATHY
o CM (all types) accounts for 2% of neonatal heart
disease
o Dilated CM detected in < 1% fetal echo cardiograms
• Likely under-represented in cardiology series as
underlying condition takes precedence
• Physiology
o Fetal anemia results in
• t Cardiac output (CO) to compensate for
decreased oxygen delivery
• t CO achieved by increasing stroke volume (SV) ±
heart rate (HR)
• t CO = increased cardiac work
• Eventually demand> supply
• End result myocardial ischemia/cardiomyopathy
o Shunt flow results in
• Increased venous return (VR)
• t VR ~ t SV ~ t CO
• t CO = increased cardiac work
• Eventually demand> supply
• End result myocardial ischemia/cardiomyopathy
o Fetal hypoxia results in
• Vasoconstriction
• Hypertension
• Bradycardia
• If prolonged ~ myocardial ischemia ~ myocardial
cell injury ~ cardiac decompensation

I CLINICAL ISSUES

I DIAGNOSTIC
Consider

• Formal fetal echo cardiography in all cases
o Exclude structural malformation
o Characterize arrhythmia
o Assess baseline function

Image Interpretation

Natural History & Prognosis
• Presence of hydrops is a poor prognostic sign
• Barth syndrome is often lethal early in infancy
• Duchenne and Becker muscular dystrophy
o Develop progressive cardiomyopathy as teenagers

Treatment
• Maternal infection screen
o Serology and direct culture
• Coxsackie B virus
• Echovirus
• Rubella
• Herpes simplex
• Parvovirus
• Cytomegalovirus (CMV)
• Detailed family history
o 30% of fetuses in one series were scanned due to
positive family history in siblings
o Consider echo cardiography of parents
• Monitor for underlying arrhythmia
o May require 24 hr monitoring
• Medically treat if found
• Correct underlying condition
o Laser/radiofrequency ablation for TITS or TRAP
o Intrauterine transfusion for fetal anemia
o Fetal surgery for tumor with large shunt flow
• Planned delivery at tertiary center with neonatology
and cardiology support
• Postnatal treatment options are few
o Survivors may require cardiac transplantation

Pearls

• Always check for shunt lesions in fetus with apparent
isolated cardiomegaly
o Placental chorioangioma
o Use color Doppler for arteriovenous fistula
• In at-risk fetus, measure ventricular shortening
fraction
o Impaired systolic function may be seen before
chamber hypertrophy or dilatation

I SELECTED REFERENCES
1.

2.
3.

4.

Presentation
• Most common signs/symptoms: Cardiomegaly
observed on routine obstetric sonogram

CHECKLIST

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

Boldt T et al: Etiology and outcome of fetuses with
functional heart disease. Acta Obstet Gynecol Scand.
83(6):531-5,2004
Brucato A et al: Proposal for a new definition of congenital
complete atrioventricular block. Lupus. 12(6):427-35,2003
Gladman G et al: Fetal echocardiographic screening of
pregnancies of mothers with anti-Ro and/or anti-La
antibodies. Am] Perinatol. 19(2):73-80, 2002
Siu BL et al: Transient dilated cardiomyopathy in a
newborn exposed to idarubicin and all-trans-retinoic acid
(ATRA)early in the second trimester of pregnancy. lnt]
Gynecol Cancer. 12(4):399-402,2002
Moak]P et al: Congenital heart block: development of
late-onset cardiomyopathy, a previously underappreciated
sequela.] Am Coil Cardiol. 37(1):238-42, 2001
von Kaisenberg CS et al: A case of fetal parvovirus B19
myocarditis, terminal cardiac heart failure, and perinatal
heart transplantation. Fetal Diagn Ther. 16(6):427-32,2001
Eronen M: Outcome of fetuses with heart disease
diagnosed in utero. Arch Dis Child Fetal Neonatal Ed.
77(1):F41-6, 1997
Krapp M et al: Venous blood flow pattern suggesting
tachycardia-induced 'cardiomyopathy' in the fetus.
Ultrasound Obstet Gynecol. 10(1):32-40, 1997
Respondek ML et al: The prevalence and clinical
significance of fetal tricuspid valve regurgitation with
normal heart anatomy. Am] Obstet Gynecol.
171(5):1265-70, 1994
Wilson N] et al: One year audit of a referral fetal
echocardiography service. N Z Med]. 107(981):258-60,
1994
Koyanagi T et al: Relationship between heart rate and
rhythm, and cardiac performance assessed in the human
fetus in utero. lnt] Cardiol. 28(2):163-71,1990
Silverman NH et al: Ventricular volume overload in the
human fetus: observations from fetal echocardiography. ]
Am Soc Echocardiogr. 3(1):20-9, 1990
Schmidt KG et al: High-output cardiac failure in fetuses
with large sacrococcygeal teratoma: diagnosis by
echo cardiography and Doppler ultrasound. ] Pediatr.
114(6):1023-8, 1989
Schmidt KG et al: Echocardiographic evaluation of dilated
cardiomyopathy in the human fetus. Am] Cardiol.
63(9):599-605, 1989
Kleinman CS et al: Fetal echocardiography for evaluation
of in utero congestive heart failure. N Engl] Med.
306(10):568-75, 1982

DILATED CARDIOMYOPATHY
IIMAGE

GALLERY
(Left) Four chambe>r vi{'\v
ultrasound shows significant
cardiomegaly
the atria are>
more dilated than the
ventricles. Note maximal
dilatation of the right atrium
(arrow). (Right) Color
Doppler ultrasound in the
same imaging plan{' shows
severe biventriculal;
atrioventricular valve
regurgitation. Blood refluxes
back into the atria (arrows)
during ventricular systole.
(LV: Left ventricle, RV: Right
ventricle) .

(Left) Four chamber view
shows significant
cardiomegaly with
pericardial effusion (arrow)
at 29 weeks gestation. The
fetus initially presented with
echogenic bowel at 78
weeks. (Right) Sagittal image
in the same fetus shows a
distended superior (arrow)
and inferior (curved arrow)
vena cava. The fetus was
delivered for poor
biophysical profile scores
and imminent hydrops.
Congenital CMV infection
was diagnosed by urine
culture.

Typical
(Left) Four chamber view
ultrasound shows
cardiomegaly with dilatation
of all four chambers in this
recipient twin in a pre>gnancy
complicated
by twin-twin
transfusion syndrome. There>
is also a pericardial eHusion
(arrow). (Right) Ultrasound
shows a large, dilated and
hypertrophied
RV (arrows)
in a fetus with Barth
syndrome, which progresSC's
in infancy to a dilated
cardiomyopathy

IRREGULAR

Pulsed
Doppler
ultrasound
shows
progressive
prolongation of the PR interval (arrows) with an atrial
contraction
(curved
arrows) not followed
by a
ventricular contraction (spikes below baseline).

ITERMINOlOGY
Abbreviations
•
•
•
•

and Synonyms

Premature atrial contractions (PAC)
Premature ventricular contraction (PVC)
Atrial flutter (AF)
Supraventricular tachycardia (SVT)

Definitions
• Irregular heart rhythm: Rate may be normal, fast or
slow

IIMAGING

FINDINGS

General Features
• Irregular heart rate observed on routine sonography

Ultrasonographic

Findings

• Grayscale Ultrasound: Asymmetric atrial/ventricular
contraction
• Pulsed Doppler
o Conducted PAC
• Early atrial contraction in cardiac cycle followed
by ventricular contraction
• Compensatory pause
• Sinus rhythm resumes
o Non-conducted PAC

RHYTHM

M-mode echocardiogram with color enhancement (red
= ventricular in/lovlI, blue = ventricular out/low) shows a
normally conducted sinus beat (curved arrow) followed
by a blocked PAC (arrow).

• Early atrial contraction in cardiac cycle not
followed by ventricular contraction
• Compensatory pause
• Sinus rhythm resumes
o PVC
• Early ventricular contraction in cardiac cycle
occurring without prior atrial contraction
• Non-compensatory
pause
• Sinus rhythm resumes

Imaging Recommendations
• Best imaging tool: Pulsed Doppler +/- color M-mode
• Formal fetal echocardiogram
o In fetus with frequent PACs
• Congenital heart defects reported in up to 2%
cases
• 2% risk of developing SVT, higher if multiple
beats are blocked
o Arrhythmias other than PAC/PVC
o Structural defects
o Valvular incompetence
• Look for signs of hydrops

I DIFFERENTIAL DIAGNOSIS
Premature atrial contraction
• Usually transient

and benign

DDx: Irregular Heart Rate

SVT

Intermittent SVT

2nd Degree HB

Atrial Flutter

IRREGULAR

RHYTHM

Key Facts
Terminology

Clinical Issues

• Irregular heart rhythm: Rate may be normal, fast or
slow

• Second degree heart block: Rare but concern for
progression to complete block
• PACs/PVCs usually require no treatment
• Weekly auscultation to monitor for development of
SVT

Top Differential
•
•
•
•
•

Diagnoses

Premature atrial contraction
Premature ventricular contraction
Supraventricular tachycardia
Atrial flutter
Second del!ree heart block

Premature ventricular

contraction

• Much less common than PACs, also transient and
benign

Supraventricular

tachycardia

• 1:1 AV relationship
• Characteristic rate 230-280, may be intermittent
• Usually re-entrant pathway

Atrial flutter
• Atrial rates typically 300-500 beats per minute
• Variable AVblock leads to irregular ventricular rate
o lf 2:1 block then ventricular rate is regular

Second degree heart block
• Type 1: Progressive increase in interval from atrial to
ventricular contraction with eventual dropped beat
o Generally benign and does not progress to complete
heart block
• Type 2: Atrial to ventricular conduction time is
prolonged and constant with intermittent
non-conducted atrial beats
o May progress to complete heart block

Diagnostic Checklist
• 90% of fetal arrhythmias

Treatment
• PACs/PVCs usually require no treatment
o Suggest reduction of maternal
caffeine/alcohol/nicotine
intake
o Weekly auscultation to monitor for development of
SVT
• SVT/atrial flutter
o Treatment recommended to prevent hydrops
o Digoxin first line

I DIAGNOSTIC

• Formal fetal echocardiogram

Image Interpretation

Pearls

• 90% of fetal arrhythmias due to PACs/PVCs

I SELECTED REFERENCES
1.

I PATHOLOGY
• Epidemiology
o 1-2% of pregnancies will have arrhythmia
• < 10% are significant, PACs/PVCs account for 90%

CHECKLIST

Consider

2.

General Features

due to PACs/PVCs

3.

Fouron ]C: Fetal arrhythmias: the Saint-Justine hospital
experience. Prenat Diagn. 24(13):1068-80, 2004
Larmay H] et al: Differential diagnosis and management of
the fetus and newborn with an irregular or abnormal heart
rate. Pediatr Clin North Am. 51(4):1033-50, x, 2004
Krapp M et al: Review of diagnosis, treatment, and
outcome of fetal atrial flutter compared with
supraventricular tachycardia. Heart. 89(8):913-7, 2003

IIMAGE GALLERY

I CLINICAL ISSUES
Presentation

.4.-~~
__
"_. ;...
.~_
-..
~ ..•...••...... -~

• Abnormal heart rate or rhythm noted on physical
exam

~~~~~~

Natural History & Prognosis
• PACs and PVCs
o Self limited: Most resolve by time of delivery,
extremely rare to cause problem in neonate
• Supraventricular tachycardia
o Usually easy to treat but 9% mortality rate
• Atrial flutter
o Occurs later in gestation, 8% mortality rate
• Second degree heart block: Rare but concern for
progression to complete block

T-T
Dist
aT

aT -4

=
=

0.03cm
0.108s

= 553bpm

(Left) M-mode ultrasound shows atrial flutter with atrial rate of 553
bpm. The ventricular rate was variable, up to 248 bpm. (Right)
Pulsed Doppler ultrasound shows two sinus beats (arrows) followed
by non-conducted premature atrial beats (curved arrows), with an
intervening conducted premature atrial beat with ventricular
contraction (open arrow) .

TACHYARRHYTHMIA

Graphic shows Doppler cursor position for evaluation of
arrhythmia. Flow during an atrial contraction (arrow) is
toward the transducer, while flow during a ventricular
contraction (curved arrow) is away from the transducer.

• M-mode
o Place M-mode cursor to include both atrium and
ventricle
• Evaluate atrial and ventricular rates and AV
conduction
• Is every atrial contraction followed by a
ventricular contraction?

ITERMINOlOGY
Abbreviations
•
•
•
•
•

and Synonyms

Sinus tachycardia
Supraventricular tachycardia (SVT)
Atrial fibrillation
Atrial Flutter (AF)
Permanent junctional reciprocating tachycardia

(PJRT)

Definitions
• SVT: Heart rate> 200 beats per minute (bpm)

IIMAGING FINDINGS
General Features
• Sustained fast heart rate> 200 bpm
oM-mode tracing or pulsed Doppler must be
performed to determine type of arrhythmia

Ultrasonographic

Findings

• Color Doppler: Useful to document atrioventricular
(AV) valve regurgitation
• Pulsed Doppler
o Cursor placed in left ventricle at junction of mitral
valve and left ventricular outflow tract
• Mitral inflow = atrial rate
• Left ventricular outflow = ventricular rate

DDx: Tachyarrhythmias

---.

-~--"',~-

-.-

-

- ..-.r

svr

.-....,

Pulsed Doppler ultrasound sample volume placed in LV
to overlap inflow and outflow shows 7: 7 conduction
with atrial flow (arrow) occurring after ventricular flow
(curved arrow) suggesting are-entrant SVT.

Imaging Recommendations
• Best imaging tool
o Pulsed Doppler for SVT
oM-mode for atrial flutter
• Formal fetal echocardiography
for structural defects
o Seen in up to 10% of tachyarrhythmias
• Look for signs of hydrops
o Abnormal fluid location
• Pericardial effusion
• Pleural effusion
• Ascites
• Skin edema
o Cardiomegaly
• Track by measuring ratio of heart to chest
circumference
• Look for signs of hemodynamic decompensation
o Flow reversal in inferior vena cava
o Flow reversal in ductus venosus
o Pulsatile flow in umbilical vein
o Significant AV valve regurgitation

And Consequences

- -

SVT: Hydrops

SVT: Hydrops

Atrial Flutter

TACHYARRHYTHMIA
Key Facts
Clinical Issues

Imaging Findings

•
•
•
•

• Sustained fast heart rate> 200 bpm

Top Differential Diagnoses
•
•
•
•
•

Supraventricular tachycardia
Atrial flutter
Atrial fibrillation
Permanent junctional reciprocating
Ventricular tachycardia

tachycardia

Pathology
• 1-2% of pregnancies have arrhythmia
• Only about 10% clinically significant
• 1-5% of fetuses with premature atrial contractions
will develop SVT
• Ventricular rates> 230 bpm ~ t fetal central venous
pressure

Most reported cases present in third trimester
Postnatal cardiac evaluation required for all
Arrhythmias can recur/persist in neonatal period
Hydrops present or develops in 50-75% fetuses with
sustained tachyarrhythmia
• Overall fetal demise:::: 10%
• Digoxin first-line drug, with 60% successful
conversion of SVT
• Hydropic fetus unlikely to convert to normal rhythm
with digoxin monotherapy

Diagnostic Checklist
• SVT is commonest fetal tachyarrhythmia
• Vital to differentiate types of tachyarrhythmia
due to
different therapies
• Presence/absence of hydrops impacts mortality
o 170-400 bpm recorded
o AV dissociation
• Rare in fetus, associated with
o Ventricular ischemia/infarction
o Ventricular aneurysm
o Perinatal stress/hypoxia

• Complete anatomic survey
• Assess fetal well-being
o Biophysical profile, daily at first

I DIFFERENTIAL DIAGNOSIS
Supraventricular tachycardia
•
•
•
•

Most common fetal tachyarrhythmia
1:1 AV relationship
Characteristic rate 230-280 bpm, may be intermittent
Usually re-entrant pathway

Sinus tachycardia
• May be response to maternal condition
o Thyrotoxicosis, fever, sepsis, or drugs
• Characteristic rate 170-200 bpm
• 1:1 AV relationship

Atrial flutter
• Atrial rate> ventricular rate
• Atrial rate 300-500 bpm, regular
• Variable AV block
o If 2:1 block then ventricular rate is regular
o Variable block leads to irregular ventricular

rate

Atrial fibrillation
•
•
•
•

Atrial rate> ventricular rate
Atrial rate 300-500 bpm, irregular
Variable conduction ~ variable ventricular
Rare in fetus

rate

Permanent junctional reciprocating
tachycardia
• 1:1 AV relationship
• Characteristic rate"" 200 bpm
• Impulse starts at AV junction and recurs along specific
re-entrant pathway
• Rare and very difficult to treat

Ventricular tachycardia
• Ventricular rate> atrial rate
o No characteristic rate

I PATHOLOGY
General Features
• Genetics
o Sporadic
o Few familial pre-excitation syndromes
• Accessory pathway identified in first degree
relatives in 1.06%
• General population prevalence 0.15%
• Etiology
o SVT usually re-entrant pathway between atrium and
ventricle
o Atrial flutter: Single re-entry circuit within atrium
o Atrial fibrillation: Multiple small intra-atrial re-entry
circuits
• Epidemiology
o 1-2% of pregnancies have arrhythmia
• Only about 10% clinically significant
o Of fetuses with tachyarrhythmia
• SVT in 65-93%
• Atrial flutter in 7-29%
• Ventricular tachycardia in < 4%
o 1-5% of fetuses with premature atrial contractions
will develop SVT
• Physiology
o Ventricular rates> 230 bpm ~ t fetal central venous
pressure
o t Venous pressure ~ flow reversal in inferior vena
cava
o Short diastole => ~ myocardial perfusion
o Ischemic ventricles dilate => AV valve regurgitation
o AV regurgitation => further increase in venous
pressures/hepatic congestion
o End result is hydrops

TACHYARRHYTHMIA
• May be given orally
• Fetal levels near 100% maternal levels
• Concern for proarrhythmic effects in mother and
fetus
• Success rate"" 60%

ICLINICALISSUES
Presentation
• Abnormal fetal heart rate noted on physical
examination
• Most reported cases present in third trimester
oRange 18-42 weeks

Natural History & Prognosis
• Postnatal cardiac evaluation required for all
• Arrhythmias can recur/persist in neonatal period
o 48% in one series of fetuses with atrial flutter/SVT
o 8-10% of fetuses with SVT will be diagnosed with
Wolf-Parkinson-White syndrome
• Prognosis generally good for intermittent SVT
• Hydrops present or develops in 50-75% fetuses with
sustained tachyarrhythmia
o Complicates treatment
o Harder to achieve therapeutic levels of medication
• Overall fetal demise "" 10%
o Worse with hydrops
• Recent reports indicate concern for ischemic brain
injury in association with hydrops

Treatment
• Multidisciplinary team approach most effective
• Delivery may be simplest treatment option if
gestational age allows
• Intermittent SVT without hemodynamic
decompensation
o Careful conservative management
• Daily scan and biophysical profile initially
• Patient compliance is key, as persistent SVT with
hydrops may develop within 24 hrs
o Spontaneous resolution has been reported
o Vagal stimulation in labor slows AV conduction ~
may decrease rate
• Persistent SVT in immature fetus
o Digoxin first-line drug, with 60% successful
conversion of SVT
• May be given orally or intravenously to mother
• Monitor maternal serum levels
• Fetal levels approximately 80% of maternal levels
o If failure to convert rhythm, additional medications
(Flecainide) raise success rate another 25%
• Hydropic fetus unlikely to convert to normal rhythm
with digoxin monotherapy
o Response rate to digoxin alone 20%
o Hydropic fetuses do not attain same blood levels as
non-hydropic
o Requires additional medications or direct therapy to
achieve success rate of 65%
• Flecainide: Potential fast response, may cause
maternal proarrhythmia
• Amiodarone: May be successful, case reports of
neonatal hypothyroidism
• Atrial Flutter
o Digoxin monotherapy is successful in 45-55% of
non-hydropic fetuses
• Add Sotalol if failure to convert rhythm; success
rate increases to 80%
o Recommend Sotalol alone or in combination with
Digoxin in hydropic fetus

I DIAGNOSTIC

CHECKLIST

Consider
• Formal fetal echocardiogram
o Look for associated structural disease
o Assess baseline function
o Look for signs of hydrops

Image Interpretation

Pearls

• SVT is commonest fetal tachyarrhythmia
• Vital to differentiate types of tachyarrhythmia due to
different therapies
• Presence/absence of hydrops impacts mortality

I SELECTED
1.

2.
3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

REFERENCES

Gimovsky ML et al: Fetal/neonatal supraventricular
tachycardia. J Perinatol. 24(3):191-3, 2004
Kleinman CS et al: Cardiac arrhythmias in the human
fetus. Pediatr Cardiol. 25(3):234-5 I, 2004
Larmay HJ et al: Differential diagnosis and management of
the fetus and newborn with an irregular or abnormal heart
rate. Pediatr Clin North Am. 51(4):1033-50, x, 2004
Un MT et al: Postnatal outcome of fetal bradycardia
without significant cardiac abnormalities. Am Heart J.
147(3):540-4,2004
Yumoto Y et al: Prenatal diagnosis of slow-rate ventricular
tachycardia using fetal electrocardiography. Prenat Diagn.
24(6):463-7, 2004
Fouron JC et al: Management of fetal tachyarrhythmia
based on superior vena cava/aorta Doppler flow recordings.
Heart. 89(10):1211-6, 2003
Krapp M et al: Review of diagnosis, treatment, and
outcome of fetal atrial flutter compared with
supraventricular tachycardia. Heart. 89(8):913-7, 2003
Laventhal NT et al: Fetal tachyarrhythmia associated with
vibroacoustic stimulation. Obstet Gynecol. 101(5 Pt
2):1116-8,2003
Nachum Z et al: Graves' disease in pregnancy: prospective
evaluation of a selective invasive treatment protocol. Am J
Obstet Gynecol. 189(1):159-65,2003
Nakata M et al: Successful treatment of supraventricular
tachycardia exhibiting hydrops fetalis with flecainide
acetate. A case report. Fetal Diagn Ther. 18(2):83-6, 2003
Oudijk MA et al: Treatment of fetal tachycardia with
sotalol: transplacental pharmacokinetics and
pharmacodynamics. J Am Coil Cardiol. 42(4):765-70, 2003
Oudijk MA et al: Persistent junctional reciprocating
tachycardia in the fetus. J Matern Fetal Neonatal Med.
13(3):191-6,2003
Porat S et al: Fetal supraventricular tachycardia diagnosed
and treated at 13 weeks of gestation: a case report.
Ultrasound Obstet Gynecol. 21(3):302-5, 2003
Simpson JM et al: Fetal tachycardias: management and
outcome of 127 consecutive cases. Heart. 79(6):576-81,
1998
Simpson JM et al: Outcome of intermittent
tachyarrhythmias in the fetus. Pediatr Cardiol. 18(2):78-82,
1997

TACHYARRHYTHMIA
IIMAGE

GALLERY

Typical
(Left) M-moclc ultrasound
with cursor placed across the
right ventricle (arrow) and
right atrium. Rapid atrial and
ventricular rates in a fetus
with SVT (248 bpm) are
demonstratccl hy the
tricuspid valvc closure
(cursor lim's!. (Right)
M-mode ultrasound shows a
run of supraventricular
tachycardia (arrows) with
spontaneous
return to sinus
rhythm (curved arrows).
Prognosis is generally goocl
for intermillcllt SVT but closc
monitoring is rCCfuired.

(Left) M-mode ultrasound
with color cnhancement
(blue ventricular outflow, rcd
ventricular inflow) shows a
rapid ventricular rate with an
atrial contraction (curved
arrows) occurring after the
ventricular contraction
(arrows) due to PIRT (Right)
M-mode ultrasound in a
fetus with atrial flulter shows
a very rapid atrial rate
(arrows) measured at 535
bpm. VariablE' AV block
resulted in a ventricular rate
of 232 bpm, measured by
the aortic valve motion
(curved arrows).

(Left) Four chamber view
shows right heart
enlargement, particularly
right atrial (arrows).
Myocardial function was
poor secondary to
tachyarrhythmia.
This
increases concern for
development
of hydrops.
(Right) Ultrasound shows
severe forehead skin edema
(arrow) in this fetus with
hydrops due to sustained
tachyarrhythmia.
It is hard"1
to achieve therapeutic serum
drug levels once hydrops
develops.

BRADYARRHYTHMIA

Graphic shows Doppler cursor position for evaluation of
arrhythmia. Flow during an atrial contraction (arrow) is
toward the transducer; while flow during a ventricular
contraction (curved arrow) is away from the transducer.

Axial oblique M-mode ultrasound shows complete heart
block with a ventricular rate oi 53 bpm in a ietus with
an atrioventricular septal deiect.

ITERMINOLOGY

IIMAGING

Abbreviations

General Features

•
•
•
•
•

and Synonyms

Sinus bradycardia
Partial atrioventricular block
Complete atrioventricular block
Complete heart block (CHB)
Blocked premature atrial contractions

FINDINGS

• Heart rate persistently

Ultrasonographic
(PAC)

Definitions
• Abnormally slow heart rate < 100 beats per minute
(bpm)
• Sinus bradycardia
o Atrial and ventricular rates same
o Due to primary slowing of atrial rate
o Normal conduction from atrium to ventricle
• Complete atrioventricular block
o Atrial rate normal
o Slow independent ventricular rate
o Due to failed conduction from atrium to ventricle
• Partial atrioventricular block
o First or second degree heart block
o Long PR interval with variable ventricular
conduction
• Blocked PACs
o Early atrial beat not followed by a ventricular beat

< 100 bpm

Findings

• Grayscale Ultrasound
o Cardiac anatomy normal in 50%
o Structural defects present in 50%
• Pulsed Doppler
o Cursor placed in left ventricle at junction of mitral
valve and left ventricular outflow tract
• Mitral inflow = atrial rate
• Left ventricular outflow = ventricular rate
• M-mode
o Place M-mode cursor to include both atrium and
ventricle
• Evaluate atrial and ventricular rates and
atrioventricular conduction
• Is every atrial contraction followed by a
ventricular contraction?

Imaging Recommendations
• Best imaging tool: Pulsed Doppler
• Formal fetal echocardiography
o Look for structural defects commonly
with CHB
• Atrioventricular septal defect

DDx: Bradycardia

Blocked

PACs

2nd Degree I-IB

Transducer Pressure

Pressure 0((

seen in fetuses

BRADYARRHYTHMIA
Key Facts
Terminology

• Risk of fetal CHB with maternal lupus up to 5%

• Abnormally slow heart rate < 100 beats per minute
(bpm)

Clinical Issues

Imaging Findings
• Cardiac anatomy normal in 50%
• Structural defects present in 50%

Top Differential Diagnoses
•
•
•
•

Transient sinus bradycardia
Blocked PAC
Complete heart block
Partial AVblock

• First trimester bradycardia associated with high
pregnancy failure rate
• Poor prognosis with structural abnormality
• Normal structure/no hydrops ~ 90% survival
• Positive antibody screen in 85% of mothers of fetuses
with CHB and normal cardiac structure
• Fetal cardiac pacing has been achieved but did not
prevent fetal demise
• Consider cesarean delivery
• Deliver at tertiary center with cardiology support

Pathology

Diagnostic Checklist

• 50% of cases in mothers with connective tissue
disease

• Fetus with CHB may be first presentation
autoimmune disease

• Atrioventricular discordance
• Heterotaxy syndromes
o Assess myocardial function
• Track by measuring ventricular shortening
fraction (VSF)
• VSF = end-diastolic diameter minus end systolic
diameter/end-diastolic diameter
o Assess heart size (cardiomegaly)
• Track by measuring ratio of heart to chest
circumference
o Look for signs of hemodynamic decompensation
• Significant atrioventricular valve regurgitation
• Reversal of flow in vena cava
• Reversal of flow in ductus venosus
• Umbilical vein pulsation
• Look for evidence of hydrops
o Abnormal fluid accumulation
• Pericardial effusion
• Pleural effusion
• Ascites
• Skin edema
• Use umbilical artery Doppler to monitor placental
vascular resistance
o t Risk of placental insufficiency
o Increasing placental resistance may precipitate
hydrops without further decrease in heart rate
o Maternal lupus may '* segmental placental
infarction
• Monitor growth
o CHB '* decreased placental perfusion '* growth
restriction

I DIFFERENTIAL

DIAGNOSIS

Transient sinus bradycardia
• May be caused by excessive transducer pressure
• Heart rate quickly returns to normal with release of
transducer pressure

Blocked PAC
• Intermittent,
ventricle

early atrial beat without conduction

to

of maternal

Complete heart block
• Independent,
contractions

disassociated atrial and ventricular

Partial AVblock
• Second degree heart block
o Type 1: Progressive increase in PR interval with
eventual dropped beat
o Type 2: Atrial-to-ventricular conduction time is
prolonged and constant, with intermittent
non-conducted beats

I PATHOLOGY
General Features
• Etiology
o 50% of cases in mothers with connective tissue
disease
o Other 50% associated with cardiac malformation
particularly atrioventricular septal defects
o Maternal antibodies cross placenta
• Mother has anti-SSAjRo +/- anti-SSB/La antibodi~s
• Fetal/neonatal myocardium contains body's
highest concentration Ro antigen
• Maternal antibody binds to fetal antigen
• Inflammation/fibrosis of fetal heart conduction
system and myocardium
• Fibrosis inhibits repolarization
o Another, as yet unknown, cofactor may also be
present
• Majority of mothers with anti-SSA/Ro and
anti-SSB/La antibodies have normal pregnancies
• Trigger to fetal cardiac damage may be viral
exposure
• Mothers of fetuses with CHB have increased
frequency of antibodies to cytomegalovirus
• Epidemiology
o 1-2% of pregnancies have arrhythmia
o CHB accounts for 9% of all fetal arrhythmias
o Risk of fetal CHB with maternal lupus up to 5%
o Risk of fetal CHB for antibody positive mother ~ 2%

BRADYARRHYTHMIA
o CHB 1:20,000 live births
• Fetal incidence likely higher due to loss rate in
association with heterotaxy syndromes
• Physiology
o Slow heart rate => progressive ventricular dilation
o Ventricular dilation => distortion of atrioventricular
valve ring
o Tricuspid regurgitation => increased right atrial
pressure
o Venous hypertension => hepatic congestion, ascites,
effusions and edema (hydrops)

I CLINICAL

ISSUES

Presentation
• First trimester bradycardia noted on viability/dating
studies
• In 2nd/3rd trimester, slow heart rate noted on physical
examination
• May initially present with irregular rate from second
degree heart block
o In utero progression from second degree heart block
to CHB has been described

Natural History & Prognosis
• First trimester bradycardia associated with high
pregnancy failure rate
o Survivors likely to have structural disease, especially
heterotaxy syndromes
• Increased mortality with heart rate < 50 bpm
o 15-25% will develop hydrops
o Intrauterine fetal demise"" 75%
• Poor prognosis with structural abnormality
o Survival < 15%
• Normal structure/no hydrops => 90% survival
• In at-risk pregnancy monitor fetal PR interval
o Prolongation may be first sign of immune-mediated
disease
• If bradycardia due to maternal antibodies, significant
risk for neonatal lupus syndrome
o Not equivalent to systemic lupus erythematosus,
self-limiting condition
• Thrombocytopenia, anemia, low white cell count
• Hepatomegaly/cholestasis
• Skin rash/photosensitivity
o Usually resolves by 6 months as antibodies clear
from infant circulation
o Syndrome resolves but damage to conducting
system is permanent
• Some series show significant incidence of progression
to dilated cardiomyopathy in childhood
o Survivors require close follow-up with pediatric
cardiology
• Recurrence risk
o 8-16% in mother with anti-Rolla antibodies and a
previous child with CHB
o 25-64% if previous child with neonatal lupus
manifesting CHB

Treatment
• Maternal evaluation by rheumatologist
o Positive antibody screen in 85% of mothers of
fetuses with CHB and normal cardiac structure

• Treatment aim
o Dampen fetal inflammatory response
• Limited efficacy using steroids, plasmapheresis,
and intravenous immunoglobulin
o Increase fetal heart rate
• Beta agonists (e.g., terbutaline)
• Poor maternal tolerance at dose sufficient to
increase fetal heart rate
• Fetal cardiac pacing has been achieved but did not
prevent fetal demise
• Consider cesarean delivery
o Stress of vaginal delivery may => acute
decompensation
o Intrapartum monitoring extremely difficult due to
bradycardia
• Deliver at tertiary center with cardiology support
o Cardiac pacing required for definitive treatment

I DIAGNOSTIC

CHECKLIST

Consider
• Formal fetal echocardiography

Image Interpretation

Pearls

• Bradycardia with structural malformation confers poor
prognosis
• Fetus with CHB may be first presentation of maternal
autoimmune disease

I SELECTED
1.

REFERENCES

Buyon]P et al: Neonatal lupus syndromes. Lupus.
13(9):705-12,2004
2. Kleinman CS et al: Cardiac arrhythmias in the human
fetus. Pediatr Cardio!. 25(3):234-51, 2004
3. Un MT et al: Postnatal outcome of fetal bradycardia
without significant cardiac abnormalities. Am Heart J.
147(3):540-4, 2004
4.
Novi JM et al: Use of a subcutaneous
beta-sympathomimetic pump for the treatment of fetal
congenital complete heart block. A case report. ] Reprod
Med. 48(11):893-5, 2003
5. Vesel S et al: Successful outcome in a fetus with an
extremely low heart rate due to isolated complete
congenital heart block. Ultrasound Obstet Gynecol.
21(2):189-91,2003
6.
Friedman OM et al: Congenital heart block in neonatal
lupus: the pediatric cardiologist's perspective. Indian J
Pediatr. 69(6):517-22, 2002
7.
Gladman G et al: Fetal echocardiographic screening of
pregnancies of mothers with anti-Ro and/or anti-La
antibodies. Am J Perinatol. 19(2):73-80,2002
8. Eronen M et al: Congenital complete heart block in the
fetus: hemodynamic features, antenatal treatment, and
outcome in six cases. Pediatr Cardio!. 22(5):385-92, 2001
9.
Moak JP et al: Congenital heart block: development of
late-onset cardiomyopathy, a previously underappreciated
sequela. J Am Coli Cardio!. 37(1):238-42, 2001
10. Eronen M et al: Short- and long-term outcome of children
with congenital complete heart block diagnosed in utero or
as a newborn. Pediatrics. 106(1 Pt 1):86-91, 2000
11. Groves AM et al: Outcome of isolated congenital complete
heart block diagnosed in utero. Heart. 75(2):190-4, 1996

BRADYARRHYTHMIA
I IMAGE GAllERY
Typical
(Left) Pulsed Doppler
ultrasound shows the normal
PR interval in a 22 week
fetus. This is measured from
the onset of the A wave
(arrow) to the onset of aortic
outflow (curved arrow).
(Right) Pulsed Doppler
ultrasound shows
prolongation of the PR
interval from onset of the A
wave (arrow) to the onset of
aortic outflow (curved
arrow). This may be the first
sign of fetal conduction
system damage. (Courtesy
D. Friedman, MD).

(Left) M-mode ultrasound
with color enhancement
(red
= ventricular inflow and blue
= outflow)
shows second
degree heart block. There is
2: 7 block, with two atrial
contractions (curved arrows)
for each ventricular
contraction (arrow). (Right)
Pulsed Doppler ultrasound
shows complete heart block,
with the rate of atrial
contraction (open arrows)
independent
of the rate of
ventricular contraction
(arrows).

Typical
(Left) M-mode ultrasound in
the first trimester shows a
heart rate of 65 bpm. The
patient had a history of
recurrent spontaneous
abortions. This ominous
finding is associated with a
high pregnancy t~li1ure rate.
(Right) Coronal ultrasound of
a hydropic fetus shows
cardiomegaly
(curved
arrow), ascites (arrow) and
skin edema (open arrow).
Mortality approximates
75';;,
when hydrops occurs with
bradycardia.

RHABDOMYOMA

Long-axis view of the fetal heart showing the left
ventricular outflow tract demonstrates a well-defined,
echogenic mass (arrow) within the left ventricle (Ao aorta).

Cross pathology of the heart in the same case shows a
well-defined mass (arrow) arising from the wall of the
left ventricle. Histology confirmed a rhabdomyoma.

• May cause hydrocephalus

!TERMINOlOGY

Echocardiographic Findings

Definitions
• Congenital cardiac hamartoma composed
myocytes
• Most common fetal cardiac tumor

of abnormal

IIMAGING FINDINGS
Ultrasonographic Findings
• Well-defined, hyperechoic, intracardiac mass
o Small masses within wall may appear as wall
thickening
• Often multiple
• Requires close follow-up to monitor growth
• Can detect as early as 22 weeks gestation
o May discover more as pregnancy progresses
• Hydrops may develop from arrhythmia or outflow
tract obstruction
o Watch for ascites, pleural effusion, pericardial
effusion, skin thickening
• Look for other findings of tuberous sclerosis
o Subependymal nodules
• Nodularity along ventricular walls
• Often difficult to discern
o Subependymal giant cell astrocytoma
• Mass near the foramen of Monro

• Tumor arising from ventricles or intraventricular
septum
• Most often affects left ventricle
• Monitor cardiac function for potential complications
o Arrhythmia
• Premature atrial or ventricular beats
• Supraventricular tachycardia
• Sinus bradycardia
o Outflow tract obstruction
o Associated cardiac anomalies are uncommon

Imaging Recommendations
•
•
•
•

Dedicated cardiac echo in all cases
Follow closely for progression/hydrops
Look for findings of tuberous sclerosis
Fetal brain MRI recommended
o Subependymal nodules and cortical/subcortical
tubers
• High signal intensity of T1 WI
• Low signal intensity on T2WI
• Postnatal brain MRI should be done in all cases even if
in utero scan is normal
o Fetal findings may be difficult to discern
o May use gadolinium

DDx: Echogenic Cardiac Masses

Hypertrophic

eM

Pericardia! Teratoma

RHABDOMYOMA
Key Facts
Terminology
•

Pathology

ongenital cardiac hamartoma
abnormal myocyte

compo ed of

Imaging Findings
• Well-defined, hyperechoic, intracardiac mass
• Require close follow-up to monitor growth
• Hydrops may d velop from arrhythmia or outflow
tract obstruction
• Most often affects left ventricle
• Associated cardiac anomalies are uncommon

Top Differential
•
•
•
•

Diagnoses

Teratoma
Fibroma
Echogenic cardiac focus (E F)
Hypertrophic cardiomyopathy
( M)

I DIFFERENTIAL

DIAGNOSIS

Teratoma
•
•
•
•

•
•
•
•

•
•

Rare tumor
Histopathologically usually benign
Fetal echocardiography
critical for diagnosis
Pericardial (not myocardial) tumor
o Exophytic growth (will not be in cardiac chamber)
o Frequently located at right anterior heart border
Heterogeneous with calcification
Solid and cystic components
Pericardial effusion often present
May cause heart failure due to pericardial effusion and
cardiac compression
o Symptoms more related to size and location than
histology
o Look for signs of hydrops
o Fetal pericardiocentesis can prevent cardiac
tamponade
Worse prognosis if associated with hydrops
Surgical removal usually curative

Fibroma
• Usually solitary
• Benign proliferation of connective tissue
o May infiltrate normal myocardium
• Often arises from intraventricular septum or free wall
of left ventricle
o Right ventricle may be involved
• Intramural solid echogenic lesion
o Occasionally can be inhomogeneous
if associated
with cystic degeneration
• May be associated with pericardial effusion
• Postnatal MRI
o Isointense on Tl WI
o Hypointense on T2WI
o Strong enhancement

Hemangioma
• Hyperechoic
• Variable vascularity with Doppler
• Avid enhancement on postnatal CT

•

omprises 901}!J of fetal cardiac tumors
of f tuses have tuberou sclerosi
• Multiple in 50% of cases
• SO-851M)

Clinical Issues
• Usually spontaneously regress postnatally
• Poor prognostic indicator if associated with cardiac
dysfunction
• on sider preterm ce arean section if hemodynamic
obstruction identified
• Genetic counseling for tuberous sclerosis

Diagnostic Checklist
• Multiple rhabdomyomas
sclerosis

strongly suggests tuberous

• Can be associated with pericardium
• Presents with cardiac symptoms
o Pericardial or pleural effusion
o Arrhythmia
o Heart failure
• Asymptomatic lesions may be observed
o Can regress spontaneously

Myxoma
• Myxomas not typically seen in utero
o Most arise from interatrial septum/region
foramen ovale
o Left atrium> right atrium

of

Echogenic cardiac focus (ECF)
•
•
•
•
•

Papillary muscle
Small (usually < 3 mm)
Very bright (similar to bone)
78% in left ventricle
Associated with both trisomy 21 and 13
o Need to evaluate for other associated findings

Hypertrophic

cardiomyopathy

(CM)

• Thickened myocardium
o Intraventricular septum and free wall
• Fetuses of diabetic mothers at risk, especially if poor
glycemic control
• Response to increased workload
o Anemia
o Masses (e.g., sacrococcygeal teratoma)
o Twin-twin transfusion syndrome
o Twin reverse arterial perfusion

Outflow

tract obstruction

• Increased cardiac work to overcome obstruction
wall hypertrophy
• Aortic atresia/stenosis
• Pulmonary stenosis/atresia
• Ductal constriction

Endocardial fibroelastosis
• Echogenic endocardium
• Poor contractility

and papillary muscles

=>

RHABDOMYOMA

I PATHOLOGY
General Features
• Genetics
o Tuberous sclerosis autosomal dominant with
variable expressivity
• About 50% of cases inherited
• Other cases due to new mutation
• Most commonly arise on ventricular septum but may
be anywhere
• Compression of adjacent lung may occur with large
masses
o Does not necessarily result in lung hypoplasia
• Critical period for lung development 18-20 weeks
• Lung compression may be minimal at that point
• Comprises 90% of fetal cardiac tumors
• 50-85% of fetuses have tuberous sclerosis
• Multiple in 50% of cases
o Increases likelihood of tuberous sclerosis (> 80%)
• Features of tuberous sclerosis
o Clinical triad
• Seizures
• Mental retardation
• Cutaneous angiofibromas
o Cardiac
• Rhabdomyomas (most common in utero finding)
o Brain
• Cortical tubers
• Subependymal nodules
o Renal
• Angiomyolipomas and cysts (not seen in utero)

Gross Pathologic & Surgical Features
• Encapsulated intramyocardial
• Benign tumor

Microscopic

or exophytic

mass

Features

• Large vacuolated myocytes
• Glycogen-rich vacuoles stretch the perinuclear
cytoplasm (spider cells)

I CLINICAL

ISSUES

Presentation
• Generally incidental finding
• Rarely presents with arrhythmia

or hydrops

Natural History & Prognosis
• Most often has benign clinical course prenatally
• May grow in conjunction with gestational age or
remain stable
o Majority of growth may occur in 2nd and 3rd
trimesters
o Growth slows after 32 weeks
o Multiple and large lesions more likely to grow in
utero
o Smaller or single lesions may remain stable or
demonstrate slow growth in utero
• Usually spontaneously regress postnatally
o Both isolated and if associated with tuberous
sclerosis
• Good prognosis if no complications in utero or first 6
months of life

• Poor prognostic indicator if associated with cardiac
dysfunction
o Arrhythmia, intracardiac flow obstruction
o Atrioventricular valve dysfunction or regurgitation
• Seizures and impaired cognitive function may be
present with tuberous sclerosis

Treatment
• Prenatal
o Consider preterm cesarean section if hemodynamic
obstruction identified
o May infrequently require prenatal therapy with
antiarrhythmics
o Genetic counseling for tuberous sclerosis
• Postnatal
o Most regress without treatment
o Cardiac evaluation after delivery
• Medical management for heart failure may
uncommonly be required as neonate
• Surgical resection if adversely affecting cardiac
function

I DIAGNOSTIC

CHECKLIST

Consider
• Fetal echo cardiography to monitor cardiac function
• Fetal MRI to evaluate for other signs of tuberous
sclerosis

Image Interpretation

Pearls

• Multiple rhabdomyomas strongly suggests tuberous
sclerosis
• Rhabdomyomas less likely to cause pericardia I
effusions than other cardiac tumors

I SELECTED
1.

REFERENCES

Isaacs H Jr: Fetal and neonatal cardiac tumors. Pediatr
Cardiol. 25(3):252-73, 2004
2. Kivelitz DE et al: MRI of cardiac rhabdomyoma in the
fetus. Eur Radiol. 14(8):1513-6,2004
3. Puligandla PS et al: Pericardia I hemangioma presenting as
thoracic mass in utero. Fetal Diagn Ther. 19(2):178-81,
2004
4. Tongsong T et al: Prenatal sonographic diagnosis of cardiac
hemangioma with postnatal spontaneous regression.
Ultrasound Obstet Gynecol. 24(2):207-8, 2004
5. Zhou QC et al: Prenatal echocardiographic differential
diagnosis of fetal cardiac tumors. Ultrasound Obstet
Gynecol. 23(2):165-71, 2004
6. Bader RSet al: Fetal rhabdomyoma: prenatal diagnosis,
clinical outcome, and incidence of associated tuberous
sclerosis complex. J Pediatr. 143(5):620-4, 2003
7. Paladini D et al: Prenatal ultrasonographic findings of a
cardiac myxoma. Obstet Gynecol. 102(5 Pt 2): 1174-6, 2003
8. Tollens M et al: Pericardial teratoma: prenatal diagnosis
and course. Fetal Diagn Ther. 18(6):432-6, 2003
9. D'Addario V et al: Prenatal diagnosis and postnatal
outcome of cardiac rhabdomyomas. J Perinat Med.
30(2):170-5,2002
10. Kim TH et al: Perinatal sonographic diagnosis of cardiac
fibroma with MR imaging correlation. AJRAm J
Roentgenol. 178(3): 727 -9, 2002

RHABDOMYOMA
IIMAGE

GALLERY
(Left) Four chamber view
shows a rhabdomyoma
(arrow) in the left ventricle
arising from the
interventricular septum.
(Right) LVOT during systole
shows this mass (arrow)
completely fills the ventricle
potentially obstructing
outflow into the aorta (Ao).
Follow-up scans are
important to evaluate for
tumor growth, hydrops from
outflow tract obstruction and
arrhythmia.

(Left) Sagittal TlWI MR from
the case above performed at
2 months of life shows
multiple high signal intensity
cortical tubers (arrows)
typical of tuberous sclerosis.
All fetuses with
rhabdomyomas should be
evaluated for tuberous
sclerosis. (Right) Axial
ultrasound shows multiple,
echogenic, intracardiac
masses (arrows) involving
both ventricles and the
interventricular septum.
Multiple rhabdomyomas
have a> 80% risk of
tuberous sclerosis.

Variant
(Left) Four chamber view
shows a right atrial
rhabdomyoma (arrow). This
is a far less common location
than the ventricles. (Right)
Fetal ultrasound on a woman
with tuberous sclerosis
shows a massive, exophytic
mass (arrows) involving the
cardiac apex. This
appearance may be difficult
to differentiate from a
teratoma but the history and
uniform echogenicity makes
a large rhabdomyoma more
likely. Teratomas are more
heterogeneous and
frequently have cystic areas.

SECTION 7: Abdominal Wall

Introduction

and Overview

Normal Abdominal Wall & Bowel Imaging

Abdominal
Omphalocele
Gastroschisis
Body Stalk Anomaly
Bladder Exstrophy
Cloacal Exstrophy
OElS Syndrome
Pentalogy of Cantrell

7-2

Wall
7-6

7-10
7-14
7-18
7-20
7-22
7-24

NORMAL ABDOMINAL

WALL & BOWEL IMAGING

Graphic shows herniation of the midgut into the
umbilicus with an initial 900 counterclockwise
rotation
(blue arrow). As il relracts into the abdomen, the bowel
undergoes an additional 7800 rotation.

20 and 3D ultrasounds show physiologic bowel
herniation (arrows). /( is important to recognize lhis as a
normal developmental appearance and not mislake it
for an omphalocele.

Ilmaging Anatomy
Ultrasound
• First trimester
o Physiologic bowel herniation begins in 8th
menstrual week (6 weeks post conception)
o Produces a focal abdominal mass at umbilical cord
insertion
• Normal sonographic finding
• Should not be mistaken for an omphalocele
o Most prominent a 9-10 weeks menstrual age
o Should not be visible by 12 weeks
o Criteria for predicting possible anomaly
• Crown-rump length> 44 mm with persistent
herniation
• Maximum dimension of abdominal mass> 7 mm
• Herniated liver is never normal
• Esophagus
o Thoracic portion visible in 87% of fetuses> 26 weeks
o Cervical esophagus only visible in 19%
o Appears as either two parallel or multiple parallel
lines
• Stomach
o Visible by 11 weeks
o Growth charts available, however there is individual
variability based on fetal swallowing and peristalsis
• Small bowel
o May transiently see fluid in duodenum with
peristalsis
• Persistent fluid is always abnormal
o Routinely seen in late 2nd and 3rd trimester
• Normal < 7 mm in diameter
• Mucosa and serosa more echogenic, muscular
layers more hypoechoic
• Fluid (succus enteric us) visible in almost all cases
o Peristalsis routinely seen at real-time examination
• Bidirectional in 2nd trimester
• Antegrade peristalsis in 3rd trimester
• Colon
o Often prominent in 3rd trimester, especially sigmoid
colon
o Normal < 18 mm in diameter

•

•

•

•

•

•

o Haustra detected at 20-25 weeks
o Peristalsis not seen
Meconium
o Composed of desquamated endothelium, bile,
swallowed amniotic fluid and vernix
o Hypoechoic compared to bowel wall and liver
• Echogenicity increases with increasing gestational
age
Abdominal wall
o Abdominal musculature
• Internal oblique
• External oblique
• Transversus abdominus
o Hypoechoic band beneath echogenic fetal skin
• Seen most prominently at interface with liver
• May potentially be confused with ascites
o Muscles insert onto ribs
• Sonolucency not see posterolaterally
Liver
o Proportionally larger in fetus than child or adult,
especially left lobe
o Fills majority of upper abdomen
Gallbladder
o Right-sided, fluid-filled structure by liver edge
o Increases in size to 30 weeks
o Seen in 98% of cases in 3rd trimester
o May need to use color Doppler to differentiate from
umbilical vein
Spleen
o Lateral to stomach bubble in left upper quadrant
o Echogenicity similar to liver
Pancreas
o Usually not seen
o May be slightly hyperechoic compared to
surrounding structu res

MRI
• Valuable supplemental tool for many abdominal
anomalies
• Meconium
o High signal intensity T1 WI
o Low signal intensity T2WI
• Rectum

NORMAL ABDOMINAL

WALL & BOWEL IMAGING
Key Facts

Normal Anatomy

Abdominal

• Normal physiologic bowel herniation most
prominent at 9-10 weeks
o Should no longer be visible by 12 weeks
• Stomach seen by 11 weeks
• Persistent fluid in duodenum never normal
• Small bowel and colon seen in 2nd trimester
• Peristalsis routinely seen at real-time examination
• MRI helpful in evaluating gastrointestinal anomalies
o Meconium
• High signal T1WI, low signal T2WI
o Fluid-filled structures (stomach, jejunum,
gallbladder)
• Low signal Tl WI, high signal T2WI
oLiver
• High signal Tl WI, low signal T2WI

• Most variable of the biometric parameters
o If cord insertion is seen, scan is oblique
• Most important measurement for indicating growth
disturbance
o Asymmetric IUGR, macrosomia

•

•

•

•

o Meconium accumulates after 20 wks
o Normally at least 10 mm below bladder neck
o Anteroposterior diameter increase with gestational
age
• 4-8 mm at 24 wks
• 9-15 mm at 35 wks
Colon
o Meconium in descending colon seen after 24 wks
o Ascending and transverse colon seen in < 50%
before 31 wks
Stomach and jejenum
o Ingested amniotic fluid
• Low signal Tl WI
• High signal T2WI
Distal small bowel
o Appearance varies with gestational age and
meconium progression
o < 32 wks often hyperintense on Tl WI
o > 32 wks 40% still remain hyperintense Tl WI
Liver
o High signal intensity Tl WI
o Low signal intensity T2WI

IAnatomy-Based Imaging Issues

Circumference

Potential Pitfalls
• Beware of mistaking first trimester physiologic bowel
herniation for an omphalocele
o Herniation of liver is never normal
• Normal hypoechoic abdominal wall musculature may
mimic ascites
• Must see normal abdominal wall on either side of
cord insertion
o May potentially miss gastroschisis if not seen

• Be careful diagnosing an omphalocele in first trimester
o Normal herniation should not be present after 12
weeks
• Normal abdominal musculature may mimic ascites
(pseudoascites)
o True ascites will be seen elsewhere in abdomen
• May outline umbilical vein, bowel and other
organs
• May be associated with generalized hydrops

Normal Measurements
• Routine measurement of abdominal circumference
(Ae) required by AlUM
• True transverse view at level of junction of umbilical
vein with portal sinus
o Stomach in same plane
o Ribs should be visible and symmetric
o If cord insertion is in image, plane is oblique
• Abdomen appears elliptical instead of round
o Circumference should be drawn at skin/amniotic
fluid line
• Important component of fetal weight determination
o Indicator of growth disturbances
• Macrosomia
• Asymmetric intrauterine growth restriction (lUGR)
• Part of gestational age calculation

Imaging Protocols
• American Institute of Ultrasound in Medicine (AlUM)
requirements on abdominal images
o Stomach
• Presence
• Size
• Situs
o Umbilical cord insertion site into fetal abdomen
o Umbilical cord vessel number
o Kidneys
o Bladder

Imaging Pitfalls
• It is imperative to show normal abdominal wall on
either side of the cord insertion
o May miss a defect if the abdominal wall is obscured
by fetal legs or is against uterine wall

I Embryology
Embryologic Events
• 4th embryologic week (post conception)
o Embryonic folding results in 3 structures
• Blind-ending cranial foregut
• Blind-ending caudal hindgut
• Midgut open to yolk sac through vitelline duct
• 5th week
o Foregut forms esophagus, stomach and proximal
duodenum
• Diverticula bud form proximal duodenum to form
liver, gallbladder and pancreas

NORMAL ABDOMINAL

WALL & BOWEL IMAGING

Axial ultrasound shows correct level for obtaining the
abdominal circumference. The umbilical vein forms a
hook (arrow) as it joins the portal venous system. The
ribs are symmetric (curved arrow - stomach).

o Midgut forms distal duodenum, jejunum, ileum,
cecum, ascending colon, and proximal two thirds of
transverse colon
o Hindgut forms distal third of transverse colon,
descending colon, sigmoid colon and eventually
rectum
• Terminates at cloacal membrane at this time
• 6th week
o Ileum grows faster than peritoneal cavity and
herniates into umbilical cord
• Undergoes a 90° counterclockwise rotation
o Urorectal septum divides cloaca into rectum and
urogenital sinus
• Distal one third of anorectal canal forms from an
ectodermal invagination (anal pit)
• Weeks 7-11
o Midgut undergoes additional 180° counterclockwise
rotation as it retracts into abdomen in 10th week
(12th menstrual week)
o Ascending and descending colon become
retroperitoneal
• Additional embryologic events
o Boundaries of gut development determined by
vascular supply
• Foregut: Celiac artery
• Midgut: Superior mesenteric artery
• Hindgut: Inferior mesenteric artery
o Endodermal proliferation in 6th week occludes gut
lumen
• Over next 2-3 weeks vacuoles develop and
coalesce until recanalization is complete
• Primarily involves duodenum

Practical Implications
• Duodenal atresia
o Failure of foregut recanalization
• Jejunal/ileal atresia
o Vascular injury most accepted theory

• One proposed mechanism is kinking of superior
mesenteric artery during bowel rotation
• Anal atresia
o Arrest in division of cloaca into rectum and
urogenital sinus

Axial ultrasound shows the fetal gallbladder (arrow) and
hypoechoic abdominal wall musculature (curved
arrows), seen between the fetal skin and liver. This
should not be mistaken for ascites.

• Omphaloceles containing small bowel
o Failure of herniated bowel to retract into abdomen
o High association with chromosomal anomalies
• Gastroschisis
o Abnormal involution of right umbilical vein,
normally occurring in 6-7th week
• Malrotation/non-rotation
o Failure of either the 90° or 180° rotation to be
completed
o Predisposition for volvulus

I Related References
1.

Veyrac C et al: MRI of fetal Gl tract abnormalities. Abdom
Imaging. 29(4):411-20, 2004
2. Saguintaah M et al: MRI of the fetal gastrointestinal tract.
Pediatr Radiol. 32(6):395-404, 2002
3. Larsen WJ: Human embryology. New York, Churchill
Livingstone. 235-264, 2001
4. Blaas HG et al: Early development of the abdominal wall,
stomach and heart from 7 to 12 weeks of gestation: a
longitudinal ultrasound study. Ultrasound Obstet Gynecol.
6(4):240-9, 1995
5. Chan L et al: Fetal gallbladder growth and development
during gestation. J Ultrasound Med. 14(6):421-5, 1995
6. Avni EF et al: Fetal esophagus: p.ormal sonographic
appearance. J Ultrasound Med. 13(3):175-80, 1994
7. Bowerman RA:Sonography of fetal midgut herniation:
normal size criteria and correlation with crown-rump
length. J Ultrasound Med. 12(5):251-4, 1993
8. Fung ASet al: Echogenic colonic meconium in the third
trimester: a normal sonographic finding. J Ultrasound Med.
11(12):676-8, 1992
9. Parulekar SG: Sonography of normal fetal bowel. J
Ultrasound Med. 10(4):211-20, 1991
10. Timor-Tritsch IE et al: First-trimester midgut herniation: a
high-frequency transvaginal sonographic study. Am J
Obstet Gynecol. 161(3):831-3, 1989

NORMAL ABDOMINAL

WALL & BOWEL IMAGING

[IMAGE GALLERY
(Left) Axial ultrasound shows

a normal umbilical cord
insertion. Note the normal
abdominal wall (arrows)
seen on either side of the
insertion site. (Right) Sagittal
3D ultrasound shows the
cord insertion site (arrow).
This view is helpful when
looking for lower abdominal
wall defects, such as bladder
or cloacal exstrophy. Open
arrows point to legs.

(Left) Axial ultrasound shows
an apparently unremarkable
umbilical cord insertion
(arrow). Note the fetal
abdominal wall is against the
uterine wall. (Right) When
the fetus moves away from
the uterine wall, a very large
gastroschisis (arrows) is seen
adjacent to the umbical cord
insertion site (curved arrow).
This demonstrates the
importance of documenting
normal abdominal wall on
both sides of the insertion
site.

(Left) Coronal T1 WI M R
shows high signal meconium
(arrows) within the sigmoid
and descending colon.
(Right) Coronal T2WI MR
shows a low-signal liver
(black arrow) with
high-signal fluid within the
stomach (white arrow),
jejunum (open arrows) and
bladder (curved arrow).

OMPHALOCELE

Graphic shows a midline abdominal wall defect with
herniation of small bowel and liver. The defect is
covered by a membrane with the umbilical cord
insertingdirectly onto the sac.

ITERMINOLOGY
Abbreviations

and Synonyms

• Exomphalos

Definitions
• Midline abdominal wall defect with herniation of
abdominal contents into base of umbilical cord

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Color Doppler shows umbilical
cord insertion on midline ventral wall mass
• Location: Central
• Size: Variable
• Morphology
o Liver and small bowel most common contents
• Spleen, bladder, stomach, and large bowel also
reported

Ultrasonographic

Findings

• Grayscale Ultrasound
o Smooth mass protruding from central anterior
abdominal wall with covering membrane
o Umbilical cord inserts onto membrane
• Usually centrally

Axial ultrasound shows a large, central abdominal wall
defect, which contains both bowel and liver. It is
covered by a smooth membrane (arrow) with the
umbilical cord insertingcentrally on the mass.

• Occasionally eccentrically
o Polyhydramnios is common
o Ascites may be present
• Color Doppler
o Demonstrates cord in'sertion onto omphalocele
o May also be helpful to demonstrate intrahepatic
vessels
• Associated structural abnormalities are common
o Cardiac defects: 50% of associated anomalies
• Ventricular and atrial septal defects most common
• Tetralogy of Fallot
o Gastrointestinal: 40% of associated anomalies
• Malrotation always present
• Congenital diaphragmatic hernia
• Atresias
o Musculoskeletal
o Genitourinary
o Central nervous system
o Umbilical cord cysts

MR Findings
• Tl WI: Meconium in bowel has high signal
• T2WI
o Liver dark
o Fluid-filled bowel manifest as serpiginous high
signal
• Midline sagittal image best shows sac and cord
insertion

DDx: Omphalocele

Physiologic Herniation

Amniotic Bands

OMPHALOCELE
Key Facts
Terminology
• Midline abdominal wall defect with herniation of
abdominal contents into ba e of umbilical cord

Pathology

Imaging Findings
• Liver and small bowel most common contents
• Smooth mass protruding from central anterior
abdominal wall with covering membrane
• Umbilical cord inserts onto membrane
• Associated tructural abnormalities are common
• Beware of "p eudo-omphalocele" cau ed by canning
obliquely or by exce ive transducer pressure
• Evaluate for possible yndromes

Top Differential

• Umbilical hernia
• loacal exstrophy
• ord cysts

Diagnoses

• Physiologic gut herniation
• Gastroschisis

•

hromosomal abnormalities

Clinical

in 30-40% in utero

Issues

• Elevated maternal serum alpha-fetoprotein (70%)
• Stillbirth and neonatal death rates correlate with
associated anomalies
• Amniocentesis for karyotype

Diagnostic Checklist
• Di tinction from gastroschisis i essential in view of
associated abnormalities and outcome
• A chromosome abnormality i more likely if an
om halocele contains onl
mall bowel

Imaging Recommendations

Gastroschisis

• High resolution ultrasound to evaluate membrane and
contents of omphalocele
• Beware of "pseudo-omphalocele" caused by scanning
obliquely or by excessive transducer pressure
• Optimal scans of fetal abdomen and cord insertion
essential
o Differentiation from gastroschisis is essential
• Careful search for other abnormalities
• Dedicated cardiac echocardiography
o Cardiac anomalies most common associated finding
• Ascites in omphalocele may cause confusion with
gastroschisis
o Look for membrane and absence of bowel wall
thickening
• Evaluate for possible syndromes
o OEIS Complex
• Omphalocele
• Exstrophy
• Imperforate anus
• Spine abnormalities
o Beckwith-Wiedemann syndrome
• Omphalocele
• Organomegaly
• Macroglossia
• Macrosomia
o Pentalogy of Cantrell
• Omphalocele
• Ectopia cordis
• Cardiac anomalies
• Sternal, pericardial, diaphragmatic defects
• Measurement of abdominal circumference inaccurate
and should be excluded from biometric calculations

• Cord inserts on abdominal wall in a paraumbilical
location
• No covering membrane
• Free floating loops of bowel
• Does not contain liver

I DIFFERENTIAL

DIAGNOSIS

Physiologic gut herniation
• Bowel returns to abdomen by 11.2 weeks
• Should not extend more than 1 cm
• Never contains liver

Umbilical hernia
• Hernia covered by skin and subcutaneous fat
• A small, bowel-containing omphalocele may be
difficult to distinguish from umbilical hernia but
hernias rare in utero

Cloacal exstrophy
•
•
•
•

Omphalocele may be present
Absent bladder
Defect involves lower abdominal wall
Associated anomalies
o Genitourinary
o Spine

Pentalogy of Cantrell
• Ectopia cordis in addition to high omphalocele

Cord cysts
• Cysts near abdominal wall may be confused with
bowel herniation
• Omphalocele and cord cyst may co-exist
• Omphalomesenteric duct cyst
o Associated with omphalocele and intraabdominal
mesenteric cysts
• Allantoic cyst
o True cyst attached to cord
o Always near fetal insertion site
o Associated with patent urachus
• Wharton jelly cyst
o Mucoid degeneration of Wharton jelly
o Associated with omphalocele

Bladder exstrophy
• Absent bladder is hallmark
• Umbilical cord inserts above defect

OMPHALOCELE
Cord hemangioma

Natural History & Prognosis

• Hypoechoic cord mass
• May mimic omphalocele if close to abdominal wall

• Survival as high as 80-90% if normal chromosomes
and no other anomalies
• Increased premature birth rate
• Stillbirth and neonatal death rates correlate with
associated anomalies
o Mortality 80-100% if associated structural or
chromosomal abnormalities
o Perinatal mortality rate 19% if karyotype normal
• Transient omphaloceles containing bowel only have
been described
o Good prognosis if no other abnormalities
• In utero rupture rare
o Difficult to differentiate from gastroschisis when
ruptured

Body stalk anomaly (limb body wall
complex)
• Fetus adherent to placenta
• No free-floating umbilical cord
• Scoliosis and limb defects

Amniotic bands
• Multiple body parts affected
• Often involves head and neck
o "Slash" defects

I PATHOLOGY

Treatment

General Features
• Genetics
o Chromosomal abnormalities in 30-40% in utero
• Trisomy 18 (most common)
• Trisomy 13
• Triploidy
• Turner syndrome (45,XO)
o Chromosomal abnormalities less common at birth
because of in utero demise or termination
• Epidemiology
o 1:4,000 births
o Gender: F > M
o Incidence increases with advanced maternal age

Gross Pathologic & Surgical Features
• Mass covered by both peritoneum and amnion, with
Wharton jelly in between
• Proposed embryologic mechanism
o Defect in fetal ventral body folding normally
occurring at 5-8 menstrual weeks
• Liver containing: Primary failure of body wall
closure
• Bowel containing: Persistence of primitive body
stalk beyond 12 weeks

Staging, Grading or Classification Criteria
• Categorized as having intra or extracorporealliver
o Risk of chromosomal abnormality much higher if
liver intracorporeal
• Small omphaloceles
o Often just small bowel
o Higher association with both structural and
chromosomal anomalies
• Giant omphaloceles
o Large abdominal wall defect with extensive
herniation of abdominal contents

• Amniocentesis for karyotype
• Delivery at tertiary care facility
o Protection of sac
o Nasogastric tube decompression
• Benefits of cesarean section controversial
o Not indicated if multiple associated anomalies
• Surgical treatment based on size
o Primary closure if small
o Complete reduction of large omphaloceles can cause
harmful elevation of intra abdominal pressure
• Temporary extra abdominal silastic pouch to cover
sac
• Gradual pressure reduction with compression

I DIAGNOSTIC

Image Interpretation

ISSUES

I SELECTED
1.
2.

3.

4.
5.

7.

Presentation
• Abdominal wall defect
• Elevated maternal serum alpha-fetoprotein

8.

(70%)

Pearls

• Distinction from gastroschisis is essential in view of
associated abnormalities and outcome
• A chromosome abnormality is more likely if an
omphalocele contains only small bowel

6.

I CLINICAL

CHECKLIST

REFERENCES

Daltro P et al: Prenatal MRI of congenital abdominal and
chest wall defects. AJRAm J Roentgenol. 184(3): 1010-6,
2005
Blazer S et al: Fetal omphalocele detected early in
pregnancy: associated anomalies and outcomes. Radiology.
232(1):191-5,2004
Heider AL et al: Omphalocele: clinical outcomes in cases
with normal karyotypes. Am J Obstet Gynecol.
190(1):135-41,2004
Wilson RD et ai: Congenital abdominal wall defects: an
update. Fetal Diagn Ther. 19(5):385-98, 2004
Langer JC: Abdominal wall defects. World J Surg.
27(1):117-24,2003
Snijders RJ et al: Fetal exomphalos at 11 to 14 weeks of
gestation. J Ultrasound Med. 14:569-74, 1995
Hughes MD et al: Fetal omphalocele: Prenatal US detection
of concurrent anomalies and other predictors of outcome.
Radiology. 173:371-6, 1989
Nyberg DA et al: Chromosomal abnormalities in fetuses
with omphalocele. Significance of omphalocele contents. J
Ultrasound Med. 8:299-308, 1989

OMPHALOCELE
IIMAGE GALLERY
(Left) Sagittal endovaginal
ultrasound in the 1st
trimester shows herniation of
the liver (arrow) through a
midline abdominal wall
defect. This is always
abnormal, as physiologic
herniation never includes
liver. (Right) Axial ultrasound
in the 2nd trimester shows a
very small, bowel-containing
omphalocele
(arrow) and a
2 vessel cord (curved arrow)
in this fetus with trisomy 78.
Bowel herniation in the 2nd
trimester is never normal, as
physiologic herniation is
complete by week /2.

Typical
(Left) Axial ultrasound of an
omphalocele
shows
herniation of small bowel
through a midline defect. It is
covered by a membrane
(curved arrow) and lhe
umbilical cord inserts
centrally (arrow). (Right)
Clinical photograph shows
the covered, midline defect
with the umbilical cord
inserling directly on the sac.
Omphaloceles
which
contain small bowel are at
greater risk for aneuploidy.
most commonly trisomy 78.

Variant
(Left) Sagillal T2WI MR
shows an eccentric cord
insertion (arrow) on a large,
liver-containing
omphalocele.
The insertion
site is nol always midline in
location bUl il is always on
the sac. (Right) Clinical
photograph of a giant
omphalocele
shows an
eccentric cord inserlion
(arrow) on lhe sac.
Omphalocele
contents
include small bowel, liver
and a large amount of
ascites.

OMPHALOCELE
I IMAGE GALLERY
(Left) Sagittal endovaginal
ultrasound in the 75t
trimester shows herniation of
the liver (arrow) through a
midline abdominal wall
defect. This is always
abnormal, as physiologic
herniation never includes
liver. (Right) Axial ultrasound
in the 2nd trimester shows a
very small, bowel-containing
omphalocele
(arrow) and a
2 vessel cord (curved arrow)
in this fetus with trisomy 18.
Bowel herniation in the 2nd
trimester is never normal, as
physiologic herniation is
complete by week 12.

(Left) Axial ultrasound of an
omphalocele
shows
herniation of small bowel
through a midline defect. It is
covered by a membrane
(curved arrow) and the
umbilical cord inserts
centrally (arrow) (Right)
Clinical photograph shows
the covered, midline defecl
with the umbilical cord
inserting directly on the sac.
Omphaloceles
which
contain small bowel are at
greater risk for aneuploidy,
most commonly trisomy 78.

Variant
(Left) Sagittal T2WI MR
shows an eccentric cord
insertion (arrow) on a large,
liver-conlaining
omphalocele.
The insertion
site is not always midline in
location but it is always on
the sac. (Right) Clinical
photograph of a giant
omphalocele
shows an
eccentric cord insertion
(arrow) on the sac.
Omphalocele
contents
include small bowel, liver
and a large amount of
ascites.

GASTROSCHISIS
Key Facts
Terminology
• Bowel herniation through
abdominal wall defect

a right paramedian

Imaging Findings

•
•
•

Pathology
0 chromosomal
associations
• Higher incidence in substance use by mothers
• Incidence is increasing
• Incidence in teenage mothers is 6-10x that of
mothers ~ 25 yrs
• Association with non-ga trointestinal abnormalities
low « 5%)
• Atresias often present (7-30(~'h)

• Best diagnostic clue: olor Doppler hows umbilical
cord insertion in normal location
• mall bowel always herniate through defect
•
0 covering membrane
• Oligohydramnios
more common than
polyhydramnios
• Intrauterine growth restriction (IUGR) common
• May be mi sed if abdominal cord insertion
incompletely evaluated

•

Top Differential

• Bowel complications
omphalocele

Diagnoses

• Omphalocele

•

• Body stalk anomaly (limb body wall complex)
• Amniotic band syndrome
• Cloacal exstrophy

o Try to get fetus to move into better position by
moving mother
Imperative to see abdominal wall on both sides of cord
insertion in every case
Do not confuse umbilical cord for exteriorized bowel
loops
MRI may add anatomic information if ultrasound
inadequate
Close follow-up for fetal distress
o Progressive bowel dilatation
o Developing IUGR
• Abdominal circumference is small making
evaluation difficult
• Evaluate umbilical artery (UA) and middle cerebral
artery (MCA) flow
• With developing IUGR, normal flow patterns
reverse
• As UA becomes high-resistance, the MCA becomes
low-resistance ("head sparing")
o Acute complications
• Volvulus with resulting bowel ischemia
o Oligohydramnios
• Sign of fetal distress

I DIFFERENTIAL DIAGNOSIS
Omphalocele
• Cord inserts on mass
• Covered by peritoneum
• Ruptured omphalocele difficult to differentiate
o Consider if liver present
o Rare

Body stalk anomaly (limb body wall
complex)
• Fetus adherent to placenta
• Extruded thoracic contents and liver in addition to
bowel
• No free-floating umbilical cord
• Spine and limb defects

Clinical Issues
much greater than for

Amniotic band syndrome
• Variable in presentation and severity
• Multiple body parts affected
• Often involves head and neck
o "Slash" defects

Cloacal exstrophy
• Absent bladder
o Bowel may protrude between bladder halves
• Omphalocele
• Cord insertion low
• Genitourinary anomalies

Bladder exstrophy
• Umbilical cord inserts above defect
• Absent bladder is hallmark
• No free-floating bowel

Physiologic gut herniation
• Bowel returns to abdomen by 11.2 weeks
• Should not extend more than 1 cm
• Always midline

I PATHOLOGY
General Features
• Genetics
o Most are sporadic
o Familial cases reported
• 3.5% recurrence risk in siblings
o No chromosomal associations
• Amniocentesis not indicated
• Etiology
o Higher incidence in substance use by mothers
• Particularly vasoactive substances (e.g. cocaine,
nicotine, decongestants, aspirin)
o Embryology: Proposed mechanisms
• Abnormal involution of right umbilical vein,
normally occurring in 6th-7th week

• Vascular accident involving omphalomesenteric
artery (less likely)
• Epidemiology

i

GASTROSCHISIS
o 1:3,000 to 5,000 births
o Incidence is increasing
o Incidence in teenage mothers is 6-lOx that of
mothers ~ 25 yrs
• Associated abnormalities
o Bowel either malrotated or non-rotated
o Association with non-gastrointestinal
abnormalities
is low « 5%)
• Cardiac anomalies most common
• Hypoplastic gallbladder, Meckel diverticulum
• Hydronephrosis

Gross Pathologic & Surgical Features
• Abdominal defect relatively small « 5 em)
• Exposed loops inflamed and edematous
• Atresias often present (7-30%)
o Often long segments
• Left-sided wall defects very rare

ICLINICALISSUES
Presentation
• Elevated maternal serum alpha-fetoprotein
(95%)
o Exposed bowel results in greater elevations than
with omphalocele
• Fetal ultrasound highly sensitive in diagnosis
• Can be diagnosed in first trimester with endovaginal
ultrasound

Treatment
• Serial ultrasound for growth evaluation and detection
of bowel complications
• Polyhydramnios correlates with severe neonatal bowel
complications
• Amnioinfusion may improve outcome (experimental
studies)
o Decreases concentration of irritants in amniotic
fluid
• Early delivery considered, if worsening bowel
dilatation (controversial)
• Cesarean section common but value is questioned
• Delivery at tertiary care center
o Careful control of body fluids and heat loss
o Extruded bowel covered with sterile plastic bag to
protect it from excessive handling and to minimize
heat and fluid loss
• Immediate surgical repair optimal to decrease risk of
sepsis and metabolic acidosis
• If return of bowel causes significant increase in
intraabdominal
pressure, the procedure is staged with
delayed fascial closure
• Parenteral nutrition post-operatively until intestinal
function returns
o May require several weeks

I DIAGNOSTIC

CHECKLIST

Natural History & Prognosis

Image Interpretation

• Bowel complications much greater than for
omphalocele
o Bowel ischemia
• Torsion around narrow vascular pedicle
• Compression of mesenteric vessels in small
paraumbilical defect
o Atresias
o Bowel obstruction
• Dilatation of both intra- and extra-abdominal
bowel
• Significant dilatation of small bowel impacts long
term morbidity
• Large variations exist in literature as to what
diameter is "significant" (10-18 mm)
o Perforation
o Bowel thickening from amniotic fluid irritation
• Associated with edema and poor function
• IUGR in up to 50%
• May resorb on follow-up exam ("vanishing gut")
o Associated with tight defects
• Ischemia causes atresia
• Short bowel syndrome
• Premature delivery common
• 90% survival
o Deaths from prematurity, sepsis or bowel
complications
o Bowel necrosis predictor of poor outcome
• 10-15% persistent disability
o Motility disorders
o Short gut syndrome

• Oligohydramnios
suggests fetal distress
• Polyhydramnios suggests bowel obstruction

Pearls
or atresia

I SELECTED REFERENCES
1.

Daltro P et al: Prenatal MRI of congenital abdominal and
chest wall defects. AJRAm J Roentgeno!. 184(3):1010-6,
2005
2.
Williams LJ et al: Epidemiology of gastroschisis in
metropolitan Atlanta, 1968 through 2000. Birth Defects
Res A Clin Mol Terato!. 73(3):177-83,2005
3. Hwang PJ et al: Omphalocele and gastroschisis: an 18-year
review study. Genet Med. 6(4):232-6, 2004
4. Wilson RD et al: Congenital abdominal wall defects: an
update. Fetal Diagn Ther. 19(5):385-98,2004
5.
Yoshioka H et al: Two cases of left-sided gastroschisis:
review of the literature. Pediatr Surg Int. 20(6):472-3, 2004
6. Japaraj RP et al: Gastroschisis: can prenatal sonography
predict neonatal outcome? Ultrasound Obstet Gynecol.
21(4):329-33,2003
7.
Langer JC: Abdominal wall defects. World J Surg.
27(1):117-24, 2003
8. Durfee SM et al: Postnatal outcome of fetuses with the
prenatal diagnosis of gastroschisis. J Ultrasound Med.
21(3):269-74, 2002
9. Rankin J et al: Congenital anterior abdominal wall defects
in the north of England, 1986-1996: occurrence and
outcome. Prenat Diagn. 19(7):662-8, 1999
10. Nichols CR et al: Rising incidence of gastroschisis in
teenage pregnancies. J Matern Fetal Med. 6(4):225-9, 1997
11. Babcock CJ et al: Gastroschisis: can sonography of the fetal
bowel accurately predict postnatal outcome? J Ultrasound
Med 13:701-6, 1994

GASTROSCHISIS
I IMAGE GAllERY
(Left) Axial endovaginal
ultrasound of a first trimester
gastroschisis (curved arrow).
The small bowel appears as
tiny echogenic rings. Also
note the 2 vessel umbilical
cord (arrow). (Right) Axial
ultrasound of gastroschisis in
a 17 wk fetus shows small
bowel herniation (curved
arrow) adjacent to a normal
cord insertion (arrow). It is
important to follow
gastroschisis cases for
developing bowel dilatation,
IUGR, oligohydramnios and
other signs of fetal distress.

Typical
(Left) Axial oblique
ultrasound shows stretching
of the superior mesenteric
artery (arrow) through the
abdominal wall defect (open
arrow - aorta, curved arrow cord insertion). This is not a
predictor of outcome.
(Right) Ultrasound shows
marked dilatation (calipers)
of free-floating bowel loops.
Significant dilatation
increases risk for postnatal
complications.

Variant
(Left) Axial ultrasound shows
another image from the case
above, which shows
herniation of the stomach
(ST - arrows) as well as the
small bowel. (Right) Gross
pathology from a case that
presented because of absent
fetal movement. The fetus
was being followed for
known gastroschisis.
Ultrasound confirmed
demise and a new focally
dilated bowel loop. Autopsy
confirmed volvulus with
bowel ischemia, a known
potential complication.

BODY STALK ANOMALY

Graphic shows a large body wall defect. Fetal
peritoneum is in continuity with the amnion, resulting in
attachment to the placenta. Scoliosis (arrow) results
from fetal tethering.

Postmortem radiograph of a body stalk anomaly. There
is obvious scoliosis with herniation of abdominal
contents (arrow), which were inseparable from the
placenta (open arrow). Attachment severed at delivery.

ITERMINOlOGY
Abbreviations

•

and Synonyms

• Body stalk complex
• Limb body wall complex
• Cyllosomas

•

Definitions
• Lethal malformation characterized by attachment of
visceral organs to the placenta, with a short or absent
umbilical cord

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Abnormal fetus inseparable from
placenta
• Size: Often large with complete evisceration
• Morphology: Gross distortion, with complete loss of
anatomic landmarks

Ultrasonographic

Findings

• Complex array of multiple malformations
• Large thoraco-abdominal
wall defect
o No covering membrane
• Grossly distorted fetus
• Absent/very short umbilical cord

•
•
•
•
•
•

o Vessels seen running from placental surface to fetal
torso
Scoliosis prominent feature
o Often severe
o May have multiple acute angulation points
Limb defects common
o Clubfoot
o Absent limbs or digits
o Arthrogryposis
o Polydactyly
o Syndactyly
o Abnormal limb positioning
Encephalocele or exencephaly
Facial defects
Neck often extended
Oligohydramnios
in second and third trimesters
Amniotic bands in 40%
First tri mester
o Fetus located outside amniotic cavity
o Amniotic membrane can be normal or ruptured
o Normal umbilical cord not seen
o Nuchal translucency may be abnormal
• Does not reflect karyotypic abnormality

Imaging Recommendations
• Fixed fetal/placental relationship essential for
diagnosis
o Scan mother in different positions

DDx: Severe Body Wall Defects

J\mniotic Bands

Amniotic Bands

Pentalog}

or Cantrell

OEiS

BODY STALK ANOMALY
Key Facts
• OEIS complex

Terminology
• Lethal malformation characterized by attachment of
vi ceral organ to the placenta, with a hort or ab ent
umbilical cord

Imaging Findings
•
•
•
•
•

omplex array of multiple malformations
Scoliosi prominent feature
May have multiple acute angulation point
Limb def cts common
Fixed fetal/placental relation hip ssential for
diagno i

Top Differential

Diagnoses

• mnioti band sequence
• atrochiis
• Omphalocele

• Look for umbilical cord
o Should be free floating and obvious
o Color Doppler essential
• Often have to search carefully for fetal/placental
connection
• 3D ultrasound has been described, and may be of
value in defining anatomic relationships

I DIFFERENTIAL

DIAGNOSIS

Amniotic band sequence

Pathology
0 known recurrence ri k
• Amnion in continuity with fetal peritoneum at edge
of defect
• Malformed umbili al cord incompletely covered in
amnion

•

Clinical

Issues

• Marked elevation maternal serum alpha-fetoprotein
•
0 abnormal karyotype reported

Diagnostic Checklist
• Fetu appears stuck to placenta with evere spinal and
limb defect
• In fir t trime ter, part or all of fetu is located out ide
the amniotic cavit
• Imperforate anus
• Spine abnormalities
• Mobile fetus

Pentalogy of Cantrell
• Omphalocele
• Cardiac anomalies
o Ectopia cordis most typical of syndrome
• Diaphragmatic hernia
• Defect of diaphragmatic pericardium
• Lower sternal defect
• Cranial and limb defects not prominent feature
• Mobile fetus

• Severe cases may be indistinguishable
• Fetus may be immobile
• Normal cord
o Cord insertion site may be involved if
abdominoschisis
o Free-floating cord loops usually identified
• Variable pattern of defects
o Limb amputations
o Limb constrictions
• Scoliosis not a major finding
• Bands may be seen in amniotic fluid
o May extend to immobile fetal part

I PATHOLOGY

Gastroschisis

General Features

• Mobile fetus
• Small abdominal wall defect
• Normal cord
o Defect is to right of cord insertion
• Defect not covered
o Bowel floats freely in amniotic fluid

Omphalocele
• Mobile fetus
• Defect is covered by membrane
• Normal cord
o Inserts on membrane
• Generally at apex but may be eccentric

OEIS complex
• Omphalocele
• Exstrophy of bladder

Cloacal exstrophy
•
•
•
•

Mobile fetus
Normal length cord
Omphalocele
Bladder exstrophy
o No normal bladder seen
o Bowel may herniate out between bladder halves

• Genetics
o Sporadic
o No karyotypic abnormalities
o No known recurrence risk
o More common in monozygotic twins
• May be discordant
• Epidemiology
o Reported incidence
• 1:7,500 to 42,000 in United Kingdom
• 1:3,000 live births in Australia
o Risk factors
• Alcohol, tobacco, marijuana use
• History of prior child with congenital anomaly
(any) in 40%
• Reported after in vitro fertilization
• Two phenotypes described
o No craniofacial defects

BODY STALK ANOMALY
• 60% of cases
• Result of embryologic maldevelopment
• Malfunction of ectodermal placodes involving
cephalic and caudal embryonic folding process
• Malformation of anterior and lateral abdominal
walls
• Body stalk/yolk stalk fusion fails: Short or absent
umbilical cord
• Amnion/chorion
fusion fails
• Amnion does not cover cord
• Amnion in continuity with fetal peritoneum at
edge of defect
o Associated craniofacial defects
• 40% of cases
• Early vascular disruption proposed as cause
• Amniotic bands present
• Also hypothesized that body stalk anomaly occurs
from early amnion rupture
o Some categorize in spectrum of amniotic band
syndrome
• Associated abnormalities in virtually all cases
o Cardiac defects
• Ectopia cordis
• Structural defect
o Renal anomalies
• Hydronephrosis, agenesis, cystic dysplasia
o Bowel atresia
o Congenital diaphragmatic hernia
o Facial clefts

o Aim for delivery of intact fetus for autopsy
• Psychological support to family
• Vaginal delivery if pregnancy not terminated
o Cesarean section avoided
o No fetal monitoring during labor
o No resuscitation of fetus

I DIAGNOSTIC
Consider

• Most likely diagnosis in setting of abdominal
defect and scoliosis

Image Interpretation

I SELECTED
1.
2.
3.

4.

• Persistence of extraamniotic coelomic cavity
• Anterior body wall defect with evisceration of organs
oliver
o Bowel
o Heart
o All organs potentially involved
• Malformed umbilical cord incompletely covered in
amnion
• Umbilical vessels embedded in amniotic sheet
connecting to skin margin of abdominal wall defect

9.

IClINICALISSUES

10.

Presentation

11.

Natural History & Prognosis
• Lethal
• Frequent spontaneous

abortion

Treatment
• Amniocentesis not required
o No abnormal karyotype reported
• Offer termination

wall

Pearls

• Fetus appears stuck to placenta with severe spinal and
limb defects
• In first trimester, part or all of fetus is located outside
the amniotic cavity

Gross Pathologic & Surgical Features

• Abnormal maternal serum screen
o Marked elevation maternal serum alpha-fetoprotein
• Can be diagnosed by end of first trimester
o Normal cord can be identified as early as 8 weeks
o Abnormal ratio of crown-rump length:cord length
• Should normally be 1:1
• Cord short or absent
o Lower portion of fetus is outside amniotic cavity,
upper portion may still be within amniotic cavity

CHECKLIST

5.
6.
7.

8.

12.
13.

14.
15.

REFERENCES

de Ravel T et al: Primary body stalk anomaly in a first
trimester fetus. Genet Couns. 15(2):237-8, 2004
Daskalakis G et al: Body stalk anomaly diagnosed in the
2nd trimester. Fetal Diagn Ther. 18(5):342-4, 2003
Liu IF et al: Prenatal diagnosis of limb-body wall complex
in early pregnancy using three-dimensional
ultrasound.
Prenat Diagn. 23(6):513-4, 2003
Daskalakis GJ et al: Monozygotic twins discordant for body
stalk anomaly. Ultrasound Obstet Gynecol. 20(1):79-81,
2002
Luehr B: Limb body wall complex: A case series. J Matern
Fetal Neonatal Med. 12:132-7,2002
Paul C et al: A case of body stalk anomaly at 10 weeks of
gestation. Ultrasound Obstet Gynecol. 17(2): 157-9, 2001
Pumberger W et al: Limb body wall complex: A compound
anomaly pattern in body wall defects. Pediatr Surg Int.
17:486-90, 2001
Chen CP et al: Prenatal diagnosis of limb-body wall
complex using two- and three-dimensional
ultrasound.
Prenat Diagn. 20(12): 1020, 2000
Colpaert C et al: Limb-body wall complex: 4 new cases
illustrating the importance of examining placenta and
umbilical cord. Pathol Res Pract. 196(11): 783-90, 2000
Daskalakis G et al: Body stalk anomaly at 10-14 weeks of
gestation. Ultrasound Obstet Gynecol. 10(6):416-8, 1997
Ginsberg
E et al: Prenatal diagnosis of body stalk anomaly
in the first trimester of pregnancy. Ultrasound Obstet
Gynecol. 10(6):419-21,1997
Takeuchi K et al: Body stalk anomaly: prenatal diagnosis.
lnt J Gynaecol Obstet. 51 (1):49-52, 1995
Russo R et al: Limb body wall complex: a critical review
and a nosological proposal. Am J Med Genet.
47(6):893-900, 1993
Van Allen MI et al: Limb-body wall complex: II. Limb and
spine defects. Am J Med Genet. 28(3):549-65, 1987
Van Allen MI et al: Limb body wall complex: I.
Pathogenesis. Am J Med Genet. 28(3):529-48, 1987

BODY STALK ANOMALY
IIMAGE

GALLERY

Typical
(Left) Ultrasound shows the
typical appearance of a body
stalk anomaly with gross
distortion of normal
anatomic landmarks. There is
a large body wall defect with
extrusion of the
thoraco-abdominal contents.
The hear! (open arrow) and
liver (arrow) were adherent
to the placenta (curved
arrows). (Right) Ultrasound
of the spine shows dramatic
scoliosis with 2 right-angle
turns (arrows). Severe
scoliosis is often a prominent
finding in body stalk
anomaly.

(Left) Ultrasound of a 16 wk
fetus shows acute angulation
of the fetal body (arrows).
The fetus remained fixed
during the exam. There is a
body wall defect with
extrusion of the bowel (open
arrow). No free floating
umbilical cord could be
identified. (Right)
Radiograph from a similar
case shows severe scoliosis
and evisceration of
thoraco-abdominal contents
(arrow), which were
adherent to the placenta.

Typical
(Left) Ultrasound of a
dramatically shortened
umbilical cord (arrows) of a
grossly distorted fetus. It runs
directly from the fetus (F) to
the placenta (P). (Right)
Gross pathology shows the
typical features of body stalk
anomaly. The fetus has been
pulled away from the
placenta to show the very
short umbilical cord (open
arrow). There is
thoraco-abdominal
evisceration and severe
scoliosis. This case is
associated with an amniotic
band and cleft lip (arrow).

BLADDER EXSTROPHY

Graphic of bladder exlrophy shows an exteriorized
bladder with exposed mucosa. There is also associated
epispadias (arrow). Genital anomalies are commonly
present with bladder exstrophy.

Sagittal ultrasound of a fetus with bladder exstrophy
shows a normal cord insertion (arrow). No normal
bladder is seen and there is a lobular irregularity of the
lower abdominal wall (open arrow).

ITERMINOlOGY

Imaging Recommendations

Definitions

• Protocol advice
o Sagittal view of abdominal wall shows defect and
mass best
o Beware of misdiagnosis in cases of a normal but
empty bladder
• Rescan after an interval of 10-15 minutes
• Any cause of anuria will cause non-visualization
of the bladder in utero

• Failure of closure of lower abdominal
exposed bladder

IIMAGING

wall resulting in

FINDINGS

General Features
• Variable severity
o Mild form associated with exstrophy of urethra and
external sphincter
o Severe form associated with wide diastasis of
symphysis pubis and genital defects

Ultrasonographic

Findings

• Grayscale Ultrasound
o Absence of bladder
o Soft tissue mass on lower anterior abdominal wall
representing posterior bladder wall
o Lower insertion of umbilical cord
• Color Doppler: Useful for identifying umbilical arteries
on either side of lower abdominal wall mass

I DIFFERENTIAL DIAGNOSIS
"Absent" bladder
• Renal anomalies resulting in anuria
• Severe placental insufficiency
• Twin-twin transfusion syndrome (TITS)
o Donor twin becomes anuric

Cloacal exstrophy
• Bowel herniation as well as bladder extrophy
• Other anomalies such as myelomeningocele
and
omphalocele

Omphalocele

Radiographic Findings

• Midline mass is more cephalad than exstrophy
• Cord inserts onto omphalocele
• Normal bladder

• Widely separated pubic bones
• Everted innominate bones

DDx: "Absent" Bladder

TTTS, Donor Twin

Cloacal Exstrophy

BLADDER EXSTROPHY
Key Facts
Imaging Findings
• Mild form associated with ex trophy of urethra and
external phincter
• evere form a sociated with wide dia tasis of
ymphy i pubis and genital def cts
• Absence of bladder
• Soft ti ue mass on lower anterior abdominal wall
repre enting po terior bladd r wall

• Beware of misdiagnosi
empty bladder

Top Differential

in ca es of a normal but

Diagnoses

• "Ab ent" bladder
• loacal ex trophy

Clinical Issues
•

ot as ociated with increased pr gnancy
complication
or perinatal mortality

Gastroschisis

Treatment

• Free-floating bowel loops
• Normal bladder

• Amniocentesis may be considered for fetal sexing if
genitalia ambiguous
• Prenatal counseling with pediatric urologist
• Cesarean section indicated for obstetric issues only
• Delivery in a tertiary care center preferable
• Surgical treatment
o Closure of bladder within first 3 days of life
o Staged functional reconstruction
o Sex reassignment almost never performed now

I PATHOLOGY
General Features
• Genetics
o Sporadic
o Reports of trisomies 21 and 13
• Etiology
o Cloacal membrane covering future bladder persists,
fails to retract normally
o Prevents ingrowth of mesenchymal cells, which
normally form lower anterior abdominal wall
o Closure of lower abdominal wall does not occur and
cloacal membrane becomes anterior bladder wall
o When cloacal membrane ruptures, bladder mucosa
is left exposed to amniotic cavity
o Occurs after descent of the urogenital septum
• Epidemiology
o 1:30,000 births
o M:F = 2:1
• Associated abnormalities
o Genitourinary anomalies
• Epispadias and short penis in males
• Maldescended testes
• Cleft clitoris and duplicated vagina in females
o Inguinal hernias
o Spinal dysraphism and scoliosis

I DIAGNOSTIC

Image Interpretation

Pearls

• Important to distinguish from cloacal exstrophy,
which has a worse prognosis

I SELECTED
1.
2.

3.
4.

REFERENCES

Cadeddu JA et al: Spinal abnormalities in classic bladder
exstrophy. Br J Urol. 79(6):975-8, 1997
Bronshtein Met al: Differential diagnosis of the
non visualized fetal urinary bladder by transvaginal
sonography in the early second trimester. Obstet Gynecol.
82(4 Pt 1):490-3, 1993
Barth RA et al: Prenatal sonographic findings in bladder
exstrophy. J Ultrasound Med. 9(6):359-61, 1990
Kandzari SJ et al: Exstrophy of urinary bladder complicated
by adenocarcinoma.
Urology. 3(4):496-8, 1974

IIMAGE
ICLINICAL

CHECKLIST

GALLERY

ISSUES

Presentation
• Most common signs/symptoms
o Absent bladder on ultrasound exam
o Elevated maternal serum alpha-fetoprotein

Natural History & Prognosis
• Not associated with increased pregnancy
complications or perinatal mortality
• Sequelae from pelvic floor defects
o Urinary and fecal incontinence
o Uterine prolapse in females
• Infertility
• Increased risk of adenocarcinoma
in extruded bladder
(4%) if repair performed after infancy

(Left) Clinical photograph of a newborn with bladder exstrophy
shows a large abdominal wall defect with exposed bladder mucosa.
The ureteral orifices (arrows) and urethral orifice (curved arrow) are
seen. (Right) Radiograph of an infant born with bladder exstrophy
shows wide diastasis of the symphysis pubis (arrows).

CLOACAL EXSTROPHY

Graphic of cloacal exstrophy shows an omphalocele
and bladder exstrophy (arrows) with prolapsed ileum
(curved arrow) between the two bladder halves. The
appearance has been likened to an elephant's trunk.

Axial oblique ultrasound through the fetal pelvis (curved
arrow - spine) shows a 50ft tissue mass (arrows)
protruding through the abdominal wall, below the level
of the cord insertion. No bladder was identified.

o Gastrointestinal
o Polyhydramnios

ITERMINOLOGY

50%

Definitions
• Spectrum of abnormalities resulting from abnormal
development of cloacal membrane

I DIFFERENTIAL DIAGNOSIS

IIMAGING

• Absence of normal bladder with mass on lower
anterior abdominal wall
• No other manifestations of cloacal exstrophy

Bladder exstrophy

FINDINGS

Ultrasonographic

Findings

• Grayscale Ultrasound
o Absence of normal bladder
o Lower abdominal wall defect
• Herniation of bowel between 2 halves of bladder
• Appearance of prolapsed ileum described as
looking like an elephant's trunk
• Omphalocele forms upper part of defect
o Splayed symphysis pubis
o Cloacal membrane may be intact until 22 weeks,
producing a cystic pelvic mass
• Color Doppler: Useful to localize umbilical arteries and
cord insertion
• Associated anomalies very common
o Vertebral 40-90%
o Myelomeningocele
30-70%
o Urinary tract, up to 60%
• Leading to oligohydramnios
o Club feet 20-45%

DDx: Abdominal

Wall Defects

Isolated omphalocele
• Contents contained within a sac
• Abdominal wall intact inferior to defect

Gastroschisis
• Free-floating bowel loops
• Normal bladder

Amniotic band syndrome
• Frequently involves head and neck
• Look for bands

Body stalk anomaly
• Large thoraco-abdominal
defect
• Fetus adherent to placenta

Pentalogy of Cantrell
• Defect higher, involving upper abdomen

and chest

CLOACAL EXSTROPHY
Key Facts
Terminology

Top Differential

•

• Bladder exstrophy
• Isolated omphalocele
• Gastroschi i

pectrum of abnormalities resulting from abnormal
development of cloacal membrane

Imaging Findings
•
•
•
•
•

Absen e of normal bladder
Lower abdominal wall defect
Herniation of bowel between 2 halves of bladder
Omphalocele forms upper part of defect
Associated anomalies ver common

I PATHOLOGY
General Features
• Etiology
o Variable severity, depending on timing and position
of disruption (menstrual weeks 6-12)
o Persistence of cloacal membrane prevents migration
of mesenchymal tissue, resulting in lack of normal
lower abdominal wall
• Cloacal membrane becomes anterior bladder wall
and exposes bladder lumen when it ruptures
o Cloacal exstrophy develops before the urogenital
septum descends and separates urogenital sinus
from hindgut
• Disruption therefore affects both genitourinary
and gastrointestinal tracts
• Epidemiology
o Rare: 1:200,000 to 400,000 live births
o More frequent in monozygotic than dizygotic twins
o More frequent after in vitro fertilization

Gross Pathologic & Surgical Features
• Spectrum ranging from epispadias to large ventral wall
defect with ambiguous genitalia
• Exposed bladder in two halves with intestinal mucosa
herniation in midline
• Distal gut blind ending: Imperforate anus
• Genetic males have bifid penis and undescended testes
• Genetic females have duplicated miillerian structures
with duplicated, exstrophied or atretic vaginas

Diagnostic Checklist
• Su peCI loacal exstrophy when there is a low
abdominal wall defect and an ab ent bladder

• Karyotyping should be offered to determine genetic
sex
o Sex reassignment has been performed in males
where creation of a functioning penis is not feasible
• Delivery at tertiary care center with immediate
consultation from multidisciplinary
team
• Complex reconstructive surgery of gastrointestinal and
genitourinary tracts

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Suspect cloacal exstrophy when there is a low
abdominal wall defect and an absent bladder

I SELECTED REFERENCES
1.

2.

3.

4.
5.

Wood HP et al: In vitro fertilization and the cloacal-bladder
exstrophy-epispadias complex: is there an association? J
Urol. 169(4):1512-5,2003
Kaya H et al: Prenatal diagnosis of cloacal exstrophy before
rupture of the cloacal membrane. Arch Gynecol Obstet.
263(3):142-4,2000
Hamada H et al: New ultrasonographic criterion for the
prenatal diagnosis of cloacal exstrophy: elephant trunk-like
image. J Urol. 162(6):2123-4, 1999
Austin PF et al: The prenatal diagnosis of cloacal exstrophy.
J Urol. 160(3 Pt 2):1179-81,1998
Meizner I et al: Cloacal exstrophy sequence: an exceptional
ultrasound diagnosis. Obstet Gynecol. 86(3):446-50, 1995

I IMAGE

ICLINICALISSUES

Diagnoses

GALLERY

Presentation
• Marked elevation of maternal
• Lower abdominal wall defect

serum alpha-fetoprotein

Natural History & Prognosis
• Increased rates of intrauterine death and stillbirth
• Pre term labor from polyhydramnios
• Prognosis dependent on severity of defect and
associated malformations
o Survival rate above 90%

Treatment
• Termination may be offered if diagnosis is made before
24 weeks, after appropriate counseling as to nature of
disorder and long term sequelae

(Left) Sagittal T2WI MR of a fetus with cloacal exstrophy shows a low
abdominal wall defect (arrows) with non-visualization of the bladder.
(Right) Clinical photograph after delivery shows bowel herniation
(arrow) between the two halves of the bladder (open arrows). There
is also a split scrotum (curved arrows).

OEIS SYNDROME

Axial T2WI MR of a twin with OEIS syndrome shows a
meningocele (curved arrow) and large omphalocele
(black arrows). The lower extremities (open arrows) are
abducted.

Coronal T2WI MR shows the length of the neural tube
defect (open arrow) and associated ventriculomegaly
(curved arrow). The bladder was never identified on US
or MR images. The co-twin (black arrow) was normal.

ITERMINOLOGY

I DIFFERENTIAL

Definitions

Cloacal exstrophy

• Full complex consists of 4 components
o Omphalocele
o Exstrophy of bladder
o Imperforate anus
o Spinal deformities
• Some authors consider OEIS to be synonymous
cloacal exstrophy

• Significant overlapping features
o Some consider these variations of same
malformation
• May see herniated bowel between halves of
exstrophied bladder

IIMAGING

with

Body stalk anomaly
• Fetus adherent to placenta
• Large gastropleuroschisis
• Severe scoliosis

FINDINGS

Ultrasonographic

DIAGNOSIS

Amniotic band syndrome

Findings

• Omphalocele
o Midline defect
o Covered by membrane
o Cord inserts on sac
• Bladder exstrophy
o Absent normal bladder
o Soft tissue mass on lower abdominal wall
• Costovertebral defects of upper and lower spine
o Hemivertebra and segmentation defects
o Myelomeningocele
o Pubic diastasis
• Imperforate anus
o Often not detected in utero

• Slash defects not conforming to an anatomic
distribution
• Craniofacial defects common

Omphalocele

(isolated)

• Normal bladder
• Normal spine

Neural tube defects (isolated)
• Normal bladder
• No omphalocele

DDx: OEIS Syndrome

Omphalocclc

Omphalocele

Myelomeningocele

Amniotic Bands

PENTALOGY OF CANTRELL

Craphic shows a high abdominal omphalocele
and
ectopia cordis (arrow). These are the most characteristic
imaging features seen with Pentalogy of Cantrell.

Sagittal ultrasound of a 2nd trimester fetus with
Pentalogy of Cantrell shows both the liver (arrow) and
heart (open arrow) outside the chest.

ITERMINOlOGY

MR Findings

Definitions

• T2WI sequences show low signal liver and heart, with
high signal pleural or pericardial effusion
• Pericardium, diaphragm and liver capsule are dark and
can be difficult to separate, unless there is intervening
fat or fluid
• Diaphragmatic defect may be difficult to characterize

• Complex malformation with 5 components
o Anterior diaphragmatic hernia
o Midline abdominal wall defect
o Cardiac anomalies
o Defect of diaphragmatic pericardium
o Lower sternal defect

I DIFFERENTIAL DIAGNOSIS
IIMAGING

FINDINGS

Ectopia cordis

General Features
• Best diagnostic clue: Ectopia cordis with omphalocele
• Location: Midline, anterior abdominal wall

Ultrasonographic

Findings

• Supra umbilical abdominal wall defect
o Omphalocele or abdominal wall schisis
o May contain stomach, liver and bowel
o May be total evisceration of abdominal contents
• Variable displacement of heart and mediastinum from
diaphragmatic/sternal defects
o Completely external with large defects
o Bulging of heart in small defects
• Pleural or pericardial effusion

DDx: Extracorporeal

• Heart protrudes through a cleft sternum
• None of other components

Cleft sternum
• Superior cleft in sternum or absence of sternum allows
heart to to bulge but chest wall is intact
o Prominent chest wall pulsations
o Associated cavernous hemangioma

Omphalocele
• Lacks cardiac and diaphragmatic

abnormalities

Body stalk anomaly (limb body wall
complex)
• Fetus adherent to placenta
• Severely distorted fetus

Heart

Body Stalk Anomaly

PENTALOGY OF CANTRELL

Graphic shows a high abdominal omphalocele and
ectopia cordis (arrow). These are the most characteristic
imaging fealUres seen with Pentalogy of Cantrell.

Sagittal ultrasound of a 2nd trimester fetus with
Pentalogy of Cantrell shows both the liver (arrow) and
heart (open arrow) outside the chest.

ITERMINOLOGY

MR Findings

Definitions

• T2WI sequences show low signal liver and heart, with
high signal pleural or pericardial effusion
• Pericardium, diaphragm and liver capsule are dark and
can be difficult to separate, unless there is intervening
fat or fluid
• Diaphragmatic defect may be difficult to characterize

• Complex malformation with 5 components
o Anterior diaphragmatic hernia
o Midline abdominal wall defect
o Cardiac anomalies
o Defect of diaphragmatic pericardium
o Lower sternal defect

I DIFFERENTIAL DIAGNOSIS
IIMAGING

FINDINGS

Ectopia cordis

General Features
• Best diagnostic clue: Ectopia cordis with omphalocele
• Location: Midline, anterior abdominal wall

Ultrasonographic

Findings

• Supraumbilical abdominal wall defect
o Omphalocele or abdominal wall schisis
o May contain stomach, liver and bowel
o May be total evisceration of abdominal contents
• Variable displacement of heart and mediastinum from
diaphragmatic/sternal
defects
o Completely external with large defects
o Bulging of heart in small defects
• Pleural or pericardial effusion

DDx: Extracorporeal

Heart

• Heart protrudes through a cleft sternum
• None of other components

Cleft sternum
• Superior cleft in sternum or absence of sternum allows
heart to to bulge but chest wall is intact
o Prominent chest wall pulsations
o Associated cavernous hemangioma

Omphalocele
• Lacks cardiac and diaphragmatic

abnormalities

Body stalk anomaly (limb body wall
complex)
• Fetus adherent to placenta
• Severely distorted fetus

PENTALOGY OF CANTRELL
Key Facts
Terminology
•
•
•
•
•
•

omplex malformation with 5 omponents
Anterior diaphragmatic hernia
Midline abdominal wall defect
ardiac anomalie
Defect of diaphragmatic pericardium
Lower ternal defect

Imaging Findings

• Supraumbilical abdominal wall defect
• Variable di placement of heart and media tinum
from diaphragmatic/
ternal defects

Top Differential
• Ectopia cordis
• left st rnum
• Omphalocele
• Body talk anomaly

Diagnoses

(limb body wall complex)

• Best diagno tic clue: Ectopia cordis with omphalocele
• No free-floating cord

Amniotic band syndrome
• Frequently involves head and neck
o "Slash" defects
• Multiple limb defects
• Look for bands

• Karyotype and careful search for other anomalies
• Surgical repair if fetus survives

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Coexisting ectopia cordis and omphalocele

I PATHOLOGY
General Features
• Genetics: Sporadic
• Etiology
o Failure of fusion of lateral folds in thorax, with
failure of development of transverse septum of
diaphragm
• Other components of pentalogy are a
consequence of this initial failure
o Midline developmental field defect believed to
account for facial clefts and encephalocele, which
are sometimes present
• Epidemiology
o Rare
o M=F
o Reported in monozygotic twins
• Associated abnormalities
o Cardiac anomalies
• Atrial septal defects 50%
• Ventricular septal defects 20%
• Tetralogy of Fallot 10%
o Craniofacial and vertebral anomalies
• Cleft lip/palate
• Exencephaly, encephalocele
o Chromosomal abnormalities
• Trisomies 13, 18
• Turner syndrome (45,XO)
o Cystic hygroma

I SELECTED
1.

2.

3.

4.

5.

specific

REFERENCES

Oaltro Pet al: Prenatal MRI of congenital abdominal and
chest wall defects. A]R Am] Roentgenol. 184(3):1010-6,
2005
Liang RI et al: Prenatal diagnosis of ectopia cordis at 10
weeks of gestation using two-dimensional and
three-dimensional
ultrasonography.
Ultrasound Obstet
Gynecol. 10(2):137-9, 1997
Carmi R et al: Pentalogy of Cantrell and associated midline
anomalies: a possible ventral midline developmental field.
Am] Med Genet. 42(1):90-5,1992
Ghidini A et al: Prenatal diagnosis of pentalogy of Cantrell.
] Ultrasound Med. 7(10):567-72, 1988
Cantrell ]R et al: A syndrome of congenital defects
involving the abdominal wall, sternum, diaphragm,
pericardium, and heart. Surg Gynecol Obstet. 107 (5):
602-14, 1958

IIMAGE

GALLERY

Gross Pathologic & Surgical Features
• Thoraco-abdominal
defect with ectopia cordis,
omphalocele, diaphragmatic defect, pericardia I defect
and sternal disruption

ICLINICAL

ISSUES

Natural History & Prognosis
• Prognosis dependent on severity but usually fatal
when discovered prenatally

(Leh) Sagittal ultrasound shows a high abdominal wall defect, above
the level of the cord insertion (arrow), with the liver (curved arrow)
by the chest. Ectopia cordis was also present. (Right) Cross pathology
in this case shows the entire liver (open arrow) and heart (curved
arrow) are extra corporeal.
Other findings at autopsy included
absence of the sternum,
deficiency
of the diaphragm
and
diaphragmatic pericardium, and a membranous ventricular septal
defect. This constellation of findings is diagnostic of Pentalogy of
Cantrell.

SECTION 8: Gastrointestinal

Bowel
Echogenic Bowel
Esophageal Atresia
Duodenal Atresia
Jejunal, Ileal Atresia
Anal Atresia
Meconium Peritonitis, Pseudocyst
Volvulus
Ascites
Enteric Duplication Cyst
Mesenteric Cyst

8-2
8-6

8-10
8-14
8-18
8-20
8-24
8-26

8-30
8-32

Hepatobiliary
Gallstones
Hepatic Calcifications
Hepatomegaly, Splenomegaly
Choledochal Cyst
Liver Tumors

8-34
8-36

8-38
8-40
8-42

ECHOGENIC BOWEL

Coronal ultrasound of the fetal abdomen shows grade 3
fB (arrows). The bowel echogenicity is heterogeneous
and some areas are more echogenic than bone (curved
arrow points to iliac crest).

ITERMINOLOGY
Abbreviations

and Synonyms

• Echogenic bowel (EB)
• Hyperechoic bowel

Definitions
• Increased echogenicity

IIMAGING

of fetal bowel

FINDINGS

General Features
• Best diagnostic clue: Second trimester increased focal
bowel echogenicity
• Morphology: Focal EB is mass-like

Ultrasonographic

Findings

• Assessing bowel echogenicity
o Compare echogenicity with liver and bone
• Normal bowel echogenicity ~ liver, < bone
o Bowel echogenicity grading
• Grade 0: < liver
• Grade 1: > liver, < bone
• Grade 2: = to bone
• Grade 3: > than bone
• Grades 0 and 1 are normal
• Grades 2 and 3 are potentially abnormal

DDx: Abdominal

Echogenicities

~ •..... ii~'I.L·1L
~

',"

'

.~~

.,.~.~
••.. ·f~"'_.

Meconium

Peritonitis

Meconium

.
",

~~~

."

Peritonitis

Axial ultrasound of the neck in the same fetus shows
nuchal thickening (calipers). The findings of fB and
increased nuchal fold thickness raise suspicion for
aneuploidy and amniocentesis revealed trisomy 27.

o Coronal and sagittal trunk images
• Compare bowel with liver
• Compare bowel with spine
o Transverse pelvis image
• Compare bowel with iliac crest
o Transducer frequency matters
• High frequency transducer falsely increases
echogenicity
• More often appears as diffuse EB
• 31% EB incidence with 8 MHz transducer
• 1-2% EB incidence with 5 MHz transducer
• EB diagnosis
o 2nd trimester diagnosis
• Part of genetic sonogram
o True EB is usually focal
• Mass-like
• Lower abdomen most often
o Adverse outcome
• 6% when isolated finding
• 50% when not isolated
• Association with trisomy 21 (T2l)
o 6,7x t likelihood of T21
• Compared to maternal apriori risk (maternal age,
serum quadruple screen)
o 1-2% of cases with EB have T21
o More likely T21 if other markers seen
• t Nuchal thickening
• Short femur/humerus

ECHOGENIC BOWEL
Key

Facts

Terminology

• 10% of EB ca e from wallowed blood

• Ilyp rechoic bowel

Top Differential

Imaging Findings

• Meconium p ritoniti
• Anal atresia (enterolithia
• wallowed debris

• Best diagno tic clue: Second trime ter increased focal
bow I chog nicity
• Grade 0: < liver
• Grade 1: > liver, < bone
• Grade 2: = to bone
• rade 3: > than bone
• Grade 0 and 1 are normal
• rade 2 and 3 are potentially abnormal
• 6.7x t likelihood of T21
• More likely T21 if other markers s en
• 1-21}'o EB from in utero infection
• ytomegaloviru
( MV) most common
• 181X) develop lUGR

•

•

•

•

• Intracardiac echogenic focus
• Renal pelviectasis
• Clinodactyly
1-2% EB from in utero infection
o Cytomegalovirus (CMV) most common
• Microcephaly
• Intracranial periventricular calcification
• Ventriculomegaly
• Hydrops
• Intrauterine growth restriction (IUGR)
o Other infections
• Toxoplasmosis
• Influenza
• Parvovirus
o Associated findings
• Hydrops
• IUGR
EB and cystic fibrosis
o Risk of fetus with echogenic bowel having cystic
fibrosis varies widely between studies (0-33%)
• Depends on population base
• Cystic fibrosis more common in Caucasians of
Northern European origin
o 11% of fetuses with cystic fibrosis have echogenic
bowel
o +/- Bowel obstruction
• Meconium ileus
EB and IUGR
o 18% develop IUGR
o Fetal Doppler
• ~ Umbilical artery diastolic flow
o EB + IUGR + t alpha fetoprotein (AFP)
• 40x increased risk for in utero demise
• Severe placental insufficiency
10% of EB cases from swallowed blood
o From intra amniotic blood
• Placental abruption
• Fetus swallows blood
• Blood travels through gastrointestinal tract
o Amniocentesis can be diagnostic
• Bloody fluid
• Stained fluid

Diagnoses
is)

Pathology
• Epidemiology:

1% of fetuses have grade 2 or 3 EB

Diagnostic Checklist
•
•
•
•

Genetic coun ling for all grade 2 or 3 EB
Follow-up ultrasound for growth
Focal EB i more likely pathologic than diffu e EB
High frequency tran ducers falsely increa e bowel
echogen icity

• Bowel-related causes
o 1-2% of cases with EB
o Ischemia
o Atresia
• Ileal most common
o Other bowel findings
• Dilatation
• Ascites

Imaging Recommendations
• Best imaging tool
o Abdomen views including bowel, liver and bone
• Longitudinal views that include spine
• Transverse views that include iliac crest
• Protocol advice
o Transducer frequency
• Avoid diagnosis of EB if transducer ~ 8 MHz
• Switch to 5 MHz and reassess bowel
• More likely an issue when EB is diffuse
o Grade 2 and 3 EB need genetic sonogram
• Genetic counseling for T21
• Assessment for risk of cystic fibrosis
o Assess risk of infection
• Maternal CMV titers
• Amniocentesis for CMV

I DIFFERENTIAL
Meconium

DIAGNOSIS

peritonitis

• Fetal bowel perforation
o Secondary peritonitis
o Peritoneal calcifications
• Linear and punctate
• Outline liver and bowel
• Mimic EB when focal
o Meconium pseudocyst
• Walled off bowel spill
• Hypoechoic fluid collection
• Often accompanied by other findings
o Ascites
o Dilated bowel
• Often from atresia

ECHOGENIC BOWEL
• Increased risk for cystic fibrosis

Anal atresia (enterolithiasis)
• Third trimester diagnosis
• Distended colon
• Calcified intraluminal meconium
o From stasis
• In utero "constipation"
o Vesico-enteric fistula
• Urine + meconium = calcification

Swallowed debris
• Fetus swallows echogenic material
o Vernix
o Protein
o Intraamniotic blood
• Usually idiopathic finding
o Transient
• Dependent layering

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Isolated finding on routine study
o EB + other anomalies/markers
o EB + IUGR
o EB + hydrops

Demographics
• Age
o Advanced maternal age at t risk for T21
• ~ 35 yrs at time of delivery

Natural History & Prognosis
• Excellent when isolated in low risk patients
• Not associated with infant bowel dysfunction
isolated

when

Treatment

I PATHOLOGY
General Features
• Genetics
o T21 association
• 6.7x t risk
• Etiology
o ~ Microvillar enzymes
• T21, cystic fibrosis
o ~ Bowel motility
o Inspissated meconium
• ~ Water content
• t Protein content
o Mesenteric ischemia
• Epidemiology: 1% of fetuses have grade 2 or 3 EB
• Associated abnormalities
o T21 anomalies
o In utero infection
• Hydrops
• Brain calcifications
• Liver calcifications
o Bowel obstruction
• Atresia
• Ischemia
o IUGR

Staging, Grading or Classification Criteria
• Grade 0 (normal)
o Bowel echogenicity = liver echogenicity
• Grade 1 (normal)
o Bowel is minimally more echogenic than liver
o Bowel is less echogenic than bone
• Grade 2 = EB
o Bowel is as echogenic as bone
o Usually focal
• Grade 3 = EB
o Bowel is more echogenic than bone
o Usually focal

• None for EB
• May be necessary for EB associations

I DIAGNOSTIC

CHECKLIST

Consider
• Genetic counseling for all grade 2 or 3 EB
• Amniocentesis in high risk patients
o Karyotype for T21
o Look for CMV
o Screen for cystic fibrosis
• Follow-up ultrasound for growth
• Doppler assessment when IUGR seen

Image Interpretation

Pearls

• Focal EB is more likely pathologic than diffuse EB
• Look for other markers of T21
• High frequency transducers falsely increase bowel
echogenicity

I SELECTED
1.

2.

3.
4.
S.

6.

7.

8.

REFERENCES

Patel Y et al: Follow-up of children with isolated fetal
echogenic bowel with particular reference to bowel-related
symptoms. Prenat Diagn. 24(1):3S-7, 2004
Kesrouani AK et al: Etiology and outcome of fetal
echogenic bowel. Ten years of experience. Fetal Diagn
Ther. 18(4):240-6,2003
Al-Kouatly HB et al: Factors associated with fetal demise in
fetal echogenic bowel. Am J Obstet Gynecol.
18S(S):1039-43,2001
Al-Kouatly HB et al: The clinical significance of fetal
echogenic bowel. Am J Obstet Gynecol. 18S(S):103S-8,
2001
Nyberg DA et al: Isolated sonographic markers for
detection of fetal Down syndrome in the second trimester
of pregnancy. J Ultrasound Med 20 (10):lOS3-63, 2001
Strocker AM et al: Fetal echogenic bowel: parameters to be
considered in differential diagnosis. Ultrasound Obstet
Gynecol. 16(6):S19-23, 2000
Vincoff NS et al: Effect of ultrasound transducer frequency
on the appearance of the fetal bowel. J Ultrasound Med.
18(12):799-803; quiz 80S-6, 1999
Nyberg DA et al: Fetal hyperechogenic bowel and Down
syndrome. Ultrasound Obstet Gynecol 3:330-3, 1993

ECHOGENIC BOWEL
IIMAGE GALLERY
(Left) Sagittal ultrasound of
the fetal trunk shows EB
(arrows) in a fetus with T2 7.
The bowel echogenicity is
greater than bone and the
finding is very focal. Focal E/3
is more likely pathologic
than diffuse. (Right) Axial
ultrasound in the same fetus
confirms the presence of
focal EB (arrows) Even as an
isolated finding, grade 3 E/3
significantly increases the risk
for trisomy 27.

(Left) Coronal ultrasound of
the fetal trunk shows focal
grade 2 echogenic bowel
(arrows) in a fetus with CMV
infection. This pregnancy
was also complicated by
oligohydramnios andlUCR.
(Right) Axial unenhanced CT
of the brain in another
neonate shows the typical
peri ventricular calcifications
(arrows) and
ventriculomegaly (curved
arrows) seen with CMV

Variant
(Left) Sagittal ultrasound of
the fetal trunk obtained with
an 8 MHz transducer shows
focal EB (arrows). The spine
(curved arrow) and EB have
similar echogenicity. (Right)
Sagittal ultrasound of the
same fetus using a 5 Mliz
transducer corrects the false
EB diagnosis. The bowel is
more diffusely echogenic
(arrows) and clearly less
echogenic than bone
(curved arrow). lligh
frequency transducers can
give the erroneous
impression of E/3.

ESOPHAGEAL ATRESIA

Graphic shows frequency and types of fA. fA with
distal fistula (A), fA with no fistula (8), "H" fistula with
no fA (C), fA with proximal and distal fistula (0), and
fA with proximal fistula (f).

Axial ultrasound through the upper abdomen in a 3rd
trimester fetus shows no stomach bubble. There is also
marked polyhydramnios.

ITERMINOlOGY
Abbreviations

•

and Synonyms

• Esophageal atresia (EA)

Definitions
• Atresia of esophagus often associated with
tracheoesophageal
fistula (TEF)
o > 90% have a fistula
o Proximal atresia with distal TEF most common

type

IIMAGING FINDINGS
•

General Features
• Best diagnostic clue: Combination of small stomach,
polyhydramnios,
and intrauterine growth restriction
(lUGR) in late 2nd and 3rd trimester
• Diagnosis often missed before polyhydramnios
develops
• Reported sensitivity of ultrasound for detection of EA
< 50%

Ultrasonographic

•

Findings

• Small or absent stomach
o Complete absence suggests either no TEF or a very
small, stenotic connection
• "Pouch" sign

•

o Transient filling of proximal esophagus with
swallowing
Frequently associated with duodenal atresia (DA)
o May not be able to diagnose combination of EA +
DA prenatally if TEF present
• Stomach secretions may decompress through
fistula
o If TEF not present, the distal esophagus, stomach,
and duodenum form a closed "C loop"
• Normal secretions accumulate in this isolated loop
• May cause marked dilatation
• Has been detected in 1st trimester
o High risk for trisomy 21
IUGR
o Seen in up to 40%
o Ingested amniotic fluid important for growth in
latter half of gestation
• Higher gastrointestinal (GI) obstructions cause
greatest growth disturbances
o Manifests in late 2nd or 3rd trimester
Polyhydramnios
o Rarely develops before 20 weeks
• Fetal swallowing not important part of amniotic
fluid dynamics until that time
Part of VACTERL association
o Vertebral anomalies
o Anal atresia
o Cardiac malformation

DDx: Absent Normal Stomach Bubble

COH

COff

ESOPHAGEAL ATRESIA
Key Facts
Terminology

Top Differential

• Atresia of e ophagus often a sociated with
tracheoesophageal
fistula (TEF)
• Proximal atresia with distal TEF most common

• Diaphragmatic hernia
• entral nervous sy tern malformations
• euromu cular di order
• left lip, palate

type

Imaging Findings
• Best diagnostic clue: Combination of small tomach,
polyhydramnio
, and intrauterine growth re triction
(IU R) in late 2nd and 3rd trimester
• Follow-up scan hould be performed on all fetu
with small tomach
• mall stomach may be tran ient finding in normal
fetus, especially in 1st and 2nd trimester
• Look p cifically at neck and upp r chest for
esophageal pouch
• Pouch will expand with fetal swallowing

o Trachea-esophageal
o Renal anomalies
o Limb malformation

fistula, esophageal

atresia

Diagnoses

Pathology
• Aneuploidy report d in 5-44(Yh
• Trisomy 18 (TI8) most common
• EA without TEF more common in T21

Clinical Issues
• 22-75% mortality for those detected in utero

Diagnostic Checklist
•

ombination of IUGR and polyhydramnios should
prompt careful search for anomalies, including EA

• Omphalocele
• Congenital diaphragmatic hernia (CDH)
• Dedicated fetal echo for cardiac malformations

MR Findings
• EA has been described using MRI
• Not a reliable method for making diagnosis
• Patentcy of esophagus difficult to determine

Imaging Recommendations
• Often difficult to define when a stomach is "small"
o No defined measurements
o Stomach size varies between patients
o Stomach size varies in same fetus over several hours
• Related to swallowing and peristalsis
o Requires experience
• Follow-up scans should be performed on all fetuses
with small stomach
o Small stomach may be transient finding in normal
fetus, especially in 1st and 2nd trimester
o Persistence on multiple exams more likely
pathologic
o Very suspicious if polyhydramnios
develops
• Perform focused exam
o Look specifically at neck and upper chest for
esophageal pouch
• Pouch will expand with fetal swallowing
o Determine location of distal end of pouch
• Termination in neck worse prognosis than
termination in mediastinum
• Evaluate
o Growth
o Amniotic fluid
o Combination of IUGR and polyhydramnios
highly
suggestive of underlying abnormality
• Always consider EA in this setting
• Search for other anomalies
o VACTERL association
o Trisomy 18
• Clenched hands with overriding 2nd finger
• Cardiac defects
• Choroid plexus cysts
• IUGR

I DIFFERENTIAL DIAGNOSIS
Diaphragmatic
•
•
•
•
•
•

hernia

Stomach in chest
May also have small bowel and liver in chest
Peristalsis within chest mass pathognomonic
Deviation of cardiac axis
Abdominal circumference small
Polyhydramnios

Abnormal swallowing
• Central nervous system malformations
• Neuromuscular disorders
o Arthrogryposis
• Cleft lip, palate

Hiatal hernia
• Stomach partially in chest
• Tubular appearance in longitudinal
chest into abdomen

plane, crosses from

I PATHOLOGY
General Features
• Genetics
o Sporadic occurrence
o No known inheritance pattern
o Chromosomal
• Aneuploidy reported in 5-44%
• Trisomy 18 (TI8) most common
• Trisomy 21 (T21)
• EA without TEF more common in T21
• Etiology
o Embryology
• Incomplete foregut division

ESOPHAGEAL ATRESIA
• Tracheo-esophageal septum normally divides
ventral (respiratory) from dorsal (digestive)
segments
• Mechanism not completely understood
• Epidemiology
o 1:2,000-3,000 live births
o Males slightly more common than females
• Associated abnormalities
o Reported in 63%
o Multiple atresias often present
• Duodenal
• Ileal
• Anorectal
o Bowel malrotation
o Cardiac anomalies
o Other anomalies in VACTERLassociation
o Case reports of biliary atresia

Staging, Grading or Classification Criteria
• Types and percentages of EA
o Proximal atresia with distal TEF (82%)
o Proximal and distal atresia, no fistula (9%)
o H-type fistula with no atresia (6%)
o Atresia with both proximal and distal fistulas (2%)
o Proximal TEF with distal atresia (1%)

• Predelivery consult with pediatric surgeon
• Deliver at tertiary care center
• Surgical resection and reanastomosis after delivery
o May need to be staged procedure if atretic segment
is long
• Gastrostomy tube in some cases

I DIAGNOSTIC

Image Interpretation

I SELECTED
1.

2.

ISSUES

Presentation
• Most common signs/symptoms
o Polyhydramnios
• Large-for-dates
• Preterm labor
• Abnormal serum screen (TI8, T21)
• Other more obvious findings in VACTERLassociation
or TI8
• After delivery
o Coughing, drooling, choking
o Recurrent pneumonia (H-type)

Demographics
• Age
o Advanced maternal age at t for T21, T18
• ~ 35 yrs at time of delivery

4.

5.
6.
7.

8.

9.

10.

Natural History & Prognosis
• 22-75% mortality for those detected in utero
• Presence of cardiac defect greatest effect on survival in
neonatal group
• Even if isolated, long term sequelae common
oEsophageal dysmotility in nearly 100%
o Strictures
o Recurrent TEF
o Aspiration
o Feeding difficulties
o Tracheomalacia
• EA without TEF more difficult to repair

11.
12.

13.

14.

15.

Treatment
• All fetuses should be karyotyped
• Amnioreduction for severe polyhydramnios
o Reduce uterine irritability
o Maternal comfort

Pearls

• Ultrasound is poor in detecting EA before the onset of
polyhydramnios
o Must have a high degree of suspicion and perform
follow-up scans
• Combination of IUGR and polyhydramnios should
prompt careful search for anomalies, including EA

3.

I CLINICAL

CHECKLIST

16.

REFERENCES

Has R et al: Pouch sign in prenatal diagnosis of esophageal
atresia. Ultrasound Obstet Gynecol. 23(5):523-4, 2004
Kovesi T et al: Long-term complications of congenital
esophageal atresia and/or tracheoesophageal fistula. Chest.
126(3):915-25, 2004
Malinger G et al: The fetal esophagus: anatomical and
physiological ultrasonographic characterization using a
high-resolution linear transducer. Ultrasound Obstet
Gynecol. 24(5):500-5, 2004
Marquette GP et al: First-trimester imaging of combined
esophageal and duodenal atresia without a
tracheoesophageal fistula. J Ultrasound Med. 23(9):1232,
2004
Samujh R et al: Oesophageal atresia and biliary atresia: a
rare association. Pediatr Surg Int. 20(6):467-8, 2004
Tonz M et al: Oesophageal atresia: what has changed in the
last 3 decades? Pediatr Surg Int. 20(10):768-72, 2004
Kalache KD et al: Prognostic significance of the pouch sign
in fetuses with prenatally diagnosed esophageal atresia. Am
J Obstet Gynecol. 182(4):978-81, 2000
Sparey C et al: Esophageal atresia in the Northern Region
Congenital Anomaly Survey, 1985-1997: Prenatal diagnosis
and outcome. Am J Obstet Gynecol. 182:427-31,2000
Kalache KD et al: The upper neck pouch sign: a prenatal
sonographic marker for esophageal atresia. Ultrasound
Obstet Gynecol. 11(2):138-40, 1998
Satoh S et al: Antenatal sonographic detection of the
proximal esophageal segment: Specific evidence for
congenital esophageal atresia. J Clin Ultrasound.
23:419-23, 1995
Stringer MD et al: Prenatal diagnosis of esophageal atresia.
J Pediatr Surg. 30:1258-63, 1995
Estroff JA et al: Second trimester prenatal findings in
duodenal and esophageal atresia without
tracheoesophageal fistula. J Ultrasound Med. 13(5):375-9,
1994
Surana R et al: Small intestinal atresia: effect on fetal
nutrition. J Pediatr Surg. 29(9):1250-2, 1994
Millener PB et al: Prognostic significance of
nonvisualization of the fetal stomach by sonography. AJR
AmJ Roentgenol. 160(4):827-30, 1993
Pretorius DH et al: Tracheoesophageal fistula in utero.
Twenty-two cases. J Ultrasound Med. 6(9):509-13, 1987
Jolleys A: An examination of the birthweights of babies
with some abnormalities of the alimentary tract. J Pediatr
Surg. 16(2):160-3, 1981

ESOPHAGEAL ATRESIA
IIMAGE

GALLERY
(Left) Sagittal ultrasound of
the left upper quadrant
shows complete absence of
a normal stomach bubble.
Careful scanning revealed
what was thought to be the
collapsed stomach (arrows).
(Right) Coronal color
Doppler ultrasound focused
on the fetal neck was then
performed, which showed a
"pouch sign" (arrows) at the
point of esophageal atresia.
Observation of this
blind-ending pouch showed
expansion and contraction
with fetal swallowing.

(Left) Frontal radiograph
from the case above shows
the nasogastric tube
terminating in the proximal
esophagus (arrow). No gas is
seen in the stomach (curved
arrow) consistent with
esophageal atresia without a
TEF. (Right) Lateral
radiograph with non-ionic
contrast shows complete
atresia, with the esophagus
ending in a pouch (arrow)
similar to the fetal ultrasound
appearance.

(Left) Axial ultrasound of a
2nd trimester fetus shows a
stomach bubble is present
but smaller than expected
(arrow). There is also
polyhydramnios.
Postnatal
work-up showed proximal
fA with a distal TEF. (Right)
Cross pathology from a fetus
with a VACTERL association
shows the dissected proximal
esophagus terminating in a
blind ending pouch (curved
arrow). The distal esophagus
communicates
with the
trachea at the level of the
carina (arrow). The stomach
is small (open arrow).

DUODENAL

Gross pathology of duodenal atresia shows the stomach
(curved arrow) communicating
with a markedly
distended duodenum
(arrow). An axial image through
these fluid-filled structures creates a "double bubble".

ITERMINOlOGY
Abbreviations

and Synonyms

• Duodenal atresia (DA), web or stenosis

Definitions
• Lack of normal duodenal canalization leading to
partial (web/stenosis) or complete obstruction (atresia)

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Stomach and duodenum can be
connected during real-time imaging
• Duodenum most common site of intestinal
obstruction
• Normal gastric incisura may mimic appearance
• Persistent fluid in duodenum is always abnormal

Ultrasonographic

Findings

• "Double bubble"
o Fluid-filled stomach and duodenum
o Generally seen after 20 weeks
• Duodenal web or stenosis may not be seen until
3rd trimester
o Has been diagnosed in 1st trimester
• May have worse prognosis

DDx: Other Abdominal

ATRESIA

Axial ultrasound through the upper abdomen shows the
classic "double bubble" appearance, typically seen with
duodenal atresia.

• Polyhydramnios
o Usually not detected before 24 weeks
o Present in most cases by 3rd trimester
• May become severe
• No fluid in distal bowel loops
• Fetal regurgitation may intermittently decompress
stomach
• Other gastrointestinal (GI) malformations common
o Esophageal atresia (EA)
• If a tracheoesophageal fistula is not present, fluid
may accumulate in distal esophagus, stomach,
and duodenum forming a "C loop"
• Normal secretions accumulate in this closed loop
• Accumulated secretions may cause marked
dilatation, much greater than typically seen with
just DA
• More likely to present in 1st trimester than
isolated DA
o Distal bowel atresia
o Malrotation
o Biliary atresia
o Gallbladder atresia
• Other associated findings
o Cardiac malformations in 37%
o Skeletal anomalies
• Vertebral body malformations
• Radial ray malformation
• Caudal regress sequence

"Bubbles"

.:

J.~~ ~"
,

~,.,

Antral Atresia

i:/:

..c;

~,

.

-

Mesenteric Cyst

Jejunal Atresia

DUODENAL

ATRESIA

Key Facts
Terminology

Top Differential Diagnoses

• Lack of normal duodenal canalization leading to
partial (web/steno is) or complete ob tru ti n
(atr ia)

•
•
•
•
•

Imaging Findings
•
•
•
•
•
•
•
•

Persistent fluid in duodenum is always abnormal
"Double bubble"
Polyhydramnios
Fetal regurgitation may intermittently decompre
stomach
Other ga trointe tinal (GI) malformation
ommon
30% of DA fetu e have tri omy 21 (T21)
ombination of EA + DA even greater ri k of T21
Must connect stomach with duodenum to confirm
diagno i

• Clubfeet
o Genitourinary
• Hydronephrosis
• Multicystic dysplastic kidney
• Intrauterine growth restriction
o Ingested amniotic fluid important for growth in
latter half of gestation
o Higher GI obstructions cause greatest growth
disturbance
• Chromosomal anomalies
o 30% of DA fetuses have trisomy 21 (T21)
o Combination of EA + DA even greater risk of T21

MR Findings
• Fluid-filled stomach and duodenum
o Low signal T1 WI
o High signal T2WI
• MR adds information about distal bowel
o If atresia is only duodenal, distal small bowel will be
unaffected
• Sufficient intestinal secretions present to give
normal appearance
• Normal size of bowel loops
• Meconium high signal T1WI, low signal T2WI
o Less likely to see normal distal bowel in setting of
multiple atresias

Imaging Recommendations
• Must connect stomach with duodenum to confirm
diagnosis
• Look for other findings of T21
o Cardiac malformations
• Atrioventricular septal defect + DA greatest risk for
T21
• Ventricular septal defect
• Tetralogy of Fallot
o GI

Distal atre ia
Antral web/atr ia
Choledochal cyst
Ovarian cyst
Duplication cyst

Pathology
• 5-15% of T21 case have DA
• 50-70% of DAs have other anomalies

Clinical Issues
• Overall mortality 15-40%
• Isolated defect, 95()1) urvival with immediate
treatment
• All fetu es should be karyotyped

• Short femur and humerus
• Echogenic bowel
• Intracardiac echogenic focus
• Renal pelviectasis
• Absent or hypoplastic nasal bone
• Fifth finger clinodactyly, sandal gap foot
• Dedicated cardiac echo
• Follow for worsening polyhydramnios

I DIFFERENTIAL

DIAGNOSIS

Distal atresias
• Jejunal, ileal, colonic, anal
• Multiple dilated distal bowel loops

Antral web/atresia
• Single "bubble"
o Dilated stomach
o Duodenum not seen
• Polyhydramnios

Abdominal cysts
• None will communicate with stomach
• Polyhydramnios not a feature
• Choledochal cyst
o Right-sided near gallbladder
o Follow bile ducts into cyst
• Ovarian cyst
o Female only
o Not usually seen until 3rd trimester
• Duplication cyst
o Duodenal duplication cyst can be difficult to
differentiate from DA
o Most duplications cysts are farther distal
• Ileum most common location
• Mesenteric cyst

• EA

• Omphalocele
o Central nervous system
• Mild ventriculomegaly
o Other minor findings
• Nuchal thickening

surgical

I PATHOLOGY
General Features
• Genetics

DUODENAL ATRESIA
o Sporadic inheritance
o Chromosomal
• 30% of DA cases have T21
• 5-15% of T21 cases have DA
• Etiology
o 2 theories of embryologic development
• Failure of normal recanalization of duodenal
lumen at 6-9 weeks (most widely accepted)
• Vascular compromise to developing gut
• Epidemiology: 1-3:10,000 births
• Associated abnormalities
o 50-70% of DAs have other anomalies
• Chromosomal
• Cardiac
• Skeletal
• Other GI
• Genitourinary

I DIAGNOSTIC

Gross Pathologic & Surgical Features

Consider

• 2nd and 3rd portions most commonly involved
• Most near ampulla of Vater
• May be incomplete (web)
o Same risk of T21
• Annular pancreas frequently present

• Coexistent EA when DA presents early in gestation
with marked dilatation ("C loop") and polyhydramnios
o High likelihood of T21

Staging, Grading or Classification Criteria
• Type I (most common)
o Intact intestinal wall and mesentery
o Septal or membranous luminal obstruction
o Diameter of proximal bowel segment> > distal
segment
• Type II
o Intestinal segments connected by fibrous cord
• Type III
o Two blind ends without intervening cord
o Wedge-shaped mesenteric defect

/ClINICALISSUES
Presentation
• Polyhydramnios
o Large-for-dates
o Preterm labor
• Abnormal serum screen (T21)
• Neonatal
o Vomiting
• 85% bilious
• 15% nonbilious: Proximal to ampulla of Vater

Natural History & Prognosis
• Dependent on associated abnormalities
• Overall mortality 15-40%
• At risk for 3rd trimester in utero demise, even if
isolated
• Isolated defect, 95% survival with immediate surgical
treatment
• Recurrence risk same as general population

Treatment
• All fetuses should be karyotyped
• Genetic counseling
• Amnioreduction for severe polyhydramnios
o Reduce uterine irritability

o Maternal comfort
• Immediate nasogastric suction after delivery
• Plain film after delivery
o If gas-filled "double bubble", no other work-up
needed prior to surgery
o If gas present distal to duodenum, perform upper GI
exam to evaluate for web/stenosis
• Surgical correction is best performed in immediate
neonatal period
o Contraindications to immediate repair
• Severe cardiac malformation may require repair
first
• Medically unstable (respiratory insufficiency, fluid
or electrolyte imbalance)

CHECKLIST

Image Interpretation

Pearls

• Continuity with stomach confirms diagnosis
• Normal peristalsis with prominent gastric incisura can
mimic appearance of DA
o Look at location of second "bubble"
• Antrum will be anteriorly located
• Duodenum medial to stomach

I SELECTED

REFERENCES

Marquette GP et al: First-trimester imaging of combined
esophageal and duodenal atresia without a
tracheoesophageal fistula. J Ultrasound Med. 23(9):1232,
2004
2. Veyrac C et al: MRI of fetal GI tract abnormalities. Abdom
Imaging. 29(4):411-20, 2004
3.
Brantberg A et al: Fetal duodenal obstructions: increased
risk of prenatal sudden death. Ultrasound Obstet Gynecol.
20(5):439-46, 2002
4.
Lawrence MJ et al: Congenital duodenal obstruction: Early
antenatal ultrasound diagnosis. Pediatr Surg Int. 16:342-5,
2000
5. Pameijer CR et al: Combined pure esophageal atresia,
duodenal atresia, biliary atresia, and pancreatic ductal
atresia: prenatal diagnostic features and review of the
literature. J Pediatr Surg. 35(5):745-7, 2000
6. Murshed R et al: Intrinsic duodenal obstruction: trends in
management and outcome over 45 years (1951-1995) with
relevance to prenatal counselling. Br J Obstet Gynaecol.
106(11):1197-9, 1999
7. Malone FD et al: Pitfalls of the 'double bubble' sign: a case
of congenital duodenal duplication. Fetal Diagn Ther.
12(5):298-300, 1997
8.
Estroff JA et al: Second trimester prenatal findings in
duodenal and esophageal atresia without
tracheoesophageal fistula. J Ultrasound Med. 13:375-9,
1994
9. Surana R et al: Small intestinal atresia: effect on fetal
nutrition. J Pediatr Surg. 29(9):1250-2, 1994
10. Grosfeld JL et al: Duodenal atresia and stenosis:
Reassessment of treatment and outcome based on
antenatal diagnosis, pathologic variance, and long-term
follow-up. World J Surg. 17:301-9, 1993
1.

DUODENAL

ATRESIA

IIMAGE GALLERY
(Left) Axial ultrasound shows
a "cyst" (curved arrow)
medial to the stomach
(arrow). (Right) I\xial
oblique ultrasound shows
the pylorus (arrow)
connecting these structures,
confirming the diagnosis of
duodenal atresia.

(Left) Coronal ultrasound
shows a very prominent
duodenal bulb (arrow) and
stomach, typical of OA A
thorough search for features
of trisomy 21 and other
associated anomalies should
be performed. (Right)
Anteroposterior radiograph
of a neonate with OA shows
findings similar to those seen
in the fetus. Fluid is replaced
with gas, which does not
extend distal to the
duodenum (arrow).

Variant
(Left) Coronal T2WI MR of a
fetus with 01\ shows high
signal fluid in the stomach
(curved arrow) and
duodenum (arrow). The
remainder of the bowel was
normal in appearance.
(Right) Axial ultrasound of a
75 week fetus shows marked
distention of the stomach
and duodenum, which form
a "C loop" (arrow). There is
also polyhydramnios. These
findings are typical of OA
combined with esophageal
atresia. This fetus is at very
high risk for trisomy 27.

JEJUNAL, ILEAL ATRESIA

Graphic shows the surgical classification system of
jejunoileal atresia; type I - membranous, type 1/- fibrous
cord, type ilia - mesenteric gap, type I/Ib - "apple peel",
and type IV - multiple atresias.

ITERMINOlOGY
Definitions
• One or more areas of stenosis or atresia involving
small bowel

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Hyperperistalsis within dilated
small bowel loops highly suggestive of obstruction
• Location
o Roughly equal involvement between jejunum and
ileum
o 7% involve both jejunum and ileum

Ultrasonographic

Findings

• Normal small bowel
o < 7 mm diameter
o Routinely seen in late 2nd and 3rd trimester
o Peristalsis routinely demonstrated
• Atresias
o Dilated, fluid-filled loops of bowel
• Bowel contents (succus entericus) commonly
echogenic
o "Triple bubble" for proximal jejunal atresia
o "Sausage-shaped" bowel loops

DDx: Dilated

Anal Atresia

Axial oblique ultrasound shows the umbilical arteries
coursing around the anechoic bladder (arrow). The
remainder of the abdomen is filled with dilated,
echogenic loops of bowel in this case of ileal atresia.

o Hyperperistalsis of obstructed segments often seen
in real time
o Enlarging bowel 3rd trimester
o Can rarely present as cyst-like mass
• Peristalsis distinguishes atresia from other
abdominal cysts
• Polyhydramnios
o May not see before 26 weeks
o Timing and severity dependent on site of atresia
• Polyhydramnios seen earlier with more proximal
atresias
• At risk for perforation and meconium peritonitis (""
6%)

o Ascites
o Peritoneal calcifications
o Pseudocysts
o More common with distal atresias
• Intrauterine growth restriction (IUGR)
o Proximal atresias more likely to have IUGR
o Ingested amniotic fluid important for fetal growth
in latter half of gestation

MR Findings
• May better delineate site of obstruction
• Obstructed fluid-filled loops
o Low signal Tl WI
o High signal T2WI
• Signal intensity may vary among isolated segments

Bowel loops

Meconium Ileus

JEJUNAL, ILEAL ATRESIA
Key Facts
Imaging Findings

Top Differential

• Best diagno tic clue: Hyperperistalsis within dilated
small bowel loops highly suggestive of obstruction
• Roughly equal involvement between jejunum and
ileum
• Dilated, fluid-filled loop of bowel
• Bowel contents (succus entericus) commonly
echogenic
• "Triple bubble" for proximal jejunal atresia
• "Sausage-shaped" bowel loops
• Can rarely present as cyst-like mass
• Polyhydramnio
seen earlier with more proximal
atresias
• At risk for perforation and meconium peritonitis (""

• Meconium ileus
• Midgut volvulus
• olonic/anal atresia
• Ureterectasis
• onnal colon

6%)

• Proximal atresias more likely to have IUGR

o May allow diagnosis of multiple atresias

Imaging Recommendations
• Protocol advice
o Frequent follow-up scans
• Fetal growth
• Polyhydramnios
• Increasing bowel dilatation
• Perforation
o Obtain sonographic views of rectum/anus to
evaluate for anal atresia
• Determining point of obstruction is difficult,
especially when multiple loops are dilated
• Jejunal vs. ileal atresia
o Jejunal
• More frequently multiple
• Greater bowel dilatation
• Less likely to perforate
• Higher association with IUGR
o Ileal
• Usually single
• Less distensible, with earlier perforation

Pathology
• Vascular injury most accepted theory of
development; multiple pos ible mechanisms
• Frequently associated with other gastrointestinal
anomalies
• Anomalies outside GI tract uncommon

Meconium

DIAGNOSIS

ileus

• Obstruction from meconium impaction in distal ileum
• Often indistinguishable
from atresia
• High association with cystic fibrosis
o Echogenic bowel on 2nd trimester scan

Midgut volvulus
• Ischemia leads to infarction
o Dilated bowel segment shows no peristalsis
o Heterogeneous lumen contents from hemorrhage
and necrosis
• May be indistinguishable
early

Colonic/anal

atresia

• Very difficult to tell large from small bowel in fetus
• Normal hypoechoic rectum and echogenic anus (anal
dimple) can not be visualized in anal atresia

(GI)

Clinical Issues
• Sensitivity for US detection

reported as high as lOOlVo

• Associated with VACTERL syndrome
o Vertebral anomalies
o Anal atresia
o Cardiac malformations
o Tracheo-esophageal fistula
o Renal malformations
o Limb anomalies

Ureterectasis
• Tubular appearance may be mistaken for bowel
• Often enlarged bladder
o Posterior urethral valves, prune belly syndrome
• Oligohydramnios
may be present
• Hydronephrosis

Normal colon
• Can appear prominent in 3rd trimester
o Normal caliber 18 mm

Duodenal

atresia

• "Double bubble"
• No bowel dilatation

Abdominal

I DIFFERENTIAL

Diagnoses

beyond duodenum

cysts

• Choledochal, duplication, ovarian, mesenteric
o Single cysts, not tubular
o No peristalsis
o Not usually associated with polyhydramnios

I PATHOLOGY
General Features
• Genetics
o Most sporadic
o Familial cases of multiple atresias reported
• Likely autosomal recessive
o "Apple-peel" atresia rare familial form of atresia
• Etiology
o Vascular injury most accepted theory of
development; multiple possible mechanisms
• Kinking of mesenteric artery during bowel
rotation (6-12 weeks)
• Fetal hypotension

JEJUNAL, ILEAL ATRESIA
• Vascular malformation
• In utero volvulus, intussusception
• Maternal cocaine use
• Epidemiology: 1:3,000
• Associated abnormalities
o Frequently associated with other gastrointestinal
(GI) anomalies
• Gastroschisis
• Volvulus
• Intussusception
• Malrotation
o Anomalies outside GI tract uncommon

Gross Pathologic & Surgical Features
• May occur as web, short segment or long segment
("apple-peel")

Staging, Grading or Classification

Criteria

• Type I: Membranous atresia
o Web or diaphragm occluding bowel segment
o No mesenteric defect
o Normal bowel length
• Type II: Blind ends separated by fibrous cord
o No mesenteric defect
o Normal bowel length
• Type IIIa: Blind ends with complete separation
o V-shaped mesenteric defect
o Short bowel
• Type IIIb: "Apple-peel" or "Christmas tree" atresia (rare
familial form)
o Affects long contiguous segment of jejunum and
ileum
• Remaining segments have a spiraled "apple-peel"
appearance
o Large mesenteric defect
• Type IV: Multiple small bowel atresia
o Mesenteric defects
o Short bowel

ICLINICAL

ISSUES

Presentation
• Dilated bowel and polyhydramnios
in 2nd and 3rd
trimester
o Sensitivity for US detection reported as high as
100%

Natural History & Prognosis
• Ileal
o More likely to perforate
• Jejunal
o Higher association with premature delivery
• Likely secondary to polyhydramnios
o IUGR more often present
• Amniotic fluid nutritional source for fetus
o More likely to have multiple atresias
• Not detectable prenatally because segments distal
to obstruction are decompressed
• > 90% survival
• Factors negatively impacting prognosis
o Increasing length of atretic segment
o Multiple sites of atresia
o Proximal worse than distal

o Perforation
o Volvulus

Treatment
• Amniocentesis to rule out cystic fibrosis
• Amnioreduction for severe polyhydramnios
o Reduce uterine irritability
o Maternal comfort
• Postnatal evaluation
o Supine and decubitus radiographs
• Look for free air
o Consider water-soluble contrast enema
• Look for multiple or more distal atresia
• Colon will often be small caliber ("microcolon")
from lack of normal meconium, especially in
distal obstructions
• Surgical resection of affected bowel
• Long term outcome dependent on length of resected
bowel and associated malformations
o Short gut syndrome, dysmotility and functional
obstruction potential complications

I DIAGNOSTIC

CHECKLIST

Consider
• Testing for cystic fibrosis is recommend in all cases of
distal obstruction
o Meconium ileus may have an identical appearance
to distal atresia

I SELECTED
1.

REFERENCES

Bilodeau A et al: Hereditary multiple intestinal atresia:
thirty years later.] Pediatr Surg. 39(5):726-30, 2004
2.
Cho FN et al: Prenatal sonographic findings in a fetus with
congenital isolated ileal atresia. ] Chin Med Assoc.
67(7):366-8, 2004
3. Benachi A et al: Determination of the anatomical location
of an antenatal intestinal occlusion by magnetic resonance
imaging. Ultrasound Obstet Gynecol. 18(2):163-5,2001
4. Kubota A et al: Congenital ileal atresia presenting as a
single cyst-like lesion on prenatal sonography.] Clin
Ultrasound. 28(4):206-8, 2000
5. Shimotake T et al: Ultrasonographic detection of
intrauterine intussusception resulting in ileal atresia
complicated by meconium peritonitis. Pediatr Surg Int.
16(1-2):43-4, 2000
6. Shinmoto H et al: MR imaging of non-CNS fetal
abnormalities: a pictorial essay. Radiographics.
20(5):1227-43,2000
7.
Surana R et al: Small intestinal atresia: effect on fetal
nutrition.] Pediatr Surg. 29(9):1250-2, 1994
8. Corteville]E et al: Bowel abnormalities in the
fetus--correlation of prenatal ultrasonographic findings
with outcome. Am] Obstet Gynecol. 175:724-9, 1996
9. Estroff]A et al: Prevalence of cystic fibrosis in fetuses with
dilated bowel. Radiology. 183:677-80, 1992
10. Heij HA et al: Atresia of jejunum and ileum: is it the same
disease? ] Pediatr Surg. 25(6):635-7, 1990
11. Nyberg DA et al: Fetal bowel. Normal sonographic
findings.] Ultrasound Med. 6:3-6, 1987

JEJUNAL, ILEAL ATRESIA
IIMAGE GALLERY
(Left) Sagittal ultrasound
through the fetal abdomen
shows a "triple bubble" in
this case of proximal jejunal
atresia. Two dilated loops of
small bowel (arrows), as well
as the stomach (curved
arrow) are seen. (Right)
Intra-operative photograph
shows the very dilated
proximal jejunum
terminating at a fibrous cord
(arrow). The mesentery is
intact (type II atresia)

(Left) Axial oblique
ultrasound shows echogenic,
fluid-filled loops of bowel
creating a tubular
"sausage-like" appearance
(arrows). Active peristalsis
was noted during the exam.
(Right) Anteroposterior
radiograph taken several
hours after delivery shows a
similar configuration of
elongated, dilated bowel
loops. A distal ileal atresia
was confirmed at surgery.

(Left) Water-soluble contrast
enema from the case above
shows a small caliber colon
(curved arrow). There is
reflux of contrast inlO the
distal ileum (arrow). The
obstructed, dilated loops are
gas-filled (open arrow).
(Right) Cross pathology from
a different case shows the
dissected small bowel with
abrupt termination at the
point of atresia (arrow). The
colon (curved arrow) is very
small, which gives the
"microcolon" appearance on
postnatal imaging studies.

ANAL ATRESIA

Sagittal ultrasound in a case of anal atresia shows
multiple, dilated bowel loops. Multiple enteroliths are
seen (arrows), which is suspicious for a colovesical
fistula. This was confirmed after delivery.

ITERMINOLOGY
Definitions
• Anorectal atresia may be high (above levator sling) or
low (below levator sling)
o High atresia more common

IIMAGING

FINDINGS

Ultrasonographic

Findings

• May go undetected prenatally
o Dilatation may not occur until 3rd trimester
• Difficult to distinguish large from small bowel
o U or V-shaped bowel in pelvis suggestive of
anorectal atresia
• Often associated with urinary tract fistula
o May see calcified meconium "marbles" moving
within bowel
• Enteroliths may also form secondary to stasis
• Part of VACTERL association
o Vertebral anomalies
o Anal atresia
o Cardiac anomalies
o Tracheo-esophageal (TE) fistula
o Renal anomalies
o Limb malformations
• Amniotic fluid usually normal

Clinical photograph of a stillborn with VACTERL
association. No anus is seen and autopsy showed a high
rectal atresia as well as multiple other anomalies.

o Oligohydramnios
anomalies
o Polyhydramnios
higher atresias

if significant urinary tract
much less common

than with

Imaging Recommendations
• Protocol advice
o Normal rectum/anus can be seen
• Hypoechoic wall with hyperechoic mucosa
• "Target" appearance in axial plane
o Rectal views in following setting
• Any bowel abnormality
• Any more obvious finding associated with anal
atresia
o Dedicated cardiac echo in all cases
• High association with cardiac malformations

I DIFFERENTIAL

DIAGNOSIS

Normal third trimester colon
• Colon, especially sigmoid, often prominent
trimester
• Normal ~ 18 mm

in 3rd

Higher atresias
• Present earlier than more distal atresias
• More likely to cause polyhydramnios
• Rectum is still intact

DDx: Prominent Bowel

..•.~

• 1\'-

.~

....
r.,~
~~ .
f

';,V

-'-"-

-'-

:.
Normal Colon

Normal Colon

.-'

.

-,

"',""

. '
.

- .

.

;1'

ANAL ATRESIA
Key Facts
Top Differential

Terminology
• Anorectal atresia may be high (above levator
low (below levator sling)

ling) or

Diagnoses

•

ormal third trimester colon
• J Iigher atre ia

Imaging Findings

Diagnostic Checklist

• May go undetected prenatally
• U or V-shaped bowel in pelvi uggestive of anorectal
atresia
• Often a ociated with urinary tract fistula
• Part of VA TERL association

• ormal colon in 3rd trim ter may appear prominent
• Take dedicated view of rectum/anus wh n any bowel
abnormality i present or associated malformations
are
n

Hirschsprung disease
• May have similar appearance, depending
and severity of aganglionic segment
• Usually not diagnosed prenatally

on extent

I PATHOLOGY
General Features
• Genetics
o Most sporadic
o Rare familial, autosomal recessive
o Chromosomal: Trisomy 18, 21
• Etiology
o Arrest in division of cloaca into rectum and
urogenital sinus in 9th week
o Teratogens: Alcohol
o Diabetes reported risk factor
• Epidemiology
o 1:5,000 live births
o M:F = 3:2
• Associated abnormalities
o Present in 50% of cases presenting at birth
o Present in 90% of cases diagnosed prenatally
• Genitourinary most common
• Skeletal malformations, caudal regression
sequence
• Other gastrointestinal anomalies, especially TE
fistula
• Cardiac malformations

ICLINICAL

ISSUES

• Consultation with pediatric surgeon
• Feeding contraindicated until repair
• Surgical repair
o Timing and type dependent on site of obstruction
• Low-lying repaired at birth
• Higher atresias have diverting colostomy with
repair at 1-3 months
o 80-90% continence rate
• Less successful if missing 2 or more sacral vertebral
bodies
• Incontinence greater with higher atresias
• Low atresias more likely to have constipation

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Normal colon in 3rd trimester may appear prominent
• Take dedicated views of rectum/anus when any bowel
abnormality is present or associated malformations are
seen

I SELECTED REFERENCES
1.
2.

3.

Taipale Pet al: First-trimester diagnosis of imperforate
anus. Ultrasound Obstet Gynecol. 25(2):187-8, 2005
Sepulveda W et al: Prenatal diagnosis of enterolithiasis: a
sign of fetal large bowel obstruction. J Ultrasound Med.
13(7):581-5, 1994
Harris RD et al: Anorectal atresia: prenatal sonographic
diagnosis. AJR AmJ Roentgenol. 149(2):395-400, 1987

IIMAGE GALLERY

Presentation
• Most common signs/symptoms: Other anomalies
usually seen first
• Anal atresia generally not seen until 3rd trimester
o Case reports of 1st trimester diagnosis
• May be missed when isolated, especially if 2nd
trimester scan is only study

Natural History & Prognosis
• Determined by associated malformations
• Isolated anal atresia good prognosis
• 3-4% recurrence risk

Treatment
• Amniocentesis

for karyotype

(Left) Coronal ultrasound of a normal fetal rectum shows hypoechoic
walls (arrows) and a hyperechoic mucosa (open arrow). (Right) Axial
ultrasound at the level of the anus (arrows) shows a normal "target"
appearance.

MECONIUM

PERITONITIS, PSEUDOCYST

Intra-operative photograph shows meconium (arrow)
within the peritoneal cavity. The bowel loops are
thickened and matted with meconium (open arrow)
seen on the serosal surface.

ITERMINOLOGY
Definitions
• Chemical peritonitis due to intrauterine
perforation

bowel

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Combination of ascites,
calcifications and dilated bowel is pathognomonic

Ultrasonographic

Findings

• Findings variable, according to timing and severity of
perforation
• Calcifications most specific finding
o Intraperitoneal calcifications in 85%
o Implants on peritoneal surfaces
o Liver capsule often most obvious
• Must differentiate from intra parenchymal
calcifications
o May also be in scrotum
• Patent processus vagina lis in fetus
• Ascites secondary to both spilled contents and
inflammatory response
o Often first sign of meconium peritonitis
• Meconium pseudocyst

DDx: Meconium

Toxoplasmosis

Axial ultrasound shows a dilated loop of bowel (curved
arrow), filled with echogenic material. There has been
an in utero perforation with formation of a large,
irregular, thick-walled meconium pseudocyst (arrows).

o Wall-off bowel perforation
o Irregular thick walls
• May calcify
o Contents variable in echogenicity
o May be multiple
• Dilated bowel
o Seen when meconium peritonitis is secondary to
obstruction
• Atresia
• Volvulus
• Intussusception
• Meconium ileus
o Not seen when perforation is secondary to ischemia
• Polyhydramnios
o Usually secondary to bowel obstruction

Imaging Recommendations
• Frequent follow-up scans after initial diagnosis
o Need to plan for delivery and postnatal work-up
o May worsen with increasing bowel dilatation and
abdominal distention
o May resolve completely with no sequelae
• Try to determine cause of perforation
o Dilated bowel makes a primary intestinal
abnormality most likely
• Are bowel loop peristalsing?
• Non-peristalsing, dilated loops concerning for
volvulus

Peritonitis

Gal/stones

Enteroliths

Echogenic Bowel

MECONIUM

PERITONITIS, PSEUDOCYST
Key Facts
Top Differential Diagnoses

Terminology
•

hemical peritonitis
perforation

due to intrauterine

bowel

Imaging Findings
• B st diagno tic clue: Combination of a cite,
calcifications and dilated bowel is pathognomonic
• alcifications most specific finding
• Intraperitoneal calcifications in 851M.
• Implants on peritoneal surface
• Liver cap ule often most obviou
• Ascite econdary to both pilled contents and
inflammatory re ponse
• Me onium pseudocy t
• Dilated bowel
• Infection may lead to vascular compromi e and
perforation
o Look for signs of infection
• Infection may lead to vascular compromise
perforation
• Intraparenchymal
as well as capsular liver
calcification
• Intracranial calcifications
• Hydrops
• Intrauterine growth restriction

I DIFFERENTIAL

and

DIAGNOSIS

Hyperechoic bowel
•
•
•
•

Increased echogenicity of bowel ~ bone
Not calcified, so does not shadow
Often appears mass-like
Careful search for associated conditions
o Aneuploidy (trisomy 21)
o In utero infection
o Intrauterine growth restriction
o Cystic fibrosis
• May progress to bowel obstruction from
meconium ileus, which is at risk for perforation

Abdominal calcifications
• Infection
o Scattered punctate calcifications within liver
parenchyma
• Often do not shadow
o May be caused by a number of organisms
• Toxoplasmosis
• Cytomegalovirus
• Parvovirus
• Hepatitis B
• Varicella
• Herpes simplex
• Rubella
• Syphilis
o Infection may be etiologic agent for ischemia, so
may have signs of both perforation and infection
• Gallstones
o One or echogenic foci within gallbladder
o 3rd trimester finding

•
•
•
•

Hyperechoic
Infection
Gall tones
Enteroliths

bowel

Pathology
•

ystic fibrosis in 8% of fetal ca e

Clinical Issues
• Calcification vi ibl 1-2 weeks after perforation
• Prognosi mu h better for fetus than neonat
• Spontaneou
in utero closure of perforation may
occur
• Mortality 11-14% for in utero diagnosis
• Genetic counseling for cy tic fibrosis

o Shadowing or "comet tail" reverberation artifact may
be present
o Usually resolve in first year of life
• Enteroliths
o Calcified intraluminal meconium
o May be seen moving within bowel lumen
• Appear as small "marbles"
o Described with vesicoenteric fistula
• Most often in setting of anal atresia
• Tumors may calcify
o Hepatoblastoma
o Teratoma
o Neuroblastoma
o All should have obvious mass

Ascites
• Urinary
o Fluid in abdomen only
o Associated with obstructed urinary tract
• Hydronephrosis
• Bladder outlet obstruction
• May have a focal fluid collection (urinoma)
• Hydrops
o Ascites + fluid in one other area
• Pleural effusion
• Skin edema
• Pericardial effusion
o Numerous causes
• Immune vs. non-immune
o Always check cardiac structure, rate and rhythm

Abdominal cysts
• Choledochocyst
o Right upper quadrant cyst
o Following bile ducts into cyst is pathognomonic
• Enteric duplication cyst
o Hypoechoic wall with hyperechoic mucosa (gut
signature)
o May cause bowel obstruction
• Mesenteric cyst
o Variable appearance
o Generally smooth, thin walls
"
o May be multiseptated

MECONIUM

PERITONITIS, PSEUDOCYST

• Ovarian cyst
o Female fetus
o Occurs in 3rd trimester
o Located anywhere in abdomen
• Supporting ligaments are lax and ovary is very
mobile
o May have internal echoes with hemorrhage or
torsion
• Urachal cyst
o Midline between bladder and cord insertion

I PATHOLOGY
General Features
• Genetics
o Cystic fibrosis in 8% of fetal cases
• 15-40% of postnatal cases
• Autosomal recessive: 25% recurrence risk
• Etiology
o 2 proposed mechanisms: Primary ischemic event or
bowel anomaly leading to perforation
• Bowel perforation => meconium spills into
peritoneum
• Intense inflammatory reaction
• Adhesions => "cyst" formation
• Bowel loops may be trapped within "cyst"
• Calcifications secondary to inflammation
o Bowel anomalies at risk for perforation
• Atresias (distal at greater risk than proximal)
• Meconium ileus
• Volvulus
• Intussusception
o Maternal cocaine use may cause fetal bowel
ischemia
o In utero infection
• Epidemiology
o Fetal incidence greater than neonatal incidence
• Reflects milder in utero cases, which resolve
without clinical sequelae

Gross Pathologic & Surgical Features
• Variable, according to severity
• May see extensive fibrous adhesions with thick,
matted bowel loops
• Pseudocysts formation around walled-off perforation
• Bowel atresias

• Incidental note of calcification on abdominal
o Mortality 11-14% for in utero diagnosis
• Neonatal diagnosis worse prognosis
o Mortality 40-50%
o Higher proportion of cases have cystic fibrosis
o > 50% mortality if primary bowel obstruction

Treatment
• Genetic counseling for cystic fibrosis
o Consider testing parents for carrier status
• If carriers, amniocentesis can test for direct
detection of gene mutation in fetus
• Simple peritonitis: Calcifications only
o Routine delivery plans
o Postnatal evaluation
• Abdominal examination
• Abdominal radiograph
• If normal, child can feed
• Very low risk of surgical intervention
• Complex peritonitis: Dilated bowel, persistent
pseudocysts, ascites
o Deliver at tertiary care facility
o Evaluation by neonatologist/pediatric
surgeon
o Abdominal radiograph and gastrointestinal contrast
studies
o 22-50% chance of surgery
o Usually resection and enterostomy
• May require parenteral nutrition

I DIAGNOSTIC

Image Interpretation

I SELECTED
1.

2.

4.

Presentation
• Most common signs/symptoms
o Incidental note of peritoneal calcifications or
abdominal cyst
o New ascites in patient being followed for dilated
bowel
• Calcification visible 1-2 weeks after perforation
• Prognosis much better for fetus than neonate
o Spontaneous in utero closure of perforation
occur
• No postnatal sequelae

5.

6.
7.

8.

Natural History & Prognosis
may

CHECKLIST
Pearls

• Liver calcifications are on the capsular surface with
meconium peritonitis, while infection causes
intra parenchymal calcifications
o Consider infection as cause of perforation when
calcifications are seen in both locations

3.

ICLINICAllSSUES

film

9.

REFERENCES

Kuroda T et al: Prenatal diagnosis and management
of
abdominal
diseases in pediatric surgery. J Pediatr Surg.
39(12):1819-22,2004
Eckoldt F et al: Meconium
peritonitis
and pseudo-cyst
formation:
prenatal diagnosis and post-natal
course. Prenat
Diagn. 23(11):904-8,
2003
Shyu MK et al: Correlation
of prenatal ultrasound
and
postnatal outcome in meconium
peritonitis.
Fetal Diagn
Ther. 18(4):255-61,2003
Tseng 11 et al: Meconium
peritonitis
in utero: prenatal
sonographic
findings and clinical implications.
J Chin Med
Assoc. 66(6):355-9, 2003
Su WH et al: Fetal meconium
peritonitis
in the infant of a
woman with fulminant
hepatitis B. A case report. J Reprod
Med. 47(11):952-4.
2002
Reynolds E et al: Meconium
peritonitis.
J Perinatol.
20:193-5,2000
Varkonyi I et al: Meconium
periorchitis:
case report and
literature review. Eur J Pediatr Surg. 10(6):404-7, 2000
Dirkes K et al: The natural history of meconium
peritonitis
diagnosed in utero. J Pediatr Surg. 30:979-82, 1995
Estroff JA et al: Fetal meconium
peritonitis
without
sequelae. Pediatr Radiol. 22(4):277-8,
1992

MECONIUM

I IMAGE

PERITONITIS, PSEUDOCYST

GALLERY

Typical
(Left) Coronal ultrasound
early in the 2nd trimester
shows a large abdominal
cyst (arrows). (Right) Axial
ultrasound latter in
pregnancy shows
calcifications around the
liver edge (arrows) and a
small amount of ascites
(curved arrow). The
pseudocyst has completely
resolved. In utero
perforations may
spontaneously seal and have
no postnatal sequelae.

Typical
(Left) Coronal ultrasound in
a 2nd trimester fetus shows
liver calcifications (arrows),
which multiple scan planes
confirmed were capsular.
There were also some mildly
dilated bowel loops (curved
arrow). No pseudocyst was
see in this case (open arrowbladder). (Righi) Radiograph
after delivery shows dense
calcifications (arrows) over
the liver, which represents
the sequelae of meconium
peritonitis. The infant began
feeding without difficulty.

Variant
(Left) Axial ultrasound shows
an unusually large, irregular
pseudocyst (arrows), which
exerted marked mass-effect
on surrounding structures
and enlarged the abdominal
circumference. (Righi)
Sagittal ultrasound of a fetus
with meconium peritonitis
shows linear calcifications
(arrows) on the serosal
surface of the small bowel.
This appearance could
potentially be confused with
echogenic bowel.

VOLVULUS

Axial ultrasound shows a single, dilated segment of
bowel (arrows) within the upper abdomen. It is filled
with echogenic debris and no peristalsis was seen
during real-time examination.

Intra-operative photograph shows the twisted loop of
infarcted small bowel (arrows), confirming the prenatal
diagnosis of volvulus.

ITERMINOlOGY

MR Findings

Definitions

• In utero diagnosis of volvulus has been described
• Dilated, low signal intensity bowel on T2WI from
intraluminal hemorrhage

• Bowel loop twisted on it's mesentery, resulting in
vascular compromise
o Fetal cases generally involve small bowel

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Dilated, non-peristalsing
loop

Ultrasonographic

bowel

Imaging Recommendations
• Real-time evaluation important
o Infarcted bowel loses ability for peristalsis
• Obstructed, but viable, bowel loops often have
hyperperistalsis
• Attempt to evaluate mesenteric vessels with Doppler
o May have a "swirled" appearance
o Often technically difficult

Findings

• Dilated bowel loops
o A single "kinked" loop is very suggestive
o May see multiple dilated loops from proximal
obstruction
• May have had a normal scan earlier in gestation
o Volvulus is in abrupt event
• Echogenic intraluminal contents from infarction and
necrosis
• Ascites
o May be seen with or without bowel perforation
• Hydrops may develop as overall fetal condition
worsens

I DIFFERENTIAL

DIAGNOSIS

Duodenal atresia
• "Double bubble"
• Able to connect stomach and duodenum during
real-time examination
• Distal bowel is normal
• Associated with trisomy 21

Jejunal/ileal atresia
• Hyperperistalsis often seen in obstructed loops
• Dilatation of loops may remain stable or progress over
time

DDx: Dilated Bowel

Duodenal Atresia

Jejunal Atresia

Ileal Atresia

Ileal Atresia

VOLVULUS
Key Facts
Terminology
• Bowel loop twi ted on it's me entery, resulting in
vascular compromise

Imaging Findings
• Best diagnostic clue: Dilated, non-peri talsing bowel
loop
• A ingle "kink d" loop is v ry uggestive
• May have had a normal scan earlier in gestation

o Differs from abrupt dilation in volvulus
• May perforate and cause meconium
peritonitis/pseudocyst
formation

Intussusception
• Difficult to make diagnosis in utero
• As with atresia, peristalsis should still be present

I PATHOLOGY
General Features
• Genetics
o Sporadic
o No chromosomal association
• Etiology: Most related to malrotation with a short,
mobile mesenteric attachment
• Epidemiology: Incidence in neonatal series inversely
proportional to maternal age
• Associated abnormalities
o Jejunal/ileal atresia may co-exist with volvulus
o Malrotation generally present
o Congenital diaphragmatic hernia, gastroschisis,
omphalocele and abdominal heterotaxy are
described in neonatal series

• Echogenic intraluminal
necro is

Top Differential

from infarction and

Diagnoses

• Jejunal/il al atresia
• Intu u eption

Diagnostic Checklist
• Ultra ound finding
bowel infarction

I DIAGNOSTIC

reflect vascular compromise

with

CHECKLIST

Consider
• In setting of a new dilated loop of bowel in a
previously normal gestation

Image Interpretation

Pearls

• Lack of peristalsis in a dilated, echogenic bowel loop is
very suspicious
o Ultrasound findings reflect vascular compromise
with bowel infarction

ISELECTED REFERENCES
1.

2.

3.

4.

5.

ICLINICALISSUES

content

Allahdin Set al: Ischaemic haemorrhagic necrosis of the
intestine secondary to volvulus of the midgut: a silent
cause of intrauterine death. j Obstet Gynaecol. 24(3):310,
2004
jequier S et al: Antenatal small-bowel volvulus without
malrotation: ultrasound demonstration
and discussion of
pathogenesis. Pediatr Radiol. 33(4):263-5, 2003
Miyakoshi K et al: Prenatal diagnosis of midgut volvulus by
sonography and magnetic resonance imaging. Am J
Perinatol. 18(8):447-50,2001
Crisera CA et al: Fetal midgut volvulus presenting at term. J
Pediatr Surg. 34(8):1280-1, 1999
Morikawa Net al: Intrauterine volvulus without
malrotation associated with segmental absence of small
intestinal musculature. J Pediatr Surg. 34(10):1549-51, 1999

Presentation
• Most common signs/symptoms
o Dilated bowel
• Reported as early as 16 wks

IIMAGE

GALLERY

Natural History & Prognosis
• May cause in utero demise
• Outcome is generally poor
o Related to length of gangrenous segment and
gestational age at time of volvulus
• Those with late presentation and immediate
resection have better prognosis

Treatment
• Consider early delivery if lungs are mature
• Consult with pediatric surgeons for urgent evaluation
upon delivery
• Surgical resection of infarcted segment

(Left) Axial oblique ultrasound from the first case shows normal,
decompressed, distal bowel (curved arrow) as well as the markedly
enlarged loop (arrow). A small amount of ascites is present. (Right)
Radiograph taken before surgery shows a distended abdomen with
abrupt termination of bowel gas (arrow) at the site of obstruction.

ASCITES

Axial ultrasound shows ascites outlining the umbilical
vein (arrow) as it traverses the abdomen towards the
liver. Pseudoascites
cannot surround the umbilical
vessels.

ITERMINOlOGY
Definitions
• Fluid in intraperitoneal

space

IIMAGING FINDINGS
Ultrasonographic

Findings

• Anechoic fluid in abdomen
o Outlines intraperitoneal structures
• Solid organs
• Bowel
• Extrahepatic umbilical vein
• Falciform ligament may also be visible
• Must distinguish from pseudoascites
o Hypoechoic/anechoic
rim peripherally around fetal
abdominal cavity
• Anterolateral location
• Just under skin surface
• Between fetal skin and liver margin
o Represents normal abdominal wall musculature
• Internal oblique
• External oblique
• Transversus abdominis
o Muscles insert onto ribs, therefore sonolucency not
seen posterolaterally

DDx: Abdominal

Mec Pseudocyst

Axial ultrasound shows a thin, hypoechoic line between
the fetal skin and liver (arrows). This is pseudoascites
caused by the abdominal musculature, and should not
be mistaken for true ascites.

• Lucency disappears posteriorly adjacent to dorsal
ribs
o Pseudoascites cannot outline umbilical vein
o True ascites can be seen in other parts of abdomen
• Look for signs of hydrops
o Pleural effusion
o Pericardial effusion
o Skin edema
o Polyhydramnios
o Placentomegaly
• Placental measurement>
4 cm

Imaging Recommendations
• Discovery of ascites requires work-up for etiology
o Determine if isolated or part of generalized hydrops
• Look for pleural fluid, pericardial effusion, skin
thickening
o If isolated, most likely from perforated viscus;
gastrointestinal or urinary tract obstructions
• Source may be difficult to determine after
perforation and decompression
• Careful screening ultrasound warranted
o Check for anatomic abnormalities
o Carefully evaluate peritoneal surfaces for
calcifications
• Meconium peritonitis from bowel perforation
o Oligohydramnios
suggests a urinary tract anomaly

Fluid Collections

Ovarian Cyst

PUV

Lymphangioma

ASCITES
Key Facts
Top Differential

Terminology
• Fluid in intrap

ritoneal spa e

Imaging Findings
•
•
•
•
•

Outline intraperitoneal
tructure
~tu t di tingui h from p udoa cite
Di covery of a cite require work-up for etiology
Determine if i olated or part of generalized hydrop
If i olated, mo t likely from perforated viscu ;
ga trointe tinal or urinary tra t obstru tion
• ource may be difficult to determine after perforation
and decompre sion
• arefully e\"aluate p ritoneal urface for
cal ification
• ligohydramnios suggests a urinary tract anomaly

I DIFFERENTIAL

DIAGNOSIS

Gastrointestinal
• Bowel anomaly with perforation
o Distal atresias
• Ileal
• Colonic
• Anorectal
• May be difficult to diagnose when bowel loops are
collapsed
o Midgut malrotation with volvulus
• Perforation of obstructed loop
• Perforation leads to meconium peritonitis
o Look for other signs
• Peritoneal calcifications
• Meconium pseudocyst
• Echogenic bowel
o Consider cystic fibrosis

Diagnoses

• Bowel anomaly with perforation
• Urinary ascites
• Immune hydrop
• onimmune hydrop

Clinical Issues
• May be earlie t ign of hydrop
• Diagno tic fetal paracente is considered when
etiology is un I ar
• on ider fetal echocardiogram to exclude cardiac
etiology

Diagnostic Checklist
• Therapeutic
warranted

paracentesis

prior to delivery may be

• Consider ovarian origin if large cyst seen in female
fetus
o "Daughter cyst" may be identified
• Represents another follicle
• Indicates ovarian origin of cyst
• Cloacal malformation with perforation
o Cystic structure in pelvis
o Look for intraluminal bowel calcifications
• Indicates GU-bowel connection

Immune hydrops
• Fetal anemia
o Maternal Rh sensitization
o Maternal anti-D titers
o Other maternal antibodies exist
• Middle cerebral artery (MCA) Doppler
o Measure peak systolic velocity
o Check for presence and severity of anemia
o Assess for need to transfuse

Genitourinary

Nonimmune

• Urinary ascites
o Perforation of an obstructed system
o Oligohydramnios
may be present
• Posterior urethral valves (PUV)
o Typical "keyhole" appearance of bladder
o Hydronephrosis
o Male fetus
o Oligohydramnios
may be severe
o Bladder may rupture into peritoneal cavity
• Ureteropelvic junction (UP]) obstruction
o Hydronephrosis
o Echogenic thinned renal parenchyma
o Renal pelvis may rupture
• Urinary ascites
• Focal urinoma
o Look for contralateral renal anomalies
• UP] obstruction (bilateral in 10-30%)
• Multicystic dysplastic kidney
• Renal agenesis
• Ureterovesical obstruction
• Ovarian cyst rupture
o Ovarian cyst may be large and extend into abdomen

• Wide range of etiologies
• Cardiac malformation
o Structural anomaly resulting in poor contractility
• Ebstein anomaly
• Arteriovenous canal
• Arrhythmias
o Tachycardia
• Treatments available
• Conversion to normal rhythm may reverse
hydrops
o Bradycardia
• More often associated with a structural anomaly
• Chromosomal anomaly
o Turner syndrome most common
o Trisomy 21
o Trisomy 18
• Fetal masses
o Hydrops from either high-output failure or
mass-effect with impaired venous return
o Cystic adenomatoid malformation
• Multiple large cysts seen if macrocystic
• Microcystic type is echogenic

hydrops

ASCITES
• May spontaneously regress in utero
o Bronchopulmonary sequestration
• Echogenic pulmonary mass
• Look for systemic feeding vessel with Doppler
• Occurs at lung bases, left> right
• May have unilateral pleural effusion
• May spontaneously regress in utero
o Congenital high airway obstruction sequence
(CHAOS)
• Uniformly echogenic, enlarged lungs
• Flattened diaphragms
• Ascites common
o Sacrococcygeal teratoma
• Mixed cystic and solid mass
• Solid masses more likely to develop hydrops
• Exophytic with intrapelvic/abdominal extension
• Can be completely internal
• Infection
o Look for scattered calcifications
• Brain
• Liver, spleen, peritoneum
o Parvovirus B19
• Most common infectious cause of hydrops
o CMV
o Varicella
o Toxoplasmosis
o Syphilis
• Hematologic disorders
o Homozygous a-thalassemia
• Placental chorioangioma

Congenital chylous ascites
• Malformation of lymphatic duct
• May require lymphatic duct ligation

ICLINICALISSUES
Presentation
• Intraabdominal fluid
• Abdominal circumference ahead of other growth
parameters

Natural History & Prognosis
• May be earliest sign of hydrops
o Associated with lower survival rate if present with
hydrops
o Gestational age at preSentation is an important
prognostic factor
• Higher fetal loss rate if seen before 24 weeks
gestation
o Close sonographic follow-up recommended
• Isolated ascites has variable prognosis
o Associated anomalies may not be readily apparent
prenatally
• If massive can compress thoracic cavity
o May lead to pulmonary hypoplasia
• Can cause abdominal dystocia during delivery

Treatment
• Tests on mother and/or fetus range from noninvasive
-+ invasive
o TORCH titers
• Mother

• Fetus: May be positive even if maternal titers
normal
o Amniocentesis
• Karyotype
o Diagnostic fetal paracentesis considered when
etiology is unclear
• Protein count
• Lymphocyte count
• Urea nitrogen
• Creatinine
• Meconium
o Fetal cordocentesis
• Consider fetal echocardiogram to exclude cardiac
etiology
• Sonographic follow-up warranted
o Monitor abdominal girth
• May require in utero therapeutic paracentesis

I DIAGNOSTIC

CHECKLIST

Consider
• Therapeutic paracentesis prior to delivery may be
warranted
o May allow vaginal delivery

Image Interpretation

Pearls

• Distinguish true ascites from pseudoascites
• Exclude hydrops as underlying etiology for ascites

I SELECTED
1.

REFERENCES

Chen FYet al: Meconium peritonitis presenting as isolated
massive fetal ascites. Prenat Diagn. 24(11):930-931, 2004
2.
Favre R et al: Nonimmune fetal ascites: a series of 79 cases.
Am J Obstet Gynecol. 190(2):407-12, 2004
3.
Eckoldt F et al: Meconium peritonitis and pseudo-cyst
formation: prenatal diagnosis and post-natal course. Prenat
Diagn. 23(11):904-8, 2003
4.
Urn FY et al: Congenital high airway obstruction
syndrome: natural history and management. J Pediatr Surg.
38(6):940-5, 2003
5. Lowenstein Let al: In utero diagnosis of bladder
perforation with urinary ascites. A case report. Fetal Diagn
Ther. 18(3):179-82, 2003
6. Schmider A et al: Etiology and prognosis of fetal ascites.
Fetal Diagn Ther. 18(4):230-6, 2003
7.
Warne S et al: Prenatal diagnosis of cloacal anomalies. BJU
Int. 89(1):78-81, 2002
8.
Mitsunaga T et al: Successful surgical treatment of two
cases of congenital chylous ascites. J Pediatr Surg.
36(11):1717-9,2001
9.
Tongsong T et al: Prenatal diagnosis of isolated anorectal
atresia with colonic perforation. J Obstet Gynaecol Res.
27(5):241-4, 2001
10. Bettelheim 0 et al: Prenatal diagnosis of fetal urinary
ascites. Ultrasound Obstet Gynecol. 16(5):473-5,2000

ASCITES
IIMAGE GAllERY
Typical
(Left) Sagittal ultrasound
shows ascites (curved
arrow), skin edema (open
arrow) and pleural effusion
(arrow) in a third trimester
fetus with hydrops fetalis.
When ascites is seen, always
look for other signs of
hydrops. (Right) Axial
ultrasound of the abdomen
shows ascites with
decompressed bowel loops
(arrows). Initially this fetus
presented with dilated
bowel. Postnatal exam
showed ileal atresia. Ascites
resulted from in utero bowel
perforation.

Typical
(Left) Sagittal T2WI MR
shows urinary ascites with
hydronephrosis and a
tortuous hydroureter (open
arrows). The markedly
distended abdomen (arrows)
is compressing the thoracic
cavity (curved arrow)
putting the fetus at risk for
pulmonary hypoplasia.
(Right) Axial oblique
ultrasound of the fetal
abdomen in another case of
urinary ascites.
Hydronephrosis (arrows)
and a distended bladder
(open arrow) are evident, as
well as oligohydramnios.

Typical
(Left) Coronal ultrasound
shows ascites and subtle,
echogenic, peritoneal foci
(arrows). This suggests the
ascites is from a bowel
perforation with subsequent
meconium peritonitis. (Right)
Axial color Doppler
ultrasound shows ascites
outlining the umbilical
arteries. TORCH titers were
normal and no obvious
abnormalities were seen.
When the etiology of ascites
is indeterminate, fetal
paracentesis may be
considered.

ENTERIC DUPLICATION CYST

Craphic shows a duplication cyst of the small bowel.
Note the thick muscular wall, which is contiguous with
the bowel wall. There is mass effect on the intestinal
lumen, which can lead to obstruction.

Coronal ultrasound shows a large duplication cyst
(white arrow) in the right mid-abdomen above the
bladder (black arrow). Despite its large size, no bowel
obstruction developed.

• Vertebral anomalies commonly associated,
especially hemivertebrae
• Rarely bowel dilatation from obstruction
o Polyhydramnios may develop
• Tubular duplications communicate with bowel and are
usually not detected in utero
• Peristalsis within cyst has been described

ITERMINOLOGY
Definitions
• Enteric duplication cyst: Enteric lining with muscular
wall
• Enteric cyst: Enteric lining with fibrous wall
• May either be cystic (80%) or tubular (20%)

Imaging Recommendations

IIMAGING
General

• Confirm cyst is intraperitoneal and separate from
urinary tract
o Most cystic abdominal masses are related to urinary
tract
• Obtain enlarged, high-resolution images looking at
wall thickness and morphology
o Posterior wall more easily evaluated
• Follow-up for bowel dilatation, polyhydramnios

FINDINGS

Features

• Best diagnostic clue: Thick-walled cyst with
hyperechoic mucosa and a hypoechoic wall
• Often difficult to differentiate from other cystic
abdominal masses

Ultrasonographic

Findings

I DIFFERENTIAL

• Fluid generally anechoic but can be echogenic
• Findings vary according to location
o Small bowel
• Solitary abdominal cyst
• Ileum most common site
o Stomach
• Appears as cyst within gastric lumen
oEsophagus
• Mediastinal cyst

DDx: Abdominal

.~,.

.

:00-...

,

"

-

'

•

• Females only, seen in 3rd trimester
• Most common abdominal cystic mass in female
• Ovarian ligaments lax so can be anywhere in abdomen

Mesenteric

~
~

',~

..
...

..

co· .. ~~
· :. .&:_~.".. ~ ""..',..;'.'

~
".'

..

_

.

cyst

• May be unilocular or multilocular
• Appearance may be identical

.~....

•

.. ......,.,.~,
....

':~

Ovarian cyst

Cysts
~

..

,

_J ••••

-

-

..

~

..-.

...-:

-~

DIAGNOSIS

_0

Meconium Pseudocyst

Ovarian Cyst

ENTERIC DUPLICATION CYST
Key Facts
Imaging Findings

Top Differential

• Best diagnostic clue: Thick-walled cyst with
hyperechoic mucosa and a hypoechoic wall
• enerally anechoic but can be echogenic
• Ileum most common site
• Rarely bowel dilatation from obstruction
• Obtain enlarged, high-re olution images looking at
wall thickness and morphology

•
•
•
•

• Less likely to cause obstruction
• Much less common

Choledochal

Clinical Issues
• Excellent prognosis

• Most present in childhood
o Intussusception, bleeding, abdominal

pain

Natural History & Prognosis

cyst

• Right upper quadrant
• Look for bile ducts entering cyst

Meconium

Diagnoses

Ovarian cyst
Mesenteric cyst
Choledochal cy t
Meconium pseudocyst

pseudocyst

• Thick, irregular wall
• Can calcify
• Other sequelae of meconium peritonitis
o Peritoneal calcifications, dilated bowel

• Excellent prognosis

Treatment
• Work-up after delivery to confirm diagnosis
• Surgical resection

I DIAGNOSTIC

CHECKLIST

Dilated bowel

Image Interpretation

• Tubular appearance
• Contents echogenic (succus entericus)
• Peristalsis confirmatory

• Always look at wall for a ringed appearance created by
a hyperechoic mucosa and hypoechoic wall

Urachal cyst

I SELECTED REFERENCES

• Midline, between bladder and cord insertion

1.

Hydrocolpos
• Midline pelvic mass, posterior to bladder
• Not seen until 3rd trimester

2.

I PATHOLOGY

4.

General Features
• Embryology: 2 theories
o Abnormal recanalization
• Alimentary tract begins as solid tube
• Normal lumen forms from coalescence of
developing vacuoles
• Duplication occurs if vacuoles split into 2 groups
with a dividing septum
o Abnormal separation from notochord
• Explains association of esophageal duplication
and vertebral abnormalities

Gross Pathologic & Surgical Features
• Occurs on mesenteric

side of bowel

IClINICALISSUES
Presentation
• In utero
o Incidental finding
• Reported as early as 12 weeks
o May cause bowel obstruction

3.

Pearls

Borgnon J et al: Antenatal detection of a communicating
duodenal duplication. Eur J Pediatr Surg. 13(2):130-3,2003
Khong PL et al: Ultrasonography of intra-abdominal cystic
lesions in the newborn. Clin Radiol. 58(6):449-54, 2003
Chen M et al: Sonographic features of ileal duplication cyst
at 12 weeks. Prenat Oiagn. 22:1067-70, 2002
Richards OS et al: The prenatal sonographic appearance of
enteric duplication cysts. Ultrasound Obstet Gynecol
7:17-20,1996

IIMAGE

GALLERY

I .'...
~
•.'

••

I

(~
(Left) A high-resolution image of an abdominal cyst shows a
hyperechoic mucosa (arrows) surrounded by a hypoechoic wall
(open arrows), a finding described with enteric duplication cysts.
(Right) Intra-operative photograph shows the large cyst attached to a
loop of small bowel (arrow). Histology confirmed an enteric
duplication cyst.

MESENTERIC CYST

Axial ultrasound of a large mesenteric cyst shows a
unilocular, thin-walled cyst filling a large portion of the
abdomen. A palpable mass was noted after delivery but
the infant was otherwise asymptomatic.

• Can be very complex, insinuating around organs
and extending out of abdomen
o Variable echogenicity of fluid, but usually anechoic

ITERMINOlOGY
Abbreviations

and Synonyms

• Cystic lymphatic malformation
• Lymphangioma

IIMAGING

Imaging Recommendations
• Confirm that it is not associated with urinary tract
o Most common source of a cystic abdominal mass
• Follow-up scans for growth
o May extend out of peritoneal cavity to involve
retroperitoneum and lower extremities
• Consider fetal MRI to look for extent of larger masses

FINDINGS

Gene'ral Features
• Location
o Small bowel mesentery most common
• Ileal region
o Omentum
o Retroperitoneum
o May also occur in solid organs
• Size: Variable but often large

Ultrasonographic

Axial oblique ultrasound of a more complicated
mesenteric cyst. Several septations (arrows) can be seen
within this otherwise, anechoic mass.

I DIFFERENTIAL DIAGNOSIS
Enteric duplication

Findings

• Variable appearance
o Thin-walled
• Does not have muscular wall as seen with
duplication cysts
o May be unilocular
• Can be large enough to mimic ascites
• Bowel is displaced, not floating in fluid
o Often multilocular, with one to multiple septations

cyst

• Can appear identical to unilocular mesenteric cyst
• Often has thicker wall
o Look for hyperechoic mucosa surrounded by
hypoechoic muscular wall
• More likely to cause obstruction and in utero bowel
dilatation
• More common

Ovarian cyst
• Females only, 3rd trimester
• Most common abdominal cystic mass in female
• Ovarian ligament lax so can be anywhere in abdomen

DDx: Other Lymphangiomas

CheSl

Che~t

Retroperitoneal

MESENTERIC CYST
Key Facts
Top Differential

Terminology

Diagnoses

Imaging Findings

•
•
•
•

•
•
•
•

• Most likely diagnosis for a large, multiloculated
abdominal mass separate from the urinary tract

• Cystic lymphatic
• Lymphangioma

malformation

Thin-walled
May be unilocular
Often multilocular, with one to multiple septations
May extend out of peritoneal cavity to involve
retroperitoneum
and lower extremities

Meconium

Diagnostic Checklist

Treatment

pseudocyst

• Thick, irregular wall
• Can calcify
• Other sequelae of meconium
o Peritoneal calcifications
o Dilated bowel

Enteric duplication cyst
Ovarian cyst
Meconium pseudocyst
Urachal cyst

peritonitis

• Postnatal work-up usually requires CT or MRI to see
full extent of large masses
• Surgical excision
o May rarely recur after resection
• More likely with retroperitoneal lymphangiomas

Urachal cyst
• Midline
• Between bladder and cord insertion

Choledochal

I DIAGNOSTIC

CHECKLIST

Image Interpretation

cyst

Pearls

• Right upper quadrant
• Look for bile ducts entering cyst

• Most likely diagnosis for a large, multiloculated
abdominal mass separate from the urinary tract
• May involve retroperitoneum
and extremities

I PATHOLOGY

I SELECTED REFERENCES

General Features

1.

• Etiology
o Thought to be proliferation of ectopic lymphatics
• Lack normal communication
with lymphatic
system
• Lymph accumulates forming a cystic mass
• Epidemiology: Rare

Microscopic

I CLINICAL

3.

4.

Features

• Has endothelial lining
• Dilated lymphatic spaces
• Fluid may be proteinaceous,
hemorrhagic

2.

serous, chylous or

Breysem Let al: The value of fast MR imaging as an adjunct
to ultrasound in prenatal diagnosis. Em Radiol.
13(7):1538-48, 2003
Khong PL et al: Ultrasonography of intra-abdominal cystic
lesions in the newborn. Clin Radiol. 58(6):449-54, 2003
Deshpande P et al: Prenatal diagnosis of fetal abdominal
lymphangioma by ultrasonography. Ultrasound Obstet
Gynecol. 17(5):445-8,2001
Kozlowski K] et al: Prenatal diagnosis of abdominal cystic
hygroma. Prenat Diagn. 8(6):405-9, 1988

I IMAGE

GALLERY

ISSUES

Presentation
• In utero
o Incidental cyst seen on routine scan
• Childhood
o Palpable mass
o Abdominal distention and pain
o May cause bowel obstruction
• Less likely to do so than duplication cysts because
they are of mesenteric orgin, rather than bowel
wall
o Cyst rupture reported

Natural History & Prognosis
• Excellent prognosis

(Left) Axial ultrasound through the abdomen of a newborn with a
palpable abdominal mass shows a very complex cystic mass filling
much of the abdomen and abutting the liver edge (arrows). (Right)
Cross pathology shows multiple septae with serous fluid (arrow)
within the locules. Histology confirmed an abdominal lymphangioma,
which was attached to the liver capsule.

GALLSTONES

Long axis ultrasound of a 3rd trimester fetal gallbladder
shows multiple non-shadowing echogenic foci (arrows)
within the lumen. No other abnormalities were seen.

ITERMINOlOGY
Abbreviations

and Synonyms

• Fetal cholelithiasis

Definitions
• Stones with shadowing
• Echogenic bile ("sludge")

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Third trimester fetal gallbladder
(GB) with echogenic material

Ultrasonographic

Findings

• Normal fetal GB
o Ovoid or teardrop shaped
o Intrahepatic early, then becomes subhepatic
• Gallstones
o Third trimester finding
o GB size variable
• Enlarged, contracted or normal
o One or more echogenic foci in gallbladder
• Most often multiple
o Shadowing
• > 3 mm stones more likely to shadow

Long axis ultrasound performed
immediately
after
delivery (left) shows multiple shadowing gallstones
(arrows) of variable sizes. A repeat exam 7 weeks later
(right) shows complete resolution of the gallstones.

• No shadowing if stone not in focal range
o Comet tail artifact
• Reverberation from cholesterol crystals
• Sludge
o Precursor to gallstones
o Hypoechoic or echogenic
• No acoustic enhancement distal to GB
• No shadowing
o Pear shaped echogenic GB if full of sludge
• Contracted GB with stones
o Look for crescent of bile anterior to stones
o Wall-echo-shadow sign
• Wall of GB
• Hypoechoic bile anterior to stones
• Echogenic stones with shadowing

Imaging Recommendations
• Protocol advice: Confirm foci are within GB lumen

I DIFFERENTIAL DIAGNOSIS
liver echogenicities
• Calcifications from infection
o Toxoplasmosis, cytomegalovirus, varicella
• Tumor + calcification
o Hepatoblastoma, teratoma, neuroblastoma
• Hemangioma
o Echogenic mass without calcification

DDx: Focal liver Echogenicities

Meconium Peritonitis

Toxoplasmosis

Varicella

GALLSTONES
Key Facts
• Meconium

Imaging Findings
• Be t diagno tic clue: Third trimester fetal gallbladder
with echogenic material
• > 3 mm tones more likely to shadow
• omet tail artifact
• Wall-echo- hadow ign
• Protocol advice: onfirm foci are within
B lumen

Top Differential

Diagnoses

• Liver echo enicities

Meconium

peritonitis

• Fetal bowel perforation
• Calcifications form on peritoneal surfaces, including
liver capsule
• Often accompanied by other findings
o Ascites
o Dilated bowel
o Meconium pseudocyst

peritonitis

Pathology
• Epidemiology:

1:200 3rd trim st r fetu e

Clinical Issues
• U ually completely

resolve in first year of life

Diagnostic Checklist
• Fetal gallstone do not always shadow
• Iud e ma be h oechoic or echo enic

I DIAGNOSTIC

CHECKLIST

Consider
• Sludge when gallbladder appears diffusely echogenic

Image Interpretation

Pearls

• Fetal gallstones do not always shadow
• Sludge may be hypoechoic or echogenic
• Obtain follow-up exams after baby is born until
resolution

I PATHOLOGY
ISELECTED REFERENCES

General Features
• Genetics: Not associated with aneuploidy
• Etiology
o Maternal estrogen effect on fetal bile
• t Cholesterol, ~ bile acids
o Placental abruption
• t Indirect bilirubin
o Other maternal causes
• Maternal narcotic use
• Maternal hemolytic anemia
• Blood group incompatibility
• Epidemiology: 1:200 3rd trimester fetuses
• Associated abnormalities
o Choledochal cyst
• Congenital dilatation of bile ducts

ICLINICAL

ISSUES

Presentation

1.

2.

3.

4.

5.

6.

Haffajee MR: The fetal gallbladder: morphology and
morphometry by microdissection. Surg Radiol Anat.
22(5-6):261-70,2000
Agnifili A et al: Fetal cholelithiasis: a prospective study of
incidence, predisposing factors, and ultrasonographic and
clinical features. Clin Pediatr (Phila). 38(6):371-3, 1999
Hertzberg BS et al: Fetal gallstones in a contracted
gallbladder: potential to simulate hepatic or peritoneal
calcification. J Ultrasound Med. 17(10):667-70, 1998
Suma V et al: Fetal gallstones: sonographic and clinical
observations. Ultrasound Obstet Gynecol. 12(6):439-41,
1998
Petrikovsky B et al: Sludge in fetal gallbladder: natural
history and neonatal outcome. Br J Radiol. 69(827):1017-8,
]996
Debray D et al: Cholelithiasis in infancy: a study of 40
cases. J Pediatr. 122(3):385-91, 1993

IIMAGE

GALLERY

• Most common signs/symptoms
o Almost always asymptomatic
o Infant cholelithiasis more often symptomatic
• Cholestatic jaundice, acholic stools, sepsis

Demographics
• Gender: M

=

F

Natural History & Prognosis
• Excellent prognosis
o Usually completely

resolve in first year of life

Treatment
• Usually none needed
• Biliary drainage if obstructive

(Left) Long axis ultrasound shows shadowing (arrows) material in the
fetal gallbladder (curved arrow). On this image, it is difficult to tell
whether this is one large stone or multiple small stones. (Right) Long
axis ultrasound in another fetus shows at least 4 separate echogenic
foci within the gallbladder (arrows). These foci do not shadow but
were seen moving freely within the gallbladder.

HEPATIC CALCIFICATIONS

Axial ultrasound shows multiple hyperechoic foci within
the fetal liver (arrows). These were calcifications seen in
the setting of toxoplasmosis infection.

• Parvovirus
• Rubella
• Syphilis

ITERMINOlOGY
Definitions
• Liver-associated calcification
o May be intraparenchymal, capsular or vascular

IIMAGING

FINDINGS

Ultrasonographic

Axial ultrasound in another patient shows multiple
hepatic calcifications in the setting of varicella infection
(arrows). The pattern of calcification is not specific to
the type of infection.

Findings

• Determination of intra parenchymal vs. capsular
location key factor in determining etiology
o Bowel perforation with meconium peritonitis most
common cause of capsular calcifications
o Parenchymal calcifications indicate a more systemic
process
• Acoustic shadowing mayor may not be present

In utero infection
• Scattered punctate echogenic foci diffusely throughout
liver
• Toxoplasmosis
• Cytomegalovirus
• Varicella zoster
• Herpes simplex

Meconium Peritonitis

peritonitis

• Present on peritoneal surfaces
o Along capsule of liver
• Evidence of bowel perforation
o Dilated bowel
o Ascites
• May be associated with peritoneal pseudocyst
• Can present asechogenic bowel
• Consider testing for cystic fibrosis
• Associated with other gastrointestinal malformations
o Gastroschisis
o Volvulus
o Bowel atresia
o Hirschsprung

Hepatic neoplasm

I DIFFERENTIAL DIAGNOSIS

DDx: Right Upper Quadrant

Meconium

• Rare
o Congenital hepatoblastoma
o Hemangioma
o Hemangioendothelioma
o Hamartoma
o Teratoma
• More likely retroperitoneal
o Metastatic
• Neuroblastoma

Echogenic Foci

Isolated Calcification

Teratoma

HEPATIC CALCIFICATIONS
Key Facts
Imaging Findings

Pathology

• Determination of intraparenchymal
vs. cap ular
location key factor in determining etiology
• coustic shadowing mayor may not be pre ent

• Malformation
reported in 21 % of fetu e with
parenchymal calcification
• A ociated with abnormal karyotype

Top Differential

Clinical Issues

Diagnoses

• Isolated, ingle hepatic calcifications are generally of
no con equence
• Multiple calcifications more likely to have a ociated
abnormalitie
adverselyaffe ting ro nosis

• In utero inf clion

• Meconium peritoniti
• Hepatic neoplasm
• Hepatic i chemic infarct

• Multiple calcifications more likely to have associated
abnormalities adversely affecting prognosis
o Malformations
o Chromosomal
o Infection

Gallstones
• Most resolve spontaneously
o Some resolve in utero
o Others asymptomatic but persist
• Eventually resolve in childhood

Hepatic ischemic infarct
• Diffuse or branching calcifications
• Presumed to be secondary to in utero vascular insult

Portal vein or hepatic vein calcification
• Result of calcified thromboemboli

I PATHOLOGY

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Fetus at increased risk for chromosomal abnormalities
o Careful anatomic survey warranted
• Look for other calcifications to assess for evidence of
in utero infection
o Intracranial
o Other intraabdominallocations

General Features
• Etiology
o Depends on underlying pathology
o Vascular insufficiency
• Venous thromboembolism
• Focal ischemic necrosis
• Could be related to focal hemorrhage
o Capsular
• Meconium peritonitis
o Intraparenchymal
• Infection
• Neoplasm
• Associated abnormalities
o Malformations reported in 21 % of fetuses with
parenchymal calcifications
• Even higher percentage if data reviewed from fetal
or neonatal autopsies
o Associated with abnormal karyotype
• Trisomy 13
• Trisomy 21
• Trisomy 18

ICLINICAL

I SELECTED
1.

2.

3.

4.

REFERENCES

Pott Bartsch EM et al: Giant fetal hepatic hemangioma.
Case report and literature review. Fetal Diagn Ther.
18(1):59-64,2003
Simchen MJ et al: Fetal hepatic calcifications: prenatal
diagnosis and outcome. Am J Obstet Gynecol.
187(6):1617-22,2002
Rigsby CK et al: Fetal varicella syndrome: association with
multiple hepatic calcifications and intestinal atresia.
Pediatr Radiol. 27(9):779,1997
Bronshtein M et al: Prenatal diagnosis of liver
calcifications. Obstet Gynecol. 86(5): 739-43, 1995

IIMAGE

GALLERY

ISSUES

Presentation
• Often incidental
• An associated finding with other malformations

Natural History & Prognosis
• Isolated, single hepatic calcifications

no consequence
o May resolve in postnatal

are generally of

(Left) Axial ultrasound shows multiple calcifications along the liver
capsule (arrows). Multiple loops of dilated bowel were also seen in

the abdomen. (RighO
period

Coronal ultrasound shows calcifications

outlining the surface of the liver (arrows). Peripheral calcifications are
with meconium
most likely the sequelae of bowel perforation
peritonitis.

HEPATOMEGALY, SPLENOMEGALY

Sagittal ultrasound shows hepatomegaly in a fetus with
hydrops. The liver (arrows) extends into the pelvis and
there is a pericardia I effusion (open arrow).

• Sonographic findings
o Skin edema
o Pleural/pericardial effusions
o Ascites
o Hepatosplenomegaly

ITERMINOlOGY
Definitions
• Enlargement

IIMAGING

of fetal liver and/or spleen

Infection

FINDINGS

Ultrasonographic

Findings

• Liver and/or spleen occupies a significant portion of
abdomen
o May extend into pelvis
o Normative values for splenic circumference have
been described
• Enlarged abdominal circumference in relation to other
growth parameters

I DIFFERENTIAL

Sagittal u!lrasound shows massive hepatomegaly
(arrows) in a fetus with congenital leukemia. The spleen
was also grossly enlarged.
(Also shown
in
Radiographics, ref 7).

DIAGNOSIS

• Cytomegalovirus
o Most common in utero infection
• Toxoplasmosis
• Parvovirus B19
o With associated hydrops
• Human immunodeficiency
virus (HIV)
o If mother is infected, interventional procedures
contraindicated
including amniocentesis
• Increases exposure risk to fetus
• Syphilis
o Dilated bowel
o Bowed long bones

Trisomy 21

Hydrops
• Immune
o Splenomegaly
• Can aid in assessing for presence of severe anemia
in initially nonhydropic fetuses
• Could be secondary to extramedullary
hematopoiesis
• Nonimmune

DDx: Upper Abdominal

• Myeloproliferative disorders
o Transient myeloproliferative disorder
• May show spontaneous remission
• May not have any detectable sonographic findings
in utero
• Variable spectrum of severity
o Congenital leukemia
• Usually presents as acute myelogenous leukemia

Mass

Teratoma

Itepatoblastoma

HEPATOMEGALY,

SPLENOMEGALY

Key Facts
Terminology
• Enlargement

of fetal liver and/or

pi en

Imaging Findings
• Enlarged abdominal circumference
other growth parameters

Top Differential

in relation to

Diagnoses

• Hydrop
• Infection
• Poor prognosis
• Extensive organ involvement
• Possibly due to defective regulation of granulocyte
maturation
• Elevated peripheral leukocyte counts with circulating
blasts
• Associated with hydrops
o If present, prognosis is poor

Glycogen storage disorder
• Gaucher disease
o Perinatal-lethal subtype
• Prenatal onset
• Hydrops
• Hepatosplenomegaly
• Hypokinesia/arthrogryposis
• Ichthyosis
• Facial dysmorphism
o Can offer prenatal testing
• Amniocentesis, cordocentesis or chorionic villus
sampling
• Test for glucocerebrosidase activity
o Most often results in fetal demise or early neonatal
death

Beckwith-Wiedemann

syndrome

• Organomegaly
o Hepatosplenomegaly
o Nephromegaly
• Macroglossia
• Omphalocele
o 4% of omphaloceles associated with
Beckwith- Wiedemann
• Typically offer prenatal testing
o Maps to genes at llp15
o 85% of cases sporadic
o 15% autosomal dominant with variable
transmission
• Most are born to female carriers
• At risk for solid organ neoplasms
o Wilms tumor
o Hepatoblastoma
• Associated with neonatal hypoglycemia at birth

• Myeloproliferative disorder
• Iycogen storage di order
• Beckwith-Wiedemann
syndrome

Diagnostic Checklist
• Toxoplasmo i , other, rubella, cytomegaloviru
herpes (TOR I I) titers for infection
• Amniocente i for karyotype
• Look for other signs of hydrops

I CLINICAL

and

ISSUES

Presentation
• Most common
circumference

I DIAGNOSTIC

signs/symptoms:

Enlarged abdominal

CHECKLIST

Consider
• Toxoplasmosis, other, rubella, cytomegalovirus
herpes (TORCH) titers for infection
• Amniocentesis for karyotype

Image Interpretation

and

Pearls

• Look for other signs of hydrops

ISELECTED REFERENCES
1.

2.

3.
4.

Woodward PJ et al: From the archives of the AFIP: a
comprehensive review of fetal tumors with pathologic
correlation. Radiographies. 25(1):215-42, 2005
Barton LL: Case 25-2003: congenital cytomegalovirus
infection. N Engl J Med. 349(16):1575-6; author reply
1575-6,2003
Mignot C et al: Perinatal-lethal Gaucher disease. Am J Med
Genet. 120A(3):338-44, 2003
Bahado-Singh R et al: Fetal splenic size in anemia due to
Rh-alloimmunization.
Obstet Gynecol. 92(5):828-32, 1998

IIMAGE

GALLERY

Hepatic neoplasm
• Hepatoblastoma, hemangioendothelioma,
mesenchymal hamartoma
• Uncommon cause of hepatomegaly
• Consider neuroblastoma if metastases suspected

(Left) Sagittal T2WI MR shows a markedly enlarged liver (arrows) in a
monochorionic twin with hydrops secondary to twin-twin transfusion
syndrome. (Right) Sagittal ultrasound shows subtle hyperechoic foci
(arrows) and hepatomegaly in a 22 week fetus with premature
rupture of membranes. Autopsy confirmed hepatomegaly, etiology
uncertain but infection was suspected.

CHOLEDOCHAL

Graphic shows marked dilatation of the common bile
duct. Note the anomalous pancreatico-biliaryjunction
(arrow) with the pancreatic duct inserting into the
common bile duct proximal to the sphincter of Oddi.

CYST

Axial ultrasound shows a choledochal cyst (white
arrow) located adjacent to the gal/bladder (curved
arrow). A small bile duct (black arrow) is seen entering
the cyst.

o Look for close relationship to gallbladder
• Color Doppler to rule out umbilical vein varix

ITERMINOlOGY
Definitions
• Congenital cystic dilatation of extrahepatic and/or
intrahepatic bile ducts

I DIFFERENTIAL DIAGNOSIS

IIMAGING

• Color Doppler confirms flow

Umbilical vein varix

FINDINGS

Duodenal atresia

General Features
• Best diagnostic clue: Following bile ducts into cyst
confirms diagnosis
• Size: Variable, often large if seen prenatally

Ultrasonographic

Findings

• Connects to stomach

Enteric duplication
Gallbladder

• Unilocular, cystic right upper quadrant mass
o Echogenic contents in cyst has been described
• May see short, tubular bile ducts entering cyst
o More extensive intra parenchymal dilatation not
reported

cyst

• Located anywhere in abdomen, ileum most common

duplication

• Same fusiform shape as normal gallbladder

Ovarian cyst
• Females only, seen in 3rd trimester
• Ovarian ligaments lax so can be anywhere in abdomen

MR Findings

liver cyst

• Bile high signal on T2WI
• MR cholangiogram may prove helpful

• Within liver parenchyma, rare

Mesenteric

cyst

Imaging Recommendations

• Located anywhere in abdomen, may be multilocular

• Follow liver contour
o Coronal view most helpful
o Subhepatic, immediately adjacent to capsule

Meconium

pseudocyst

• Thick, irregular wall

DDx: Cystic Mass By liver

Duodenal Atresia

Umbilical Vein Varix

Umbilical Vein Varix

Duplication

Cyst

CHOLEDOCHAL

CYST

Key Facts
Imaging Findings

Pathology

• Unilocular, ystic right upper quadrant ma
• May see short, tubular bile ducts entering cyst

• 1/3 of all ca e from Japan

Top Differential

• Untreated lead to cholesta
eventual liver failure

•
•
•
•

Diagnoses

Umbilical vein varix
Duodenal atre ia
Enteric duplication cyst
Gallbladder duplication

Diagnostic Checklist

• Good outcome with early treatment
damage

with bile

before irreversible

Treatment

I PATHOLOGY
General Features
• Etiology
o Possible mechanisms (likely multifactorial)
• Strong association with anomalous
pancreatico-biliary junction
• Insertion of pancreatic duct into common bile
duct (CBD) above sphincter complex
• Reflux of pancreatic enzymes into bile duct with
weakening of wall
• Does not completely explain very early cysts
o Alternate theories
• Abnormal recanalization during organogenesis
• Abnormal epithelium resulting in wall weakness
• Epidemiology
o Rare in western population
o More common in Asia
• 1/3 of all cases from Japan
o M< F

Biliary atresia

Staging, Grading or Classification Criteria
• Type 1: Saccular or fusiform dilatation of CBD
o 80-90% of cases
o Type seen in utero
o Subclassified based on portion of CBD involved
• Type 2: CBD diverticulum
• Type 3: Choledochocele
• Type 4: Intrahepatic and extrahepatic dilatation
• Type 5: Intrahepatic dilatation (Caroli disease)

I CLINICAL

i , biliary cirrhosis and

• Right upper quadrant cyst communicating
ducts is pathognomonic

• Other sequelae of meconium peritonitis
o Peritoneal calcifications, dilated bowel

• Associated abnormalities:

Clinical Issues

• Complete work-up in neonatal period
• Surgical resection with choledochojejunostomy
or
hepaticojejunostomy
o May delay up to 6 months of age if asymptomatic

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Right upper quadrant cyst communicating
ducts is pathognomonic

with bile

I SELECTED REFERENCES
1.

2.

3.
4.

Okada T et al: Postnatal management for prenatally
diagnosed choledochal cysts. J Pediatr Surg. 39(7):1055-8,
2004
Casaccia G et al: Cystic anomalies of biliary tree in the
fetus: is it possible to make a more specific prenatal
diagnosis? J Pediatr Surg. 37(8):1191-4, 2002
Redkar R et al: Antenatal diagnosis of congenital anomalies
of the biliary tract. J Pediatr Surg 33:700-4, 1998
Lugo-Vicente HL: Prenatally diagnosed choledochal cysts:
Observation or early surgery? J Pediatr Surg 30:1288-90,
1995

IIMAGE GALLERY

ISSUES

Presentation
• Incidental finding in utero
o Diagnosed as early as 15 weeks
• Childhood presentation
o Jaundice (most common), pain, right upper
quadrant mass

Natural History & Prognosis
• Untreated leads to choIestasis, biliary cirrhosis and
eventual liver failure
• Risk factor for cholangiocarcinoma

(Left) Color Doppler ultrasound shows an avascular, cystic mass
communicating
with dilated bile ducts (arrows). This finding is
pathognomonic for a choledochal cyst. (Right) Ultrasound of the liver
after delivery confirms a dilated bile duct (arrow) entering the
choledochal

cyst.

LIVER TUMORS

Axial ultrasound of a hepatoblastoma
shows a large,
well-defined, solid liver mass (arrows). A "spoke-wheel"
appearance is used to describe the pattern of alternating
echogenicities within the mass.

Gross pathology of the liver shows the well-defined
mass with prominent fibrous bands extending to the
pseudocapsule (arrows), correlating with the ultrasound
appearance. (Also shown in Radiographies, ref 7).

ITERMINOLOGY
Definitions
• Variety of benign and malignant tumors derived from
both endodermal and mesenchymal tissues

•

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Well-defined, right upper
quadrant mass
• Size: Generally large
• Morphology
o Most tumors are well-defined, large liver masses
o Leukemia is the exception and most commonly
presents as hepatosplenomegaly
o Generally solid, but cystic masses occur

Ultrasonographic

•

Findings

• Infantile hemangioendothelioma
o Variable sonographic appearance
• Hypoechoic, hyperechoic or mixed echogenicity
o Detected as early as 16 wks
o Vascular masses
• Increased flow on color Doppler
• Flow void described on fetal MRI
o Hydrops may develop from

•

•

• Arteriovenous shunting
• Kasabach-Merritt sequence: Hemolytic anemia,
thrombocytopenia and consumptive
coagulopathy
Mesenchymal hamartoma
o Predominately cystic or mixed echogenicity mass
o Does not have increased vascularity
o May develop hydrops
• Secondary to rapid fluid shifts within expanding
cysts
Hepatoblastoma
o Solid, echogenic masses
o Pseudocapsule around lesion creates well-defined
borders
o "Spoke-wheel" described with alternating hypo- and
hyperechoic areas
o Moderate vascularity by color Doppler
o Calcifications occasionally seen
o Can have spontaneous hemorrhage
o Hydrops potential complication
Leukemia
o Hepatosplenomegaly most common finding
o Hydrops may develop from
• Fetal anemia
• Leukemic infiltration of myocardium
• Visceral fibrosis with increased vascular resistance
Metastases
o Neuroblastoma

DDx: Hepatomegaly

Leukemia

Leukemia

Neuroblastoma

Mets

LIVER TUMORS
Key Facts
Imaging Findings

Clinical Issues

• Most tumors are well-defined, large liver masses
• Leukemia is the exception and most commonly
presents as hepatosplenomegaly
• Generally solid, but cystic masses occur

• Consider cesarian section
• Intrapartum tumor rupture has been reported

Top Differential

Diagnoses

• Nonimmune hydrops
• Immune hydrops
• Infection

Pathology
• 15-20x increased risk of leukemia in trisomy 21
• Benign primary tumors (hemangioendothelioma,
mesenchymal hamartoma) are more common than
malignant ones (hepatoblastoma)

• Most common primary fetal tumor to metastasize
to liver
• 25% of neuroblastoma cases have liver metastases
• Solid primary tumors are more likely to
metastasize than cystic ones
• Liver is most common site of metastases
• May be either infiltrative or focal
o Other metastatic fetal tumors exceedingly rare

Imaging Recommendations
• Protocol advice
o Confirm mass is within liver
• Large renal, adrenal and retroperitoneal masses
may be mistaken for liver mass
o Careful Doppler analysis
• Significant vascularity with arteriovenous
shunting favors hemangioendothelioma
o Follow-up scans
• Monitor size of tumor
• Development of hydrops
• In-utero treatment or early delivery may be
considered if mass is rapidly growing and/or signs
of impending cardiovascular compromise

Diagnostic Checklist
• Hemangioendothelioma
most likely diagnosis for a
vascular intrahepatic mass
• Mesenchymal hamartoma most likely diagnosis for a
multilocular, cystic liver mass
• Hepatoblastomas are well-defined, solid masses,
which may exhibit a "spoke-wheel" pattern of
echogenicity
• Consider leukemia in setting of diffuse
hepatosplenomegaly,
especially if fetus has Down
syndrome

• Other alloimmune syndromes (Kell, Duffy, C, c, E
and others)
• Splenomegaly may be prominent feature
o Infection
• Cytomegalovirus
• Toxoplasmosis
• Parvovirus B19
o Gaucher disease
• Perinatal-lethal subtype
• Hepatosplenomegaly
• Hydrops
• Hypokinesia/arthrogryposis
• Ichthyosis
• Facial dysmorphism
• Prenatal testing available
o Beckwith-Wiedemann
syndrome
• Macrosomia
• Nephromegaly
• Omphalocele
• Hepatosplenomegaly
• Predisposition to embryonal tumors

I PATHOLOGY
I

DIFFERENTIAL DIAGNOSIS

Conditions causing hepatomegaly
• Most conditions cause splenomegaly as well as
hepatomegaly
o Most tumors are well-defined liver masses (except
leukemia)
• Large number of causes
o Nonimmune hydrops
• Skin edema
• Pleural/pericardial effusions
• Ascites
• Hepatosplenomegaly
• Multitude of causes, including cardiac, multiple
types of masses, chromosomal and placental
o Immune hydrops
• Rhesus (Rh) alloimmunization

General Features
• Genetics
o Sporadic
o 15-20x increased risk of leukemia in trisomy 21
• Epidemiology
o Rare
o "" 5% of fetal tumors occur in liver
o Benign primary tumors (hemangioendothelioma,
mesenchymal hamartoma) are more common than
malignant ones (hepatoblastoma)
• Associated abnormalities
o 10-15% of hemangioendotheliomas
have
hemangiomas elsewhere
• Liver, spleen, cutaneous most common
o Leukemia associated with Down syndrome

Microscopic

Features

• Infantile hemangioendothelioma

LIVER TUMORS
o Lesion composed of large endothelial-lined vascular
channels
• Mesenchymal hamartoma
o Large fluid-filled cysts
o Loosely organized mesenchymal tissue containing
small bile ducts
• Hepatoblastoma
o Malignant tumor classified histologically as
epithelial or mixed (epithelial + mesenchymal)
• Leukemia
o Acute myelogenous leukemia
o Possibly due to defective granulocyte maturation
o Elevated peripheral leukocyte counts with
circulating blasts

ICLINICALISSUES
Presentation
• Most common signs/symptoms
o Large right upper quadrant mass
o Hydrops
• Postnatal
o Unexplained congestive heart failure
o Palpable abdominal mass

o Corticosteroids first line of treatment
• Thought to cause vasoconstriction of aberrant
vessels
o Corticosteroids have been successfully used in
fetuses with rapidly growing masses
• Both maternal administration and direct umbilical
vein injection have been described

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Hemangioendothelioma
most likely diagnosis for a
vascular intrahepatic mass
• Mesenchymal hamartoma most likely diagnosis for a
multilocular, cystic liver mass
o May be rapidly expanding
• Hepatoblastomas are well-defined, solid masses, which
may exhibit a "spoke-wheel" pattern of echogenicity
• Consider leukemia in setting of diffuse
hepatosplenomegaly, especially if fetus has Down
syndrome
• Metastatic neuroblastoma may cause either focal liver
mass or diffuse infiltration
o Diffuse infiltration may be difficult to diagnose

Natural History & Prognosis
• Variable according to histologic type
• Hemangioendothelioma
o Rapid, proliferative growth in first 6 months of life
• Significant vascular shunting may lead to
congestive heart failure
o Tumors commonly regress and involute after 6
months
• Mesenchymal hamartoma is benign and surgery is
curative
o Not always possible, depending on size and location
of mass
• Hepatoblastoma
o Malignant neoplasm
o Very poor prognosis for those diagnosed in perinatal
period
• Leukemia
o Variable spectrum of severity
o Transient myeloproliferative disorder
• Described in Down syndrome
• May spontaneously resolve
o Congenital leukemia may rapidly progress and be
fatal
• Much poorer prognosis than those presenting
latter in childhood

Treatment
• If diffuse hepatosplenomegaly consider cordocentesis
o Diagnosis of leukemia is based on white blood cell
analysis
o Karyotype of trisomy 21
• Pediatric surgery consult prior to delivery
• Delivery at tertiary care facility
o Consider cesarian section
• Intrapartum tumor rupture has been reported
• Hemangioendotheliomas
o May not require treatment if asymptomatic
• May spontaneously regress

ISELECTED REFERENCES
Woodward PJ et al: From the archives of the AFlP: a
comprehensive review of fetal tumors with pathologic
correlation. Radiographies. 25(1):215-42, 2005
Bayoumy M et al: Prenatal presentation supports the in
2.
utero development of congenital leukemia: a case report. J
Pediatr Hematol Oncol. 25(2):148-52, 2003
Kamata S et al: Fetal mesenchymal hamartoma of the liver:
3.
report of a case. J Pediatr Surg. 38(4):639-41, 2003
4. Robertson Met al: Prenatal diagnosis of congenital
leukemia in a fetus at 25 weeks' gestation with Down
syndrome: case report and review of the literature.
Ultrasound Obstet Gynecol. 21(5):486-9, 2003
5.
Shih JC et al: Congenital hepatoblastoma. Ultrasound
Obstet Gynecol. 16(1):103, 2000
6. Morris J et al: Antenatal diagnosis of fetal hepatic
hemangioma treated with maternal corticosteroids. Obstet
Gynecol. 94(5 Pt 2):813-5, 1999
7. Isaacs H Jr: Liver tumors. In:Tumors of the fetus and
newborn. Philadelphia, Saunders. 278-297, 1997
8.
Macones GA et al: Fetal hepatosplenomegaly associated
with transient myeloproliferative disorder in trisomy 21.
Fetal Diagn Ther. 10(2):131-3, 1995
9. Mejides AA et al: Prenatal diagnosis and therapy for a fetal
hepatic vascular malformation. Obstet Gynecol. 85(5 Pt
2):850-3, 1995
10. Abuhamad AZ et al: The use of color flow Doppler in the
diagnosis of fetal hepatic hemangioma. J Ultrasound Med.
12(4):223-6, 1993
11. Hirata GI et al: Ultrasonographic diagnosis of a fetal
abdominal mass: a case of a mesenchymal liver hamartoma
and a review of the literature. Prenat Diagn. 10(8):507-12,
1990
12. Keslar PJ et al: From the archives of the AFIP.Infantile
hemangioendothelioma
of the liver revisited.
Radiographies. 13(3):657-70, 1993
1.

LIVER TUMORS
IIMAGE

GALLERY
(Left) Axial ultrasound of a
hemangioendothelioma
shows a large, irregular,
heterogeneous mass
(arrows) essentially replacing
the liver. (Right) Axial
ultrasound of the liver after
delivery shows the mass is
very heterogeneous with a
hyperechoic rim (arrows)
and an irregular hypoechoic
center (open arrow).

(Left) Anteroposterior
radiograph in the same case
shows obvious congestive
heart failure with cardiac
enlargement and soft tissue
edema. Also note the fullness
in the right upper quadrant
and displacement of bowel
loops (arrow) by the
enlarged liver. (Right) Cross
pathology at autopsy shows
areas of fibrosis (arrows) and
hemorrhage (open arrow).
Histology confirmed a
hema ngioendothelioma.
(Also shown in
Radiographies, ref 7 )

(Left) Axial ultrasound of a
mesenchymal hamartoma
shows a predominately
cystic mass (arrow)
associated with the liver. No
flow was seen in these cystic
spaces (Right) Cross
pathology of the resected
mass shows the typical large
cystic spaces in a
background of disorganized
mesenchymal tissue. (Also
shown in Radiographies, ref
7).

SECTION 9: Genitourinary

Introduction

and Overview

Genitourinary Development & Imaging

9-2

Kidney
Renal Developmental Variants
Duplicated Collecting System
Mild Pelviectasis
Ureteropelvic]unction
Obstruction
Obstructive Cystic Dysplasia
Renal Agenesis
Multicystic Dysplastic Kidney
Autosomal Recessive Polycystic Kidney Disease
Mesoblastic Nephroma

9-6
9-10
9-14
9-18
9-22
9-26
9-30
9-34
9-38

Adrenal
9-42

Neuroblastoma

Bladder
Posterior Urethral Valves
Prune Belly Syndrome
Ureterocele
Urachal Anomalies

9-46
9-50
9-52
9-56

Genitalia
Ambiguous Genitalia
Hypospadias
Hydrocele
Testicular Torsion
Ovarian Cyst

9-58
9-62
9-64
9-66
9-68

GENITOURINARY

DEVELOPMENT & IMAGING

Cross pathology in the 2nd trimester shows the relative
large size of the fetal adrenal (curved arrow) compared
to the kidney (arrow). It is important not to mistake
adrenal glands for kidneys in cases of renal agenesis.

ITerminology
Definitions
• Components of genitourinary system
o Kidneys, ureters, bladder, urethra
o Adrenal glands
o Internal and external genitalia

IAnatomy-Based

Imaging Issues

Key Concepts or Questions
• Are there two kidneys?
-+
o Bilateral renal agenesis -+ anhydramnios
pulmonary hypoplasia -+ lethal anomaly
o Unilateral renal agenesis -+ normal amniotic fluid
volume -+ not associated with pulmonary
hypoplasia
• Must follow for contralateral reflux, ureteropelvic
junction obstruction
• Is renal size and echogenicity normal?
o Bilateral large kidneys
• Autosomal recessive polycystic kidney diseases
(ARPKD)
• Beckwith-Wiedemann
syndrome
• Multicystic dysplastic kidneys (MCDK)
o Unilateral large kidney
• MCDK, mesoblastic nephroma
o Increased renal echogenicity
• ARPKD, cystic dysplasia
o Are there obvious renal cysts?
• Macroscopic cysts -+ MCDK, cystic renal dysplasia,
autosomal dominant polycystic kidney disease
• Are the ureters visible?
o Normal ureters never seen sonographically
o If ureters are dilated consider obstruction, reflux,
primary mega ureter
• Is the bladder visible?
o "Absent" bladder most commonly due to failure of
urine production
o Some structural malformations prevent normal
bladder development

Coronal color Doppler ultrasound shows the abdominal
aorta, renal arteries (arrows) and right adrenal artery
(curved arrow). Urine is seen within bladder (open
arrow).

o Soft tissue mass in midline, inferior to cord insertion
-+ bladder extrophy
o Look for bifid scrotum/penis with bladder/cloacal
extrophy
• Is the bladder normal in size?
o Should fill and empty during course of a scan
o If bladder is too large
• Posterior urethral valves, urethral atresia, prune
belly syndrome
• Are the adrenal glands normal in morphology and
position?
o Normal adrenal has characteristic "ice-cream
sandwich" appearance
• Hypoechoic cortex -+ "sandwich"
• Hyperechoic medulla -+ "ice-cream" filling
o Normal adrenal is triangular or V-shaped
• Flat, "lying down" adrenal useful sign that kidney
not in renal fossa
• Discoid, enlarged adrenals seen in congenital
adrenal hyperplasia (look for virilization of female
fetus)
o Unilateral adrenal mass has narrow differential
diagnosis
• Neuroblastoma
• Adrenal hemorrhage
• Extralobar sequestration
• Are the genitalia normal?
o Anomalous genitalia seen in structural
malformation sequences that affect bladder
development, aneuploidy, syndromes

Imaging Approaches
• Ultrasound (US)
o Endovaginal scans useful in early gestation with low
fluid
o Kidneys can be identified by 12-14 weeks gestation
o Internal architecture seen as early as 16-18 weeks
• Hypoechoic medullary pyramids arranged
symmetrically around renal sinus
• Renal sinus appears as a fluid-filled "slit" in center
of kidney
• Cortex is thin in early gestation

GENITOURINARY

DEVELOPMENT & IMAGING
Key Facts

Fetal Kidneys Have little Impact On
Amniotic Fluid Volume < 16 Wks Gestation
• Normal fluid volume in early pregnancy does not
exclude significant renal pathology

Bladder Should Be Visible On Every 2nd/3rd
Trimester Scan
• Fluid-filled structure that changes volume during
scan
• If absent, establish cause
o Lack of urine production
• Look for renal anomalies, IUGR, TITS
o Structural malformation of bladder
• Look for calcified meconium -+ mixing of urine
with meconium -+ cloacal malformation, anal
atresia with fistula

• Look for soft tissue mass inferior to cord
insertion -+ bladder extrophy
• Bladder filling is a criterion for grading system in
TITS
o Used to assess severity and need for intervention

Beware large Fetal Adrenal Glands
• May be mistaken for fetal kidneys
• Renal agnesis is lethal, important to make diagnosis
so that families may be counseled appropriately

Oligohydramnios
Diagnosis

Has A Wide Differential

• Early onset oligohydramnios carries poor prognosis
but not all causes are lethal
o Bilateral renal agenesis, bilateral MCDK, severe
ARPKDare lethal

• By 3rd trimester renal sinus/perinephric fat
deposition -+ increased conspicuity
o Doppler ultrasound to identify renal arteries
o Amnioinfusion in setting of oligohydramnios
• Fluid instilled around fetus to provide acoustic
window for imaging
• Invasive: Modern approach is non-interventional
use of MRI
• MRI
o T2WI essential for evaluation of renal anatomy
• Kidneys parenchyma intermediate in signal «
fluid, > liver or muscle)
• Renal collecting system, bladder should contain
high-signal urine
• Adrenal glands seen best in later gestation, low
signal similar to liver on T2WI
o May be helpful in ovarian cyst evaluation
• Cysts are high signal on T2WI, arise from adnexa
o TlWI
• Helpful to look at course of colon, rectum if
concern for associated cloacal, bowel anomalies
• May allow differentiation of adrenal hemorrhage
(high signal blood products) from fetal
neuroblastoma (intermediate signal)

• Adrenal/lumbar arteries confused with renal arteries
on color Doppler evaluation
• Bladder pitfalls
o No urine production --+ bladder not seen
• It is anatomically present but not visible as
fluid-filled structure, may contain mucus
secretions
• Renal agenesis, severe growth restriction (IUGR),
donor twin in twin-twin transfusion syndrome
(TITS)
o Must see change in volume of fluid-filled structure
to verify urine production
• Beware other fluid-containing entities (e.g.
ovarian cyst, persistent cloaca)
• Normal amniotic fluid does not always indicate
normal renal function
o Renal function has no significant impact on fluid
volume before 16 weeks
• Ambiguous genitalia
o Gender determination important in X-linked
conditions
o Ambiguous genitalia associated with aneuploidy,
syndromes

Imaging Protocols

• Normative data available for renal size throughout
gestation
• Ratio of renal circumference to abdominal
circumference stable throughout pregnancy
o 0.27-0.30
• Renal pelvis AP diameter
o < 4 mm at gestational age < 22 weeks
o < 7 mm from 33 weeks to term
o Larger collecting system concerning for obstruction
or reflux
• Infants need postnatal evaluation
• Do not scan at < 72 hours of age: Postnatal fluid
shifts -+ dehydration -+ risk for underestimation
of collecting system dilatation

• American Institute of Ultrasound in Medicine
guidelines
o Document presence of kidneys/bladder in all
2nd/3rd trimester scans
o Assess fluid volume
• MRI
o Very helpful when US visualization is limited
• Oligohydramnios/anhydramnios,
large maternal
body habitus
• Lack of amniotic fluid less of an issue for MRI
than for US

Imaging Pitfalls
• "Lying down" adrenals
o Fetal adrenals are relatively large compared to
kidney -+ mistaken for kidneys
• Adrenal hypertrophy described in renal agenesis

Normal Measurements

GENITOURINARY

DEVELOPMENT

Sagittal ultrasound shows a normal kidney (cursors)
with pyramids (curved arrows) arranged symmetrically
around the renal pelvis (arrow). The AP diameter of the
pelvis should be < 7 mm in the 3rd trimester.

Axial T2WI MR in a 25 week fetus shows normal
kidneys (arrows) with high signal urine in the renal
pelves, similar to the gallbladder (curved arrow) and
cerebrospinal fluid (open arrow).

a By 7th week, cloacal folds meet posteriorly to form
urogenital and anal folds
a Urogenital membrane breaks down to urogenital
sinus
a Urogenital sinus -+ penile urethra in males, vaginal
vestibule in females
a Male/female differentiation occurs after 12 weeks

I Embryology
Embryologic Events
• Renal development
o Intermediate mesoderm -+ renal precursors of
increasingly sophisticated design: Pronephros,
mesonephros, metanephros
o Pronephros
• Transient, non-functional
o Mesonephros
• Two longitudinal swellings -+ rudimentary renal
tissue -+ minimum urine formation 6-10 weeks
• Mesonephric (wolffian) ducts connect cloaca to
rudimentary kidney
a Metanephros
• Mesonephric duct -+ ureteral bud -+ ureters,
pelvis, calyces, collecting tubules
• Connection of ureteral bud with metanephric
blastema induces nephron formation
• Kidneys functional by 10 weeks
• Bladder development
a Anterior cloaca forms part of bladder neck, proximal
urethra, remainder of bladder arises from allantois
• Bladder separated from rectum by urorectal
septum
• Adrenal development
a Neural crest cells -+ sympathetic ganglia -+ adrenal
medulla
a Mesodermal cells -+ cortex, which engulfs medulla
• Gonads
a Primordial germ cells -+ genital ridges -+ primitive
gonads
o Male-female differentiation occurs in 8th week
• In male: Primitive gonad -+ testis, mesonephric
ducts -+ vas deferens
• In female: Primitive gonad -+ ovary, mesonephric
ducts atrophy, paramesonephric
(mullerian) ducts
develop -+ fallopian tubes, uterus, superior vagina
• External genitalia
a Cloacal folds fuse anteriorly -+ genital tubercle by
5th week

& IMAGING

Practical Implications
• Failure or ureteric bud to induce metanephric
-+ renal agenesis
• Failure of communication
between nephrons
collecting ducts -+ cystic renal disease

blastema
and

I Clinical Implications
Clinical Importance
• Amniotic fluid required for normal lung development
-+
a Anhydramnios/severe
oligohydramnios
pulmonary hypoplasia
• Any cause of severe oligohydramnios
carries poor
prognosis
a Important to recognize conditions, which are
definitely lethal (e.g. renal agenesis, bilateral MCDK)
for proper counseling and pregnancy management

I Related References
1.

2.

3.

4.
5.

Farhataziz N et al: Fetal MRI of urine and meconium by
gestational age for the diagnosis of genitourinary and
gastrointestinal abnormalities. AJR Am J Roentgenol.
184(6):1891-7,2005
Cassart M et al: Complementary role of MRI after
sonography in assessing bilateral urinary tract anomalies in
the fetus. AJRAm J Roentgenol. 182(3):689-95, 2004
Michailidis GO et al: The use of three-dimensional
ultrasound for fetal gender determination in the first
trimester. Br J Radiol. 76(907):448-51,2003
Warne S et al: Prenatal diagnosis of cloacal anomalies. BJU
lnt. 89(1):78-81, 2002
Geipel A et al: Diagnostic and therapeutic problems in a
case of prenatally detected fetal hydrocolpos. Ultrasound
Obstet Gynecol. 18(2):169-72,2001

GENITOURINARY

DEVELOPMENT

& IMAGING

IIMAGE GAllERY
(Left) Axial ultrasound in a
third trimester shows the
typical "ice-cream
sandwich" appearance of
the adrenals (arrows). The
cortex is hypoechoic and the
medulla hyperechoic. This is
quite different from the
normal kidney. (Right)
Coronal T2WI MR shows the
low signal, triangular adrenal
(white arrows) superior to
the kidney (black arrows)
and medial to the stomach
(curved arrow) and spleen
(open arrow).

(Left) Axial oblique color
Doppler ultrasound shows a
normal bladder being
flanked by the umbilical
arteries (arrows). The
bladder should change
appearance during the exam,
as it fills and empties. (Right)
Coronal T2WI MR shows a
normal fetal bladder (open
arrow) containing high signal
urine. The liver (curved
black arrow), spleen (black
arrow), small bowel (curved
white arrow) and lungs
(white arrow) are well seen.

(Left) Axial ultrasound shows
normal male genitalia with
the penis (curved arrow) and
scrotum (arrow) seen in an
image obtained through the
fetal pelvis. The open arrow
indicates the bladder. (Right)
Axial ultrasound shows the
normal appearance of female
genitalia. The labia create
multiple parallel echoes
(arrows).

RENAL DEVELOPMENTAL VARIANTS

Renal developmental variants include unilateral renal
agenesis (A), pelvic kidney (8), crossed fused renal
ectopic (C) and horseshoe kidney (0). Errors of
formation, fusion and ascent lead to these anomalies.

o Left> right
• 57% empty renal fossa on left

ITERMINOLOGY
Definitions
• Causes of developmental variants
o Absent renal tissue
o Ectopic renal tissue
o Abnormal fusion
o Abnormal ascent
• Unilateral renal agenesis
o One kidney does not form
• Pelvic kidney
o Kidney located in pelvis
• Horseshoe kidney
o Kidneys fused in horseshoe configuration
• Lower> upper pole fusion
o Isthmus = bridging tissue
• Crossed renal ectopia
o Both kidneys on one side
o 95% of cases are fused; Crossed fused renal ectopia

IIMAGING

Axial ultrasound shows crossed renal ectopia with
fusion. The left and right kidneys are fused and form a
bilobed single kidney (arrows). In this case, the right
kidney has crossed and fused with the left.

FINDINGS

General Features
• Best diagnostic clue
o Empty renal fossa
o Abnormal renal morphology
• Location

DDx: Poorly Visualized Kidneys

Prominent Adrena/s

Ultrasonographic

Findings

• Unilateral renal agenesis
o Empty renal fossa
• First seen on axial view
• Confirm on longitudinal view
o Compensatory renal hypertrophy
• Normal kidney compensates for absent kidney
• Size> 95th percentile
• Seen in 44% of cases, as early as 22 wks
o Color Doppler confirms diagnosis
• Coronal aorta view
• Absent renal artery
o Adrenal gland fills empty renal fossa
• "Laying down" appearance
• Globular instead of triangular
• Can mimic kidney
o Colon in empty renal fossa may mimic kidney
• Pelvic kidney
o Empty renal fossa
o Kidney in fetal pelvis
• Located superior to bladder
• Often difficult to see
• Echogenicity similar to bowel
o Contralateral kidney is normal-sized
• No compensatory hypertrophy

RENAL DEVELOPMENTAL VARIANTS
Key Facts
• Renal cystic dysplasia
• Renal or adrenal mass

Terminology
•
•
•
•

Unilateral renal agene is
Pelvic kidney
Horseshoe kidney
Crossed renal ectopia

Pathology
• Aneuploidy/syndromes

Empty renal fossa
Abnormal renal morphology
Adrenal gland fills empty renal fossa
Look in fetal pelvis if one kidney missing
Use color Doppler to find renal arteries
onsider MR if visualization is limited

Top Differential

Diagnoses

• ormal adrenal gland
• Severe oligohydramnios

if other anomalies

Clinical Issues

Imaging Findings
•
•
•
•
•
•

common

(normal kidneys)

o Color Doppler helpful
• Follow renal artery to pelvic kidney
o Adrenal gland in renal fossa
• Horseshoe kidney
o Kidney lower poles connected by isthmus
• Parenchymal or fibrous connection
• Isthmus is anterior to aorta
• Seen best on axial and coronal views
o Kidneys more inferior than normal
• Isthmus "snags" on inferior mesenteric artery
during ascent
o Malrotation common
• Medial deviation of lower poles
• Anteriorly directed extra-renal pelvis
o Upper pole fusion is rare variant
• Inverted horseshoe morphology
o Associations
• Turner syndrome
• Trisomy 18
• Other genitourinary anomalies
• Crossed renal ectopy
o Ectopic kidney located in opposite flank
• 95% are fused
• Left crosses to right most often
o Large bilobed kidney
• One renal fossa is empty
• Other contains atypical large kidney
o Color Doppler
• 2 renal arteries
• One normal and one low
o Associations
• Vertebral segmentation anomalies
• Sacral agenesis
• Spina bifida
• Causes of unilateral empty renal fossa
o Unilateral renal agenesis (54%)
o Pelvic kidney (37%)
o Horseshoe kidney (5%)
o Crossed renal ectopia (4%)

MR Findings
• May be modality of choice with oligohydramnios
• Helpful for differential diagnosis

• Excellent prognosis when isolated
• Uterine anomalies associated with renal anomalies,
especially renal agenesis

Diagnostic Checklist
•
•
•
•
•

Empty renal fossa is not always renal agenesis
Horseshoe kidney may be missed if isthmus is thin
Measure normal kidney if only one kidney found
Compensatory hypertrophy suggests agenesis
ormal bladder/amniotic
fluid important prognostic
indicators
o Large field-of-view
• Better able to find pelvic kidney
o Improved contrast in some cases
• Fibrous isthmus of horseshoe kidney
• Pelvic kidney vs. bowel

Imaging Recommendations
• Best imaging tool
o Careful assessment of renal fossa
• Axial and longitudinal views
o Renal morphology assessment
• Look for fusion
• Protocol advice
o Look in fetal pelvis if one kidney missing
o Use color Doppler to find renal arteries
o Consider MR if visualization is limited
o Look at renal orientation on coronal view
• Horseshoe kidney lower poles point medial

I DIFFERENTIAL DIAGNOSIS
Normal adrenal gland
• Prominent in early 2nd trimester
o May be mistaken for kidney
• Globular morphology if kidney absent
• "Laying down" adrenal
o Long axis parallel to spine

Severe oligohydramnios

(normal kidneys)

• Poor visualization mimics agenesis
o Consider MR
• Color Doppler
o Identify renal arteries
• Amnioinfusion
o Saline placed in uterus
o Improve visualization for sake of diagnosis

Renal cystic dysplasia
• Multifactorial etiology
o Obstructive
o Multicystic dysplastic kidney
o Aneuploidy

RENAL DEVELOPMENTAL
o Syndromic
• Often results in small kidney
o May mimic renal agenesis
• Acute cystic dysplasia with bizarre morphology
o Lose reniform shape
• Mimics fused kidneys

Renal or adrenal mass
• Rare in prenatal life
• Mesoblastic nephroma most common
o Solid, large, homogeneous mass
o Indistinct margins
• Neuroblastoma
o Adrenal mass
o Displaces normal kidney inferiorly

I PATHOLOGY
General Features
• Genetics
o Aneuploidy/syndromes
common if other anomalies
o Turner syndrome
• Horseshoe kidney + other anomalies
• Etiology
o Normal renal embryology
• Kidneys arise from metanephric blastema (MB)
• MB develops on either side of dorsal body wall
• Ureter bud (UB) arises from mesonephric ducts
• UB penetrates MB + induces kidney formation
• UB divides into collecting system and ureter
• Kidneys ascend at 6-9 wks
• Kidneys function by 10 wks
o UB fails to reach MB
• Renal agenesis
o Failure/poor ascent
• Pelvic kidney
• Horseshoe kidney
o Fusion of MB
• Crossed fused ectopia
• Horseshoe kidney
o MB or UB cross midline
• Ectopic kidney
• Epidemiology
oM> F
o Horseshoe kidney
• 1:400 in general population
o Pelvic kidney
• 1:700
o Unilateral renal agenesis
• 1:1,000
o Crossed renal ectopia
• 1:7,000

• Suggests bilateral process
• Anomaly + obstruction

Natural History & Prognosis
• Long term complications
o Infection
o Obstruction
o Stones
o Vesicoureteric reflux
• Unilateral renal agenesis
o t Renal insufficiency and proteinuria
o 50% develop hypertension as adults
• Horseshoe kidney
o Excellent prognosis when isolated
o Often with other genitourinary anomalies
• Hypospadias/cryptorchidism
• Duplex collecting system

Treatment
• Postnatal ultrasound to confirm diagnosis
o Include uterus in females
• Uterine anomalies associated with renal
anomalies, especially renal agenesis
• Treatment for complications

I DIAGNOSTIC

ISSUES

Image Interpretation

I SELECTED
1.

2.

3.

4.

6.

Presentation
• Most common signs/symptoms
o Isolated anomaly
• Incidentally noted during anatomic survey
o Often associated with other anomalies
• Other signs/symptoms
o Oligohydramnios

CHECKLIST
Pearls

• Empty renal fossa is not always renal agenesis
o Look for pelvic kidney
o Look on opposite side for ectopic kidney
• Horseshoe kidney may be missed if isthmus is thin
o Better clue may be lower pole medial orientation
• Routinely obtain longitudinal views of kidneys
o Adrenals mimic kidney on axial views
• Measure normal kidney if only one kidney found
o Compensatory hypertrophy suggests agenesis
• Normal bladder/amniotic
fluid important prognostic
indicators

5.

I CLINICAL

VARIANTS

7.
8.

REFERENCES

Cassart M et al: Complementary
role of MRI after
sonography
in assessing bilateral urinary tract anomalies in
the fetus. AJR Am J Roentgenol.
182(3):689-95,
2004
Yuksel A et al: Sonographic
findings of fetuses with an
empty renal fossa and normal amniotic fluid volume. Fetal
Diagn Ther. 19(6):525-32,
2004
Hill LM et al: Fetal compensatory
renal hypertrophy
with a
unilateral functioning
kidney. Ultrasound
Obstet Gynecol.
15(3):191-3,2000
Strauss S et al: Sonographic
features of horseshoe kidney:
review of 34 patients. J Ultrasound
Med. 19(1):27-31,2000
Dillon E et al: A 10 year audit of antenatal
ultrasound
detection of renal disease. Br J Radiol. 71(845):497-500,
1998
James CA et al: Antenatally
detected urinary tract
abnormalities:
changing incidence and management.
Eur J
Pediatr. 157(6):508-11,
1998
Seeds JW: Borderline genitourinary
tract abnormalities.
Semin Ultrasound
CT MR. 19(4):347-54,
1998
DeVore GR: The value of color Doppler sonography
in the
diagnosis of renal agenesis. J Ultrasound
Med. 14(6):443-9,
1995

RENAL DEVELOPMENTAL VARIANTS
IIMAGE GALLERY
(Left) Axial ultrasound
through the fetal flank shows
a single kidney (arrows).
Open arrow points to the
spine. A careful search for a
second kidney ensued.
(Right) Coronal oblique
ultrasound shows a second
kidney in the pelvis (arrows)
above the partially filled
bladder (open arrmv). Pelvic
kidneys are often eMf/cult to
see and the (etus may be
misdiagnosed
as having only
one kidney.

Typical
(Left) Coronal oblique
ultrasound shows a
horseshoe kidney (arrows).
The inferior poles of the
kidneys are connected by an
isthmus (open arrows) of
renal tissue. These kidneys
are also echogenic from
cystic dysplasia and the fetus
had multiple other anomalies
as well. (Right) Coronal gross
pathology nicely shows the
horseshoe morphology. The
ureters (arrows) arise
medially and travel anterior
to the isthmus.

Typical
(Left) Axial ultrasound sholl's
only one kidney (arrows).
Postnatal ultrasound of the
pelvis shows a duplicated
uterus (open arrmvs point to
two endometrial canals).
Uterine duplication
anomalies are associated
with unilateral renal
agenesis. (Right) Coronal
color Doppler ultrasound
shows unilateral renal
agenesis. Only one renal
artery (arrow) arises from the
aorta. Open arrows point to
the single kidney.

DUPLICATED COLLECTING SYSTEM

Graphic shows a duplicated left-sided collecting system.
The upper pole moiety is obstructed, with ureteral
dilatation and an ectopic ureterocele that herniates into
the bladder lumen.

Coronal ultrasound of a duplicated kidney shows a
band of renal parenchyma (open arrow) separating the
upper and lower poles. Both moieties are dilated, the
upper from obstruction and the lower from reflux.

ITERMINOlOGY

Ultrasonographic

Definitions

• Kidney
o Asymmetric renal size
• Affected kidney larger than contralateral side
• Unilateral renal enlargement may be only clue
that duplication is present
o Dilatation of upper pole collecting system
• May appear "cyst-like"
o Reflux can intermittently dilate lower pole
o Severe obstruction may result in dysplastic changes
• Upper pole parenchyma may be replaced with
large cysts that displace lower pole
• Cysts may shrink over time -+ kidney starts to
appear more normal
• Ureters
o Often dilated
• Ectopic: Dilated from obstruction
• Normotopic: May be dilated from reflux
o Ectopic ureter: Most commonly inserts into bladder
o Extravesicular insertion sites also possible
• Ejaculatory ducts
• Vas deferens
• Epididymis
• Seminal vesicles
• Uterus
• Vagina
• Urethra (least common)

• Renal collecting system split into separate upper and
lower pole moieties

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Dilatation of upper pole
collecting system + ureterocele is diagnostic
• Upper and lower pole moieties separated by band of
renal parenchyma
• Two separate ureters drain upper and lower poles
o Upper pole drained by ectopic ureter
• Ureterocele usually present at distal end
• Ureter often dilated from obstruction
o Lower pole drained by normotopic ureter
• Ureterovesical junction of normotopic ureter
distorted by ectopic ureterocele
• Vesicoureteral reflux may occur
• Contralateral duplication in 10-20%
• Weigert-Meyer rule
o Ectopic ureter inserts inferior and medial to
normotopic ureter, in trigone of bladder
o Upper pole obstructs
o Lower pole refluxes

DDx: Renal Duplication

UP} Obstruction

Mesoblastic Nephroma

Findings

DUPLICATED COLLECTING SYSTEM
Key Facts
Terminology
• Renal coli ting y tern plit into
lower pole moieti s

Top Differential
eparate upper and

• Ureteropelvic
• Reflux

Imaging Findings

Pathology

• Be t diagno tic clue: Dilatation of upp r pole
collecting system + ureterocele i diagno tic
• Upper and lower pole moieties separat d by band of
r nal parenchyma
• Upp r pole drained by ectopic ureter
• Lower pole drained by normotopic ureter
• Ectopic ur ter in erts inferior and medial to
normotopic ureter, in trigone of bladder
• E aluate kidney in both transv r e and longitudinal
plan s
• Tran ver e view alone can lead to erroneou
diagnosis of ureteropelvic junction (UP) obstruction

•

• Bladder
o Ureterocele associated with ectopic ureter
o Ureterocele = thin-walled, "balloon-like" structure in
bladder
• Often large
• May cause bladder outlet obstruction
• May obstruct contralateral kidney
• May prolapse in and out of bladder
• Oligohydramnios can occur if ureterocele obstructs
bladder outlet

Imaging Recommendations
• Protocol advice
o Always search for other signs of duplication in
presence of hydronephrosis
• Normal lower pole moiety
• Asymmetric renal size
• Dilated ureter(s)
• Ureterocele
• Evaluate kidney in both transverse and longitudinal
planes
o Transverse views alone can lead to erroneous
diagnosis of ureteropelvic junction (UP) obstruction
o Lower pole moiety may be displaced inferiorly and
difficult to see
o Measure length
• > 95% for gestational age
• Evaluate bladder several different times during study
o Ureterocele may be misinterpreted as bladder if
bladder is empty
o Distended bladder may compress ureterocele
• Follow collecting system in real-time
o Renal pelvis -+ ureter -+ ureterocele
• Whenever one anomaly found, look for others
o Contralateral renal malformation
• May change prognosis and management
o Multiple anomaly syndromes (e.g. VACTERL
sequence)

Diagnoses

junction

ynecological
female

(UP) obstruction

abnormalitie

in 50% of affected

Clinical Issues
• Excellent prognosis with early correction
• In utero treatment not usually indicated
• omplete work-up after delivery

Diagnostic Checklist
• Alway

hydron

evaluate for duplication in pre ence of
phro i (unilateral or bilateral)

I DIFFERENTIAL
Ureteropelvic

DIAGNOSIS

junction (UPJ) obstruction

• Pelvis dilated
• Ureter not seen
• No ureterocele

Reflux
• Entire collecting system dilated
• No ureterocele
• Findings may vary between scans

Simple ureterocele
• Simple ureteroceles insert in normal location
• Not associated with renal duplication
• Not usually seen in utero

Congenital
•
•
•
•
•

megaureter

Fusiform dilatation of ureter
Hydronephrosis variable
Usually unilateral (left> right)
Mainly affects males
Normal bladder

Other causes of renal enlargement
• Multicystic dysplastic kidney
• Mesoblastic nephroma
• Beckwith Wiedemann syndrome
o Associated with omphalocele, macroglossia
• Autosomal recessive polycystic kidney disease
o Bilateral, echogenic kidneys

I PATHOLOGY
General Features
• Genetics: Sporadic
• Epidemiology
o Duplication with ectopic ureterocele
• 1:9,000 live births
o Duplication without ureterocele (partial,
incomplete)

DUPLICATED COLLECTING SYSTEM
• Ureters join into single ureter before bladder
insertion
• 1:150 in general population
• No clinical significance
o Incidence of ureterocele parallels that of duplication
• Associated abnormalities
o Gynecological abnormalities in 50% of affected
females
o Renal anomalies (including duplications) are
commonly present with other anomalies
• Embryology
o Accessory ureteric bud inserts separately into
metanephric blastema
o Ureteral bud divides or duplicates prematurely

ICLINICALISSUES
Presentation
• Most common signs/symptoms: Usually incidental
finding at routine 2nd trimester ultrasound
• Other signs/symptoms: Evaluation of hydronephrosis

Natural History & Prognosis
• Prognosis depends on degree of renal damage from
reflux and obstruction
• Prenatal diagnosis decreases risk of urosepsis and renal
damage
o Obstructed upper pole moiety prone to infection
due to urinary stasis
• When diagnosis is known prophylactic antibiotics
administered from birth
• Decreases rate of neonatal urinary tract infection
• Improved outcome with prenatal vs. postnatal
diagnosis
o Much lower incidence of preoperative infection
o Much lower recurrent infection after correction
o Higher rate of resolution of reflux
o Younger age at correction
• Early surgical intervention preserves renal function
o Excellent prognosis with early correction
• If not diagnosed in utero, duplication with
obstruction/reflux
usually presents in infancy
o Recurrent urinary tract infections
o Hydronephrosis
o Urinary retention
o Unsuccessful toilet training in girls, epididymitis in
boys
• From ectopic insertion

o Radionuclide renal scan to assess renal function
o Intravenous pyelogram not usually necessary
• Delayed nephrogram and pyelogram of upper pole
moiety due to obstruction
• Helpful to evaluate extravesicular ectopic ureteral
insertion sites
o MR

• May be helpful in complex cases
• Useful in females to evaluate associated
gynecological abnormalities
• Postnatal surgical options based on severity of
abnormality
o Endoscopic incision of ureterocele
• Particularly if infected or obstructed
• May convert obstructing ureterocele into refluxing
one
o Ureteral reimplantation
• Ureteroureterostomy
• Ureteropyelostomy
o Heminephroureterectomy
• Performed if poorly functioning upper pole

I DIAGNOSTIC
Consider

• Always evaluate for duplication in presence of
hydronephrosis (unilateral or bilateral)
• Postnatal MR in females to search for associated
gynecological malformations

Image Interpretation

Pearls

• Dilated upper pole moiety + cystic mass in bladder is
diagnostic for duplication + ureterocele
• Majority of duplicated kidneys are> 95th percentile in
length

I SELECTED REFERENCES
1.

2.

3.

4.

Treatment
• In utero treatment not usually indicated
o Consider incision of ureterocele if causing bladder
outlet obstruction and oligohydramnios
• Complete work-up after delivery
o Urology consult
o Ultrasound of kidneys and bladder
o Voiding cystourethrogram
(VCUG) to visualize
dynamic nature of ureterocele
o "Drooping lily" sign on VCUG
• Reflux into lower pole moiety via normotopic
ureter
• Obstructed upper pole moiety pushes lower pole
calyces inferiorly

CHECKLIST

5.

6.

7.

8.

Chertin B et al: Does prenatal diagnosis influence the
morbidity associated with left in situ nonfunctioning
or
poorly functioning renal moiety after endoscopic puncture
of ureterocele? J Urol. 173(4):1349-52,2005
Gundeti MS et al: Renal outcome following
heminephrectomy
for duplex kidney. J Urol.
173(5): 1743-4, 2005
Davidovits M et al: Unilateral duplicated system:
comparative length and function of the kidneys. Clin Nucl
Med. 29(2):99-102, 2004
Urn DJ et al: Clinical characteristics and outcome of
hydronephrosis detected by prenatal ultrasonography. J
Korean Med Sci. 18(6):859-62, 2003
Whitten SM et al: Accuracy of antenatal fetal ultrasound in
the diagnosis of duplex kidneys. Ultrasound Obstet
Gynecol. 21(4):342-6, 2003
Vergani P et al: Accuracy of prenatal ultrasonographic
diagnosis of duplex renal system. J Ultrasound Med.
18:463-7, 1999
Kang AH et al: Antenatal ultrasonographic
development of
ureteroceles. Implications for management. Fetal Diagn
Ther. 13:157-61, 1998
Abuhamad AZ et al: Renal duplication anomalies in the
fetus: clues for prenatal diagnosis. Ultrasound Obstet
Gynecol. 7(3):174-7, 1996

DUPLICATED

COLLECTING

SYSTEM

IIMAGE GALLERY
(Left) Coronal ultrasound of
a renal duplication shows
hydronephrosis of the upper
pole moiety (arrow). There is
mild caliectasis in the lower
pole (open arrow). This
finding should prompt a
search for an associated
ureterocele. (Right) Axial
ultrasound shows a
ureterocele as a thin-walled,
cystic lesion (arrow) within
the lateral aspect of the
bladder.

(Left) Ultrasound shows
dilatation of the upper
calyces (arrows), which
prompted a careful
evaluation of the bladder,
where a ureterocele (curved
arrow) was identified.
(Right) Axial image through
the upper pole of the kidney
(top) shows dilatation of the
pelvis (calipers). This could
easily be mistaken for a UP}
obstruction unless
longitudinal views are
obtained. A coronal view
(bottom) shows a duplicated
kidney (calipers).

(Left) Coronal ultrasound
shows marked dilation of the
upper pole moiety (arrow),
displacing the minimally
dilated lower pole (open
arrow). The lower pole may
not be visible if upper pole
hydronephrosis is severe.
(Right) Cross pathology from
a similar, case shows severe
parenchymal thinning in the
upper pole (arrow) from
obstruction, with mild
dilatation of a lower pole
calyx (open arrow).

MILD PELVIECTASIS

Axial ultrasound shows bilateral pelviectasis in a fetus
with trisomy 27. The renal pelves are distended with
urine (arrows) and measure greater than 4 mm. Note
the lack of calyceal distention.

ITERMINOLOGY
Abbreviations

and Synonyms

• Mild pelviectasis (MP)
• Pyelectasis
• Transient hydronephrosis

Definitions
• Renal pelvis distended with urine

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Enlarged fluid-filled renal pelvis
• No caliectasis (distension of renal calyces)
o Renal pelvis diameter (RPD) > 4 mm (2nd trimester)
• RPD = Anteroposterior (AP) diameter of pelvis
o RPD > 7 mm (3rd trimester)
• Location
o Most often bilateral
oR> L when unilateral

Ultrasonographic

Findings

• Normal 2nd/3rd trimester kidney
o Echogenicity
• Renal parenchyma initially homogeneous

Axial ultrasound through the fetal heart in the same
fetus, with trisomy 27, shows lack of central valvular
structures (arrow), consistent with AV canal. In fetuses
with T27, MP is uncommonly an isolated finding.

• Hypoechoic pyramids can mimic caliectasis
• Echogenic renal hilum
o Transverse kidney view
• Axial view through spine and flank
• Two symmetric kidneys easily seen
• Best view to measure RPD
• Normal RPD < 3 mm
o Longitudinal views
• Sagittal and coronal kidney views
• Best view to rule out calicectasis
• Can measure renal length
o Renal vessels at hilum can mimic pelviectasis
• Color Doppler helpful
• Mild pelviectasis
o Fluid-filled renal pelvis
• "Ballooned" renal pelvis
o Measure RPD on axial image
o Longitudinal views helpful
• Rule out hydronephrosis
• Look for distended ureter
• Ultrasound criteria for MP diagnosis
o RPD should not measure> 0.28 renal diameter
o RPD criteria for diagnosis of MP
• > 3 mm in first trimester
• > 4 mm at 14-22 wks
• > 5 mm at 22-32wks
• > 7 mm after 32 wks
• > 10 mm always pathologic

DDx: Hydronephrosis

UP}

UP}

Renal Duplication

PUV

MILD PELVIECTASIS
Key Facts
Terminology

Top Differential

• Mild P lviectasis (MP)
• Pyelectasis

• Ureteropelvic junction (UP)) obstruction
• Lower tract obstruction
• Renal hilum ve el

Imaging Findings
• Enlarged fluid-filled renal pelvis
•
0 caliectasis (distension of renal calyces)
• Renal pelvi diameter (RPD) > 4 mm (2nd trimester)
• RPD > 7 mm (3rd trimester)
• Mo t often bilateral
• RPD hould not measure> 0.28 renal diameter
• > 10 mm always pathologic
• 3% of normal fetuses have MP
• MP is minor marker for tri omy 21 (T21)
• May progress to hydronephrosis
• Repeat can in 4 weeks to look for progression

• MP most often transient and idiopathic
o 3% of normal fetuses have MP
o MP most often resolves or remains stable
• MP is minor marker for trisomy 21 (T21)
o 1.6x t risk when MP seen (14-22 wk)
• Compare with maternal baseline risk
o Look for other T21 markers
• t Nuchal fold
• Echogenic bowel
• Echogenic intracardiac focus
• Short femur/humerus
o Look for associated T21 major anomalies
• MP and other genetic disorders
o MP rarely isolated finding
o Trisomy 13
• Holoprosencephaly
is hallmark finding
o Turner syndrome
• Cystic hygroma is hallmark finding
o Other rare genetic disorders
• Translocations, XXX, trisomy 8
• Decision for amniocentesis
o Rarely indicated for isolated MP
• Assess maternal baseline risk
o Often indicated with 2 minor markers
• Example: MP + echogenic bowel
o Often indicated for MP + major anomaly
• May progress to hydronephrosis
o More likely if unilateral or asymmetric MP
o Obstructive causes
• Ureteropelvic junction obstruction
• Ureterovesicle junction obstruction
• Ureterocele
• Bladder outlet obstruction
o Vesicoureteral reflux
o Duplex kidney
• Upper moiety with ureterocele
• Lower moiety with reflux

Imaging Recommendations
• Best imaging tool
o Routine renal views at screening ultrasound
• Obtain axial + longitudinal views in every case
• 18-20 wks common time for diagnosis of MP

Diagnoses

Pathology
• 0.46% fetuse

with isolated MP have aneuploidy

Clinical Issues
• Prognosis dep nds on degree of pelviectasis
• Postnatal follow up if RPD > 7 mm after 32 wk

Diagnostic Checklist
• Most case of MP are transient and idiopathic
• Postnatal work up e sential if MP persi t /progres e
• Increased ri k of sub equent fetus also having MP

• Protocol advice
o Rule out hydronephrosis when MP is seen
• Look carefully for caliectasis
• Look for distended ureter
• Look for normal bladder filling and emptying
o Follow-up ultrasound
• Repeat scan in 4 weeks to look for progression
• Most resolve
• Some progress to hydronephrosis and require
postnatal evaluation
o Look carefully for additional anomalies
• At time of diagnosis and at follow-up
o Consider amniocentesis
• Determine maternal risk for aneuploidy

I DIFFERENTIAL
Ureteropelvic

DIAGNOSIS

junction (Upn obstruction

• Obstruction at junction of ureter and renal pelvis
• Most common cause of congenital hydronephrosis
• Renal pelvis distention
o May be massive
• Calyceal distention variable
• Rarely presents early as MP

Lower tract obstruction
• Ureter distention
o Ureterovesicle junction obstruction
o Duplex collecting system
• Upper pole with ureterocele
• Lower pole with reflux
• Bladder outlet obstruction
o Markedly distended bladder
o Posterior urethral valves (PUV)
• Variable hydronephrosis
• +/- Ureteral distention
• +/- Renal cystic dysplasia
o Urethral atresia
• Rarely presents initially as MP

Renal hilum vessels
• Renal artery and vein

MILD PELVIECTASIS
• Linear anechoic structures at renal hilum
o May mimic MP
• Color Doppler shows flow

I PATHOLOGY
General Features
• Genetics
o Minor marker for aneuploidy
• T21 most common
o Possible genetic predisposition for MP
• 2/3 will have another fetus with MP
• Etiology
o Physiologic factors influencing RPD
• Maternal hydration
• Full fetal bladder
o Extrarenal pelvis
• Renal pelvis located outside of hilum
• Considered normal variant
o Vesicoureteral reflux
• Epidemiology
o 3% of normal fetuses have MP
o 1.7% of all fetuses with MP have aneuploidy
o 0.46% fetuses with isolated MP have aneuploidy
o Recurrence risk is 6.1
• 6.1x t risk that subsequent fetus will have MP

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Seen at time of genetic sonogram
• Sonographer searching for T21 markers
• +/- Other markers
• +/- Major anomalies
o Incidental finding in low-risk patient
• Other signs/symptoms
o t Maternal serum alpha-fetoprotein
(AFP)
• Etiology unknown

Demographics
• Age
o Isolated MP and maternal age
• > 36 yo; 1:45 risk for aneuploidy (2.2%)
• < 36 yo; 1:303 risk for aneuploidy (0.33%)
• Gender: M:F = 2:1

Natural History & Prognosis
• Prognosis depends on degree of pelviectasis
o MP > 4mm but < 7 mm
• 80% resolve antenatally
• 17% resolve postnatally
• 3% need postnatal work-up
o MP> 7 mm
• Rarely resolve antenatally
• 44% resolve postnatally
• MP ...•hydronephrosis antenatally
o t Likelihood postnatal uropathy
• Obstruction
• Reflux
• Duplex kidney

Treatment
• Postnatal follow up if RPD > 7 mm after 32 wks
o Follow-up ultrasound
• Not earlier than 72 hrs after birth
• Neonatal dehydration minimizes obstruction
o Voiding cystourethrogram
• Rule out reflux
o Renal nuclear medicine scan may be considered to
assess function
• Obstructive lesions often need surgical intervention

I DIAGNOSTIC

CHECKLIST

Consider
• Assess maternal risk for aneuploidy
o Maternal age
o Serum screening biochemistry results

Image Interpretation

Pearls

• Most cases of MP are transient and idiopathic
o Measure RPD when fetal bladder is empty
• Some cases of MP are associated with aneuploidy
o Determine if MP is isolated finding
o Determine maternal risk profile
• Use "hydronephrosis" term sparingly
o Renal pelvis + calyceal distention
o Often obstructive process
• Any amount of cali ectasis is abnormal
o More suggestive of obstruction than MP alone
• Follow-up antenatal ultrasound after 32 wks
o Postnatal work-up not necessary if RPD < 7 mm
o Reduce number of postnatal tests
• Postnatal work up essential if MP persists/progresses
o Renal function preservation depends on early
diagnosis of renal obstruction/reflux
• Increased risk of subsequent fetus also having MP

I SELECTED
1.

2.

3.
4.

5.

6.

REFERENCES

Signorelli M et al: Prenatal diagnosis and management of
mild fetal pyelectasis: implications for neonatal outcome
and follow-up. Eur J Obstet Gynecol Reprod BioI.
118(2):154-9, 2005
Damen-Elias HA et al: Variability in dilatation of the fetal
renal pelvis during a bladder filling cycle. Ultrasound
Obstet Gynecol. 24(7):750-5, 2004
John U et al: The impact of fetal renal pelvic diameter on
postnatal outcome. Prenat Diagn. 24(8):591-5, 2004
Odibo AO et al: Prenatal mild pyelectasis: evaluating the
thresholds of renal pelvic diameter associated with normal
postnatal renal function. J Ultrasound Med. 23(4):513-7,
2004
Chudleigh PM et al: The association of aneuploidy and
mild fetal pyelectasis in an unselected population: the
results of a multicenter study. Ultrasound Obstet Gynecol.
17(3):197-202,2001
Chudleigh T: Mild pyelectasis. Prenat Diagn.
21(11):936-41,2001

MILD PELVIECTASIS
IIMAGE GAllERY
Typical
(Left) Axial ultrasound shows
bilateral, mild pelviectasis in
a fetus with normal
chromosomes.
The kidneys
are located on either side of
the spine (open arrow) and
the fluid-filled renal pelves
(arrows) are easily seen.
(Right) Sagittal ultrasound
confirms that only the renal
pelvis (arrows) is distended.
Hypoechoic
renal pyramids
(open arrows) should not be
confused with calyceal
distention.

(Left) Axial ultrasound shows
second trimester isolated
mild pelviectasis (arrows).
Follow-up ultrasound was
recommended.
(Right) Axial
(upper) and sagittal (lower)
images at 32 wks shows the
right MP resolved (curved
arrow) but the left
progressed to
hydronephrosis.
The left
renal pelvis (arrows) and
calyces (open arrows) are
clearly distended. Postnatal
ultrasound confirmed
hydronephrosis
from UP}
obstruction.

(Left) Axial ultrasound shows
mild pelviectasis (arrows) in
a fetus with trisomy 73. The
kidneys are also slightly
enlarged and echogenic.
(Right) Sagittal ultrasound of
the face in the same fetus
shows a premaxillary" mass"
(arrow) secondary to
bilateral cleft lip and palate.
A cardiac anomaly was also
seen. Although MP is
associated with trisomy 13, it
is almost never an isolated
finding.

URETEROPELVIC JUNCTION OBSTRUCTION

Sagittal graphic
shows
focal narrowing
at the
ureteropelvic junction (arrow) causing renal pelvis and
calyceal dilatation. Notice the abrupt transition between
the distended renal pelvis and the ureter.

ITERMINOlOGY
Abbreviations

and Synonyms

• Ureteropelvic junction (UP]) obstruction
• Pelviureteric junction obstruction
• Congenital hydronephrosis

Definitions
• Renal pelvis obstruction
o At point where pelvis meets ureter

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Hydronephrosis
hydroureter or bladder dilatation
• Location: 10% bilateral

Ultrasonographic

without

Findings

• Moderate to severe hydronephrosis
o Dilated renal pelvis
• Hallmark finding
• Central renal fluid collection
• Can become massive
o Caliectasis
• Distended renal calyces
• May appear cyst-like

Sagittal ultrasound shows a UP! obstruction in a second
trimester fetus. The renal pelvis (curved arrow) and
calyceal (arrows) distention ends abruptly at the ureteral
junction. Open arrows point to the adrenal gland.

• Calyces connect with renal pelvis
• Seen best on sagittal views
o Enlarged kidney
• Follow renal length
• +/- Cortical thinning
• Distention ends abruptly at UP]
o Blunted or "bullet nosed" renal pelvis
• Seen best on coronal view
o Normal ureters
• < 2 mm, if seen at all
o Normal bladder if UP] obstruction is unilateral
• Fills and empties every 20-30 minutes
• Thin wall
o Small or absent bladder with bilateral UP]
obstruction
• Renal pelvis measurement
o Kidney imaged in transverse plane
• Renal pelvis anteroposterior (AP) diameter
o Renal pelvis AP diameter, diagnostic criteria
• Variable numbers given in literature
• ~ 10 mm always considered abnormal
• ~ 7 mm after 33 wks needs follow-up
• ~ 4 mm before 20 wks needs follow-up
• Renal pelvis/kidney ratio> 0.28
• Caliectasis abnormal, regardless of AP diameter
• Secondary renal dysplasia
o Obstruction causes renal damage
o t Renal echogenicity

DDx: Hydronephrosis

Renal Pyramids

Pelviectasis

MCDK

MCDK

URETEROPELVIC JUNCTION OBSTRUCTION
Key Facts
•

Terminology
•

ongenital

hydronephro

is

Imaging Findings
• Be t diagno tic clue: Hydronephro i without
hydroureter or bladder dilatation
• Oi tention end abruptly at UPj
• Bilateral UPj ob truction in 10%
• ontralateral renal abnormality in 25%
• Extrar nal anomalie in 10%
• Polyhydramnios in 1/3
• Oligohydramnio
if ob truction is bilateral and severe

Top Differential

Diagnoses

• Multicy tic dysplastic kidney (M OK)
• Bladder or ureter obstruction
• Mild renal pelviectasis

•

•

•

•
•

• Microscopic cysts
o Macroscopic renal cysts
• Most often cortical
Urinoma
o Fluid adjacent to obstructed kidney
• Obstruction may be relieved by leak
o Rare finding
o Seen with severe obstruction only
Bilateral UPj obstruction in 10%
o +/- Oligohydramnios
o Fetus at risk for pulmonary hypoplasia
• Severe early obstruction
Contralateral renal abnormality in 25%
o Renal agenesis
o Renal cystic dysplasia
o Vesicoureteric reflux
Extrarenal anomalies in 10%
o No specific associations
Amniotic fluid
o Most often normal
o Polyhydramnios in 1/3
• Impaired renal concentrating ability
• t Urine output
o Oligohydramnios
if obstruction is bilateral and
severe

Imaging Recommendations
• Best imaging tool
o Adequate renal imaging in 2nd/3rd trimester
• Axial + longitudinal views
• Protocol advice
o Hydronephrosis needs follow-up
• Every 4-6 wks
• Follow AP diameter of renal pelvis
o Look for obstructive cystic dysplasia
• Suggests significant renal damage
o Recommend postnatal renal ultrasound
• Wait at least 72 hours after delivery
• Relative dehydration in immediate newborn
period minimizes hydronephrosis

ormal renal pyramids

Pathology
• Isolated UPj obstruction not a sociated with
aneuploidy
• 1/3 of UPj obstruction
have an a cessory cros ing
vessel
• 1:2,000 live births

Clinical Issues
• Overall excellent prognosi
• t Risk of renal impairment if prenatal
10mm
• Ultrasound> 72 hrs after delivery
• Prenatal intervention rarely indicated

P diameter>

Diagnostic Checklist
• UPj obstruction

often

I DIFFERENTIAL

ro ressive

DIAGNOSIS

Multicystic dysplastic kidney (MCDK)
• Kidney tissue replaced by cysts
o Cysts do not communicate
o Reniform shape often lost
• Large kidney in fetal life
o Atrophy with time
• May be sequelae of early obstruction
• Poor or absent renal function
• "Hydronephrotic form" of MCDK can mimic UPj
obstruction
o Large central cyst + cortical cysts
o Cysts do not communicate

Bladder or ureter obstruction
• Distended ureter
o Serpiginous, redundant morphology
• Can mimic MCDK or hydronephrosis
o Ureterovesicle junction obstruction (UVj)
• +/- Ureterocele
o Duplicated ureter
• Superior ureter with ureterocele
• Inferior ureter with reflux
o Vesicoureteral reflux
• Diagnosis rarely made prenatally
• Bladder outlet obstruction
o Enlarged bladder
• Often thick-walled
o Posterior urethral valves
• Look for distended urethra
• "Key-hole" morphology
o Urethral atresia
• Variable degrees of hydronephrosis

Mild renal pelviectasis
• Mild renal pelvis distention
o > 4 mm before 22 wks
o Often bilateral
o No calyceal distention

in 2nd trimester

• Often idiopathic and non-obstructive
o Seen in 2-3% of prenatal cases

URETEROPELVIC JUNCTION OBSTRUCTION
• Minor marker for aneuploidy
o Trisomy 21 most often
o Look for other markers/anomalies
o Rarely an isolated finding in low-risk patients
• May progress to UP] obstruction
o Follow-up ultrasound

Normal renal pyramids
• Hypoechoic parenchymal structures
o Triangular more than round
• Can mimic hydronephrosis
o Do not confuse with calyces
• Pyramids superficial to calyces
• Pyramid "point" ends in calyx

I PATHOLOGY
General Features
• Genetics
o Sporadic
o Isolated UP] obstruction not associated with
aneuploidy
• Etiology
o Abnormal interwoven muscularis layer of wall
• Impairs distensibility
o 2° to crossing vessel
• 1/3 of UP] obstructions have an accessory crossing
vessel
• Vessel lies anterior to UP]
• Perhaps leaves fibrous scar
o Abnormal neural innervation at UP]
• "Hirschsprung equivalent"
• Epidemiology
o 1:2,000 live births
o M>F
• Associated abnormalities
o 25% with contralateral renal anomaly
o 10% with bilateral UP] obstruction
o 10% with non-genitourinary anomalies

Gross Pathologic & Surgical Features
• Junction of pelvis with ureter usually patent
o Complete atresia rare

o Abdominal mass
o Urinary tract infection
o Hematuria
o Abdominal or flank pain
• Neonatal work-up
o Ultrasound> 72 hrs after delivery
o Nuclear medicine renal scan for renal function
o Voiding cystourethrogram to evaluate for reflux
• CT angiography
o Look for crossing renal artery
• Finding affects treatment plan
o Replaced digital subtraction angiography

Treatment
• Prenatal intervention rarely indicated
• Corrective surgery if renal function impaired
o Pyeloplasty
• Open surgery
• Resection of narrow UP] segment
'0 Endoscopic surgery
• Endopyelotomy
• Must know if crossing vessel present
o Percutaneous drainage
• Temporizing measure
• Infection control
• Postnatal follow-up
o Pelviectasis persists for years
• Even with successful surgery
o Follow renal growth
• Suggests successful therapy
o Nuclear medicine renal scans
• Assess renal function
• Assess renal drainage

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Severe UP] obstruction may look like renal cysts
o Document that "cysts" connect with renal pelvis
• Obtain follow-up ultrasound
o UP] obstruction often progressive

I SELECTED REFERENCES

I CLINICAL

ISSUES

Presentation

1.

2.

• Most common signs/symptoms
o Incidental finding
o In association with contralateral renal anomaly
o In association with amniotic fluid abnormality

3.

Natural History & Prognosis

4.

• Overall excellent prognosis
• t Risk of renal impairment if prenatal AP diameter>
10 mm
• Factors associated with poor prognosis
o Bilateral renal anomalies
o Early oligohydramnios
• Pulmonary hypoplasia
o Other (non-genitourinary) anomalies
• Postnatal symptoms

5.
6.

7.

De 5iati M et al: Congenital
ureteropelvic
junction
obstruction:
definition
and therapy. Arch Ital Urol Androl.
77(1):1-4,2005
Carr MC: Prenatal management
of urogenital disorders.
Urol Clin North Am. 31(3):389-97,
vii, 2004
Csaicsich D et al: Management
of congenital
hydronephrosis
with ureteropelvic
junction obstruction:
the Vienna-AKH experience
1986-2001. Wien Klin
Wochenschr.
116(21-22):725-9,2004
Csaicsich D et al: Upper urinary tract: when is obstruction
obstruction?
Curr Opin Urol. 14(4):213-7,2004
Kraus 51: Genitourinary
imaging in children. Pediatr Clin
North Am. 48:1381-424,
2001
junction obstruction:
use of
Rouviere 0 et al: Ureteropelvic
helical CT for preoperative
assessment--comparison
with
intraarterial
angiography.
Radiology. 213(3):668-73,
1999
Anderson N et al: Detection of obstructive
uropathy in the
fetus: Predictive value of sonographic
measurements
of
renal pelvic diameter at various gestational
ages.
A1R.164:719-23,1995

URETEROPELVIC JUNCTION OBSTRUCTION
I IMAGE GALLERY
Typical
(Left) Coronal ultrasound
shows bilateral UPI
obstruction. The renal pelves
(arrows) communicate with
the calyces (open arrows). In
this case, the amniotic fluid
volume was normal. UPI
obstruction is bilateral in
70% of cases. (Right)
Coronal CECT urography
shows obstructive linear
bands at the UPI (arrows) in
a child with bilateral
hydronephrosis. Typically,
UPI obstruction is not
complete.

Typical
(Left) Axial ultrasound shows
severe UPlobstruction
presenting as an abdominal
cyst. With careful scanning,
"budding cysts",
representing calyces, can
often be seen. (Right) CECT
shows severe UP;
obstruction in the neonate.
There is massive distention of
the renal pelvis (arrows) and
calyces (open arrows) as
well as significant renal
cortical thinning.

(Left) Axial ultrasound shows
a UPI obstruction (arrows) of
one kidney and cystic
dysplasia of the other (open
arrows point to the
echogenic, cystic kidney).
The bladder (curved arrow)
is empty and there is
oligohydramnios. (Right)
Postnatal radiograph shows
mass effect from the dilated
renal pelvis (arrows) and
bilateral pneumothoraces
(open arrows) from
pulmonary hypoplasia. The
presence of early severe
oligohydramnios is a bad
prognostic sign.

OBSTRUCTIVE CYSTIC DYSPLASIA

Axial ultrasound shows a distended urinary bladder
(curved arrow) and hydronephrosis (calipers measure
renal pelves) in a fetus with PUV Several scattered
subcortical renal cysts (arrows) suggest OCD.

Coronal gross pathology of OCD shows variable-sized
cysts within the renal parenchyma
(arrows). The
kidneys are small and dysplastic. The renal pelves and
ureters are distended from obstruction.

ITERMINOLOGY
Abbreviations
•
•
•
•

and Synonyms

Obstructive cystic dysplasia (OCD)
Cystic renal dysplasia
Obstructive uropathy
Potter type IV

Definitions

•

• Genitourinary tract (GU) obstruction - renal cysts
•

IIMAGING

FINDINGS
•

General Features
• Best diagnostic clue
o Renal macrocysts + GU obstruction
• Hydronephrosis, hydroureter, bladder distension
• Location
o Unilateral
o Bilateral
o Segmental (rare)
• From obstruction of duplicated ureter
• Morphology: Reniform shape maintained

Ultrasonographic

Findings

• Renal cysts
o Variable number of cysts

•

• None to few cysts
• Kidney completely replaced by cysts
o Variable-sized cysts
• Many small cysts
• Few large cysts
o Cortical cysts common
• "Rosary beads"
• Subcapsular cortex
Intervening renal parenchyma often discernible
o Kidney maintains reniform shape
Cortical echogenicity often increased
o Microscopic cysts
o Renal dysplasia
Renal size may be t, ~, or normal
o Enlarged kidneys
• Associated hydronephrosis
• Large cysts
o Small kidneys
• Long-standing obstruction
• Often diffusely echogenic
Urethral obstruction
o Distended bladder is cardinal finding
• +/- Bladder wall thickening
• +/- Hydroureter
o Cystic kidneys
• Small or large
• +/- Hydronephrosis
o Common causes

DDx: Renal Cysts And Mimics

MCDK

UP!

Normal Pyramids

OBSTRUCTIVE CYSTIC DYSPLASIA
Key Facts
Terminology

Pathology

•

• Obstruction => t fluid in upper tract
• Fluid retention in nephrons
• Secondary cy t formation
• yst di turb nephron/tubular
induction

y tic r nal dysplasia

Imaging Findings
•
•
•
•
•
•

Renal macrocysts + GU obstruction
ortical cysts common
Interv ning renal parenchyma often di cernible
S ver 0 D from early obstruction
Ultra ound may show OCD d velopment
Bilateral 0 D -+ oligohydramnio

Top Differential

Diagnoses

• Multicy ti dy pia tic kidney (M DK)
• I Iydron phrosis
• Renal cy tic dy plasia 2° to aneuploidy/syndrome

•

•

•

•

•

•

•

• Posterior urethral valves (PUV)
• Urethral atresia
Vesicoureteral junction obstruction
o Hydroureter
• Serpiginous morphology
• Can mimic distended bowel
• Can mimic renal cysts
o Look for ureterocele
• "Balloon-like" structure in bladder
• Associated with renal duplication
• Upper pole ureter with ureterocele
• Can be cause of partial OCD
Upper urinary tract obstruction
o Ureteropelvic junction (UP]) obstruction
• t Renal pelvis diameter
• Calyceal distention
• Bilateral in 30%
o Differentiate cysts from distended calyx
• Calyces communicate with renal pelvis
Severe OCD from early obstruction
o Innumerable cysts
• Little intervening normal kidney
• Poor renal function
o Lower GU tract obstruction
• Bilateral OCD
• Severe and early oligohydramnios
Ultrasound may show OCD development
o 1st scan shows obstruction only
o Follow-up scan shows cysts
o Cysts can grow during pregnancy
• Drainage may help preserve renal function
Most often OCD seen at time of 1st scan
o Early obstruction
• First 1/2 of pregnancy
o Worse prognosis
Endstage OCD
o Can mimic multicystic dysplastic kidney (MCDK)
• Kidney replaced by cysts
• Reniform shape lost
o No renal function
• Original hydronephrosis/hydroureter
not seen
Amniotic fluid volume is variable

Clinical Issues
•
•
•
•

Unilateral 0 D mo t often noted on routine exam
Prognosis depends on r nal function
BilateralO
D ha a grim prognosis
Antenatal cyst drainage can be considered

Diagnostic Checklist
• Look for renal cy t wh n GU obstruction diagno d
• May be impossible to differentiate OCD from M DK
• Look carefully for other anomalies once 0 D een

o Unilateral process with normal fluid
o Bilateral OCD -+ oligohydramnios
• Depends on severity of obstruction
• Kidney function

Imaging Recommendations
• Look carefully for OCD when GU obstruction seen
o Renal views
• Longitudinal
• Transverse
• Measure anterior-posterior
diameter of renal pelvis
o Adequate bladder imaging
• Size
• Wall thickness
• Voiding
o Sequential ultrasound necessary
• OCD may develop during pregnancy
• Assess amniotic fluid objectively
o Follow amniotic fluid index
• Sex determination for PUV
o Males only

I DIFFERENTIAL DIAGNOSIS
Multicystic dysplastic kidney (MCDK)
• Renal tissue replaced by cysts
o From ureter/pelvinfundibular
atresia
• < 10 weeks menstrual age
o Kidney looses reniform shape
• Associated ureter/bladder dilatation not seen
o Helps differentiate from OCD
• 90% without renal function
• Survival depends on function of contralateral kidney
o 20% bilateral MCDK
o 40% with contralateral renal anomaly

Hydronephrosis
• Renal collecting system distention
o UP] obstruction most common cause
• Distended calyces may appear "cyst-like"
• Calyces connect with renal pelvis
o Longitudinal views best

OBSTRUCTIVE CYSTIC DYSPLASIA
• Severe UP] obstruction

often associated with OCD

Renal cystic dysplasia 2° to
aneuploidy/syndromes

Demographics
• Gender: M > F

• Rarely isolated finding
• Common chromosome abnormalities
o Trisomy 18
o Trisomy 13
• Syndromes
o Meckel-Gruber syndrome
• Cystic kidneys
• Occipital cephalocele
• Polydactyly
o Tuberous sclerosis
o Von Hippel-Lindau disease

Natural History & Prognosis
• Prognosis depends on renal function
o Number of healthy nephrons
• Early vs. late obstruction
• Severity of obstruction
• Bilateral OCD has a grim prognosis
o Early oligohydramnios
• Pulmonary hypoplasia
o Severe renal insufficiency

Treatment

Autosomal recessive polycystic kidney
disease (ARPKD)
•
•
•
•

Bilateral large echogenic kidneys
No fluid filled bladder
Severe oligohydramnios
Most often fatal

Normal renal pyramids
• Hypoechoic renal parenchyma
• Adjacent to calyx

I PATHOLOGY
• Etiology
o Obstruction ~ t fluid in upper tract
o Fluid retention in nephrons
o Secondary cyst formation
o Cysts disturb nephron/tubular
induction
• J. Number of normal nephrons
• Renal dysplasia

Gross Pathologic & Surgical Features

Microscopic

• Newborn
o Ultrasound to confirm diagnosis
o Nuclear medicine renal scan
• Assess renal function
o Treat cause of GU obstruction
• Surgery for severe UP] obstruction
• Posterior urethral valves
• Ureterocele
• Antenatal cyst drainage can be considered
o J. Pressure on adjacent tissue
o J. Renal dysplasia
o Improve renal function

I DIAGNOSTIC

General Features

• Cysts are often cortical
o Form in subcapsular nephrogenic

• t Risk for aneuploidy/syndromes

zone

Features

• Cysts can develop in any portion of nephron
o Glomeruli
o Tubuli
o Collecting ducts
• Islands of normal nephrons, between cysts

Consider
• Look for renal cysts when GU obstruction
• Perform careful follow up exam

Image Interpretation

I SELECTED
1.

ISSUES

3.

Presentation
• Most common signs/symptoms
o Unilateral OCD most often noted on routine exam
• Hydronephrosis + renal cysts
• Hydroureter + renal cysts
o Bilateral OCD
• Oligohydramnios
• Distended bladder + bilateral cysts
• Small for dates
• Other signs/symptoms
o Non-GU anomalies

4.

5.

diagnosed

Pearls

• May be impossible to differentiate OCD
o Hydronephrosis/hydroureter
suggests
o May not be important to differentiate
• Similar prognosis
• Poor or no renal function for both
• Look carefully for other anomalies once
o Genetic testing recommended if OCD

2.

I CLINICAL

CHECKLIST

from MCDK
OCD

OCD seen
is not isolated

REFERENCES

Shibata S et al: Pathogenesis
of human renal dysplasia: an
alternative
scenario to the major theories. Pediatr Int.
45(5):605-9, 2003
Mercado-Deane
MG et al: US of renal insufficiency
in
neonates. Radiographies.
22(6):1429-38,
2002
Nagata M et al: Pathogenesis
of dysplastic kidney
associated with urinary tract obstruction
in utero. Nephrol
Dial Transplant.
17 SuppI9:37-8,
2002
Friedmann
W et al: Perinatal differential diagnosis of cystic
kidney disease and urinary tract obstruction:
anatomic
pathologic,
ultrasonographic
and genetic findings. Eur J
Obstet Gynecol Reprod BioI. 89(2):127-33,
2000
Poucell-Hatton
S et al: Fetal obstructive
uropathy: patterns
of renal pathology. Pediatr Dev Pathol. 3(3):223-31, 2000

OBSTRUCTIVE CYSTIC DYSPLASIA
IIMAGE

GALLERY
(Left) Coronal ultrasound
shows unilateral OCD. At
least 5 cysts (arrows) are
seen within the left kidney.
Some normal intervening
renal parenchyma
is present
(curved arrow). Calipers
measure the normal right
kidney. (Right) Axial
ultrasound through the fetal
bladder in the same case
shows a large ureterocele
(arrows). The distal ureter
"balloons" into the bladder
and causes severe
obstruction in this case.

(Left) Axial ultrasound shows
bilateral, severe OCD in a
fetus with posterior urethral
valves. Innumerable small
cysts have replaced the
kidneys (arrows), however,
subcortical cysts are most
numerous. (Right) Coronal
ultrasound in the same case
shows a markedly distended,
thick-walled urinary bladder
(open arrows) and bilateral
hydroureter (curved arrows).
Severe oligohydramnios
was
also seen.

(Left) Coronal ultrasound
shows postnatal OCD from
posterior urethral valves. The
kidney is hydronephrotic
(curved arrows point to
distended calyces) and there
are scaltered renal cysts
(arrows). (Right) Sagiltal
oblique radiograph
performed during voiding
cystourethrography
in the
same case shows a dilated
posterior urethra (arrows),
with an abrupt caliber
change at the level of the
valve (curved arrow) (open
arrow - bladder).

RENAL AGENESIS

Coronal color Doppler ultrasound shows flow in the
aorta and common iliac arteries (arrows). There are no
kidneys and no renal arteries. Note anhydramnios due
to bilateral renal agenesis.

ITERMINOLOGY
Abbreviations

and Synonyms

• Potter syndrome
o Anhydramnios associated with abnormal facies,
limb deformities

Definitions
• Absence of renal tissue
o Bilateral is lethal
o Unilateral compatible with normal life expectancy

IIMAGING

• Measure ratio of cardiac/chest circumference
o Clubfeet, other joint contractures
o Congenital heart disease in 14%
o Color Doppler
• No demonstrable renal arteries
• Unilateral renal agenesis
o Normal amniotic fluid volume
o Bladder seen to fill and empty
o One kidney seen
o May see "lying down" adrenal ipsilateral to absent
kidney
• 2 vessel cord seen with many renal anomalies

MR Findings

FINDINGS

Ultrasonographic

Cross pathology shows the typical facies in the Potter
sequence. The nose is flattened, the ears are low-set and
abnormally
folded
(black arrow) and there is
micrognathia (white arrow).

Findings

• Bilateral renal agenesis
o Anhydramnios
o "Absent" bladder
• No urine being produced, so bladder can not be
visualized
o "Lying down," flattened adrenals
• Adrenal gland does not fold into "Y"or "tricorn
hat" configuration if no kidney
• Fetal adrenal glands are relatively large, almost
same size as kidneys early in gestation
• Occupy renal fossa in absence of kidneys
o Pulmonary hypoplasia

• Normal urinary tract
o Normal kidneys well seen by 15 weeks gestation
o Renal parenchyma is intermediate signal
o Urine in collecting system is high signal on T2WI
o Adrenal glands lower signal than normal renal
parenchyma
• Signal approximates that of skeletal muscle
• Bilateral renal agenesis
o No demonstrable renal tissue
o Flattened, discoid adrenals in renal fossa
o No urine in fetal bladder
o Anhydramnios
• Unilateral renal agenesis
o One normal-appearing kidney

DDx: No Urine In Fetal Bladder

Bilateral MCDK

Severe IUGR

ARPKD Disease

Bladder TTTS Donor

RENAL AGENESIS
Key Facts
• Characteri tic facies: Broad, flattened, beaked nose,
low- et ears, receding chin, widely eparated eyes
with prominent infraorbital folds

Imaging Findings
•
•
•
•
•
•

Anhydramnio
"Absent" bladder
"Lying down," flattened adrenal
Pulmonary hypoplasia
lubfeet, other joint contracture
ongenital heart disease in ]4%

Top Differential

Clinical Issues
• Amniotic fluid volume i normal in first trimester,
even with bilateral renal agenesis
• Renal contribution to amniotic fluid is minimal
before 17 weeks
• Bilateral agenesis is lethal
• Recurrence risk 3%

Diagnoses

• Premature rupture of membranes
• Severe intrauterine growth re triction (IUGR)
• Sirenomelia

Diagnostic Checklist

Pathology
• Potter sequence (oligohydramnios
sequence)
• Physical findings secondary to lack of movement
compression by uterine wall

and

o Absence of renal tissue in contralateral renal fossa
• Perform all three scan planes to avoid false positive
diagnosis
o Check for pelvic kidney or other anatomic variant

Imaging Recommendations
• Beware pitfalls in diagnosis of bilateral renal agenesis
• Differentiate kidneys from adrenal glands
o Fetal adrenals very prominent, especially early in
gestation
• Adrenal hypertrophy described in pathologic
series of renal agenesis
o Adrenals have "ice-cream sandwich" appearance
• Echogenic adrenal medulla between layers of
hypoechoic cortex
• In renal agenesis, adrenals have flattened, discoid,
"lying down" appearance
o Kidneys do not have a layered appearance
• Kidneys are "bean-shaped" in long axis, oval or
round in cross section
• Corticomedullary differentiation is evident, with
hypoechoic pyramids (becomes more obvious
with advancing gestation)
• Color Doppler shows flow in multiple abdominal
vessels, which may be confused for renal arteries
o Celiac axis, superior mesenteric artery are present
o Adrenal arteries are present and may be enlarged
with adrenal hypertrophy
o Lumbar arteries may also be mistaken for renal
arteries
• The bladder is anatomically present but not seen when
empty
o May see small bladder containing mucus secretion
especially with MRI
• Do not mistake for urine production
• Watch for changes of bladder size and shape; if
seen, there must be some urine production
• Use endovaginal ultrasound
o Fetal kidneys can be seen as early as 12 weeks
• Consider fetal MRI
o Preferable to amnioinfusion for better anatomic
visualization
o Non-invasive

• Adrenal gland can be mi taken for kidneys
• Adrenal gland has an "ice-cr am sandwich"
appearance

• In cases of apparent unilateral agenesis
o Look for pelvic kidney
o Look for anomalous second kidney (e.g. multicystic
dysplastic)

I DIFFERENTIAL

DIAGNOSIS

Premature rupture of membranes
• Fetal bladder will fill and empty
• Kidneys present and normal
• Talk to the patient
o Can usually give history of "gush" of fluid
o Sterile speculum examination for diagnosis

Severe intrauterine
(IUGR)

growth restriction

• Kidneys present and normal
• Fetal bladder will fill and empty
• Umbilical artery Doppler likely abnormal

Sirenomelia
• Bilateral renal agenesis
• Need to look at extremities carefully
o Fused lower extremities
• Cardiac/abdominal
wall defects

Autosomal recessive polycystic kidney
disease (ARPKD)
• Kidneys present, often very large, hyperechoic

Bilateral multicystic dysplastic kidneys
• Kidneys present
• Variably-sized cysts are dominant

Differential

imaging feature

diagnosis for "absent" bladder

• No urine formation
o Either poor renal perfusion or abnormal/absent
parenchyma
• In twin twin transfusion syndrome emS) "donor"
twin shunts blood to "recipient"
• Donor renal perfusion is decreased

RENAL AGENESIS
• Decreased perfusion -+ decreased urine production
-+ "absent" bladder
o Abnormal parenchyma
• Bilateral multicystic dysplastic kidneys (MCDK)
• Bladder exstrophy
o Urine produced as usual -+ normal amniotic fluid
volume
o Bladder open to abdominal wall
• Look for soft tissue mass inferior to cord insertion
• Bladder rupture
o Urinary ascites will be present
o Usually associated with distal obstruction (e.g.
posterior urethral valves)
o Look for secondary obstructive nephropathy

I PATHOLOGY
General Features
• Genetics
o Trisomy 7, 10, 21, 22
o Branchio-oto-renal dysplasia (BaR) syndrome
• Autosomal dominant with variable expression
• Renal anomalies, including agenesis
• Deafness/malformed
ears/branchial cysts
o Cerebro-occulo-facial syndrome
• Autosomal recessive
• Micrognathia, joint contractures, renal anomalies
• Etiology
o Embryology
• Failed induction of metanephric blastema by
ureteric bud
• No nephron formation
• Epidemiology
o Bilateral 1:3,000 births
• M > F

o Unilateral 1:1,300 births
• Associated abnormalities
o Potter sequence (oligohydramnios
sequence)
• Physical findings secondary to lack of movement
and compression by uterine wall
• Characteristic facies: Broad, flattened, beaked
nose, low-set ears, receding chin, widely separated
eyes with prominent infraorbital folds
• Clubbed hands and feet
o Renal agenesis may be part of VACTERL association
• Vertebral, anorectal, cardiac anomalies,
tracheoesophageal
fistula, renal and limb
anomalies

o Survivors die of respiratory failure due to pulmonary
hypoplasia
• Longest documented survival 39 days
• Unilateral agenesis associated with
o Genital anomalies
• Males 12%: Seminal vesicle cysts
• Females 40%: Mullerian duct anomalies
o Vesicoureteric reflux in single kidney 30%
o Increased incidence of vesicoureteric/ureteropelvic
junction (UP]) obstruction
• Recurrence risk 3%
o Higher if part of multiple anomaly complex

Treatment
• Bilateral
o Offer termination
o If pregnancy progresses
• Do not monitor in labor
• Stress importance of non-intervention
at birth
• Unilateral
o Follow regularly with special emphasis on single
kidney, fluid volume
o Progressive UP] obstruction may change delivery
timing

I DIAGNOSTIC
Consider

• Any condition with early onset severe
oligohydramnios
carries poor prognosis
o Bilateral renal agenesis is lethal
o Aim to make specific diagnosis in order to counsel
parents appropriately

Image Interpretation

ISELECTED REFERENCES
1.
2.

3.

ISSUES

Presentation
• Amniotic fluid volume is normal in first trimester,
even with bilateral renal agenesis
o Renal contribution to amniotic fluid is minimal
before 17 weeks
o Fluid comes from membranes, gastrointestinal tract

5.

6.

7.

Natural History & Prognosis
• Bilateral agenesis is lethal
o 33% stillborn

Pearls

• Adrenal gland can be mistaken for kidneys
o Adrenal gland has an "ice-cream sandwich"
appearance
o Use MRI in difficult cases

4.

ICLINICAL

CHECKLIST

8.

5gro M et al: False diagnosis of renal agenesis on fetal MRI.
Ultrasound Obstet Gynecol. 25(2):197-200, 2005
Cassart M et al: Complementary role of MRI after
sonography in assessing bilateral urinary tract anomalies in
the fetus. AJRAm J Roentgenol. 182(3):689-95, 2004
Breysem Let al: The value of fast MR imaging as an adjunct
to ultrasound in prenatal diagnosis. Eur Radiol.
13(7):1538-48,2003
Kemper MJ et al: Antenatal oligohydramnios of renal
origin: postnatal therapeutic and prognostic challenges.
Clin Nephrol. 56(6):59-12, 2001
Herndon CD et al: Consensus on the prenatal management
of antenatally detected urological abnormalities. J Urol.
164(3 Pt 2):1052-6, 2000
Zeijl C et al: Clinical outcome and follow-up of
sonographically suspected in utero urinary tract anomalies.
J Clin Ultrasound. 27(1):21-8, 1999
Bronshtein M et al: The early prenatal diagnosis of renal
agenesis: Techniques and possible pitfalls. Prenat Diagn
14:291-7, 1994
McGahan JP et al: Adrenal hypertrophy: Possible pitfall in
the sonographic diagnosis of renal agenesis. J Ultrasound
Med 5:265-8, 1986

RENAL AGENESIS
IIMAGE

GALLERY
(Left) Axial T2WI MR shows
normal liver (curved arrow),
gallbladder (white arrow),
extremities (black arrows)
and cerebrospinal fluid
(open arrow) in the spinal
canal. The kidneys are
absent and there is
anhydramnios.
(Right) Axial
T2WI MR of a normal fetal
abdomen for comparison
shows obvious kidneys
(white arrows) as well as the
liver (curved arrow), spinal
canal (open arrow) and an
extremity (black arrow).

(Left) Cross pathology shows
the relatively large size of the
fetal adrenal (curved arrow)
compared to the kidney
(arrow). This can lead to the
erroneous assumption that
kidneys are present, when
the visualized tissue is
actually an adrenal gland.
(Right) Axial ultrasound
shows the fetal adrenal
glands with their "ice-cream
sandwich" appearance
(arrows), compared to the
kidneys (curved arrows),
which are more round and
have hypoechoic pyramids.

(Left) Ultrasound focused on
the fetal adrenal gland
(cursors) shows the
characteristic flattened,
"lying down" appearance
seen with renal agenesis. A
postmortem
T2WI MR shows
the correlative appearance 01
absent kidneys and
elongated, discoid adrenals
(arrows). (Right) Coronal
color Doppler ultrasound
shows multiple lumbar
arteries (arrows) in this case
of renal agenesis. This is a
potential pitfall in attempted
identification of the renal
arteries.

MULTICYSTIC DYSPLASTIC KIDNEY

Sagittal ultrasound shows a unilateral MCDK. Multiple
unilocular cysts of variable size are seen throughout the
kidney
(arrows). Intervening renal parenchyma
is
echogenic.

Cross pathology shows the kidney replaced by multiple
cysts of varying size. Minimal intervening dysplasdc
tissue is seen and the ureter is atretic.

ITERMINOlOGY
Abbreviations

and Synonyms

• Multicystic dysplastic kidney (MCDK)
• Renal cystic dysplasia
• Potter type II

•

Definitions
• Renal tissue replaced by cysts

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Multiple variable-sized cysts in
renal fossa
• Location
o Unilateral in 80%
• L> R
o Bilateral in 20%
• Size: t Overall kidney size in 90%
• Morphology
o Variable appearance of both cysts and kidney
o Cysts do not communicate

Ultrasonographic

•

•

Findings

0

• Paraspinous mass with macroscopic cysts
o Reniform shape is lost

DDx: Genitourinary

Hydronephrosis

• Normal renal parenchyma not discernible
o Multiple cysts of variable size and shape
• Cysts may t or .j. during pregnancy
• Rarely require prenatal drainage
o Overall kidney size is enlarged
• Renal length > 95th percentile in 90%
Bilateral MCDK in 20%
o Bilateral cystic kidneys
o No amniotic fluid
o No fluid-filled bladder seen
o Anomalies associated with restricted space
• Club feet
• Abnormal posturing
• Small chest
o Grim prognosis from pulmonary hypoplasia
MCDK is rarely segmental
o Only upper pole cystic change
o Suggests duplex collecting system
MCDK may be late sequelae of renal obstruction
o Hydronephrosis initially seen
• Early and severe
o Renal parenchymal cysts appear secondarily
• Normal intervening renal tissue still present
o Cysts predominate by 3rd trimester
• No normal renal parenchyma
• Appearance identical to 1 MCDK
Contralateral renal anomaly (non-MCDK) in 40%
o Vesicoureteric reflux most common

Obstructive

Hydronephrosis

•

Cystic And Cyst-like

Mega ureter

lesions

Obst Cystic Dysplasia

MULTICYSTIC DYSPLASTIC KIDNEY
Key Facts
Terminology

Pathology

• Potter type II
• Renal ti ue replaced by cysts

• Genetics: Isolated MCDK not associated with
aneuploidy

Imaging Findings

Clinical Issues

•
•
•
•
•
•

•
•
•
•
•
•
•
•

Paraspinous ma s with macro copic cysts
Overall kidney size is enlarged
Bilateral M OK in 20%
ontralateral renal anomaly (non-M OK) in 40%
on-renal anomalies in 5%
Follow amniotic fluid volume carefully

Top Differential

Diagnoses

• Hydronephrosis
• Obstructive cystic dysplasia

M:F = 2:1
Unilateral M OK has excellent prognosis
on-functioning kidney in 90%
M OK kidney usually involutes with time
Rare development of Wilm tumor
Bilateral MCDK almost always fatal
on ervative management
Surgical exci ion reserved for complications

Diagnostic Checklist
• Amniocentesis, if any other anomalies seen
• Beware of "hydronephrotic
type" of MCDK

• Postnatal diagnosis
o Ureteropelvic junction (UP]) obstruction
• Hydronephrosis
o Renal agenesis
• Color Doppler confirms absent renal artery
o Renal hypoplasia
• MCDK and amniotic fluid
o Unilateral MCDK most often with normal fluid
• Normal bladder
o Unilateral MCDK + contralateral renal anomaly
• Fluid depends on health of contralateral kidney
o Bilateral MCDK ~ severe oligohydramnios
• Bladder not visualized
• Common associations
o Meckel-Gruber syndrome
• Encephalocele
• Postaxial polydactyly
o Trisomy 13
• Intrauterine growth restriction
• Holoprosencephaly
• Facial anomalies
• Cardiac defects
• Polydactyly
o Trisomy 18
• Intrauterine growth restriction
• Cardiac defects
• Clenched hands
• Choroid plexus cysts
• Bowel-containing omphalocele
• Non-renal anomalies in 5%
o Amniocentesis recommended

Imaging Recommendations
• Protocol advice
o Kidney documentation
part of every 2nd/3rd
trimester exam
• Longitudinal views + transverse views
o When MCDK present, look at contralateral kidney
carefully
o Follow-up ultrasound every 3-4 wks
• Contralateral renal problem can develop
• MCDK cysts can enlarge dramatically
o Follow amniotic fluid volume carefully

• Objective measurements preferable
• Amniotic fluid index (AFI)
• Maximum vertical pocket (MVP)
o Determine if MCDK is isolated
• Careful fetal anatomic survey
o Genetic counseling for non-isolated MCDK

I DIFFERENTIAL

DIAGNOSIS

Hydronephrosis
• Renal collecting system distention
o UP] obstruction
o Reflux
• Distended calyces may appear "cyst-like"
• Show that calyces connect with renal pelvis
o Longitudinal views best

Obstructive

cystic dysplasia

• Cystic parenchymal change from obstruction
o Hydronephrosis -+ cortical cysts
• Often see some normal renal tissue
o Reniform shape often retained
• Rarely can appear identical to MCDK
o Early obstruction « 10 wks)

Simple renal cyst
• Isolated unilocular renal cyst (rare)
• Vast majority resolve during pregnancy
o 4% progress to MCDK
• Not associated with aneuploidy

Autosomal recessive polycystic kidney
disease
• Bilateral large echogenic kidneys
o Rare or no macroscopic cysts
• Oligohydramnios
• Most often fatal in neonatal period if severe
involvement

Autosomal dominant
disease
• Rarely seen in fetal life

polycystic kidney

MULTICYSTIC DYSPLASTIC KIDNEY
o Few unilocular cysts
o + Liver/pancreatic cysts
• Family history important
o Scan parents for occult disease
• Normal fluid

Dilated ureter
• Often from obstruction
o Posterior urethral valves
o Ureterovesicle obstruction
• Serpiginous course of distended ureter
o Can mimic MCDK
• Careful ultrasound shows separate kidneys

I PATHOLOGY
General Features
• Genetics: Isolated MCDK not associated with
aneuploidy
• Etiology
o Normal metanephric embryology
• Ureter bud signals metanephros -+ nephrons
o Early ureter obstruction/atresia
• Metanephric tissue does not form nephrons
• End result is dysplastic cystic tissue
o Segmental MCDK
• Atresia of duplex ureter
• Most often upper pole ureter
• Epidemiology: 1:3,000 live births
• Associated abnormalities: 5% with non-renal
anomalies

Gross Pathologic & Surgical Features
• Enlarged kidney replaced by cysts
o Non-reniform shape
• Intervening dense fibrotic stroma
• Ureter and renal pelvis atresia

Microscopic

Features

• Smooth-walled

I CLINICAL

cysts

ISSUES

Presentation
• Most common signs/symptoms
o Unilateral MCDK
• Incidentally seen during prenatal scan
o Bilateral MCDK
• Severe oligohydramnios
o Neonatal presentation
• Palpable mass
• Symptoms of contralateral UP] obstruction

Demographics

• Determined by nuclear medicine renal scan
o MCDK kidney usually involutes with time
• 20% in 1st yr of life
• 50% by 5th yr of life
• May take up to 20 yrs
o Compensatory hypertrophy of contralateral kidney
o Rare complications
• Infection
• Hypertension
• Mass effect
• Rare development of Wilms tumor
• MCDK + contralateral renal abnormality
o Bilateral MCDK almost always fatal
o Severe contralateral anomaly
• Often fatal
• Renal insufficiency
o Mild contralateral anomaly
• Often correctable, with excellent prognosis

Treatment
• Conservative management
o Neonatal work-up required in every case
• Ultrasound to confirm diagnosis
• Voiding cystourethrogram
to evaluate for reflux
• Isotope renal scan for function
o Ultrasound surveillance
• Every 6 months for one year
• Yearly until involution
• Surgical excision reserved for complications
o Recurrent infections
o Hypertension
o Wilms tumor
• Pregnancy termination offered for bilateral MCDK

I DIAGNOSTIC
Consider

• Careful evaluation of contralateral kidney
o Follow-up ultrasounds indicated
o Follow API
• Reflects renal function
• Amniocentesis, if any other anomalies seen

Image Interpretation

Pearls

• Beware of "hydronephrotic type" of MCDK
o Large central cyst with small peripheral cysts
o Careful scan shows cysts do not communicate

I SELECTED
1.
2.

• Gender
o M:F=2:1
o Female fetus has worse prognosis
• 2x more likely to have bilateral MCDK
• 4x more likely to have aneuploidy

4.

Natural History & Prognosis

5.

• Unilateral MCDK has excellent prognosis
o Non-functioning
kidney in 90%

CHECKLIST

3.

REFERENCES

van Eijk L et al: Unilateral multicystic dysplastic kidney: a
combined pre- and postnatal assessment. Ultrasound
Obstet Gynecol. 19(2):180-3, 2002
Lazebnik N et al: Insights into the pathogenesis and
natural history of fetuses with multicystic dysplastic kidney
disease. Prenat Diagn. 19(5):418-23, 1999
Minevich E et al: The importance of accurate diagnosis and
early close followup in patients with suspected multicystic
dysplastic kidney. J Urol. 158(3 Pt 2):1301-4, 1997
Anderson et al: Detection of obstructive uropathy in the
fetus. AJR. 164:719-23, 1995
StrifeJL et al: Multicystic dysplastic kidney in children: US
follow up. Radiology. 186:785-8, 1993

MULTICYSTIC DYSPLASTIC KIDNEY
IIMAGE GALLERY
Typical
(Leh) Coronal ultrasound
shows an enlarged lelt-sided
MCDK (calipers) at 20
weeks. The kidney extends
Irom the stomach (curved
arrow) to the iliac crest
(open arrow). (Right)
Coronal ultrasound
performed 4 weeks later
shows the cysts have
enlarged and there is mass
ellect upon the diaphragm
(curved arrows) and
abdominal vessels (color
Doppler image). MCDK tend
to grow during pregnancy.

(Left) Coronal T2WI MR
shows bilateral MCDK in a
neonate who died shortly
alter birth. The kidneys are
enlarged with cysts (arrows)
and are more "ball-like" than
renilorm. (Right) Cross
pathology 01 bilateral MCDK
(kidneys are bisected in the
coronal plane) shows
innumerable cysts. MCDK
do not lunction and
therelore, the bladder
(arrow) is atretic. Bilateral
MCDK is almost always latal.

Variant
(Left) Axial ultrasound shows
a lelt-sided MCDK (open
arrow) and right-sided UP}
obstruction (curved arrowdistended renal pelvis). The
lower image shows a
hypoplastic lelt ventricle
(arrows). MCDK is
associated with both
contralateral renal and
non-renal anomalies. (Right)
Coronal ultrasound shows a
MCDK on the right (RK) with
a central cyst (arrow) and
multiple peripheral cysts, a
pattern which mimics
hydronephrosis
(open
arrows - normal IeIt kidney).

I AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE

Coronal ultrasound of ARPKO shows anhydramnios
and symmetrically
enlarged kidneys (arrows). The
kidneys are diffusely hyperechoic, with very tiny cysts
discernible within the parenchyma.

ITERMINOlOGY
Abbreviations

and Synonyms

• Autosomal recessive polycystic kidney disease (ARPKD)
• Infantile polycystic kidney disease

Definitions
• Single gene disorder resulting in bilateral, symmetric,
cystic renal disease
o Involves distal convoluted tubules + collecting ducts
(i.e. medulla)
• Cortex is spared

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Enlarged, hyperechoic

Ultrasonographic

kidneys

Findings

• Kidney size> 2 standard deviations (SD) above mean
for gestational age (GA)
o By late fetal life, kidneys may be anywhere from
3-10x normal size
• Renal enlargement may not occur until mid 2nd
trimester
• Kidneys are diffusely hyperechoic
• Cysts may be visible but do not predominate

Cross pathology of a bisected kidney shows the dilated
tubules arranged in a radial pattern towards the
collecting system. The multiple interfaces between
ectatic tubules cause increased echogenicity.

• Normal hypoechoic cortex is present
o Look for thin hypoechoic rim around echogenic
medulla
• May be difficult to discern with severe disease
• Oligohydramnios
• Fetal bladder not visible
• Musculoskeletal abnormalities
o Oligohydramnios
limits movement ...•contractures

MR Findings
• Large kidneys of uniformly high signal intensity on
T2WI
o Small, discrete cysts may be visible
o Look for low signal rim of cortex
• Bladder with little or no urine
• Oligo/anhydramnios
• Thorax looks small in relation to abdomen

Imaging Recommendations
• Obtain serial renal measurements in at-risk fetuses
o Parents are known carriers
• Measure ratio of renal circumference to abdominal
circumference
o > 2 SD above mean is abnormal
• Monitor amniotic fluid volume
o Early onset oligohydramnios
~ poor prognosis
• Look for signs of pulmonary hypoplasia
o Thorax looks small in relation to large abdomen
o Measure thoracic circumference

DDx: Renal Anomalies And Oligohydramnios

Bilateral MCDK

Posterior UV

Meckel-Gruber

I AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE
Key Facts
Imaging Findings
• Best diagno tic clue: Enlarged, hyperechoic kidney
• Large kidney of uniformly high ignal intensity on
T2WI
• Renal enlargement may not occur until mid 2nd
trimester

Top Differential

Diagnoses

• Bilateral multicy tic dysplastic kidney (M DK)
• Trisomy 13
• Meckel-Gruber yndrome

Pathology
• Ectatic di tal convoluted

tubules and collecting ducts

Clinical Issues
• Diagnosis reported at 16 week

in at-ri k fetus

• Normative data available
o Measure acceleration time/ejection time (AT/ET
ratio) in pulmonary artery
• Predictor of pulmonary hypoplasia
• Consider MRI
o Helpful with difficult maternal habitus
o Image quality less compromised by lack of amniotic
fluid than ultrasound

I DIFFERENTIAL DIAGNOSIS
Bilateral multicystic dysplastic kidney
(MCDK)
• Macroscopic renal cysts are a dominant
• Anhydramnios

feature

• Most kidneys look normal up to 20 weeks
• Milder ca e may not b apparent on prenatal
ultrasound
• Recurrence risk 25%
• Prenatal diagno i i an area of continued re earch
• Chorionic villus ampling/amniocentesis
to te t for
specific mutation
• Specific mutation in family known from tissue or
blood of affected child

Diagnostic Checklist
• Phenotypic expres ion highly variable within
individual families
• Cannot exclude juvenile form on basis of prenatal U
alone
• MRI can be helpful to refine diagnosis of renal
anomalies associated with oligo/anhydramnio

Beckwith-Wiedemann

Autosomal dominant
disease

!PATHOlOGY

• Cystic dysplasia seen in 50%
o Kidneys usually echogenic, enlarged, cysts may be
visible
• Holoprosencephaly
• Polydactyly
• Facial anomalies
o Cyclops, proboscis, cleft lip/palate, midline facial
cleft

General Features

syndrome

• Encephalocele: Microcephaly is a clue if
oligohydramnios limits views
• Polydactyly
• Cystic renal dysplasia
o Usually macroscopic cysts
o Enlarged hyperechoic kidneys have been described

Tuberous sclerosis
• Family history
o Autosomal dominant transmission but 2/3 of cases
are new mutations
• Rhabdomyoma: Echogenic cardiac mass
• Tubers: Subependymal nodules
• Renal cysts/solid masses not usually seen in utero

polycystic kidney

• Check family history, scan parental kidneys
• Asymmetric renal enlargement
• Rarely presents in fetus: Cysts may be visible late 3rd
trimester
o Renal echogenicity generally normal but
hyperechoic kidneys have been described
• Amniotic fluid normal

Trisomy 13

Meckel-Gruber

syndrome

• Macrosomia, often associated polyhydramnios
• Omphalocele
• Macroglossia

• General path comments
o Ectatic distal convoluted tubules and collecting
ducts
• Increased volume of medulla ~ renal enlargement
• Increase in reflective interfaces ~ high
echogenicity on ultrasound
• Increased "water" content in multiple
tubules/cysts ~ high-signal intensity T2WI
• Genetics
o Autosomal recessive
• Mutation of PKHD1gene which maps to
chromosome 6p12
o Mutations are "private" (Le. specific to individual
families)
o HNF1beta transcription factor regulates expression
of PKHD1 in kidney
• HNF1beta mutations also cause ARPKD
• Epidemiology
o 1:20,000 to 50,000 births
o M::::F
• Associated abnormalities
o Potter sequence secondary to oligohydramnios
• Pulmonary hypoplasia

I

AUTOSOMAL

RECESSIVE POLYCYSTIC KIDNEY DISEASE

• Abnormal facies
• Limb contractures

ICLINICAl

o Chorionic villus sampling/amniocentesis to test for
specific mutation
o Specific mutation in family known from tissue or
blood of affected child
o Much more complicated without confirmed
diagnosis in prior child

ISSUES

Presentation
• Majority detected < 24 weeks
o Diagnosis reported at 16 weeks in at-risk fetus
o Most kidneys look normal up to 20 weeks
• Milder cases may not be apparent on prenatal
ultrasound

Natural History & Prognosis
• Disease has variable phenotype
o Perinatal, neonatal, infantile and juvenile forms
described
o Disease expression may vary widely within affected
families
• Fetal diagnosis
o Oligohydramnios => pulmonary hypoplasia =>
majority stillborn or neonatal death
• Perinatal form 30-50% death
o Severe renal disease
o Pulmonary hypoplasia
o Minimal hepatic fibrosis
• Juvenile form
o Minimal renal disease, marked hepatic fibrosis
o Liver disease more relevant in survivors
• Neonatal survivors
o 1 yr survival 85%
o 10 yr survival 82%
o Need for artificial ventilation at birth strongly
correlates with mortality
o Mean age of diagnosis of chronic renal failure 4 yrs
o Actuarial renal survival (end point defined as start of
dialysis or death from renal failure)
• 86% at 5yrs
• 71% at 10 yrs
• 42% at 20 yrs
o 75% develop systemic hypertension
o 44% develop portal hypertension
• Incidence increases with age, no correlation with
onset chronic renal failure/insufficiency
• Severity and outcomes vary within affected families
o Cannot predict outcome of future children based on
severity of index case
• Recurrence risk 25%

I DIAGNOSTIC
Consider

• Phenotypic expression highly variable within
individual families
o Cannot exclude juvenile form on basis of prenatal
US alone
• Prenatal diagnosis is possible if specific mutation
known
o Strongly encourage autopsy/renal biopsy in lethal
cases

Image Interpretation

Pearls

• MRI can be helpful to refine diagnosis of renal
anomalies associated with oligo/anhydramnios

I SELECTED
1.

2.

3.

4.

5.

6.

7.

8.

Treatment
• Genetic counseling
o Family history
o Increased incidence of occult renal disease in family
members
• Offer termination
• If pregnancy continues, plan delivery at tertiary center
o Infants may require respiratory support
• Monitor abdominal circumference
o Risk of abdominal dystocia
o May influence timing of delivery
o Avoid cesarean section for non-viable fetus
• Encourage autopsy confirmation for intrauterine or
neonatal demise
• Prenatal diagnosis is an area of continued research

CHECKLIST

9.

10.

11.

12.

13.

REFERENCES

Bergmann C et al: Clinical consequences of PKHD1
mutations in 164 patients with autosomal-recessive
polycystic kidney disease (ARPKD).Kidney Int.
67(3):829-48, 2005
Hiesberger T et al: Role of the hepatocyte nuclear
factor-1beta (HNF-1beta) C-terminal domain in Pkhd1
(ARPKD)gene transcription and renal cystogenesis. J Bioi
Chern. 280(11):10578-86, 2005
Bergmann C et al: PKHD1 mutations in families requesting
prenatal diagnosis for autosomal recessive polycystic
kidney disease (ARPKD).Hum Mutat. 23(5):487-95, 2004
Bergmann C et al: PKHD1 mutations in autosomal
recessive polycystic kidney disease (ARPKD).Hum Mutat.
23(5):453-63, 2004
Cassart M et al: Complementary role of MRI after
sonography in assessing bilateral urinary tract anomalies in
the fetus. AJRAm] Roentgenol. 182(3):689-95, 2004
Harris PC et al: Molecular genetics of autosomal recessive
polycystic kidney disease. Mol Genet Metab. 81(2):75-85,
2004
Shukla AR et al: Unilateral nephrectomy as palliative
therapy in an infant with autosomal recessive polycystic
kidney disease. J Urol. 172(5 Pt 1):2000-1, 2004
Zerres K et al: New options for prenatal diagnosis in
autosomal recessive polycystic kidney disease by mutation
analysis of the PKHD1 gene. Clin Genet. 66(1):53-7, 2004
Capisonda R et al: Autosomal recessive polycystic kidney
disease: outcomes from a single-center experience. Pediatr
Nephrol. 18(2): 119-26, 2003
Guay-Woodford LM et al: Autosomal recessive polycystic
kidney disease: the clinical experience in North America.
Pediatrics. 111(5 Pt 1):1072-80, 2003
Zerres K et al: Autosomal recessive polycystic kidney
disease (ARPKD).] Nephrol. 16(3):453-8, 2003
Lonergan GJ et al: Autosomal recessive polycystic kidney
disease: radiologic-pathologic correlation. Radiographies.
20(3):837-55,2000
Cohen L et al: Normal length of fetal kidneys. Sonographic
study in 397 obstetric patients. A]R. 157:545-8 1991

I

AUTOSOMAL

RECESSIVE

POLYCYSTIC

KIDNEY DISEASE

I IMAGE GAllERY
(Left) Axial ultrasound

in a
75 week fetus, of a couple
with one affected child,
shows increased
echogenicity
of the kidneys
(arrows). Amniotic fluid
volume is normal but that
does not imply normal renal
function at this gestational
age. (Right) Axial color
Doppler ultrasound shows a
very small bladder (curved
arrow) between the
umbilical arteries (arrows).

DIST=

3.31cm

(Left) Coronal ultrasound
from the case above at 22
weeks now shows severe
oligohydramnios.
The chest
is small (arrows) and the
kidneys are large and
echogenic (calipers). (Right)
Sagittal ultrasound in a
different case of ARPKD
shows an enlarged,
hyperechoic kidney
(calipers). There is
preservation of the normal
hypoechoic
cortex (arrows).
This is a characteristic
finding, but may be difficult
to discern on prenatal scans.

(Left) Coronal T2WI
postmortem
MR shows a tiny
thoracic cavity (white
arrows). The kidneys (black
arrow) are massively
enlarged with no normal
remaining parenchyma.
High
signal intensity is caused by
the dilated tubules. (Right)
Cross pathology from the
autopsy confirms massively
enlarged kidneys (arrows).
The thoracic cavity is small
and the lungs (curved
arrows) are severely
hypoplastic.

MESOBLASTIC NEPHROMA

Coronal color Doppler ultrasound of a mesoblastic
nephroma shows a large, predominately solid, left flank
mass (arrows). The aorta is displaced but the renal
artery (open arrow) is clearly identified.

ITERMINOLOGY
Abbreviations
•
•
•
•
•

and Synonyms

Congenital mesoblastic nephroma
Fetal renal hamartoma
Leiomyomatous hamartoma
Mesenchymal hamartoma
Bolande tumor

Definitions
• Benign mesenchymal renal tumor composed
predominately of spindle cells

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Solid renal mass +
polyhydramnios
• Morphology
o Variable growth pattern
o May see distinct, well-defined, intra renal mass
o Infiltrative growth pattern
• Smaller masses retain reniform shape
• Larger masses may fill abdomen, displacing bowel

Ultrasonographic

Findings

• Generally solid

Ultrasound of the uterus in the same case shows severe
polyhydramnios with an AFI of 40. Polyhydramnios is a
common associated finding. A small cystic component
(arrow) is seen in the upper portion of this mass.

o Iso- to slightly hyperechoic compared to normal
renal parenchyma
o May rarely have cystic areas
• Large masses may exert considerable mass effect
o Abdominal circumference increased
o Abdominal vessels and organs displaced
o Bowel obstruction may occur
• Polyhydramnios in "" 70%
o Often severe
• Color Doppler
o Vascular mass
• Hydrops may occur with significant arteriovenous
shunting or from obstruction of venous return
o Ring sign
• Hypoechoic ring surrounding tumor
• Vascular with Doppler imaging

MR Findings
• Helpful for confirming renal origin of mass
• Solid mass with uniform signal intensity
• Mild increased signal on T2WI

Imaging Recommendations
• Confirm renal origin of mass
o Look for normal kidney and adrenal on side of mass
• Adjacent mass may fill renal fossa and be confused
for renal mass
• Look for displaced kidney

DDx: Enlarged Kidneys

Crossed r used Ectopy

Duplication

ARPKD

MESOBLASTIC NEPHROMA
Key Facts
Terminology

Pathology

• Benign mesenchymal renal tumor composed
pr dominately of spindle cell

• Mo t common renal neoplasm in fetus and newborn
• "In utero polyuria" from hypercalcemia most likely
cause of polyhydramnio

Imaging Findings
• Be t diagnostic clue: Solid renal ma
polyhydramnio
• Variable growth pattern
• Generally solid
• Polyhydramnios in "" 70%
• Va cular mass

Top Differential

+

Diagnoses

• Wilm tumor
• ro d fused ectopy
• Adr nalle ion

• Perinatal complications in 71%
• Acute fetal di lre s requiring emergency ce arean
section
• eonatal hyperten ion
• eonatal hypercalcemia
• Surgical re ection u ually curative

Diagnostic Checklist
• Mesobla tic nephroma has an excellent oncologic
outcome but is at high-risk for perinatal
complications

o Consider MRI if ultrasound cannot determine if
mass is renal
• Color Doppler
o Assess vascularity
o Look for renal artery
• Confirms mass in renal
• Calculate amniotic fluid index (AFI)
o Polyhydramnios if API > 24
• Frequent follow-up exams
o Worsening polyhydramnios
• May become severe, resulting in preterm labor
o Enlarging abdominal circumference
o Rarely complicated by hydrops

I DIFFERENTIAL

Clinical Issues

DIAGNOSIS

Renal tumors
• Wilms tumor
• Ultrasound appearance identical to mesoblastic
nephroma
• Extraordinarily rare in utero
o Average age at presentation 3.6 years
• Rhabdoid tumor also reported

Crossed fused ectopy
• Unilateral enlargement
• Fused kidneys may cross midline
• Opposite renal fossa is empty

Renal collecting system duplication
• Unilateral renal enlargement
• Upper pole often hydronephrotic
o Drained by ectopic ureter
o Often obstructs
• Lower pole mayor may not be dilated
o Drained by orthotopic ureter
o Often refluxes
• Look in bladder for ureterocele

Autosomal recessive polycystic kidney
disease (ARPKD)
• Bilateral, symmetric renal enlargement

• Diffusely hyperechoic kidneys
• Scattered small cysts may be seen, but not a dominant
feature
• May have oligohydramnios

Beckwith-Wiedemann
•
•
•
•
•
•
•
•

syndrome

Organomegaly, including enlarged kidneys
Macrosomia
Macroglossia with protruding tongue
Omphalocele
Hemihypertrophy
Polyhydramnios
Hypoglycemia in neonatal period
At risk for neonatal tumors
o Wilms tumor, hepatoblastoma

Multicystic dysplastic kidney
• Cystic, not solid
• Multiple, non-communicating

cysts of various sizes

Adrenal lesions
• Neuroblastoma, adrenal hemorrhage,
sequestration
• Suprarenal location
• Kidney displaced inferiorly
• Normal adrenal gland not identified

Retroperitoneal

extralobar

teratoma

• May be large
o May be difficult to find displaced kidney
• Point of origin difficult to discern
• Heterogeneous masses
o Mixed cystic and solid
o Calcifications are most specific diagnostic feature

I PATHOLOGY
General Features
• Genetics
o Sporadic
o Has been reported in siblings
• Epidemiology
o Rare, overall

MESOBLASTIC NEPHROMA
o Most common renal neoplasm in fetus and newborn
o 5% of perinatal tumors arise from kidney
• Majority are mesoblastic nephroma
• Rare reported cases of Wilms or rhabdoid tumor
o M>F
• Associated abnormalities: Polyhydramnios and
hypercalcemia
• Theories of polyhydramnios
o Polyuria
• Often seen in neonates with mesoblastic
nephroma and is associated with hypercalcemia
• "In utero polyuria" from hypercalcemia most
likely cause of polyhydramnios
o Bowel obstruction
• May contribute but does not explain all cases
• May see significant polyhydramnios
without
bowel obstruction
o Mass causes increased blood flow to kidney '* t
urine output
o Impaired concentrating ability of affected kidney

Gross Pathologic & Surgical Features
• Whorled appearance
o Similar to uterine fibroid
• No capsule
o Still appears well-defined by ultrasound

Microscopic

Features

• Benign mesenchymal tumor
• Spindle-shaped cells infiltrate normal renal
parenchyma
• Cellular variant may be more aggressive

ICLINICAllSSUES
Presentation
• Fetal
o Rapid, acute onset of polyhydramnios
in 3rd
trimester
• Large for dates
• Preterm labor
o Increased abdominal circumference
o Solid abdominal mass
• Neonatal
o Obvious palpable mass on exam
o Hypertension
• Increased renin production
o Hypercalcemia
• Attributed to parathormone and prostaglandin
production
o Both hypercalcemia and hypertension resolve after
resection

Natural History & Prognosis
• Can show rapid growth despite benign histology
• Perinatal complications in 71%
o Severe polyhydramnios
o Hydrops
o Acute fetal distress requiring emergency cesarean
section
o Premature delivery
o Respiratory distress
o Neonatal hypertension

o Neonatal hypercalcemia
• Large abdominal circumference may result in dystocia
at delivery
• Surgical resection usually curative
o Surgical complications reported in 26%
• Rare local recurrence or metastases for cellular
mesoblastic nephroma
o Lung most common site

Treatment
• Referral to tertiary care center for close monitoring
• Amnioreduction for polyhydramnios
for patient
comfort or preterm labor
• Tocolytics for preterm labor
• May require cesarean section
• Referral to pediatric urologist
• Resection in neonatal period
o Nephrectomy with wide margins usually curative

I DIAGNOSTIC

CHECKLIST

Consider
• MRI to confirm mass is renal and not from
surrounding structures
• Mesoblastic nephroma has an excellent oncologic
outcome but is at high-risk for perinatal complications

Image Interpretation

Pearls

• Mesoblastic nephroma is most likely diagnosis of a
unilateral, solid renal mass

I SELECTED

REFERENCES

1.

Canning DA: Prenatal diagnosis of congenital mesoblastic
nephroma associated with renal hypertension in a
premature child. J Urol. 173(3):983, 2005
2. Khashu M et al: Congenital mesoblastic nephroma
presenting with neonatal hypertension. J Perinatol.
25(6):433-5, 2005
3. Leclair MD et al: The outcome of prenatally diagnosed
renal tumors. J Urol. 173(1):186-9,2005
4.
Woodward PJ et al: From the archives of the AFIP: a
comprehensive review of fetal tumors with pathologic
correlation. Radiographies. 25(1):215-42, 2005
5. Chen WY et al: Prenatal diagnosis of congenital
mesoblastic nephroma in mid-second trimester by
sonography and magnetic resonance imaging. Prenat
Diagn. 23(11):927-31, 2003
6.
Kelner M et al: The vascular "ring" sign in mesoblastic
nephroma: report of two cases. Pediatr Radiol. 33(2):123-8,
2003
7.
Won HS et al: Prenatal detection of mesoblastic nephroma
by sonography and magnetic resonance imaging.
Ultrasound Obstet Gynecol. 19(2):197-9,2002
8. Irsutti M et al: Mesoblastic nephroma: prenatal
ultrasonographic and MRI features. Pediatr Radiol.
30(3):147-50,2000
9.
Isaacs H Jr: Renal Tumors In: Tumors of the fetus and
newborn. Saunders. Philadelphia. 244-77, 1997
10. Uu YC et al: The presence of hydrops fetalis in a fetus with
congenital mesoblastic nephroma. Prenat Diagn.
16(4):363-5, 1996
11. Fung TY et al: Polyhydramnios and hypercalcemia

associated with congenital mesoblastic nephroma: Case
report and a new appraisal. Obstet Gynecol. 85:815-7, 1995

MESOBLASTIC NEPHROMA
IIMAGE

GALLERY

Typical
(Left) Coronal oblique
ultrasound of the kidney
shows a markedly enlarged
lower pole (calipers),
extending into the pelvis and
abutting the bladder (arrow).
The upper pole of the kidney
(open arrows) is preserved.
(Right) Cross pathology after
resection shows a
well-defined, fleshy, lower
pole mass with dense
stromal architecture. (Also
shown in Radiographics, ref
7).

(Left) Axial ultrasound
through the fetal abdomen is
most striking for severe
polyhydramnios.
There is a
large solid mass in the region
of the right kidney (arrow).
The left kidney is normal
(curved arrow). (Right) Axial
CECT after delivery shows
shows dramatic enlargement
of the right kidney with
essentially complete
replacement
by the tumor.
Despite its large size,
mesoblastic nephroma is
generally benign and cured
with resection. (Also shown
in Radiographics, ref 7).

(Left) Axial ultrasound shows
a mass (calipers) in the left
renal fossa with no
identifiable normal kidney on
that side. The right kidney
(arrow) is normal. (Right)
Cross pathology of the
resected kidney shows only a
small crescent of remaining
renal parenchyma
(arrow).
The kidney has otherwise
been replaced by a fleshy
mass. Histology confirmed a
mesoblastic nephroma.

NEUROBLASTOMA

Coronal ultrasound of the fetal abdomen (top) shows a
solid, echogenic mass (calipers) above the right kidney
(arrow). Sagittal ultrasound after delivery (bottom)
confirms a solid, suprarenal mass (calipers).

ITERMINOlOGY
Definitions
• Malignant tumor composed of neuroblasts, arising
within sympathetic neural plexus or adrenal medulla

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o No identifiable adrenal gland on side of mass
o Kidney is displaced inferiorly
• Location
o May occur anywhere along sympathetic chain
o > 90% occur in adrenal gland
• Contrasts to pediatric population in which only
35% occur in adrenal gland
• Cervical and thoracic tumors also reported
o 60% are right-sided
• Morphology
o Approximately 50% are cystic
• May represent involuting tumor
o Remainder are solid or complex
• Solid masses are more likely to metastasize

Ultrasonographic

Cross pathology shows the adrenal mass compressing
the upper pole of the kidney. Histology confirmed a
neuroblastoma, which was confined to the adrenal
gland. (Also shown in Radiographies, ref 7).

o Complex cystic mass with thick septations
o Uniformly echogenic solid mass
o Rarely calcified
• Much less common than pediatric age group
• Color Doppler shows diffuse vascularity
o Does not have single feeding vessel
• Helps to differentiate from extra lobar
sequestration
• May have hydrops
o Large masses
o Metastases
• Hepatic metastases
o May be diffusely infiltrating or discrete masses

MR Findings
• Confirm anatomic location
• Signal characteristics, variable depending on cystic or
solid composition
o Cystic: Marked increased signal on T2Wl
o Solid: Moderate increased signal on T2WI
• Can help exclude adrenal hemorrhage from
differen tial
• Useful for staging and evaluating metastases
o Diffusely infiltrating liver metastases may be missed

Imaging Recommendations
• Confirm adrenal origin of mass
o Document mass is separate from kidney
o Look for normal adrenal

Findings

• Variable appearance

DDx: Neuroblastoma

Sequestration

Sequestration

Teratoma

Hemorrhage

NEUROBLASTOMA
Key Facts
Terminology

Pathology

• Malignant tumor composed of neuroblasts, ari ing
within sympathetic neural plexus or adrenal medulla

• Most common congenital malignancy
• Tumors may "mature" to more benign hi tologic type
• > 90% of fetal have a favorable tage (I, II and lV- )

Imaging Findings
•
•
•
•
•

> 90(M, occur in adrenal gland
Approximately 50% are cystic
olid ma e ar more likely to metasta ize
Liver mo t common location for m ta ta e
Diffu Iy infiltrating liver metasta e are difficult to
diagno e

Top Differential

Diagnoses

• Extralobar equestration
• Duplicated renal collecting system
• Adrenal hemorrhage

• Assess vascularity with color Doppler
o Rule out a dominant feeding vessel
• Careful examination for metastases
o Liver most common location for metastases
• Diffusely infiltrating liver metastases are difficult
to diagnose
• Be suspicious when hepatomegaly or hydrops is
present
o Placenta (rare)
• Microscopic tumor emboli
• Bulky, hydropic placenta
• Discrete masses less likely
• Consider MRI if mother has preeclampsia
o Suggests advanced disease
o Look for metastases
• Close follow-up
o Mass may either grow or regress
o Look for hydrops

I DIFFERENTIAL DIAGNOSIS
Extralobar sequestration
• More likely than neuroblastoma as cause of left-sided
suprarenal mass, especially if solid
o 10-15% occur below diaphragm
o 90% on left
o Uniformly echogenic solid mass
o Stomach is displaced anteriorly
o Present earlier (2nd trimester)
• Dominant feeding vessel from aorta
• Separate adrenal gland may be identified
• Histologically may be hybrid lesion
o Sequestration + congenital cystic adenomatoid
malformation

Duplicated

renal collecting system

• Hydronephrotic upper pole may be mistaken for cystic
suprarenal lesion
• Need to examine kidney carefully in both axial and
longitudinal planes
• Look for ectopic ureterocele in bladder
• Separate adrenal gland may be identified

Clinical Issues
• Progno i affected by tage and biologic markers
• Most fetal tumor have both favorabl stage and
markers
• > 90% overall survival
• 70% mortality rate if mother pre ent with
preeclampsia from placental meta ta

Diagnostic Checklist
• Only half of uprarenal ma e are neurobla tomas,
so mu t carefully evaluate for oth r cause, especially
extralobar sequestration

Adrenal hemorrhage
•
•
•
•

Reported in utero but uncommon
Will involute over time
No color flow within mass
MRI can confirm blood products

Teratoma
• May infiltrate retroperitoneum
and appear similar to
stage III or IV neuroblastoma
• Often large, so usually can not identify normal adrenal
gland
• Complex, mixed cystic-solid masses
• Calcifications most specific finding

Mesoblastic nephroma
• Renal mass
• Adrenal gland is normal

I PATHOLOGY
General Features
• Genetics: Rare familial cases
• Etiology
o Normal fetal adrenal contains neuroblastic nodules
• Histologically indistinguishable
from
neuroblastoma
• Peak number of nodules 17-20 wks gestation
o Nodules involute over time
• Seen in 100% of fetal adrenals in 2nd trimester
• Present in only 0.5-2.5% of newborn adrenal
glands
o Fetal neuroblastoma may represent temporary defect
in growth of these nodules that are destined to
involute over time
• May explain non-aggressive nature of fetal tumors
when compared to those in pediatric age group
• Epidemiology
o Most common congenital malignancy
o 30% of all fetal tumors
• 2nd only to teratomas

NEUROBLASTOMA
Gross Pathologic & Surgical Features

Treatment

• Approximately half of all fetal tumors are cystic
o Cystic change may indicate ongoing involution
• Cystic tumors have small aggregates of neuroblasts
in cyst wall
• Solid tumors have sheets of tumor cells

• Consider early delivery if rapidly growing or
metastases detected
• Surgical resection after delivery
o Curative in most cases
• Given often indolent course, some advocate more
conservative postpartum approach
o Monthly sonograms for 6 months for small « 3 cm)
cystic tumors
o Biopsy solid masses
• If favorable biologic markers and stage => follow
• Poor biologic markers/stage or failure to involute
=> surgery

Microscopic

Features

• Derive from primordial neural crest cells
• Tumors may "mature" to more benign histologic type
o Neuroblastoma: Malignant tumor composed of
neuroblasts
o Ganglioneuroblastoma:
Malignant tumor with both
immature and mature elements
o Ganglioneuroma: Benign tumor composed of
mature ganglion cells
• Biologic markers
o Myc-N amplification
• Proto-oncogene on chromosome 2p
• Multiple copies (> 10) in aggressive tumors
o DNA index
• Tumors with an increased DNA content (index>
1) have a more favorable prognosis
o Most fetal neuroblastomas have a favorable DNA
index (> 1) and no Myc-N amplification

Staging, Grading or Classification Criteria
• Stage I: Confined to adrenal gland
• Stage II: Extension beyond adrenal but does not cross
midline
• Stage III: Extension across midline
• Stage IV: Distant metastases
• Stage lV-S: Unique grouping of metastases, with an
excellent prognosis
o Skin, liver, and < 10% of bone marrow (not bone)
• > 90% of fetal have a favorable stage (I, II and IV-S)

I CLINICAL

ISSUES

I DIAGNOSTIC
Consider

• Overall prognosis for fetal neuroblastoma is excellent
• Majority of tumors have a favorable stage and biologic
markers

Image Interpretation

I SELECTED
1.

2.

3.

4.
5.

Natural History & Prognosis
• Prognosis affected by stage and biologic markers
o Most fetal tumors have both favorable stage and
markers
o > 90% overall survival
o Poor prognosis for stages III and IV
o 70% mortality rate if mother presents with
preeclampsia from placental metastases
• Variable course
o May resolve spontaneously
o Most remain stable without complications
o A minority progress to hydrops and even death

Pearls

• Only half of suprarenal masses are neuroblastomas,
must carefully evaluate for other causes, especially
extra lobar sequestration
o Neuroblastoma
• More likely cystic
• More often on right
• Not usually seen until 3rd trimester
o Extralobar sequestration
• Solid
• Significantly more common on left
• Usually seen by 2nd trimester
• May see feeding vessel from aorta

Presentation
• Reported as early as 20 weeks
• Generally incidental finding in 3rd trimester
o Adrenal most common
o Thoracic and cervical masses reported
• Rarely, mother presents with preeclampsia or
headaches.
o Fetal catecholamines may reach maternal circulation
o Concerning for placental metastases

CHECKLIST

6.
7.

8.

9.

so

REFERENCES

Woodward PJ et al: From the archives of the AFlP: a
comprehensive review of fetal tumors with pathologic
correlation. Radiographies. 25(1):215-42, 2005
Houlihan C et al: Prenatal diagnosis of neuroblastoma with
sonography and magnetie resonance imaging. J Ultrasound
Med. 23(4):547-50, 2004
Lonergan GJ et al: Neuroblastoma, ganglioneuroblastoma,
and ganglioneuroma: radiologic-pathologic correlation.
Radiographies. 22:911-34, 2002
Hamada Y et al: Prenatally diagnosed cystic
neuroblastoma. Pediatr Surg Int. 15(1):71-4, 1999
Kesrouani A et al: Prenatal diagnosis of adrenal
neuroblastoma by ultrasound: a report of two cases and
review of the literature. Ultrasound Obstet Gynecol.
13(6):446-9, 1999
Acharya S et al: Prenatally diagnosed neuroblastoma.
Cancer. 80:304-10, 1997
Curtis MR et al: Prenatal ultrasound characterization of the
suprarenal mass: distinction between neuroblastoma and
subdiaphragmatic extra lobar pulmonary sequestration. J
Ultrasound Med. 16:75-83, 1997
Vollersen E et al: Prenatal sonographic diagnosis of fetal
adrenal gland hemorrhage. Fetal Diagn Ther. 11(4):286-91,
1996
Ho PT et al: Prenatal detection of neuroblastoma: a
ten-year experience from the Dana-Farber Cancer Institute
and Children's Hospital. Pediatrics. 92(3):358-64, 1993

NEUROBLASTOMA
IIMAGE

GALLERY
(left) Coronal ultrasound
and gross specimen of a
cystic neuroblastoma
shows
a complex, cystic mass
(curved arrow) above the
kidney (arrow). (Right)
Sagittal ultrasound
performed on day 7 of life
for a cystic mass seen in
utero. Thick septations are
present within the mass. The
mass was resected and
neuroblastoma
was
confirmed. Approximately
half of all fetal
neuroblastomas
are cystic
and have an excellent
prognosis.

(left) Coronal ultrasound
shows a very large, solid
mass (arrows) above the
kidney (open arrow). (Right)
Axial ultrasound shows the
adrenal mass (black arrows).
In addition, the liver is
heterogeneous,
with several
discrete metastases (open
arrows) and there is ascites
(white arrow). Solid tumors
are more likely to
metastasize than cystic ones.
(Also shown in
Radiographies, ref 7).

(left) Gross pathology of the
liver from the above case
shows diffuse metastatic
disease. (Right) Axial
ultrasound in another case of
metastatic neuroblastoma
shows a complex cystic and
solid mass infiltrating the
abdomen and obliterating
normal anatomy. There is
hydrops, with skin thickening
(arrow) and ascites (open
arrow). The mother
presented with preeclampsia
from placental metastases.
This carries a very poor
prognosis, and the infant
died shortly after birth.

POSTERIOR

URETHRAL VALVES

Ultrasound at 75 wks shows gross distention of the
bladder, with severe oligohydramnios
and a small,
bell-shaped chest (arrow). The inset shows dilatation of
the posterior urethra (open arrow), the "keyhole" sign.

Gross pathology from the same case shows marked
distension of the abdomen due to the grossly dilated
bladder. Note the very small chest (arrow). Early
oligohydramnios results in lethal pulmonary hypoplasia.

ITERMINOlOGY
Abbreviations

and Synonyms

• Posterior urethral valves (PUV)

•

Definitions
• Urethral membrane acts as valve, resulting in bladder
outlet obstruction
o Posterior urethra obstructed by valves
o Obstruction is usually partial
o Occurs exclusively in males

IIMAGING FINDINGS
•

General Features
• Best diagnostic clue
o "Keyhole" sign
• Distended bladder "funnels" into dilated, posterior
urethra

Ultrasonographic

Findings

• Male fetus
o May be difficult to determine gender if severe
oligohydramnios
• Findings vary with degree of obstruction
• Renal findings
o Ureterectasis

•

•

o Caliectasis
o Hydronephrosis
o Renal dysplasia
o Cortical cysts
Bladder findings
o Variable degrees of bladder distention
• May fill entire abdomen
o Thick-walled
• May not see with severe dilatation
o Dilated "keyhole" appearance of posterior urethra
• If present, strongly suggests diagnosis of PUV
• Not always seen
• Urethral atresia can potentially give similar
appearance
Renal dysplasia
o Echogenic parenchyma thought to be due to fibrosis
• Suggests, but is not diagnostic of, dysplasia
o Likely due to back pressure from outflow obstruction
o Irreversible
• Persists in spite of intervention to relieve
obstruction
Degree of hydronephrosis does not necessarily
correlate with degree of dysplasia
o May have severe dysplasia with no hydronephrosis
o Fibrotic dysplastic kidney
• Parenchyma resists distention
• Dysplasia -+ decreased urine production
Renal cortical cysts

DDx: Dilated Bladder

Urethral Atresia

Prune Belly Syndrome

Cloacal Malformation

POSTERIOR URETHRAL VALVES
Key
Terminology

Top Differential

• Urethral membrane acts as valve, re ulting in bladder
outlet obstruction
• ccurs exclu ively in males

• Urethral atre ia
• Prune belly syndrome
• Megacystis-microcolon
• loacal malformation

Imaging Findings
• "Keyhole" ign
• Distended bladder "funnels" into dilated, po terior
urethra
• Hydronephro i
• Renal dy pi asia
• Oligohydramnios
• Urinary ascites
• Follow all fetus s with large bladder
• Evaluate for poor prognostic sign :

•
•

•

•

Facts

o 100% predictive for dysplasia
• Seen in 44% of dysplastic kidneys
o Indicate irreversible damage
• Fetus unlikely to benefit from in utero
intervention if present
• Usually suggests a fatal outcome
o Described as early as 20 weeks gestation
Renal atrophy is a poor prognostic sign
Oligohydramnios
o Small, bell-shaped chest -+ pulmonary hypoplasia
o Poor prognosis
o 80% fatality rate
Associated malformations in 43%
o Cardiac malformations
o May be seen with VACTERL association
Bladder rupture -+ urinary tract decompression
o Favorable prognostic sign, relieves pressure on
kidneys
• Urinary ascites
• Urinothorax
• Peritoneal calcifications
o May also see ruptured collecting system
• Perinephric fluid collection = urinoma

MR Findings
• Potential role in evaluating renal parenchyma
dysplastic changes
• May help confirm diagnosis in certain cases
o Severe oligohydramnios
o Large maternal body habitus

for

Imaging Recommendations
• Follow all fetuses with large bladder
o Likely transient finding if otherwise normal urinary
tract and amniotic fluid volume
• Evaluate for poor prognostic signs:
o Echogenic kidneys (with or without cysts)
• May precede abnormal urine chemistries
o Worsening bilateral hydronephrosis
• Unilateral "protects" other kidney (better
prognosis)
o Oligohydramnios

Diagnoses

Clinical Issues
• Wide range of everity
• Degree of fetal renal damage affects survival
• Karyotype fetus with either amniocentesis or bladder
tap
• > 32 wks, worsening oligohydramnios
~ deliver ~
en do copic valve ablation
• < 32 wks, assess renal function
• on ider intervention for those in good progno tic
category with wor ening oligohydramnios
and/or
hydronephrosi

I DIFFERENTIAL

DIAGNOSIS

Urethral atresia
• May have identical appearance
• Obstruction is complete
• Degree of oligohydramnios
usually more severe, may
progress to anhydramnios
• Male and female
• Much less common

Prune belly syndrome
• Lax or absent abdominal musculature
• Bladder thin-walled
• Entire urethra dilated
o Does not show characteristic "keyhole"

Megacystis-microcolon
•
•
•
•

Bladder thin-walled
No dilated posterior urethra
Amniotic fluid normal to increased
More common in females (4:1)

Cloacal malformation
• Rare cause of urinary outlet obstruction
• Complex anomaly
o Failure of embryonic cloacal division
o Convergence of bladder, rectum, genitalia, perineum
o Single perineal opening
• Females and males

I PATHOLOGY
General Features
• Genetics: Sporadic
• Etiology: Abnormal thickening and/or fusion of
normal circular mucosal folds
• Epidemiology
o Rare
o 1:8,000 to 25,000 live-born males
o Higher incidence in utero
• Reflects high mortality due to oligohydramnios

POSTERIOR
• Pulmonary
demise

hypoplasia

URETHRAL VALVES

is ultimate cause of fetal

Gross Pathologic & Surgical Features
• Valve tissue is thin but forms a membrane
antegrade flow

Microscopic

obstructing

Features

• Smooth muscle hypertrophy in bladder/ureteral
o May progress to fibrosis
o Ureters remain distended despite relief of
obstruction

I CLINICAL

•

walls

ISSUES

Presentation

•

• Bladder distention
• Oligohydramnios
• Has been detected in 1st trimester

•

Natural History & Prognosis
• Wide range of severity
• Overall mortality 25-50%
o > 90% with oligohydramnios
• Mild and moderate cases in utero = best prognosis
o Very mild cases may remain undetected until
childhood
o Need to rule out puv postnatally in all males with
persistent bladder dilatation and/or hydronephrosis
in utero
• Degree of fetal renal damage affects survival
• Characteristic phenotypic features, if severe
oligohydramnios
o Potter facies
o Flexion contractures
o Pulmonary hypoplasia
• Vesicoureteral reflux may persist in childhood
• Renal insufficiency develops in up to 45% of survivors

Treatment
• Karyotype fetus with either amniocentesis or bladder
tap
o Prognosis worse with aneuploidy
o Can also evaluate sex chromosomes if fetal sex
uncertain
• Termination may be offered
• > 32 wks, worsening oligohydramnios
~ deliver ~
endoscopic valve ablation
• < 32 wks, assess renal function
o Perform serial bladder drainages over 3-4 days
o Third sample most useful ("fresh" urine)
• Normal fetal urine is hypotonic
• Isotonic urine ~ poor renal function
o Good prognostic indicators
• Na < 100 mEq/L
• Cl < 90 mEq/L
• Osmolarity < 210 mOsm/L
• ~2 microglobulin < 4 mg/L
• Ca < 8 mg/dL
• Sonographically normal kidneys (normal
echogenicity, no cysts, preserved corticomedullary
differentiation)
o Beta 2 microglobulin

•
•

• Found in fetal serum
• Filtered by glomerulus, reabsorbed by proximal
tubule
• Large amounts in fetal urine ~ renal damage
Consider intervention for those in good prognostic
category with worsening oligohydramnios and/or
hydronephrosis
o Vesicoamniotic shunt
• Goal is to prevent pulmonary hypoplasia
• May occlude or migrate
• Often pulled out by fetus
• Anterior placenta relative contraindication
o Vesicostomy if shunt fails
• Shown to potentially improve pulmonary
function, but no effect on renal outcome
Generally no intervention if amniotic fluid volume
normal
No improvement in outcome for intervention late in
pregnancy
Experimental studies are on-going using in utero
endoscopic valve ablation
Long term sequelae from poor bladder function may
necessitate urinary diversion surgery

I DIAGNOSTIC

CHECKLIST

Consider
• Early oligohydramnios
~ poor prognosis regardless of
cause
o Early diagnosis of PUV allows consideration of
intervention
o Type and timing of intervention very controversial
o UCSF series1981 to 1999: Fetal mortality rate 43%
• Intervention may result in live birth but 45% of
survivors still have renal insufficiency

Image Interpretation

Pearls

• Dilated bladder + oligohydramnios
in male fetus
highly suspicious for PUV
o Same findings in a female, likely to be urethral
agenesis

I SELECTED REFERENCES
1.

2.
3.
4.

5.

6.

7.

Eckoldt F et al: Posterior urethral valves: prenatal
diagnostic signs and outcome. Urol Int. 73(4):296-301,
2004
Vanderheyden
T et al: Fetal renal impairment.
Semin
Neonatol. 8(4):279-89, 2003
Holmes N et al: Fetal surgery for posterior urethral valves:
long-term postnatal outcomes. Pediatrics. 108(1):E7, 2001
Herndon CD et al: Consensus on the prenatal management
of antenatally
detected urological abnormalities.
J Urol.
164(3 Pt 2):1052-6, 2000
Freedman AL et al: Fetal therapy for obstructive uropathy:
Diagnosis specific outcomes [corrected]. J UroI156:720-3;
discussion 23-4, 1996
Crombleholme
TM et al: Fetal intervention
in obstructive
uropathy: Prognostic indicators and efficacy of
intervention.
Am J Obstet Gynecol. 162:1239-44, 1990
Mahony BS et al: Fetal renal dysplasia: Sonographic
evaluation. Radiology. 152:143-6, 1984

POSTERIOR URETHRAL VALVES
IIMAGE

GALLERY
(Left)

Ultrasound shows a
thick-walled (arrows),
distended bladder. The
"keyhole" sign is created by
funneling of the bladder into
the dilated posterior urethra
(open arrow). (Right)
Ultrasound shows a needle
(arrow) in the bladder for
urine aspiration. This allows
karyotype analysis, as well as
assessment of urinary
osmolality and electrolyte
concentration.
The later
provide an indirect measure
of renal function.

(Left) Axial oblique
ultrasound shows a markedly
dilated bladder (open
arrows) and bilateral
hydronephrosis
(arrows) in a
fetus with posterior urethral
valves. (Right) Coronal
ultrasound in the same fetus
after vesicoamniotic
shunting
shows urinary ascites
surrounding the liver
(arrows) and bowel (curved
arrow). This was attributed
to shunt migration with urine
leak through the bladder
puncture site.

(Left) Sagittal ultrasound
shows typical findings of
PUv, with distension of the
bladder (arrow), a dilated
posterior urethra (open
arrow), and male genitalia
(curved arrow). (Right)
Coronal ultrasound in a 16
week male fetus with PUV
shows a portion of the
bladder (arrow) and bilateral
hydronephrosis
(open
arrows). Renal parenchymal
echogenicity
is greater than
normal, increasing suspicion
for renal dysplasia.

PRUNE BELLY SYNDROME

Coronal
ultrasound
shows
massive,
bilateral
hydronephrosis (arrows) in a male fetus, with a dilated
bladder (open arrows). This appearance is very difficult
to distinguish from posterior urethral valves.

ITERMINOLOGY
Abbreviations

and Synonyms

• Eagle-Barrett syndrome

Definitions
• Rare congenital disorder characterized by dramatic
collecting system dilatation, deficiency of abdominal
musculature and cryptorchidism

IIMAGING

Cross pathology shows a very distended abdomen and
small chest. Lack of musculature gives the abdominal
wall a flaccid, wrinkled appearance, hence the name
prune belly syndrome.

• Angled scan shows bladder funneling into dilated
posterior urethra ("keyhole" sign)
o Prune belly syndrome does not have a dilated
posterior urethra
• No "keyhole"
• Entire urethra may be dilated
• Look at ureters and kidneys
o Always dilated with prune belly syndrome
o May be normal with PUV
• Scan genitalia, looking for undescended testes
o Difficult if oligohydramnios
is present

FINDINGS

Ultrasonographic

I DIFFERENTIAL

Findings

DIAGNOSIS

• Gross dilatation of collecting system
o Large, thin-walled bladder
o Bilateral hydroureter
o Bilateral hydronephrosis
• Entire urethra dilated
o No obvious point of obstruction
o May be difficult to visualize
• Oligohydramnios often present

• May appear identical
o Some cases of prune belly may be end result of early
obstruction from valves
• Look for dilated posterior urethra ("keyhole" sign)
• Hydronephrosis/ureter
not always present
• Thick-walled bladder

Imaging Recommendations

Megacystis-microcolon

• Very difficult to differentiate from posterior urethral
valves (PUV)
• Need to focus scan on urethra
o PUV has dilatation of proximal portion of urethra

• Massive distention of urinary bladder with
h ydroureteronep hrosi s
• Normal amniotic fluid volume
• More common in females (4:1)

DDx: Obstruction

Posterior urethral valves

Causing Hydronephrosis

PUV

PUV

Duplicated System

PRUNE BELLY SYNDROME
Key Facts
Terminology
• Rare congenital disorder characterized by dramatic
collecting y tern dilatation, deficiency of abdominal
musculature and cryptorchidi m

Imaging Findings
•
•
•
•

Large, thin-walled bladder
Bilateral hydroureter
Bilateral hydronephrosis
Entire urethra dilated

eed to focus can on urethra
can genitalia, looking for undescended

Top Differential

testes

Diagnoses

• Po terior urethral valve
• Megacystis-micro olon

Pathology
• Large bladder inhibit de cent of te te
• Rarely reported in females

• Bladder aspiration shows normal renal function
• No other malformations
• Neonatal renal transplant may be required

I PATHOLOGY
General Features
• Etiology
o Multiple proposed mechanisms
• Primary urinary tract obstruction
• Primary abnormality in mesodermal development
• Genetic defect
o Underlying obstructive lesion thought by many to
be most likely cause, but may not be identified
• Possibly related to underlying prostatic hypoplasia
o No specific primary histologic abnormality of
abdominal wall found
o Sporadic reports of other underlying abnormalities
causing similar appearance of lax abdominal wall
• Giant liver cysts
• Large ovarian cysts
o Large bladder inhibits descent of testes
• Epidemiology
o 1:30,000 to 1:50,000
o Rarely reported in females
o More common in twin pregnancies

ICLINICAL

•
•

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Consider prune belly syndrome when there is massive
dilatation of the entire collecting system

I SELECTED
1.

2.

3.

4.

REFERENCES

Salihu HM et al: Prune belly syndrome and associated
malformations. A 13-year experience from a developing
country. West Indian Med J. 52(4):281-4, 2003
Perez-Brayfield MR et al: In utero intervention in a patient
with prune-belly syndrome and severe urethral hypoplasia.
Urology. 57(6):1178, 2001
Leeners B et al: Prune-belly syndrome: therapeutic options
including in utero placement of a vesicoamniotic shunt.]
Clin Ultrasound. 28(9):500-7, 2000
Shimada K et al: Histology of the fetal prune belly
syndrome with reference to the efficacy of prenatal
decompression. Int] Urol. 7(5):161-6, 2000

ISSUES
IIMAGE GALLERY

Presentation
• Most common signs/symptoms
o Massive collecting system dilatation
o Oligohydramnios
• Postnatal
o Flaccid, "doughy" abdomen
• Wrinkled appearance resembles a prune
o Potter facies may be seen if severe oligohydramnios

Natural History & Prognosis
• Dependent on severity of oligohydramnios
damage
• Renal failure common in survivors

and renal

Treatment
• Serial sonography required throughout pregnancy
o Monitor degree of dilatation and amniotic fluid
volume
• Vesicoamniotic shunt may aid in decompressing
bladder and improving amniotic fluid status
o Consider early intervention for best possible
outcome
o Performed only if certain criteria met
• Karyotype normal

(Left) Cross pathology shows the thin abdominal wall, with no
musculature (arrow), a dramatically dilated bladder (open arrow)
and a portion of a very tortuous, dilated ureter (curved arrow).
Undescended testes were also present. (Right) Cystogram on an
infant with prune belly syndrome shows a grossly dilated bladder
(open arrow), with reflux into severely ectatic ureters (arrows). The
contrast appears less dense than normally seen, as it is diluted by the
large amount of urine within the collecting system. (Courtesy G./.
Lonergan, MO).

URETEROCELE

Graphic shows a simple ureterocele (arrow) in the
normal insertion position. In a duplicated system, the
ectopic ureter (curved arrow) enters the bladder inierior
and medial to the normotopic ureter (open arrow).

Axial ultrasound shows a ureterocele as a thin-walled,
cystic lesion (arrow) within the lateral aspect oi the
bladder lumen. When large, a ureterocele may be
mistaken ior the bladder.

ITERMINOlOGY

IIMAGING FINDINGS

Definitions

General Features

• Congenital dilatation of intra mucosal segment of
ureter
o Dilated segment prolapses into bladder lumen
• Variable types: Simple, ectopic and cecoureterocele
• Simple
o Occur at normal ureterovesicle junction
o Located at trigone of bladder
o Not usually seen in utero
• Ectopic
o Almost always associated with renal duplication
o Inserts medial and inferior to trigone, near bladder
base
o Ectopic ureter usually has a stenotic opening into
bladder
o Ectopic ureter may potentially insert outside of
bladder
• Females: Vagina, uterus
• Males: Epididymis, seminal vesicles, ejaculatory
ducts, vas deferens
• Directly onto perineum
• Urethra
• Cecoureterocele
o Uncommon type of ectopic ureterocele
o Dissects submucosally into urethra
o Can cause intermittent bladder outlet obstruction

• Best diagnostic clue
o Thin-walled, cystic mass inside bladder lumen
o Hydronephrosis predominately involving upper pole
of kidney
• Weigert-Meyer rule in renal duplication
o Upper moiety ureter inserts inferior and medial to
normal ureteric insertion site
• Ectopic implantation '* upper pole obstructs
• Lower renal pole moiety inserts normally in bladder
trigone
o Distortion of orifice by adjacent upper moiety
ureterocele may result in reflux

DDx: Abnormal

Ultrasonographic

Bladder Or Collecting System

Posterior UV

Findings

• Bladder findings
o Anechoic, "balloon-like", thin-walled cyst inside
bladder lumen represents ureterocele
• May prolapse in and out of bladder
• If ureterocele obstructed -+ hydroureter
• Look for connection of "cyst" to distal ureter
• Color Doppler may show ureteral jet
• If ureterocele is large
o May obstruct contralateral kidney
o May cause bladder outlet obstruction
• Ureteral findings

URETEROCELE
Key Facts
Terminology
•

ongenital dilatation of intramucosal
egment of
ureter
• Dilat d segm nt prolapses into bladder lumen
• Almost alway a ociated with renal duplication
• Ectopic ureter may potentially ins rt out ide of
bladder

Imaging Findings
• Thin-wall d, cystic mass in ide bladd r lumen
• Hydron phro i predominately involving upper pole
of kidn y
• Upper moiety ureter in erts inferior and medial to
normal ureteri insertion site
• Lower r nal pole moiety in erts normally in bladder
trigon

o Dilated ureter
• Fluid-filled tube connects to renal pelvis
• May "touch" spine (dilate bowel loops tend to be
more central)
• May see peristalsis
o Both upper and lower pole ureters can be dilated in
renal duplication
• Ureterocele with obstructed ectopic ureter
• Normotopic ureter dilated from reflux
• Renal findings
o Hydronephrosis usually worse in upper pole
(obstructed system)
o Lower pole may also have hydronephrosis from
re!lux
o Kidney large relative to contralateral,
non-duplicated kidney
o Obstructive cystic dysplasia of upper pole renal
parenchyma if obstruction severe
• Dilated collecting system/cysts replace upper renal
parenchyma => displaces normal lower pole
• Mass effect -+ lower pole pushed down
• Oligohydramnios
o May develop if ureterocele obstructs bladder outlet

Imaging Recommendations
• Protocol advice
o When hydronephrosis present, always search for
other signs of renal duplication
• Normal lower pole moiety (I.e. dilated collecting
system upper pole only)
• Ureterectasis
• Ectopic ureterocele
o Ureterocele + dilatated upper pole collecting system
= duplication
• Evaluate bladder several times during any fetal
ultrasound
o Ureterocele best seen when bladder partially full
• If is bladder empty, ureterocele may be
misinterpreted as bladder
• When distended, bladder may compress
ureterocele
• Evaluate kidney in both transverse and longitudinal
view

• Evaluate bladder everal time during any fetal
ultrasound
• Ureterocele be t se n when bladder partially full
• If is bladder empty, ureterocele may be
misinterpreted as bladder
• When distended, bladder may compress ureterocele

Top Differential

Diagnoses

• Bladder mass
• Ve icoureteral reflux
• ongenital megaureter

Diagnostic Checklist
•

y tic ma in bladder is overwhelmingly likely to be
an ectopic ureter cele
• Examine kidneys in both axial and longitudinal
planes to look for duplicated coli cling sy t m

o Transverse view alone may mimic ureteropelvic
junction (UP) obstruction
o Lower pole moiety may be displaced inferiorly and
difficult to see
• Follow collecting system in real-time
o Renal pelvis -+ ureter -+ ureterocele

I DIFFERENTIAL

DIAGNOSIS

Bladder mass
• Rhabdomyosarcoma
o Solid mass
o Lacks communication
with distal ureter
• Bladder hematoma
o May be solid or cystic
o No communication
with distal ureter
o Extremely uncommon in fetus

Mass effect from sigmoid colon
• Distal bowel dilation -+ multiple low echogenicity
structures in pelvis
• Urine is anechoic, meconium produces low-level
echoes
• Look for changing shape as bladder fills and empties
• Colonic loops do not undergo significant peristalsis

Vesicoureteral

reflux

• Dynamic changes may be observed
• Common
• Normal bladder

Congenital
•
•
•
•
•

megaureter

Fusiform dilation of the ureter
May have hydronephrosis
Usually unilateral (left> right)
Mainly affects males
Normal bladder

UPJ obstruction
• Collecting system dilatation
• Ureter not dilated
• No ureterocele

URETEROCELE
Bladder "Hutch" diverticulum
• Periureteral diverticulum of bladder
• Extrinsic, does not prolapse into bladder lumen
• Separate from distal ureter

I PATHOLOGY
General Features
• Genetics: Sporadic
• Etiology
o Stenosis of distal ureteric orifice
o Distal ureter lumen expands between mucosa and
muscle of bladder wall
o Ectopic ureterocele distorts adjacent normal ureteral
orifice allowing reflux into lower pole moiety
o Embryology theories
• Delayed canalization of Chawalle membrane
during embryogenesis
• Accessory ureteric bud inserts separately into
metanephric blastema
• Epidemiology
o Incidence of ectopic ureterocele parallels that of
renal duplication
o Renal duplication with ectopic ureterocele
• 1:9,000 live births
o Renal duplication without ureterocele (partial
duplication)
• 1:150 in general population
• Ureters unite before bladder insertion
• Partial duplication less likely to have ureterocele
• No clinical significance
o Ectopic:simple ureterocele = 3:1
• Associated abnormalities
o Gynecological abnormalities in 50% of females with
duplication
o Contralateral duplication in 10-20%

I CLINICAL ISSUES
Presentation
• Incidental finding in utero
• Found in work-up of hydronephrosis
• Typical presentation in infancy
o Hematuria, urinary tract infection
o Hydronephrosis, urinary retention
o Boys with extravesicle insertion
• Epididymitis or scrotal symptoms
o Girls with extravesicle insertion
• Unsuccessful toilet training
• Underwear always damp
• Simple ureteroceles maybe asymptomatic

o Consider incision of ureterocele if bladder outlet
obstruction/ oligohydramnios
• Postnatal work-up in all cases
o Ultrasound of bladder and kidneys
o Voiding cystourethrogram (VCUG)
• Filling defect in bladder best seen on early filling
image
• Vesicoureteral reflux into lower pole
• "Drooping lilly" sign: Obstructed upper pole
pushes lower pole calyces inferiorly
o Intravenous pyelogram not usually necessary
• Delayed nephrogram and pyelogram of upper pole
moiety due to obstruction
• May see extravesicular ectopic ureter insertion
o MRI may be helpful for complicated duplications
• MR urogram may show extra vesicular ureteral
insertion site
• Delineate associated gynecological abnormalities
o Radionuclide renal scan to assess function
• Surgical options based on consequences of ureterocele
o Endoscopic ureterocele incision
• Particularly if infected or obstructed
o Ureteral reimplantation surgery
o Heminephroureterectomy
• Performed if poorly functioning upper pole

I DIAGNOSTIC
Consider

• Cystic mass in bladder is overwhelmingly likely to be
an ectopic ureterocele
o Examine kidneys in both axial and longitudinal
planes to look for duplicated collecting system
• Always consider collecting system duplication as a
cause of hydronephrosis

Image Interpretation

Treatment
• In utero treatment not usually indicated

Pearls

• Dilated upper pole moiety + cystic mass in bladder
ureteral duplication with ureterocele

I SELECTED
1.

2.

3.

4.
5.

Natural History & Prognosis
• Prognosis depends on degree of obstruction
o Excellent if no obstruction or reflux
o Variable outcome if high grade reflux or prolonged
obstruction

CHECKLIST

6.

7.

=

REFERENCES

Sepulveda Wet al: Prenatal sonographic diagnosis of
bilateral ureteroceles: the pseudoseptated fetal bladder. J
Ultrasound Med. 22(8):841-4; quiz 845-6,2003
Sooth ill PW et al: Ultrasound-guided laser treatment for
fetal bladder outlet obstruction resulting from ureterocele.
AmJ Obstet Gynecol. 188(4):1107-8,2003
Whitten SM et al: Accuracy of antenatal fetal ultrasound in
the diagnosis of duplex kidneys. Ultrasound Obstet
Gynecol. 21(4):342-6, 2003
Kraus SJ: Genitourinary imaging in children. Pediatr Clin
North Am. 48(6):1381-424, 2001
Staatz G et al: Magnetic resonance urography in children:
evaluation of suspected ureteral ectopia in duplex systems.
J Urol. 166(6):2346-50, 2001
Quintero RAet al: In-utero treatment of fetal
bladder-outlet obstruction by a ureterocele. Lancet.
357(9272):1947-8,2001
Kang AH et al: Antenatal ultrasonographic development of
ureteroceles. Implications for management. Fetal Diagn
Ther. 13(3):157-61, 1998

URETEROCELE
IIMAGE GALLERY
(Left) Axial color Doppler
ultrasound shows a cyst
(arrow) within the bladder
lumen, a typical appearance
for a ureterocele. (Right)
Coronal ultrasound of the
kidney shows
hydronephrosis
of the upper
pole moiety (arrow) of this
renal duplication. The lower
pole shows minimal
caliectasis (open arrow). In a
duplicated system, the upper
pole obstructs secondary to
the ectopic ureterocele and
the lower pole may reflux.

(Left) Coronal ultrasound
shows a dilated, ectopic
ureter (arrow) leading to a
large ureterocele (curved
arrow) within the bladder.
Both the upper (not shown)
and lower poles (open
arrow) of the kidney were
dilated. (Right) Lateral view
from a VCUC shows a large,
smooth filling defect (arrow)
at the bladder base, created
by an ectopic ureterocele.

Variant

(Left) Axial ultrasound

shows
(arrow) in
the bladder. (Right) Coronal
oblique ultrasound of the
kidneys shows multiple cysts
within the left kidney
(arrows). Chronic severe
obstruction associated with
the ureterocele resulted in
obstructive cystic dysplasia
of the kidney. The right
kidney (calipers) is normal.

a large ureterocele

URACHAL ANOMALIES

Graphic shows a urachal cyst (arrow) located between
the dome of the bladder and the umbilical cord
insertion. Midline, anterior location is a key diagnostic
feature of a urachal anomaly.

Coronal oblique ultrasound shows a cystic midline mass
(arrows) extending cephalad from the dome of lhe
bladder (open arrow), consistent with a patent urachus.

ITERMINOlOGY

Imaging Recommendations

Definitions

• Follow-up scans
a May resolve as gestation progresses
• Still requires complete postnatal work-up with
voiding cystourethrogram
(VCUG)

• Group of disorders resulting from incomplete
involution of allantois
a Patent urachus
• Most common form seen in utero
a Urachal cyst
a Urachal diverticulum
a Urachal sinus

IIMAGING

FINDINGS

General Features
• Location
a Midline, anterior pelvis
a Urachus lies in space of Retzius, between
transversalis fascia and peritoneum

Ultrasonographic

Findings

• Cystic mass above bladder
a Communication
with bladder confirms patent
urachus
• May extend into base of umbilical cord
a Associated with allantoic cord cysts

I DIFFERENTIAL

DIAGNOSIS

Other abdominal

cysts

• Location most important finding in differentiating
from urachal anomaly
a Other cystic masses are not restricted to anterior
midline
• Ovarian cyst, enteric duplication cyst, mesenteric cyst
• Bowel obstructions, meconium pseudocyst

Bladder outlet obstruction
• Dilated bladder may extend up to umbilicus
a Ureterectasis, hydronephrosis,
cystic kidneys
a Look for "key hole" appearance with posterior
urethral valves (PUV)
• Oligohydramnios

Omphalocele
• Potential source of confusion
with umbilical cord cyst

if urachus communicates

DDx: Pelvic Fluid Collections

Ovarian Cyst

PUV

OUp/iCdlion

Cyst

URACHAL ANOMALIES
Key Facts
Terminology

Top Differential

• Group of disorders resulting from incomplete
involution of allantois

• Other abdominal

Imaging Findings

• Bladder outlet obstruction i ri k factor
• U ually an isolated finding

• ystic mass above bladder
• Communication
with bladder confirms patent
urachus
• May extend into ba e of umbilical cord
• Associated with allantoic cord cyst

I PATHOLOGY
General Features
• Etiology
o Embryology
• Allantois forms from caudal end of yolk sac
• Functions as primitive bladder and early blood
forming organ
• Involutes to become median umbilical ligament
• Any persistent segments are termed urachal
remnants
o Bladder outlet obstruction is risk factor
• Urachus serves as "pop-off valve" to decompress
bladder
• Epidemiology
o Patent urachus 1:40,000 live births
o M:F=2:1
• Associated abnormalities
o Usually an isolated finding
o Umbilical cord cyst or thickening
• Thickening may be from urine absorption into
Wharton jelly
• Association with aneuploidy reported
o Other genitourinary anomalies
• PUV, cryptorchidism, renal anomalies
o Omphalocele

Pathology

Diagnostic Checklist
• Anterior, midline location mo t important
finding

Presentation
• Most common signs/symptoms: Incidental
abdominal mass
• Other signs/symptoms
o Umbilical cord cyst
o Postnatal
• Persistent drainage from umbilicus
• Urinary tract infection

cystic

diagnostic

o Ultrasound appearance depends on type and
amount of persistent remnant
• Typically thick, well-defined wall
• Resection of entire tract
o May need to be done as a staged procedure if
presenting with infection/inflammation
• Patent urachus with bladder outlet obstruction
o Correct obstruction first
o Urachus may spontaneously close when pressure
relieved

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Anterior, midline location most important diagnostic
finding
o Located between bladder and umbilicus
o Most other cystic abdominal masses may be
excluded based on paramedian location

I SELECTED REFERENCES
1.

2.
3.

I CLINICAL ISSUES

Diagnoses
cy ts

Yu]S et al: Urachal remnant diseases: spectrum of CT and
US findings. Radiographics. 21(2):451-61, 2001
Awwad] et al: Sonographic diagnosis of a urachal cyst in
utero. Acta Obstet Gynecol Scand. 73(2):156-7, 1994
Hill LM et al: The sonographic diagnosis of urachal cysts in
utero. J Clin Ultrasound. 18(5):434-7, 1990

I IMAGE GALLERY

Natural History & Prognosis
• Cystic mass may spontaneously close in utero
o Patent urachus or urachal sinus may remain
• Excellent prognosis with repair
• Risk of infection and malignancy if not resected

Treatment
• Complete postnatal work-up, even if anomaly appears
to have resolved in utero
o VCUG best test to document patency of urachus

(Left) A VCUC after delivery, on the same infant from the preceding
page, shows the bladder (arrows) in direct continuity superiorly with
the patent urachus (curved arrow). (Right) Intra-operative
photograph in another case shows an allantoic cyst (arrow) within
the base of the umbilical cord. The cyst is filled with urine and
communicates with the bladder via a patent urachus.

AMBIGUOUS

Axial ultrasound shows ambiguous genitalia. A small
phallus (arrow) is seen between 2 sacs (open arrows).
They could
be labia or an empty
scrotum.
Amniocentesis results were male with trisomy 73.

Clinical
photograph
shows
severe
penoscrotal
hypospadias and cryptorchidism as a cause of AG. The
penis is small and dysmorphic.
The urethral orifice
(arrow) is ventral and at the base of the penis.

o Secondary structures rarely seen in utero
• Uterus
• Ovaries
• Non-descended testes

ITERMINOlOGY
Abbreviations

GENITALIA

and Synonyms

• Ambiguous genitalia (AG)
• Fetal genital anomaly
• Intersex conditions

Ultrasonographic

Definitions
• Confusing appearance of external genitalia
• Cannot determine if fetus is male or female
• AG is morphologic diagnosis with many causes

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Perineal region seen well and
gender is indeterminable
• Morphology: Extremely variable
• General AG issues
o Cannot differentiate penis from clitoris
• Early phallic structure similar in males and
females
• Mild clitoromegaly normal in fetal life
o Cannot differentiate scrotum from labia
• Cryptorchidism (non-descended testes)
• Empty scrotum resembles labia
• Fused labia resembles scrotum

Findings

• AG findings in XY fetus
o Hypospadias
• Abnormal ventral penile urethral opening
• Penoscrotal, scrotal, perineal are most severe
• Distal penile hypospadias is least severe
• Blunt-ending penis
• +/- Small penis
• +/- Chordee (ventral curvature of penis)
• 10% with cryptorchidism
o Epispadias
• Abnormal dorsal urethral opening
• More rare than hypospadias
• Small bifid penis
• Associated with bladder extrophy
o Microphallus
• Small penis
• +/- Cryptorchidism
o Chordee
• Ventral curvature of penis
• Penis is foreshortened
o Cryptorchidism
• Undescended testes

DDx: Normal Genital Morphology

Normal Male

Normal Female

Normal Labia

Normal Scrotum

AMBIGUOUS

GENITALIA

Key Facts
Terminology

Pathology

•
•

•
•
•
•
•
•
•
•
•

onfusing appearance of external genitalia
G i morphologic diagno is with many causes

Imaging Findings
•
•
•
•
•
•
•
•
•
•

Hypospadias
Microphallus
Cryptorchidi m
litoromegaly
Fusion of labia
Evaluate genitals in axial + agittal planes
litoris point caudal on agittal view
Penis points cranial on sagittal view
Look for teste in scrotum after 25 wks
Use color Doppler to see urine stream

Trisomy 13
Triploidy
Congenital adrenal hyperplasia
Female pseudohermaphrodi
m (46,XX)
Male pseudohermaphrodism
(46,XY)
Mixed gonadal dysgenesis (45,XO/46,XY)
Pure gonadal dysgene i
True hermaphrodism
(rare)
1:5,000 live births

Clinical Issues
•

ongenital
treated

adrenal hyperplasia

Diagnostic Checklist
• Do not a ign gender prenatally

• Can not diagnose if < 32 wks
• Scrotum mimics labia
o Blind ending vagina
• Rarely seen prenatally
• AG findings in XX fetus
o Clitoromegaly
• Can mimic penis
• Can mimic hypospadias + cryptorchidism
o Fusion of labia
• Posterior most often
• Mimics empty scrotum
o Prominent labial folds
• Redundant labia minora
• Normal variant
• AG + other anomalies
o Aneuploidy
• Trisomy 13
• Triploidy
o Many syndromes
• Smith-Lemli-Opitz
• Prader-Willi
• Velocardiofacial syndromes
• AG and congenital adrenal hyperplasia
o Important treatable cause of AG
o AG secondary to virilized female (XX)
• Clitoromegaly
• +/- Fused labia
o Congenital adrenal hyperplasia
• Bilateral enlarged adrenal glands
• Discoid morphology
• Indistinct cortex/medullary
differentiation
• Normal adrenal glands have are triangular with an
"ice-cream sandwich" appearance (hypoechoic
cortex and hyperechoic medulla)
o Other causes of t adrenal gland size or suprarenal
mass are usually unilateral
• Neuroblastoma
• Hemorrhage
• Extralobar sequestration

Imaging Recommendations
• Best imaging tool
o Evaluate genitals in axial + sagittal planes

may be fatal if not

if G

• Penis resembles clitoris on axial views
• Clitoris points caudal on sagittal view
• Penis points cranial on sagittal view
o Consider 3D ultrasound
• Multiplanar capacity
• Surface rendered views helpful
• Protocol advice
o Look for testes in scrotum after 25 wks
• 97% descend by 32 wks
o Use color Doppler to see urine stream
• Find urethral orifice (tip vs. ventral vs. dorsal)
o Genetic counseling
• Amniocentesis
o Do not assign gender during fetal life if ambiguous
• Even when karyotype is known
• Best done after full physical exam
• Family may need significant counseling
o Look carefully for other anomalies
• AG associated with aneuploidy and syndromes

I DIFFERENTIAL

DIAGNOSIS

Normal female genitalia
• Labia
o 2-4 parallel echogenic lines
• Clitoris
o Between labia on transverse views
o Points caudad on sagittal views
• Uterus
o Can often be seen after 20 wks
o Echogenic mass between bladder and rectum
• Ovaries
o Rarely seen unless with cyst (3rd trimester)

Normal male genitalia
• Normal scrotum
o Testes descend at 25-32 wks
o Small hydroceles common
• Often transient
• Normal penis
o Tapered end
o Urine stream from tip

AMBIGUOUS
• Color Doppler
o Points cephalad on sagittal views
• "Dome sign"
o Use nomograms for penile length vs. gestational
if concerned about size

First trimester genitalia
• Phallic structure seen as early as 11 wks
o Same size in males and females
o Different orientation on sagittal views
• Penis points cranial
• Clitoris points caudal
• AG often develops after 1st trimester

I PATHOLOGY
General Features
• Genetics
o Trisomy 13
o Triploidy
o Klinefelter (47XXY)
o Many duplication and deletion syndromes
o Congenital adrenal hyperplasia
• Autosomal recessive (25% recurrence)
• Etiology
o Heterogeneous group with many etiologies
o Congenital adrenal hyperplasia
• Cortisol/aldosterone
synthesis enzyme defect
• > 90% from 21-hydroxylase defect
o Female pseudohermaphrodism
(46,XX)
• Fetus has 2 ovaries
• Excess androgenesis
• Congenital adrenal hyperplasia
• Maternal ingestion of androgens
o Male pseudohermaphrodism
(46,XY)
• Fetus has 2 testes
• + End organ testosterone response (80%)
• + Testosterone production
• + Mullerian inhibiting factor
o Mixed gonadal dysgenesis (45,X0/46,XY)
• Mosaicism
• Streak ovary + dysgenetic testis
• Turner phenotype common
o Pure gonadal dysgenesis
• Variable karyotype (46,XO; 46,XX; 46,XY)
• Streak gonads
• Female phenotype
o True hermaphrodism
(rare)
• Most 46,XX + variable Y-chromatin
• Variable external genitalia
• Epidemiology
o 1:5,000 live births
o 1:15,000 live births with congenital adrenal
hyperplasia

age

GENITALIA
o Prior child with congenital adrenal hyperplasia
• Amniocentesis/chorionic
villus sampling to rule
out congenital adrenal hyperplasia in 2nd child
• Molecular analysis for CYP21 gene
• Other signs/symptoms
o Maternal hormone ingestion during 1st trimester
• Progesterone for threatened abortion
• Androgens for endometriosis

Natural History & Prognosis
• Congenital adrenal hyperplasia may be fatal if not
treated
o + Aldosterone/cortisone
o Salt wasting
• Hyponatremia, hyperkalemia
o Progressive virilization
• AG in females

Treatment
• Consultant team approach is best for family
o Genetics, urology, psychiatry
• Gender assignment only after neonatal work-up
o Physical examination
o Laboratory tests (including endocrine function)
• Surgical treatment often necessary
• Congenital adrenal hyperplasia treatment
o Prenatal dexamethasone

I DIAGNOSTIC
Consider

• AG diagnosis only if perineum is seen well
• Beware of mild normal clitoromegaly
• Amniocentesis
o Determine genetic sex
o Rule out aneuploidy
o Rule out congenital adrenal hyperplasia

Image Interpretation

I SELECTED
1.

2.

3.

5.

Presentation
• Most common signs/symptoms
o Incidentally noted during routine ultrasound
• Parents desire to know gender of child
o In association with other anomalies

Pearls

• Do not assign gender prenatally if AG
o Even when amniocentesis results are available
o Genetic sex not always followed
• Examine fetal adrenal glands if virilized female seen
o Rule out congenital adrenal hyperplasia

4.

IClINICAllSSUES

CHECKLIST

6.

REFERENCES

Bidarkar SS et al-:-Evaluation and management of the
abnormal gonad. Semin Pediatr Surg. 14(2):118-23,2005
Saada] et al: Sonography in prenatal diagnosis of
congenital adrenal hyperplasia. Prenat Diagn. 24(8):627-30,
2004
Pinette MG et al: Normal growth and development of fetal
external genitalia demonstrated by sonography.] Clin
Ultrasound. 31(9):465-72, 2003
Naylor CS et al: Use of three-dimensional
ultrasonography
for prenatal diagnosis of ambiguous genitalia.] Ultrasound
Med. 20(12):1365-7, 2001
Zalel Y et al: The development of the fetal penisuan in
utero sonographic evaluation. Ultrasound Obstet Gynecol.
17(2):129-31,2001
Bronshtein M et al: Prenatal sonographic signs of possible
fetal genital anomalies. Prenat Diagn. 15(3):215-9, 1995

AMBIGUOUS

GENITALIA

IIMAGE GALLERY
(Left) Axial ultrasound shows
a small, heart-shaped scrotal
sac (arrows) which mimics
labia in a 3rd trimester fetus
with a normal XY karyotype
(penis - open arrow).
Prenatal diagnosis of
cryptorchidism
was
suggested. (Right) Axial
ultrasound performed after
delivery shows bilateral
empty scrotum (arrows).
One testis was found in the
inguinal canal and the other
was intra-abdominal

(Left) Axial ultrasound shows
ambiguous genitalia (arrows)
in a fetus with multiple other
anomalies and growth
restriction. The genital
mound is amorphous.
Chromosome
results were
male triploidy. (Right)
Clinical photograph in the
same fetus shows a
microphallus (arrow) and
"labia-like" scrotum,
consistent with
cryptorchidism.
AC is
common with trisomy 73
and triploidy, bulnol as an
isolated finding.

Variant
(Left) Axial ultrasound shows
confusing genital
morphology in a 3rd
trimester letus. The
echogenic lines (arrows)
suggest labia but we were
unsure and therefore, 3D
ultrasound was performecl.
(Right) 20 (top) and 3D
reconstruction
(bottom)
shows labia majora (arrows)
and labia minora (open
arrows) folds. The baby was
born with prominent labial
folds, considered a normal
variant.

HYPOSPADIAS

Ultrasound shows distal penile hypospadias. The tip of
the penis is not tapered but instead ends bluntly
(arrow), resembling a "squashed cone". Two echogenic
lines (open arrows) represent prepuce lateral folds.

ITERMINOlOGY
Definitions
• Urethra opens on ventral side of penis, not tip

IIMAGING

o Fills and empties with micturition
• Associated anomalies
o 40% with other urogenital anomalies
o 10% with cryptorchidism
o 7-9% with extra-urogenital anomalies

Imaging Recommendations

FINDINGS

General Features
• Best diagnostic clue: "Blunt-ended" penis
• Location: Anywhere along expected course of urethra

Ultrasonographic

Clinical photograph shows that the urethral opening
(arrow) is ventral to the penis tip. Lateral folds of the
prepuce (open arrows) and ventral curve of the penile
shaft (curved arrow) are classic findings of hypospadias.

• Fetal sex determination
o Accurate in > 90% after 20 wks
• Look at morphology of penis

I DIFFERENTIAL DIAGNOSIS

Findings

• Tip of penis is blunted instead of pointed
o "Squashed cone"
o Often see 2 echogenic lines at tip
• Prepuce lateral folds
• Small penis (nonspecific)
• Chordee (ventral curving of penis)
• Abnormal stream (color Doppler)
o From ventral penis instead of tip
o Fan-shaped instead of linear
• "Tulip sign" of severe hypospadias
o Small blunt-ended penis between 2 scrotal folds
• Undescended testicles (cryptorchidism)
o Difficult to differentiate from female genitalia
• Associated penile cyst (rare)
o Cyst from urethrocutaneous fistula

Ambiguous genitalia
• Can not determine sex based on morphology
• Heterogeneous disorders
o Etiologies
• Chromosome defect
• Hormone influence
o Common diagnoses
• Clitoromegaly
• Cryptorchidism (+/- hypospadias)
• Amniocentesis results helpful

Micropenis
• Small penis with normal shape
• Normal stream
• Many different causes

DDx: Ambiguous Genitalia

Clitoromegaly

Clitoromegaly

Cryptorchidism

HYPOSPADIAS
Key Facts
Terminology

Top Differential

• Urethra opens on ventral side of penis, not tip

Imaging Findings

• Ambiguous genitalia
• Micropenis
• ormal early male genitalia « 20 wks)

•
•
•
•
•

• 50% anterior (glans)
• 30% middle (penile)
• 20% posterior (penoscrotal,

Best diagnostic clue: "Blunt-ended" penis
Often see 2 echogenic line at tip
hordee (ventral curving of penis)
Abnormal stream (color Doppler)
40% with other urogenital anomalie

• Associated cryptorchidism

Pathology
scrotal, perineum)

o Inability to guide stream during micturition
o Abnormal erection (penile curvature)
o Infertility

common

Normal early male genitalia «

Diagnoses

20 wks)

• Fusion of labioscrotal folds not complete
• Testes may not descend until> 26 wk

Treatment

!PATHOlOGY

• Surgery
o Ureteroplasty
o Glanuloplasty
o Multiple revisions often required
• Mild hypospadias may not need surgery

General Features
• Genetics
o Most often normal chromosomes
o XXV and XXXXY syndromes
o Trisomy 13, trisomy 18, triploidy
• Etiology
o Failure of complete urethral groove fusion
• Fusion falls short of tip of glans
o Hormone etiology theory
• Organ testosterone insensitivity
• !Androgen receptors
• Can not convert testosterone to
dihydrotestosterone
• Epidemiology
o Most common congenital defect of genitalia
o 0.2-4.1 per 1,000 births
o 4-12% recurrence risk for male fetuses

Staging, Grading or Classification Criteria
• Classification based on meatal position
o 50% anterior (glans)
o 30% middle (penile)
o 20% posterior (penoscrotal, scrotal, perineum)

I CLINICAL

I SELECTED REFERENCES
1.

2.

3.

4.

5.

Boopathy Vijayaraghavan S: Sonography of fetal
micturition. Ultrasound Obstet Gynecol. 24(6):659-63,
2004
Cafici D et al: Prenatal diagnosis of severe hypospadias
with two- and three-dimensional sonography. J Ultrasound
Med. 21(12):1423-6, 2002
Meizner I et al: The 'tulip sign': a sonographic clue for
in-utero diagnosis of severe hypospadias. Ultrasound
Obstet Gynecol. 19(3):250-3, 2002
Un SKet al: Prenatal diagnosis of a rare variant of
hypospadias and review of the literature. Ultrasound
Obstet Gynecol. 18(6):678-80, 2001
Devesa R et al: Prenatal diagnosis of isolated hypospadias.
Prenat Diagn. 18(8):779-88, 1998

I IMAGE

GAllERY

ISSUES

Presentation
• Most common signs/symptoms: Incidental
time of sex determination
• Other signs/symptoms
o Associated with many syndromes
• Opitz-Frias, Smith-Lemli-Opitz, 4p-,
Aniridia-Wilms

Demographics
• Age: t Risk with advancing

maternal

Natural History & Prognosis
• Early complication
o Meatal stenosis
• Late complications

age

finding at

(Left) Ultrasound shows a penile cyst (arrow). Severe posterior
hypospadias can be associated with urethral cutaneous fistulae and
penile cyst. The finding is rare and in this case caused bladder
obstruction. (Right) Sagittal ultrasound through the fetal pelvis in the
same case shows a large fluid collection, which communicates
posteriorly with the rectum (arrow). This child had multiple
anomalies, including high anal atresia. Extra-urogenital anomalies
occur in 7-9% of cases.

HYDROCELE

Coronal ultrasound shows bilateral, asymmetric, simple
hydroceles. Anechoic fluid (arrows) is present in both
scrotal sacs. The testes (curved arrows) and scrotal skin
(open arrows) are otherwise normal.

• Complex hydrocele (rare)
o Fluid with linear/focal echoes
o Suggests a secondary process
• Hemorrhage
• Testicular infarction/torsion
o Associated testicular abnormality
• Acutely enlarged, followed by atrophy
• Heterogeneous echotexture
o Extratesticular findings
• Enlarged epididymis
• Skin thickening
o Meconium peritonitis is rare cause
• Complex peritoneal fluid enters scrotum
• May see calcifications
• Normal testis

ITERMINOLOGY
Definitions
• Fluid in scrotal sac

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Fluid surrounds testis
• Location
o Most commonly unilateral
o Bilateral in 1/3
• May be asymmetric
• Morphology
o "Half moon" crescent around testis
o Large hydrocele may completely surround

Ultrasonographic

testis

Findings

• Simple hydrocele (common)
o Anechoic fluid
o Normal testis
• Homogeneous echotexture
• Symmetric size
o Normal epididymis
o Often transient
• 50% resolve by 37 wks
• Most resolve by birth

DDx: Abnormal

Coronal ultrasound shows a unilateral, simple hydrocele
(arrow) with a "half moon" morphology. The testes
(open arrows) are otherwise normal. It is difficult to see
the testis that is not surrounded by fluid.

Imaging Recommendations
• Protocol advice: Look carefully at testes if complex
hydrocele seen

I DIFFERENTIAL DIAGNOSIS
Testicular torsion
• Testis twists upon vascular pedicle
o Testis almost never viable at birth
• Acutely enlarged, heterogeneous testis
• Hydrocele often an early finding
o Complex> simple

Scrotal Morphology

Inguinailiernia

Cryptorchidism

HYDROCELE
Key Facts
• Inguinoscrotal hernia

Terminology
• Fluid in scrotal sac

Pathology

Imaging Findings

• 15% of male fetuses> 27 wks
• ommunicating hydrocele (patent processus
vagina lis)
• on-communicating hydrocele

• "Half moon" crescent around testis
• Simple hydrocele (common)
• Complex hydrocele (rare)

Top Differential

Clinical Issues

Diagnoses

• Most often physiologic and transient

• Testicular torsion

Inguinoscrotal

Treatment

hernia

• Peritoneal contents herniate into scrotum
• Multicystic scrotal mass is bowel
o Look for peristalsis
• Associated hydrocele common

• Surgery if hydrocele not resolved by 12-18 months
o Hydrocele sac removed
o Muscle wall reinforced to prevent hernia

Cryptorchidism

I DIAGNOSTIC

(undescended

testis)

• Hypoechoic, empty sac may mimic hydrocele
• Can not make diagnosis before 32 wks

CHECKLIST

Image Interpretation

Pearls

• Many simple hydroceles resolve by birth
• Consider hematocele, if fluid is complex

I PATHOLOGY
General Features
• Etiology
o Normal testicular descend at 25-32 wks
o Processus vaginalis forms from extension of
peritoneal cavity
• Aids in descent of testis
• Normally obliterates and becomes tunica vagina lis
o Hydrocele forms if persistent patent processus
vaginalis or fluid not resorbed
• Epidemiology
o 15% of male fetuses> 27 wks
• 21% at 27-32 wks
• 11% > 32 wks
• Associated abnormalities
o Inguinal hernia
o Hydrops fetalis
o Meconium peritonitis
o Testicular infarction/torsion

I SELECTED
1.

2.

3.

4.

REFERENCES

Das A et al: Fetal meconium peritonitis: the "vanishing
hydrocele" sign. Arch Dis Child Fetal Neonatal Ed.
88(1):F74,2003
Herman A et al: Antenatal sonographic diagnosis of
testicular torsion. Ultrasound Obstet Gynecol. 20(5):522-4,
2002
Achiron R et al: Development of fetal male gender:
prenatal sonographic measurement of the scrotum and
evaluation of testicular descent. Ultrasound Obstet
Gynecol. 11(4):242-5, 1998
Pretorius DH et al: Hydroceles identified prenatally:
common physiologic phenomenon? J Ultrasound Med.
17(1):49-52, 1998

I IMAGE

GALLERY

Staging, Grading or Classification Criteria
• Communicating hydrocele (patent processus vagina lis)
o Fluid communicates with peritoneum
• Non-communicating hydrocele
o Fluid confined to scrotum

I CLINICAL

ISSUES

Presentation
• Most found on newborn exam
o Palpation and transillumination
• Light shone on scrotum shows intra-sac contents
o Communicating hydrocele
• Can move fluid from scrotum into peritoneum

Natural History

& Prognosis

• Most often physiologic and transient

(Left) Coronal ultrasound shows a complex, right scrotal hydrocele
with fine linear echoes (arrows) and scrotal skin thickening (open
arrows). A small simple hydrocele is seen on the left (curved arrow).
(Right) Sagittal ultrasound of the right testis after birth shows a large,
hypoechoic, avascular area (arrows) consistent with infarction.
Interestingly, the hydrocele was anechoic after birth, suggesting that

the prenatal fluid contained hemorrhage that subsequently resorbed.

TESTICULAR TORSION

Ultrasound of a 3rd trimester scrotum shows an
enlarged left testis (arrow) and a normal-sized right testis
(curved arrow). The left hydrocele contains fine linear
echoes (open arrows), secondary to hemorrhage.

ITERMINOlOGY
Definitions
• Twisting of spermatic cord ~ testicular infarction

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Asymmetric testis size + complex
scrotal fluid
• Location: L > R, rarely bilateral
• Size: Testis may be either large (acute) or small
(chronic)

Ultrasonographic

Findings

• Normal scrotum
o Testes descend at 25-32 wks
o Symmetric testicular size
o Homogeneous echotexture
o Transient anechoic hydroceles
• Acute torsion
o Enlarged testis + epididymis
• Appear as single undifferentiated
mass
o Variable echotexture
• Diffusely hypoechoic from edema
• Heterogeneous from infarction
o Scrotal edema

After delivery, the left hemiscrotum was noted to be
swollen and dusky. Torsion with hemorrhagic infarction
of the testis (arrow) and epididymis (curved arrows)
was found at surgery.

o Complex hydrocele
• Hemorrhage
• Linear and focal echoes
o Contralateral simple hydrocele
• Chronic torsion
o Small testis
o Echogenic capsule
• "Echogenic halo"
o Intraparenchymal
calcification
o +/- Hydrocele
• "Double ring hemorrhage" variant
o Testis surrounded by 2 concentric fluid layers
o 2° to hemorrhage into 2 spaces
• Between visceral and parietal tunica vaginalis
• Between tunica vagina lis and scrotum
• Doppler rarely helpful
o Difficult to show flow if < 1 cc volume

Imaging Recommendations
• Careful evaluation of testes when complex hydrocele
seen
• Doppler not helpful unless flow seen on normal side

I DIFFERENTIAL

DIAGNOSIS

Unilateral cryptorchidism
• One undescended testis
• Scrotal asymmetry can mimic mass

DDx: Enlarged Scrotum

Inguinal Hernia

Hydrocele

TESTICULAR TORSION
Key Facts
Terminology

Top Differential

• Twisting of spermatic cord ~ te ticular infarction

• Unilateral cryptorchidism
• Inguinal hernia
• Large simple hydrocele

Imaging Findings
•
•
•
•
•

Enlarged te tis + epididymis
omplex hydrocele
E hogenic cap ule
"Double ring hemorrhage" variant
Doppler rarely helpful

Pathology
• Extravaginal tor ion (almost all fetal/pediatric

ca

s)

Clinical Issues
• Fetal/neonatal

Inguinal hernia
• Abdominal contents herniate through
• Cystic/echogenic mass in scrotum
• Look for peristalsis

Diagnoses

inguinal canal

torsion has low salvage rate

o Orchiectomy and contralateral orchiopexy
• Acute torsion
o Surgery to untwist spermatic cord
o Bilateral orchiopexy

I DIAGNOSTIC

Large simple hydrocele
• Fluid remains anechoic
• Can be early sign of torsion
o Torsion unlikely if testis is normal

CHECKLIST

Consider
• Testicular torsion diagnosis when complex scrotal
fluid seen

Testicular tumor
• Extremely rare in prenatal life
• Solid mass
• Yolk sac tumor most common

Image Interpretation

Pearls

• Doppler is not very helpful
• Simple hydrocele is much more common than torsion
• Testis is rarely saved when diagnosed in utero

I PATHOLOGY
I SELECTED REFERENCES

General Features

1.

• Etiology
o Spermatic cord torsion
• Venous flow affected before arterial
• Epidemiology: 1:4,000 newborn males

2.

Staging, Grading or Classification Criteria
• Extravaginal
o Spermatic
• Intravaginal
o Spermatic

ICLINICAL

torsion (almost all fetal/pediatric cases)
cord + tunica vaginalis twist as a unit
torsion (adults)
cord twists inside tunica vaginalis

3.

Herman A et al: Antenatal sonographic diagnosis of
testicular torsion. Ultrasound Obstet Gynecol. 20(5):522-4,
2002
YoussefBAet al: Case Report. Pre-natally diagnosed
testicular torsion ultrasonographic features. Clin Radiol.
55(2):150-1,2000
Devesa R et al: Prenatal diagnosis of testicular torsion.
Ultrasound Obstet Gynecol. 11(4):286-8, 1998

IIMAGE

GALLERY

ISSUES

Presentation
• Difficult prenatal diagnosis
o Enlarged testis surrounded by a hydrocele
• Hydrocele usually complex
• Scrotum may be swollen and dusky on newborn
physical exam
• Acute torsion: Enlarged, painful testis
• Chronic presentation: Hard, shrunken testis

Natural History & Prognosis
• Fetal/neonatal

torsion has low salvage rates

Treatment
• Fetus not delivered emergently
o Salvage rates are abysmal

for unilateral

torsion

• Consider emergency delivery if torsion is bilateral
• Chronic torsion

(Left) Scrotal ultrasound from the same case as the preceding page,
performed immediately after delivery, shows marked heterogeneity of
the left testis. No blood flow was demonstrated. (Right) Ultrasound of
the testes, in another case, shows bilateral torsion diagnosed shortly
after birth. The right testis and epididymis (curved arrow) are swollen
and heterogeneous, consistent with an acute event. The left testis is
shrunken and contains calcifications (arrows), consistent with chronic
torsion.

OVARIAN CYST

Sagittal ultrasound of a third trimester female fetus
shows a cystic mass with a "daughter cyst" (arrow) Just
above the bladder (open arrow). This appearance is
highly suggestive of an ovarian cyst.

• Umbilical cord compression
• Partial small bowel obstruction

ITERMINOlOGY
Definitions
• Benign functional cyst within fetal ovary

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Abdominal cyst containing
"daughter cyst" in a female fetus
• Most unilateral
• Can be bilateral
• Vary in size but may be large
o Up to 10 cm
• Ascites develops if cyst ruptures
• Usually found in lower lateral abdomen or pelvis
o Occasionally found in upper abdomen
• Supporting ligaments are lax, allowing for
displacement
• Very hard to differentiate a displaced ovarian cyst
from other intra-abdominal cysts
o May cleave from ovary
• Position in abdomen changes between scans
• Polyhydramnios may develop
o 10% of cases
o Cause unknown
o Proposed theories

DDx: Intra-Abdominal

MCDK

Postnatal ultrasound shows that in addition to the
"daughter cyst" (arrow), there is a thin crescent of
ovarian tissue with small follicles (curved arrows),
confirming ovarian origin of the cyst.

Ultrasonographic

Findings

• Simple
o Generally anechoic
o Unilocular
o Imperceptible walls
o May have occasional septations
o "Daughter cyst sign"
• Small cyst along the wall of cystic mass
• Highly specific (up to 100%) sign for ovarian
origin (82% sensitive)
• Small cyst represents an ovarian follicle
o Well-circumscribed
o Avascular
• Complex
o Internal echoes indicate hemorrhage
• Usually secondary to torsion
o Appearance varies based on age of blood products
• Diffusely echogenic with acute hemorrhage
• Fluid-fluid level seen with repeat bleeds or as clot
separates from serum
• Crescentic or rounded echogenic "mass" formed
by clot retraction
• Apparent septations due to fibrin strands
• Appears solid if organized hematoma

Cystic Mass

UP; Obstruction

Enteric Duplication

Patent Urachus

OVARIAN CYST
Key Facts
Pathology

Terminology
• Benign functional

cy t within fetal ovary

Imaging Findings
• Be t diagno tic clue: Abdominal
yst containing
"daughter cy t" in a female fetus
• Most unilateral
• Vary in ize but may be large
• A cites dev lops if cyst rupture
• Internal echoes indi ate hemorrhage
• Torsion uggested by presence of new fluid-fluid level
• on ider MRI in difficult ase

Top Differential
• Urachal yst
• Enteric duplication
• Mesenteric
y t

Diagnoses
cyst

• May develop thin echogenic wall from dystrophic
calcification
• Cyst torsion
o Common in utero: Reported as high as 40%
o Increased risk if cyst> 6 cm
o May occur even with smaller cysts
o Torsion suggested by presence of new fluid-fluid
level
o Suggested if previously anechoic or hypoechoic cyst
becomes hyperechoic
o Consider if new fetal tachycardia
• Due to peritoneal irritation
o Cyst may be extremely mobile
• Torsion -+ necrosis of cyst pedicle or fallopian
tube
• Cyst may break loose and float in peritoneal
cavity
o Doppler not helpful
• Ascites
o Result of fluid transudation or cyst rupture

MR Findings
• Cystic mass separate from urinary tract
• Septations or hemorrhage may be visible
o Look for high signal contents on TI WI

Imaging Recommendations
• Look at fetal gender
o Most intra-abdominal
cysts occur in either sex
o Ovarian cyst can be confidently ruled out if fetus is
male
• Confirm normal urinary tract
o High number of cystic abdominal masses are related
to urinary tract
• Confirm normal appearance of GI and hepatobiliary
system
o Use high-resolution transducer to look for "layered"
cyst wall
• Characteristic of enteric cyst: "Gut signature"
• Look for cyst complications
o Torsion
o Hemorrhage
o Necrosis

• Result from fetal ovarian re p nse to increased
hormone I vels
• Most common cau e of intra-abdominal cy tin
female fetu
•
0 malignant potential

Clinical Issues
• Usually incidental finding in 3rd trime ter female
• Most how sub tantial r gre sion by 6 month of age
• Prognosi excellent, if no torsion

Diagnostic Checklist
• Precise prenatal diagnosis of ovarian cyst may not be
po sible
• "Daughter cyst" ign is highly pecific for ovarian
origin

o Rupture
o Bowel obstruction
• Monitor for development of polyhydramnios
• Monitor cyst size: Risk of dystocia if large enough to
cause abdominal distension
• Consider MRI in difficult cases
o Useful to confirm normal renal/liver anatomy if
maternal habitus limits sonographic image quality

I DIFFERENTIAL
Intra-abdominal

DIAGNOSIS
cysts

• Urachal Cyst
o Between dome of bladder and cord insertion
o Occurs in both males and females
• Enteric duplication cyst
o Presents earlier, in 2nd trimester
o Occurs in both males and females
o Look for "gut signature"
o May appear identical to ovarian cyst
• Mesenteric Cyst
o Occurs in both males and females
o May appear identical to ovarian cyst
o Much less common
• Choledochal Cyst
o Right upper quadrant
o Associated with liver, look for bile ducts

Gastrointestinal

abnormalities

• Dilated Bowel
o Tubular configuration
o Contents echogenic
o Peristalsis confirmatory
• Meconium Pseudocyst
o Often irregular contour
o Wall can calcify
o Other sequelae of meconium
• Peritoneal calcifications
• Dilated bowel

Renal abnormalities
• Hydronephrosis/UP]

obstruction

peritonitis

OVARIAN CYST
o If severe, hydronephrosis can appear as a cystic mass
o No ipsilateral "normal" kidney
o Surrounded by renal parenchyma
• Multicystic dysplastic kidney
o Usually multiple cysts present
o Replaces normal renal parenchyma
o Normal kidney can not be identified

• In utero or during delivery
• If cyst large enough to distend abdomen, may cause
dystocia
• Most show substantial regression by 6 months of age
o Postnatal decrease in hormone stimulation
• May take up to 2 years for complete resolution
• Prognosis excellent, if no torsion

Intra-abdominal

Treatment

neoplasms

• Cystic teratoma
• Lymphangioma

Hydrocolpos
• Midline pelvic mass
• Posterior to bladder

I PATHOLOGY
General Features
• Etiology
o Result from fetal ovarian response to increased
hormone levels
• Placental human chorionic gonadotropin
• Maternal estrogen
• Fetal gonadotropins
o Associated with fetal hypothyroidism
• Check for goiter
o Increased incidence with certain maternal
conditions
• Diabetes
• Rhesus isoimmunization
• Toxemia of pregnancy
• Epidemiology
o 1/3 of infant girls have ovarian "cysts"
• Most microscopic
• Rarely large enough for sonographic detection
o Most common cause of intra-abdominal cyst in
female fetus

Gross Pathologic & Surgical Features
• Most are follicular in origin
• Other types reported
o Theca lutein
o Corpus luteum
o Simple cyst, origin unknown
• No malignant potential

I CLINICAL

ISSUES

Presentation
• Usually incidental finding in 3rd trimester female
o Very unlikely cyst is ovarian if seen before 3rd
trimester

Natural History & Prognosis
• May resolve spontaneously in utero
• Large cyst> 6 cm associated with increased risk of
o Hemorrhage
o Torsion
o Infarction
o Intestinal obstruction
o Rupture

• Prenatal cyst drainage
o Controversial
o Effects often temporary, cyst may recur
o Can result in intracystic bleeding
o May increase risk of infection
o May increase risk of preterm labor
o Usually only done for large cysts with bowel
obstruction
o Some authors advocate aspiration for cysts> 4 cm to
prevent torsion
o Elevated progesterone and estradiol in fluid is
diagnostic of ovarian cyst
• Consider elective cesarian section if large cyst
o Or aspiration prior to induction of labor
• Postnatal ultrasound
o Confirm cyst is truly ovarian
o Follow monthly until resolution
• Indications for surgical resection
o Evidence of torsion
o Bowel or urinary tract obstruction
• Surgery should aim to preserve ovarian parenchyma
o Fenestration with ovarian preservation
o Oophorectomy may be necessary if hemorrhagic
infarction from torsion

I DIAGNOSTIC

CHECKLIST

Consider
• MRI to help further delineate anatomy and cyst origin

Image Interpretation

Pearls

• Precise prenatal diagnosis of ovarian cyst may not be
possible
• "Daughter cyst" sign is highly specific for ovarian
origin

I SELECTED
1.

2.
3.

4.
5.

6.

REFERENCES

Quarello E et al: The 'daughter cyst sign': a sonographic
clue to the diagnosis of fetal ovarian cyst. Ultrasound
Obstet Gynecol. 22(4):433-4, 2003
McEwing R et al: Foetal cystic abdominal masses. Australas
Radiol. 47(2):101-10, 2003
Heling KSet al: Fetal ovarian cysts: prenatal diagnosis,
management and postnatal outcome. Ultrasound Obstet
Gynecol. 20(1):47-50, 2002
Crombleholme TM et al: Fetal ovarian cyst decompression
to prevent torsion.] Pediatr Surg 32:1447-9, 1997
Muller-Leisse C et al: Ovarian cysts in the fetus and
neonate-changes in sonographic pattern in the follow-up
and their management. Pediatr Radiol 22:395-400, 1992
Meizner I et al: Fetal ovarian cysts: Prenatal
ultrasonographic detection and postnatal evaluation and
treatment. Am] Obstet GynecoI164:874-8, 1991

OVARIAN CYST
IIMAGE GALLERY
(Left) Coronal T2WI MR
shows a large ovarian cyst in
the right abdomen (arrows).
The other fluid-filled
structures are the bladder
(8) and stomach (5). (Right)
Sagittal T2WI MR shows a
septation (arrow) within the
cyst (open arrowgallbladder). Postnatal
ultrasound should be
performed for confirmation,
with follow-up scans as
needed. Most ovarian cysts
resolve in the first 6 months
of life but can take up to 2
years.

(Left) Color Doppler
ultrasound shows an ovarian
cyst (arrow) just below the
liver. There is a "daughter
cyst" (open arrow) within it.
Supporting ligaments are lax,
so ovarian cysts may be
located anywhere within the
abdomen.
(Right) Sagittal
ultrasound in a diHerent case
shows a cystic mass with an
echogenic focus (open
arrow), likely due to
retracting clot. The arrow
points to the bladder.

Variant
(Left) Sagittal T2WI MR
shows a large, ovarian cyst
filling the fetal abdomen and
abutting the liver. The cyst is
heterogeneous,
with low
signal areas (arrow)
representing hemorrhage.
/-Iydrops with skin edema
(open arrows) is also seen.
(Right) Intra-operative
photograph shows a large,
hemorrhagic ovarian cyst.
Fetal hydrops was lelt to be
caused by anemia Irom the
hemorrhage. No torsion was
present in this case, but
should always be considered
when hemorrhage is present.

SECTION 10: Mus«:uloskeletal

Dysplasias
Achondrogenesis
Achondroplasia
Amelia, Micromelia
Asphyxiating Thoracic Dysplasia
Campomelic Dysplasia
Hypophosphatasia
Osteogenesis Imperfecta
Short Rib-Polydactyly
Thanatophoric Dysplasia

10-2
10-6
10-10
10-14
10-16

10-18
10-20
10-24
10-26

Extremity Malformations
Clubfoot
Rockerbottom Foot
Sandal Gap Foot
Radial Ray Malformation
Polydactyly
Syndactyly
Clinodactyly
Ectrodactyly
Arthrogryposis, Akinesia Sequence
Multiple Pterygium Syndrome

10-30
10-34
10-36
10-38
10-42
10-46
10-50
10-52
10-54
10-58

ACHONDROGENESIS

Ultrasound shows nearly absent ossification of the spine
(curved arrow) in this case of type /I achondrogenesis.
The skull (arrow) is normally ossified and is large in
proportion to the body.

o No rib fractures
o Posterior pedicles of spine may be ossified
o Crenated ileum
o Distal femora with metaphyseal irregularities
• Type II
o Normal skull ossification
o Deficient spine mineralization
o Hypoplastic ileum with medial spike
o Flared metaphyses

ITERMINOlOGY
Abbreviations
• 3
o
o
o

main
Type
Type
Type

and Synonyms

subtypes based on clinical features
IA achondrogenesis (Houston-Harris)
IE achondrogenesis (Fraccaro)
II achondrogenesis (Langer-Saldino)

Definitions
• Group of lethal osteochondrodysplasias due to failure
of cartilaginous matrix formation
• Characterized by severe micromelia, unossified spine,
short trunk and disproportionately large head
• 2nd most common lethal short-limb chondrodysplasia

IIMAGING FINDINGS
General Features
• Type IA
o Most severely affected
o Poorly ossified skull
o Completely unossified spine
o Short ribs with multiple fractures
o Proximal femora with metaphyseal spikes
o Arched ileum with hypoplastic ischium
• Type IE
o Poorly ossified skull

Radiograph in the 3rd trimester shows a "floating head"
(arrows) in a fetus with type /I achondrogenesis. The
ribs are barely visible (curved arrows) and the spine is
completely unossified (open arrow).

Ultrasonographic

Findings

• Severe micromelia
• Lack of vertebral ossification
• Disproportionately large head with either normal or
deficient ossification
• Small thorax with protuberant abdomen
• Short flared ribs with or without fractures
• Polyhydramnios
• Cystic hygroma
• Hydrops in 1/3 of cases
• Micrognathia
• Hypoplastic midface

Other Modality

Findings

• Fetal skeletal survey findings
o Type II: "Floating head"
• Only skull ossified well enough to be seen

DDx: Short limb Chondrodystrophies

Hypophosphatasia

01 Type /I

TO Type I

ACHONDROGENESIS
Key Facts
•

Terminology
• 3 main ubtyp
ba don Iinical featur
• roup f I thai 0 teo hondrody pIa ia du
of cartilaginou
matrix formation
• 2nd m t ommon I thai hort-Iimb
chondr d pIa ia

art a 12-14w

an b

k

to failure

Imaging Findings
•
r mi romelia
• Lack f rt bral
ifi ati n
• Oi prop rtionatel
larg head with ith r normal or
d fi i nt 0 ification
• mall thorax with pr tub rant abdom n
• hort nared rib with r without fracture
• ysti h groma
• Hydrop in 1/3 of a
• T P II: "Floating had"

onfirm
fra tur

•
•

o rib fracture in t p lB
b nt pine 0 ification with n rmal
t p II a hondrogene i

Imaging Recommendations

Homozygous

• Best imaging tool
o 1st trimester endovaginal ultrasound
• Can be diagnosed as early as 12-14 weeks
• Diagnosis reported at 9 weeks with positive family
history
• Protocol advice
,
o Careful evaluation of skeleton
• Ossification of spine, calvarium
• Morphology of long bones
o Radiographs in 3rd trimester
• Directed fluoroscopic images focused on spine,
cranium and long bones

• Normal calvarial ossification

I DIFFERENTIAL

DIAGNOSIS

• Skull demineralized
• Fractures uncommon
• Diffuse under ossification of all bones

Osteogenesis imperfecta

•
•
•
•

(01)

Fractures are predominant finding in 01 types II-IV
Skull poorly mineralized in 01
Rib fractures severe in type II
Long bone bowing in types III-IV
Abnormal type 1 collagen

Atelosteogenesis

II

Thoracic platyspondyly
Bowed radius, ulna, tibia
Clubfeet
Better ossification of vertebrae

Hypochondrogenesis
• Findings less severe with better ossification of vertebral
bodies
• Tubular bones less short
• Mild cases of achondrogenesis II and severe

hypochondrogenesis

al arium in

dysplasia (TD)

Normal ossification
Micromelia less extreme
Hydrops uncommon
Cloverleaf skull

Short rib-polydactyly

syndrome

• Polydactyly
o Both preaxial and postaxial
• May appear hydropic

I PATHOLOGY
General Features

Hypophosphatasia

•
•
•
•
•

P

achondroplasia

Thanatophoric
•
•
•
•

in t

difficult to distinguish

• Genetics
o Types IA and IE: Autosomal recessive
• 25% recurrence risk
o Type IA: Molecular basis not known
o Type IE: Mutations in diastrophic dysplasia sulfate
transporter gene (DTDST)
• Results in abnormal sulfation of chondroitin
sulfate-containing
proteoglycans
• Achondrogenesis IE and diastrophic dysplasia are
allelic disorders
• Prenatal diagnosis possible by chorionic villus
sampling (CVS) if specific mutation known
o Type II: Sporadic
• Mutations in type II collagen gene COL2A1
• Negligible recurrence risk
• Recurrence in case of siblings attributed to
germline mosaicism
• Epidemiology
o 1:40,000-50,000 live births
o May account for 1:650 perinatal deaths
• Associated abnormalities
o Type II with occasional cleft soft palate

o Hydrops in 113
o Polyhydramnios

ACHONDROGENESIS
o Type IA occasional encephaloceles

Microscopic

o
o
o
o

Features

• Disorganization of chondrocytes
o Failure of alignment in columns
• Cartilage matrix stains irregularly for
mucopolysaccharides

Staging, Grading or Classification Criteria

Cell culture
Bone/cartilage biopsy
Karyotype generaHy low yield
International Skeletal Dysplasia Registry at
Cedars-Sinai for atypical cases

I DIAGNOSTIC

CHECKLIST

• Definitive diagnosis of subtype possible with
histopathologic studies
o Type IA: Pathognomonic
period acid-Schiff-positive
intracytoplasmic inclusion bodies
o Type IE: Decrease in type II coHagen
• Fibers in cartilage matrix arranged in rings around
chondrocytes
o Type II: StructuraHy abnormal type II coHagen
• Electron microscopy: Retention of type II coHagen
within vacuoles
• Increased amounts of types I coHagen seen in
cartilage

• Rib fractures in absence of long bone fractures in type
IA
• No rib fractures in type IE
• Absent spine ossification with normal calvarium in
type II achondrogenesis
• Transverse view shows less than 3 ossification centers
per spinal segment

I CLINICAL ISSUES

I SELECTED

Presentation

Dertinger S et al: Matrix composition of cartilaginous
anlagen in achondrogenesis type II (Langer-Saldino). Front
Biosci. 10:446-53, 2005
2. Forlino A et al: A diastrophic dysplasia sulfate transporter
(SLC26A2) mutant mouse: morphological and biochemical
characterization of the resulting chondrodysplasia
phenotype. Hum Mol Genet. 2005
3.
Faivre Let al: Recurrence of achondrogenesis type II within
the same family: evidence for germline mosaicism. Am J
Med Genet A. 126(3):308-12,2004
4.
Krakow D et al: Use of three-dimensional ultrasound
imaging in the diagnosis of prenatal-onset skeletal
dysplasias. Ultrasound Obstet Gynecol. 21(5):467-72, 2003
5. Corsi A et al: Achondrogenesis type IE: agenesis of cartilage
interterritorial matrix as the link between gene defect and
pathological skeletal phenotype. Arch Pathol Lab Med.
125(10):1375-8, 2001
6. Karniski LP: Mutations in the diastrophic dysplasia sulfate
transporter (DTDST) gene: correlation between sulfate
transport activity and chondrodysplasia phenotype. Hum
Mol Genet. 10(14):1485-90, 2001
7.
Korkko J et al: Widely distributed mutations in the
COL2A1 gene produce achondrogenesis type
I1/hypochondrogenesis. Am J Med Genet. 92(2):95-100,
2000
8.
Mortier GR et al: Report of five novel and one recurrent
COL2A1 mutations with analysis of genotype-phenotype
correlation in patients with a lethal type II collagen
disorder. J Med Genet. 37(4):263-71, 2000
9. Gabrielli S et al: Can transvaginal fetal biometry be
considered a useful tool for early detection of skeletal
dysplasias in high-risk patients? Ultrasound Obstet
Gynecol. 13(2):107-11, 1999
10. Tretter AE et al: Antenatal diagnosis of lethal skeletal
dysplasias. Am J Med Genet. 75(5):518-22, 1998
11. Jaeger H et al: The boneless neonate: A severe form of
achondrogenesis type 1. Pediatr Radiol. 24:319-21, 1994
12. Borochowitz Z et al: Achondrogenesis type I: delineation of
further heterogeneity and identification of two distinct
subgroups. J Pediatr. 112(1):23-31, 1988

• Most common signs/symptoms: Severe micromelic
skeletal dysplasia associated with deficient spine
ossification
• Other signs/symptoms: Polyhydramnios

Demographics
• Age: No association with increased parental age
• Gender: Reported cases show excess of males
• Consanguinity found in families affected with type I

Natural History & Prognosis
• Lethal
• Increased incidence of prematurity
• Majority stillborn or die in first few hours due to
pulmonary hypoplasia
• Longest survivor less than a month

Treatment
• No prenatal or postnatal treatment
• Offer pregnancy termination
• If pregnancy continued and diagnosis certain
o Avoid fetal monitoring in labor
o No intervention for preterm labor
o Psychological support for family
• If diagnosis unclear and live born infant, resuscitation
appropriate until confirmatory tests performed
• Deliver in tertiary center with expertise in
fetopathology and skeletal dysplasias
• Stress importance of fuH genetic evaluation
o Recurrence risk
o Genetic counseling
• Autopsy important for final specific diagnosis
o Complete set of X-rays
• Absent mineralization of spine
• Large skuH with wormian bones
• Bell-shaped rib cage
• Short, abnormal long bones with variety of
abnormalities

Consider
• Fetal radiography in 3rd trimester to confirm
abnormal ossification, evaluate spine

Image Interpretation

1.

Pearls

REFERENCES

ACHONDROGENESIS
IIMAGE GALLERY
(Left) Radiograph shows
poor skull ossification
(arrows) and thin, wavy ribs
secondary 10 multiple
fractures (curved arrow) in
type IA achondrogenesis.
Lack of spine ossification is
apparent (open arrow).
(Right) Radiograph shows a
well ossified calvarium
(arrows) with lack of spine
ossification (curved arrow)
in type /I achondrogenesis.
This results in the "floating
head" appearance on
fluoroscopy. Note the
absence of rib fracture (open
arrow).

(Left) Ultrasound shows
severe micromelia and
clubfeet (arrows) in a
mid-trimester fetus with
achondrogenesis. Note the
severely deficient long bone
ossification (open arrow).
(Right) Axial ultrasound
shows the calvarium is
normally shaped and exhibits
near normal ossification
(curved arrows) typical of
type /I achondrogenesis. A
cystic hydroma (open
arrows) is also present,
which is a described
association.

Typical
(Left) Clinical photograph
shows a premature, stillborn
infant with type /I
achondrogenesis. Note the
hypoplastic midface (arrow)
and the hydropic facies.
(Right) Clinical photograph
shows the body of the same
infant. Note the extreme
micromelia (arrows),
protuberant abdomen
(curved arrow) and the
nuchal edema (open arrow).

ACHONDROPLASIA

Sagittal ultrasound shows the typical 3rd trimester
profile of a fetus with achondroplasia. Note the frontal
bossing (arrow) and the depressed nasal bridge (curved
arrow).

!TERMINOlOGY
Definitions
• Most common heritable, non-lethal skeletal dysplasia
• Characterized by disproportionately short limbs
(rhizomelia), large head with frontal bossing,
depressed nasal bridge, and short digits
• Homozygous achondroplasia is lethal
o Occurs when mutation inherited from each of 2
affected parents

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Normal early scan, with long
bone shortening noted after 22 weeks
• Morphology
o Rhizomelia
• Proximal limb shortening

Ultrasonographic

Findings

• Grayscale Ultrasound
o Normal ossification without fractures
o No bowing or angulation seen prenatally
o Progressive macrocephaly with frontal bossing
•. May be a late finding
o Depressed nasal bridge with upturned nasal tip

Lateral radiograph shows the calvarial shape of an infant
with achondroplasia. The bone is well ossified. Note
prominent frontal bossing (arrow) and depressed nasal
bridge (curved arrow).

o Chest normal to mildly bell shaped
o Spine
• Prominent thoracolumbar kyphosis
• Platyspondyly not pronounced on ultrasound
• Decreased interpedicular distance in lumbar spine
o Trident hands
• Short fingers, appear same length
• Gap between 3rd and 4th fingers
o Bone growth
• Shortening manifests between 21-27 weeks
• Progressively discrepant growth
• Often more obvious in 3rd trimester
• Head circumference (HC)/femur length (FL) ratio
increases (function of both short femur and large
head)
• Upper extremities more severely affected than
lower
o Polyhydramnios may develop in 3rd trimester
• Usually mild to moderate
o Homozygous (lethal) achondroplasia
• Findings more severe and seen earlier
• At risk fetuses (one or both affected parents)
should have serial sonograms for growth
• FL < 3rd percentile at 17 weeks
• FL < 34 mm at 26 weeks by biparietal diameter
(BPD)
• 3D: Useful for evaluating hands and spine

DDx: Short limb Chondrodysplasias

TO Type I: Thorax

TO Type I: Femur

TO Type II: Skull

01 Type II: Ribs

ACHONDROPLASIA
Key Facts
Terminology

• Follow-up sonogram if femur lagging behind other

..
• Most com.mon hen.table, no.n-leth~1 s~elet~! db plasla
• haractenzed by dl proportIonate y s or~ IlTI s
(rhizomelia), large head with frontal bOSSing,
depressed nasal bridge, and hort digit
• Homozygous achondropla ia i lethal

mea urements
• Heterozygous form becomes obvious in 3rd trimester
• R I
t lethal skeletal dyspla ia
u e ou

Imaging Findings
• Be t diagnosti clue: ormal early can, with long
bone shortening noted after 22 w eks
• Radiograph may be taken in 3rd trime ter to better
evaluate bone morphology and os ification
• ormal ossification without fractur s
•
0 bowing or angulation
en prenatally
• Progres ive macrocephaly with frontal bossing
• Prominent thoracolumbar kypho is

Radiographic Findings
• Radiography
o Radiographs may be taken in 3rd trimester to better
evaluate bone morphology and ossification
• Positioning under fluoroscopy with spot films
better than frontal film
• Fetal bones often overlap maternal spine

Imaging Recommendations
• Best imaging tool: Late 2nd to early 3rd trimester
ultrasound
• Protocol advice
o Follow-up sonogram if femur lagging behind other
measurements
• Heterozygous form becomes obvious in 3rd
trimester
o Rule out lethal skeletal dysplasia
• Micromelia
• Small chest
• Severe polyhydramnios
o Consider radiography in 3rd trimester

I DIFFERENTIAL DIAGNOSIS
FGFR3 mutation-associated

disorders.

• Hypochondroplasia
o Limb shortening less severe
o Learning, behavioral disability
o 2 common mutations, both resulting in N540K
substitution
o Clinical and radiographic distinction from
achondroplasia may be difficult
o Continuum of clinical characteristics between
typical achondroplasia and hypochondroplasia
• Thanatophoric dysplasia (TD)
o More severe limb shortening (micromelia)
o Small chest with pulmonary hypoplasia
o Curved long bones, especially in TD type I
o "Cloverleaf" skull in TD type II
o Severe polyhydramnios
in 3rd trimester
• Homozygous achondroplasia

Top Differential

Diagnoses

• Hypochondropla

ia

• Thanatophoric dysplasia (T~)
• ~omozygous .achonfdr~Pl(~:)a
• steogenesls Imper ec a
Pathology
• uto omal dominant single gene disorder
• Fibrobla t growth factor receptor-3 (FGFR3)
mutations
• 80% of case are new mutations (sporadic)

o Lethal disorder
o Occurs in 25% of offspring when 2 parents affected
with achondroplasia
o Severe limb shortening
o Pulmonary hypoplasia
• SADDAN syndrome
o Severe Achondroplasia with Developmental Delay
and Acanthosis Nigricans
o Bony changes as severe as TD
o Differentiation from TD and achondroplasia may be
difficult without molecular analysis

Type I collagen abnormalities
• Osteogenesis imperfecta (01)
o Fractures dominant feature
o Decreased ossification

Cartilage oligomeric matrix protein (COMP)
associated disorders
• Pseudoachondroplasia
o Disproportionate
short stature
o Abnormal joints
o Osteoarthritis requiring joint replacement
• Spondyloepiphyseal
dysplasia
o Rhizomelic dysplasia with similar long bone features
o No frontal bossing
o Micrognathia +/- Robin sequence (cleft palate)

I PATHOLOGY
General Features
• Genetics
o Autosomal dominant single gene disorder
• Fibroblast growth factor receptor-3 (FGFR3)
mutations
• 97% of cases involve a glycine to arginine
substitution in codon 380 of FGFR3
transmembrane domain (G380R)
• Results in receptor overactivation
• FGFR located on short arm of chromosome 4
o 80% of cases are new mutations (sporadic)
o Homozygous achondroplasia is lethal

ACHONDROPLASIA
o Recurrence risk: 1 affected parent
• 50% of offspring with achondroplasia
• 50% of offspring unaffected
o Recurrence risk: Both parents affected
• 50% of offspring with achondroplasia
• 25% with lethal (homozygous) achondroplasia
• 25% unaffected
o Recurrence risk: Both parents unaffected
• Sporadic: No increased risk
• Etiology
o FGFR tyrosine kinase expressed by chondrocytes in
the growth plate of developing long bones
o Overactivity of FGFR3 signaling may impair
chondrocyte function within the epiphyseal growth
plates
o Decreased endochondral ossification
• Epidemiology
o Heterozygous: 1:20,000-28,000 live births
o Homozygous: Rare
• Both parents must be affected or one parent + new
mutation

I CLINICAL

I DIAGNOSTIC

CHECKLIST

Consider

ISSUES

• 3rd trimester radiography

Presentation
• Most common signs/symptoms:
in late 2nd, 3rd trimesters

• Prenatal diagnosis available
o Diagnosis suspected by ultrasound or prenatal
radiography
o Molecular analysis of FGFR3 mutations
• Amniocentesis
• Chorionic villus sampling (CVS)
o Preimplantation
genetic diagnosis (PGD) if
mutations known
• Prevent homozygous lethal form in cases of 2
affected parents
• Pregnancy termination in cases of homozygous
achondroplasia
• Postnatal treatments
o Limb lengthening and straightening procedures
o Cervicomedullary decompression in cases of spinal
stenosis
o Bracing and spinal fusion procedures
o Facial distraction for midface hypoplasia, airway
obstruction

Long bone shortening

Demographics
• Age: Associated with increased paternal age
• Gender: No gender predilection
• Ethnicity: Found in all ethnic groups

Natural History & Prognosis
• Generally normal lifespan
o Some studies suggest risk of premature death
compared with general population
o Increased incidence of death in first year of life
• Often sudden and unexpected
• Associated with acute foraminal compression of
cervical spine or brainstem
• Normal intelligence
• Increased incidence of orthopedic and neurologic
complications
o Cervical instability, stenosis
o Limb bowing
o Thoracolumbar kyphosis
o Midface hypoplasia with upper airway obstruction
• Pregnancy in women with achondroplasia
o Cesarean delivery necessary even if fetus affected
due to inadequate pelvic proportions
o Increased preterm birth
o Lordosis and back pain may worsen
• Affected fetus in unaffected mother
o Cesarean delivery often necessary due to
macrocephaly
o Polyhydramnios in 3rd trimester

Treatment
• Genetic counseling
o One or both parents affected
• Significant recurrence risk with each pregnancy
o Prenatal or neonatal diagnosis of affected infant

Image Interpretation

Pearls

• Normal 2nd trimester scan does not rule out
achondroplasia
• Progressive limb shortening in late 2nd and 3rd
trimester

I SELECTED REFERENCES
Ruano R et al: Prenatal diagnosis of fetal skeletal dysplasias
by combining two-dimensional and three-dimensional
ultrasound and intrauterine three-dimensional helical
computer tomography. Ultrasound Obstet Gynecol.
24(2):134-40,2004
2. Schrijver I et al: Rapid combined genotyping assay for four
achondroplasia and hypochondroplasia mutations by
real-time PCRwith multiple detection probes. Genet Test.
8(2):185-9, 2004
3. Brodie SG et al: Mouse models orthologous to
FGFR3-relatedskeletal dysplasias. Pediatr Pathol Mol Med.
22(1):87-103,2003
James PAet al: Molecular diagnosis in a pregnancy at risk
4.
for both spondyloepiphyseal dysplasia congenita and
achondroplasia. Prenat Diagn. 23(10):861-3, 2003
5. Krakow D et al: Use of three-dimensional ultrasound
imaging in the diagnosis of prenatal-onset skeletal
dysplasias. Ultrasound Obstet Gynecol. 21(5):467-72, 2003
6. PariUa BV et al: Antenatal detection of skeletal dysplasias. J
Ultrasound Med. 22(3):255-8; quiz 259-61, 2003
7.
Yamanaka Yet al: Molecular basis for the treatment of
achondroplasia. Horm Res. 60 Suppl 3:60-4, 2003
8. Gooding HC et al: Issues surrounding prenatal genetic
testing for achondroplasia. Prenat Diagn. 22(10):933-40,
2002
9.
Patel MD et al: Homozygous achondroplasia: US
distinction between homozygous, heterozygous, and
unaffected fetuses in the second trimester. Radiology.
196:541-5,1995
10. Rouse GA et al: Short-limb skeletal dysplasias: evaluation of
the fetal spine with sonography and radiography.
Radiology. 174(1):177-80, 1990
1.

ACHONDROPLASIA
IIMAG E GALLERY
(Left)

Ultrasound shows the
typical appearance of a
"trident" hand of a fetus with
achondroplasia.
Note the
brachydactyly,
similar
lengths of all the digits, and
mildly splayed appearance
(arrow). (Right) Radiograph
shows typical hand findings
of an infant with
achondroplasia.
Note the
significant brachydactyly,
with hypoplasia of the distal
phalanges (arrow).

(Left) Sagittal ultrasound
shows the
thoraco-abdominal
profile of
a fetus with achondroplasia.
Note the slightly small chest
(arrow) with a protuberant
abdomen (open arrow).
(Right) Sagittal ultrasound
shows the spine in a 3rd
trimester fetus with
achondroplasia.
There is a
very prominent kyphosis of
the lumbar spine (arrows), a
finding common in
achondroplasia.

(Left) Ultrasound shows the
femur (arrows) of a 3rd
trimester fetus with
achondroplasia.
The length is
less than the 5th percentile,
but the morphology and
ossification is relatively
normal. These are important
dirrerentiating features when
evaluating skeletal
dysplasias. (Right) Chart
shows femur length (FL) and
head circumference
(HC)
plots. Initially the FL is
normal with shortening
becoming obvious in the 3rd
trimester. HC plot shows an
enlarged head.

AMELIA, MICROMELIA
".'

t~_'' ' '..; ..

• 't

.'

..•

-

.

~.:

..
._14~-.
~ ~~~

.

""

..•

Clinical photograph shows a stillborn term infant with
tetra-amelia. Note absence of all 4 limbs with a single
rudimentary humerus (open arrow). Micrognathia is
apparent (curved arrow).

ITERMINOlOGY
Abbreviations

and Synonyms

• Phocomelia

•
....
~

_

~r

.;.

m

..•

_

_.,

•••••

-::;

~.

"\1'0,"':

.

t'\..~
--"
~~
--:r'.

.-f

....
.•r'

""~

Coronal oblique ultrasound shows a normal scapula
(arrow) and absent upper extremity (open arrow) in a
mid-trimester fetus with tetra-amelia.

• Hands and feet present/abnormal?
• Which segment(s) of limbs affected?
o Careful search for associated anomalies,
orofacial clefts, cardiac malformations
o Search for evidence of amniotic bands

especially

Definitions
• Amelia: Absence of 1 or more limbs
• Micromelia: Shortening of both proximal and distal
segments of limb
o May further subdivide into mild or severe
micromelia
• Phocomelia: Shortening of the limb with hand/foot
arising near trunk
• Limb reduction defect (LRD): Absence of any portion
of skeletal structures or soft tissues of limb
o May be a transverse, longitudinal or intercalary
deficiency
• Hemimelia: Absence of distal limb

IIMAGING

FINDINGS

Imaging Recommendations
• Protocol advice
o Pattern of involvement key in formulating
differential diagnosis
• Symmetric vs. asymmetric limb anomalies
• Upper or lower limbs more severely affected?

DDx: Short limbs

I DIFFERENTIAL

DIAGNOSIS

Amelia
• Roberts syndrome/Roberts SC syndrome
o SC-phocomelia considered same syndrome
o Clinical characteristics
• Tetraphocomelia 90% (only upper limbs affected
in 10%)

•
•
•
•

Facial clefts in 80%
Severe pre- and postnatal growth restriction
Dysmorphic facies
Other anomalies: Genitourinary (GU), cardiac,
syndactyly, ear and nose, anterior encephalocele,
microcephaly
o Autosomal recessive
o Most die in utero or shortly after birth
• Rare report of longer term survivor
o Characteristic cytogenetic features: Premature
centromere separation

AMELIA, MICROMELIA
Key Facts
Terminology
• Amelia: Absence of 1 or more limbs
• Micromelia: hortening of both proximal and distal
segments of limb
• Phocomelia: Shortening of the limb with hand/foot
arising near trunk
• Limb reduction defect (LRD): Absence of any portion
of skeletal structures or soft tissues of limb

Imaging Findings
• Careful search for associated anomalies,
orofacial clefts, cardiac malformations

Top Differential

Diagnoses

• Roberts syndrome/Robert
• Tetra-amelia
• Amniotic bands

•

•
•

•

•

especially

SC syndrome

• Centromeric puffing in chromosomes with
secondary constrictions (1, 9, 16, short arm of
acrocentrics, short arm of Y)
• Very specific for Roberts syndrome
• Sensitivity in prenatal diagnosis unknown
• Reported discordance with pre- and postnatal
analysis
Tetra-amelia
o Rare: 0.4/100,000 live births
o Reported associated anomalies include
• Pulmonary agenesis, hypoplasia
• Orofacial clefts
• Absent ears and nose
• Cardiac anomalies
• GU anomalies including ambiguous genitalia
• Imperforate anus
• Ectodermal dysplasia
o Absence of visceral anomalies very rare
o High perinatal lethality
o Autosomal recessive tetra-amelia due to mutations
in WNT3 gene
Isolated phocomelia/amelia
of 1 or more limbs
Amniotic bands
o Asymmetric: Single or multiple limbs involved
o Bizarre orofacial clefting
o Body wall schisis defects
o Strands of amnion may be seen in amniotic fluid on
ultrasound or by gross examination of placenta
o Constriction rings around extremities, digits
Thrombocytopenia-absent
radius (TAR) syndrome
o Upper limb phocomelia, may be severe
o Lower limb anomalies in 50%
o Hypomegakaryocytic
thrombocytopenia
o Facial capillary hemangiomata
o Autosomal recessive
o Distinct from Fanconi anemia
• No abnormality of thumb
• No increased chromosome breakage in TAR
DK-phocomelia
o Von Voss-Cherstvoy syndrome
o Phocomelia, encephalocele, thrombocytopenia,
GU
anomalies

•
•
•
•

Thrombocytopenia-absent
radius (TAR) syndrome
Thalidomide embryopathy
Achondrogenesis
Osteogenesis imperfecta type II

Clinical Issues
• Most common signs/symptoms: Missing or severely
shortened extremities on 1st or 2nd trimester
ultrasound
• Most chondrodystrophies
with severe micromelia
lethal in perinatal period

Diagnostic Checklist
• Which segment of limb affected and symmetry of
involvement important in determining differential
diagnosis

o Autosomal recessive
• Thalidomide embryopathy
o Common sedative, morning sickness drug used in
Europe in the 1950s and early 1960s
o Removed from market in 1962: Recognition of
severe limb anomalies in offspring of mothers
treated with thalidomide in early pregnancy
o Mechanism of action: Interference with
angiogenesis
o Characteristic pattern of anomalies:
Tetraphocomelia, cardiac, GU, facial, nervous
system
o Approved by FDA in 1998 for treatment of
complications of leprosy
• Experimental treatment of human
immunodeficiency
virus (HIV), ulcerative diseases
and inflammatory conditions
• Single dose in a pregnant woman confers full risk
of embryopathy

Micromelia
• Achondrogenesis
o Lack of vertebral ossification
o Disproportionately
large head with normal or
deficient ossification
o Short ribs +/- fractures
o Micrognathia
o Hydrops common
o Autosomal recessive lA, IE; II sporadic
• Atelosteogenesis
o Macrocephaly, micrognathia, cleft palate
o Short trunk with small chest, protuberant abdomen
o Clubfeet, "hitchhiker" thumb
o Short tubular bones with metaphyseal flaring
o Wide gap 1st and 2nd toes
o Autosomal recessive: Mutations in diastrophic
dysplasia sulfate transporter gene (DTDST)
• Dyssegmental dysplasia
o Irregular vertebral bodies with multiple ossification
centers (anisospondyly)
o Short spine, small thorax with short ribs
o Short, thick ischial and pubic bones
o Short, wide, angulated tubular bones

AMELIA, MICROMELIA
o Autosomal recessive
• Fibrochondrogenesis
o Wide fontanels and sutures with protuberant eyes
o Short tubular bones with bulbous ends
o Defective posterior ossification of vertebral bodies
with coronal clefts
o Broad iliac bones with medial and lateral spurs
o Autosomal recessive
• Osteogenesis imperfecta type II
o Defects in type I collagen (COLlA1, COLlAZ)
o Severe abnormality in ossification, including skull
o Multiple fractures of ribs, long bones
o Sporadic; recurrences due to gonadal mosaicism
• Short rib-polydactyly syndrome types I and III
o Postaxial polydactyly
o Narrow thorax with protuberant abdomen
o Multiple internal anomalies, including cardiac, GU,
orofacial
o Short tubular bones with ragged ends
o Autosomal recessive
• Diastrophic dysplasia family
o Mutations in the DTDST gene
o Encompasses diastrophic dysplasia, achondrogenesis
IE and atelosteogenesis I
o Diastrophic dysplasia
• Progressive kyphoscoliosis
• Cleft palate
• Clubfeet
• "Hitchhiker" thumbs
• Increased perinatal mortality; normal life span if
no severe spinal complications
• Autosomal recessive

I PATHOLOGY
General Features
• Genetics
o Autosomal recessive: Roberts, TAR, DK-phocomelia
o Micromelia: Most autosomal recessive
o Cases of recurrent tetra-amelia in consanguineous
families: Presumed autosomal recessive
• Etiology
o Mutations of WNT3 genes in autosomal recessive
tetra-amelia
o Mutations in DTDST gene involved in diastrophic
dysplasia, achondrogenesis IE, atelosteogenesis I
o Mutations in COLlA1, 1AZ in 01 II
• Associated abnormalities: Tetra-amelia without other
visceral anomalies very rare

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms: Missing or severely
shortened extremities on 1st or Znd trimester
ultrasound
• Other signs/symptoms
o Roberts syndrome: Orofacial clefting with
phocomelia/amelia
o Evidence of skeletal dysplasia with micromelia

Natural History & Prognosis
• Most chondrodystrophies
lethal in perinatal period

with severe micromelia

Treatment
• No prenatal treatment
• Survivors need orthopedic surgical management
progressive spinal, limb abnormalities

I DIAGNOSTIC

of

CHECKLIST

Consider
• Cytogenetic analysis of centromeric
suspected Roberts syndrome

Image Interpretation

separation in

Pearls

• Which segment of limb affected and symmetry of
involvement important in determining differential
diagnosis
• Evaluation of bone morphology of bones of
extremities to exclude skeletal dysplasia
• Careful search for other structural anomalies

I SELECTED
1.

REFERENCES

Niemann S et al: Homozygous WNT3 mutation causes
tetra-amelia in a large consanguineous family. Am J Hum
Genet. 74(3):558-63,2004
2.
Bates AW: Autopsy on a case of Roberts syndrome reported
in 1672: the earliest description? Am J Med Genet A.
117(1):92-6, 2003
3. Greenhalgh KL et al: Thrombocytopenia-absent radius
syndrome: a clinical genetic study. J Med Genet.
39(12):876-81, 2002
4.
Megier P et al: Three-dimensional ultrasound in the
diagnosis of left upper limb amelia and right upper limb
deficiency at 10 weeks' gestation. Ultrasound Obstet
Gynecol. 20(3):303-4, 2002
5.
Qin Pet al: PBX, MEIS, and IGF-l are potential mediators of
retinoic acid-induced proximodistallimb reduction defects.
Teratology. 66(5):224-34, 2002
6. Christensen CP et al: Lower extremity deformities
associated with thrombocytopenia and absent radius
syndrome. Clin Orthop Relat Res. (375):202-6, 2000
7.
Dreyfus M et al: Thrombocytopenia with absent radii (TAR
syndrome): new advances in the mechanism of
thrombocytopenia. Pediatr Hematol Oneal. 17(7):521-2,
2000
8.
Stephens TD et al: Mechanism of action in thalidomide
teratogenesis. Biochem Pharmacal. 59(12):1489-99, 2000
9. Rijhsinghani A et al: Prenatal ultrasound diagnosis of
amelia. Prenat Diagn. 15(7):655-9, 1995
10. Ohdo S et al: Association of tetra-amelia, ectodermal
dysplasia, hypoplastic lacrimal ducts and sacs opening
towards the exterior, peculiar face, and developmental
retardation. J Med Genet. 24(10):609-12, 1987
11. Zimmer EZ et al: Tetra-amelia with multiple malformations
in six male fetuses of one kindred. Eur J Pediatr.
144(4):412-4, 1985

AMELIA, MICROMELIA
IIMAGE GALLERY
(Left) Axial ultrasound of the
pelvis shows hypoplastic ilia
(arrows) and absent lower
extremities in fetus with
tetra-amelia. (Right)
Anteroposterior
radiograph
shows a stillborn fetus with
tetra-amelia. Note the
absence of all 4 limbs and
the hypoplastic clavicles
(arrows) and pelvis (open
arrow).

Typical
(Left) Clinical photograph
shows absence of the lower
extremity with a fleshy
protuberance
(arrow).
Perineal structures are
normal. (Right) Clinical
photograph of the opposite
side shows a cutaneous
dimple (arrow) over area of
the missing extremity.

(Left) Ultrasound shows
severe upper extremity
micromelia (arrow) in a
mid-trimester fetus with
(Right)
achondrogenesis.
Clinical photograph shows
severe micromelia (arrows)
in a premature stillborn
infant with achondrogenesis.

ASPHYXIATING

THORACIC

Coronal ultrasound shows a mid-trimester fetus with
leune syndrome. The long, narrow thorax is evident
(arrows).

DYSPLASIA

Anteroposterior radiograph shows a very long and
narrow thoracic configuration of a newborn with }eune
syndrome. The ribs are short with a horizontal
configuration (arrows).

ITERMINOLOGY

Radiographic Findings

Abbreviations

• Abnormalities most marked in infancy, tend to
normalize in childhood
• Short, horizontal ribs with small thorax
• Short iliac, ischia and pubic bones
• Medial and lateral iliac spurs
• Short extremities
• Cone-shaped epiphyses
• Postaxial polydactyly

and Synonyms

• Jeune syndrome
• Jeune asphyxiating thoracic dystrophy
• Thoracic-pelvic-phalangeal
dystrophy

Definitions
• Rare osteochondrodysplasia
o Characterized by a severely constricted, long, narrow
thorax and cystic renal dysplasia
• Speculation exists that Jeune and short rib-polydactyly
syndrome type III (Verma-Naumoff) are variants of
same disorder

IIMAGING

FINDINGS

Ultrasonographic

Findings

• Small chest with short ribs
o Thoracic circumference < 5th percentile with normal
abdominal circumference
• Cystic kidneys
• Short tubular bones
• Increased nuchal thickness reported
• Oligohydramnios
if severe renal disease
• Postaxial polydactyly

I DIFFERENTIAL

Short rib-polydactyly
•
•
•
•
•
•

syndrome (SRPS)

SRPS type III (Verma-Naumoff)
Severely shortened, horizontal ribs
Small iliac bones
Micromelia with metaphyseal spurs
Small irregular vertebral bodies
Perinatal lethal

Ellis van Creveld syndrome
•
•
•
•
•
•

Chondroectodermal
dysplasia
Pelvic configuration indistinguishable
from Jeune
Less severe thoracic involvement
Cardiac defect in 50%
Postaxial polydactyly
Progressive distal shortening of extremities

DDx: Similar Findings In Short-Rib

Short Rib-Polydactyly

DIAGNOSIS

Short Rib-Polydactyly

Polydactyly

SharI Rib-Polydactyly

ASPHYXIATING THORACIC DYSPLASIA
Key Facts
Terminology

Top Differential

• Jeune syndrom
• Rare osteochondrodysplasia
• haracterized by a everely constricted,
thorax and cystic renal dyspla ia

• Short rib-polydactyly syndrome
• Ellis van reveld syndrome
• Barne yndrome

long, narrow

• Genetics:

•

Clinical Issues

bnormaliti
most marked in infancy, tend to
normalize in childhood

normal with normal intelligence

Barnes syndrome
•
•
•
•

• Phenotype

uto omal reces ive
is highly variable

• Severe liver involvement
hypertension

~ biliary cirrhosis ~ portal

Treatment

Small thorax, small pelvis, laryngeal stenosis
Rib shortening milder than Jeune syndrome
Absence of iliac spurs, renal disease
Autosomal dominant

Uniparental

•
•
•
•

disomy 14 (paternal)

Genetic counseling should be offered
Rib/thoracic cage expansion procedures
Ursodeoxycholic acid: Stabilize hepatic function
Renal transplantation

• Recognizable phenotype with thoracic dystrophy
• Characteristic "coat hanger" rib sign (caudal anterior
rib bowing) on radiograph

I SELECTED REFERENCES

I PATHOLOGY

2.

1.

General Features
• Genetics: Autosomal recessive
• Etiology
o Specific gene(s) unknown; maps to 15ql3
o Ellis van Creveld region on 4p excluded
• Epidemiology: Rare: 1/70,000 births
• Associated abnormalities: Hepatic fibrosis, pancreatic
fibrosis, retinal degeneration

Microscopic

Features

• Irregular, patchy enchondral ossification
• Pulmonary hypoplasia with marked reduction
number of alveoli
• Cystic renal dysplasia
• Periportal hepatic fibrosis

I CLINICAL

( RPS)

Pathology

Imaging Findings

• Lifespan potentially

Diagnoses

3.

4.

5.

6.

in

Davis JT et at: Lateral thoracic expansion for Jeune
syndrome: evidence of rib healing and new bone
formation. Ann Thorac Surg. 77(2):445-8, 2004
Stevenson DA et at: Paternal uniparental disomy of
chromosome 14: confirmation of a clinically-recognizable
phenotype. Am J Med Genet A. 130(1):88-91, 2004
Morgan NV et al: A locus for asphyxiating thoracic
dystrophy, ATD, maps to chromosome 15gB. J Med
Genet. 40(6):431-5, 2003
den Hollander NS et al: Early prenatal sonographic
diagnosis and follow-up of Jeune syndrome. Ultrasound
Obstet Gynecol. 18(4):378-83,2001
Ho NC et al: Jeune asphyxiating thoracic dystrophy and
short-rib polydactyly type 1Il (Verma-Naumoff) are variants
of the same disorder. Am J Med Genet. 90(4):310-4, 2000
Chen CP et at: Prenatal diagnosis of asphyxiating thoracic
dysplasia Geune syndrome). Am J Perinatol. 13(8):495-8,
1996

I IMAGE GALLERY

ISSUES

Presentation
• Most common signs/symptoms
o Phenotype is highly variable
o Long narrow thorax
o Brachydactyly, short limbs
o Cystic renal dysplasia
o Postaxial polydactyly in 14%

Natural History & Prognosis
• Neonatal and infantile deaths due to pulmonary
hypoplasia in 70%
• Survival associated with growth of thoracic cavity
• Mild cases present in childhood with short stature +/-

renal disease
• Renal insufficiency,

renal failure by late childhood

(Left) Sagittal ultrasound shows a fetus in the third trimester with
Jeune syndrome. Severe constriction of the thorax is noted (arrows)
when compared with the fetal abdomen (curved arrow). (Right) Axial
ultrasound shows a significantly shortened rib in the mid-trimester
(arrows). The heart appears large and the cardiothoracic ratio is
mildly increased, reflecting the small thoracic size.

CAMPOMELIC DYSPLASIA

Ultrasound shows femoral angulation (arrow) in a
mid-trimester
fetus with
campomelic
dysplasia.
Ossification is normal and there were no fractures.

Anteroposterior radiograph shows angulation of the
femora and tibia (arrows) in the same infant with
campomelic dysplasia. Ambiguous genitalia are also
present (open arrow).

ITERMINOlOGY

Radiographic

Abbreviations

•
•
•
•
•

•
•
•
•

Findings

Normal ossification without fractures
Anterolaterally bowed femora, tibiae
Thoracic kyphoscoliosis
Absent/delayed ossification of thoracic pedicIes
Hypoplastic scapulae
• 11 pairs of ribs

and Synonyms

Campomelic dysplasia (CD)
Campomelic syndrome
Campomelic dysostosis
Camptomelic dysplasia

Definitions
• Campomelia = bowed limbs
• Rare, semi-lethal osteochondrodystrophy
• Characterized by bowed extremities with absence of
fractures, cutaneous dimpling, hypoplastic scapulae,
sex-reversal in males

Imaging Recommendations
• Best imaging tool: Mid-trimester

I DIFFERENTIAL DIAGNOSIS
Osteogenesis imperfecta

IIMAGING

(01)

• Decreased mineralization of skull, long bones
• Fractures are prominent feature

FINDINGS

Ultrasonographic

ultrasound

Findings

Kyphomelic dysplasia

• Severe angulation of femora, tibiae, fibulae
• Ambiguous genitalia
o XY sex-reversal (male to female)
• Genotypic males appear phenotypically as females
• Hypoplastic scapulae
• No fractures
• Bell-shaped chest
• 1st trimester increased nuchal translucency or cystic
hygroma

• Scapulae are normal
• Primarily femoral involvement

Acampomelic

campomelic

dysplasia

• Absence of bowing of extremities
• Hypoplastic scapulae

Femur-fibula-ulna

complex

• Short limb dwarfism

DDx: Bowed Extremity Syndromes

01 Type IV

01 Type III/IV

Kyphomelic

CAMPOMELIC

DYSPLASIA

Key Facts
Terminology

Top Differential

• ampomelia = bow d limbs
• Rare, semi-lethal 0 teochondrodystrophy

•
•
•
•

Imaging Findings
• ormalo sification without fracture
• Severe angulation of femora, tibiae, fibulae
• Ambiguou genitalia
• Hypopla ti capulae

• Varying degrees of femoral and fibular deficiency,
upper limb abnormality

Fibular hemimelia
• Absence of fibulae with defects in femora, tibiae, feet

Proximal femoral focal deficiency
• Deficiency of proximal femora with fibular
abnormality in 50%

I PATHOLOGY

Clinical Issues
• 3/4 of males are ex-reversed (appear phenotypi
female) or have ambiguous genitalia

• Genetics
o Sporadic autosomal dominant
o Recurrences likely due to gonadal mosaicism
o Rare cases of mild phenotypic features in parent
attributed to possible somatic mosaicism
• Etiology
o Haploinsufficiency of SRY-related gene (SOX9)
• SOX9: Transcription factor
• Located at 17q24.3-q25.1
• Key regulator in cartilage differentiation and early
testis development
o Milder phenotype, longer survival in some cases
• Epidemiology: 0.05-1.6 per 10,000 live births
• Associated abnormalities: Bronchomalacia

I CLINICAL ISSUES

ally

• Occasional longer term survivors

Treatment
• No prenatal treatment
• Delivery in tertiary care facility
o Risk of respiratory insufficiency
o Expertise in genetic fetopathology, skeletal
dysplasias
• Orthopedic treatment of musculoskeletal
abnormalities in survivors

I DIAGNOSTIC

General Features

Diagnoses

Osteogene i imperfecta (O!)
Kyphomelic dy pia ia
Acampomelic campomelic dy pia ia
Femur-fibula-ulna complex

CHECKLIST

Image Interpretation

Pearls

• Prenatal diagnosis centers around ultrasound
with postnatal radiographic confirmation

findings

I SELECTED REFERENCES
1.

2.

3.

Velagaleti GV et al: Position Effects Due to Chromosome
Breakpoints that Map -900 Kb Upstream and -1.3 Mb
Downstream of SOX9 in Two Patients with Campomelic
Dysplasia. Am J Hum Genet. 76(4):652-62,2005
Sock E et al: Loss of DNA-dependent dimerization of the
transcription factor SOX9 as a cause for campomelic
dysplasia. Hum Mol Genet. 12(12):1439-47,2003
Moog U et al: Acampomelic campomelic syndrome. Am J
Med Genet. 104(3):239-45, 2001

I IMAGE GALLERY

Presentation
• Most common signs/symptoms
o Symmetric angulation of femora, tibiae and fibulae
o Hypoplastic scapulae
o Ambiguous genitalia
• Other signs/symptoms: Cutaneous dimpling,
especially pretibial

Demographics
• Gender
o Chromosomal sex ratio 1:1
o Preponderance of phenotypic females due to XY
sex-reversal
• 3/4 of males are sex-reversed (appear
phenotypically female) or have ambiguous
genitalia

Natural History & Prognosis
• Most die in infancy due to respiratory

insufficiency

(Left) Frontal radiograph shows the chest of a newborn with
campomelic dysplasia. Note the hypoplastic scapula (arrows), 77
pairs of ribs and bell-shaped
thorax (open arrows).
(Right)
Radiograph of the right leg of the same infant shows mid-shaft
angulation of the femur, tibia and fibula (arrows). Ossification is
normal.

HYPOPHOSPHATASIA

Ultrasound shows femoral bowing (arrow) in a
mid-trimester fetus at risk for infantile hypophosphatasia
based on family history. Note the poor posterior
shadowing due to hypomineralization.

Radiograph shows thin, bowed bones in a newborn
with infantile hypophosphatasia (arrows). Note the
hypomineralization. Thin straight ribs without fractures
are also seen (curved arrow).

o Profound hypomineralization of membranous skull
• Brain seen "too well"
• Compressible with normal transducer pressure
o Long bones
• Micromelia
• Thin with bowing (fractures uncommon)
• Poor or absent posterior shadowing
• Spurs along mid-shaft
o Spine
• Absent neural arch ossification +/- vertebral body
ossification

ITERMINOlOGY
Definitions
• Rare osteochondrodysplasia with deficient
mineralization and deficiency of tissue nonspecific
alkaline phosphatase (ALP)
• 3 subtypes
o Perinatal lethal
• Micromelia and severe hypomineralization
o Infantile
• Rickets-like skeletal changes, fractures, premature
shedding of teeth
o Late onset (adult form)
• Often limited to biochemical findings
• Bowing, pseudofractures, ectopic calcifications in
spinal ligaments and joint cartilage, rachitic
changes in ribs

IIMAGING FINDINGS

Radiographic

Findings

• Infantile form with delayed ossification of cranium,
ribs and tubular bones
o Metaphyseal ossification defects
o Bowing of long bones

I DIFFERENTIALDIAGNOSIS
Osteogenesis imperfecta

General Features
• Best diagnostic clue: Perinatal lethal type: Micromelia
and severe undermineralization of bones and
calvarium on mid-trimester ultrasound

•
•
•
•

Ultrasonographic

Achondrogenesis

Findings

• Perinatal lethal type

type IA

• Absent spine ossification

DDx: Hypomineralization

01 Type /I

(01)

Fractures predominate finding in 01 types II-IV
Rib fractures severe in type II
Poor skull mineralization
Serum alkaline phosphatase normal

HYPOPHOSPHATASIA
Key Facts
Terminology

Top Differential

• Rare osteochondrodysplasia
with deficient
mineralization and deficiency of tissue nonspecific
alkaline phosphatase (ALP)

• Osteogenesis imperfecta (01)
• Achondrogenesis type IA

Imaging Findings

• Perinatal hypophosphatasia:
Lethal
• Prenatal diagnosis: Measure ALP activity in chorionic
villi, cultured amniocytes or fetal blood
• Direct mutational analysis possible

• Best diagnostic clue: Perinatal lethal type: Micromelia
and severe undermineralization
of bones and
calvarium on mid-trimester ultrasound

Clinical

Diagnoses

Issues

I PATHOLOGY

o Spontaneous improvement in limb bowing may
occur
• Late onset
o Bone, joint pain from fractures, crystal deposition
o Foot pain from metaphyseal stress fractures may be
first sign of late onset disease
o Short stature common
o Osteopenia, fractures after menopause

General Features

Treatment

• Genetics
o Perinatal lethal/infantile: Autosomal recessive
• 25% recurrence risk
o Adult form both autosomal recessive and dominant
o Carriers with t serum ALP/t urinary
phosphoethanolamine
• Etiology
o Mutations in tissue nonspecific ALP (TNSALP or
ALPL) gene
o Decreased enzyme activity impairs bone
mineralization, dentinogenesis
o Degree of deficiency correlates with severity of
clinical features
• Epidemiology: 1/100,000 births (perinatal lethal type)

• Prenatal diagnosis: Measure ALP activity in chorionic
villi, cultured amniocytes or fetal blood
o Direct mutational analysis possible
• Aggressive dental care to preserve teeth
• Hypercalcemia responsive to dietary restriction
• Intramedullary rods may stabilize fractures
,
• Disappointing results with enzyme therapy, calcitonin
• Avoid vitamin D supplements (hypercalcemia)
• Bone marrow transplantation

o Affects vertebral body to greater extent than neural
arch
• Multiple rib fractures
• Poor calvarial ossification
• Tubular bones 'short and thick

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms: Hypomineralization,
bowed limbs
• Other signs/symptoms
o In infancy
• Premature shedding of teeth
• Decreased/absent serum ALP activity
• t Plasma pyridoxal 5'-phosphate
• Hypercalcemia and hypercalcuria
• t Serum phosphate in 50%

I SELECTED
1.

2.
3.

REFERENCES

Brun-Heath I et al: Characterization of 11 novel mutations
in the tissue non-specific alkaline phosphatase gene
responsible for hypophosphatasia and genotype-phenotype
correlations. Mol Genet Metab. 84(3):273-7, 2005
Whyte MP et al: Marrow cell transplantation for infantile
hypophosphatasia. J Bone Miner Res. 18(4):624-36,2003
Mornet E: Hypophosphatasia: the mutations in the
tissue-nonspecific alkaline phosphatase gene. Hum Mutat.
15(4):309-15, 2000

IIMAGE

GALLERY

Natural History & Prognosis
• Perinatal hypophosphatasia:
Lethal
• Infantile hypophosphatasia
o Hypercalcemia: Irritability, poor feeding, vomiting,
failure to thrive
o Craniosynostosis: t intracranial pressure
o Nephrocalcinosis
o Increased mortality: Cardiorespiratory,
t intracranial
pressure
o Delayed walking, abnormal gait

(Left) Ultrasound shows a short, underossified radius (arrow) and
ulna in an affected fetus with hypophosphatasia.
(Right) Sagittal
radiograph shows the hypomineralized skull of an newborn affected
with infantile hypophosphatasia (arrows).

OSTEOGENESIS

Cross pathology of a fetus with 01 shows bowing of the
femurs as well as multiple, obvious fractures with
pseudoarthroses (arrows).

ITERMINOLOGY
Abbreviations

and Synonyms

• Osteogenesis imperfecta (OT)
• "Brittle bone disease"
• 01 type I: Osteogenesis imperfecta tarda
o Van der Hoeve syndrome
• 01 type II: Perinatal lethal
o 01 type IIA: Vrolik/thick bone type of lethal or
• 01 type III: Progressively deforming or
• 01 type IV: Lobstein disease; Ekman-Lobstein disease

Definitions
• Connective tissue disorder due to abnormalities in
type I collagen (COLlAl, COLlA2) associated with
osseous fragility and fractures

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Presence of fractures distinguishes
01 from other skeletal dysplasias

Ultrasonographic

Findings

• Extremities
o Long bone shortening/angulation
fractures

secondary to

IMPERFECTA

Ultrasound of the lower leg of a third trimester fetus with
01 shows multiple tibial fractures (arrows), with
displacement and irregular callus formation.

o Pseudoarthrosis formation
o Callus formation gives bones a "crumpled"
appearance
o Decreased mineralization
• May see posterior cortex (Le., no shadowing from
anterior cortex)
• Chest
o Small circumference
o Multiple rib fractures ("beading")
• Brain
o Anatomy "too well seen"
• Poorly mineralized skull
• No reverberation artifact
o Skull deformation from transducer pressure ("soft"
bones)

Radiographic

Findings

• Radiography
o Fractures may be better demonstrated on fetal
skeletal survey
o Major radiographic features
• Generalized osteopenia
• Delayed calvarial bone formation with wormian
bones
• Tubular bones with thin cortex, thin shafts
• Severe cases with collapsed vertebral bodies, rib
fractures, broad tubular bones due to compression
fractures

DDx: Short Limb Skeletal Dysplasias: Femurs

Hypophosphatasia

TO Type I

Campomelic

Achondrogenesis

OSTEOGENESIS
Key
Terminology
•

onnective tissue di order due to abnormalities in
type I collagen ( OLlA1, COLlA2) associated with
osseous fragility and fractures

Imaging Findings
• Best diagnostic clue: Presence of fractures
distinguishes 01 from other skeletal dysplasias
• Callus formation gives bones a "crumpled"
appearance
• Decreased mineralization
• Multiple rib fractures ("beading")
• Skull deformation from transducer pressure ("soft"
bones)

Top Differential

Diagnoses

• Hypophosphata

IMPERFECTA
Facts
• Achondrogenesis
• Campomelic dysplasia
• Thanatophoric dysplasia (TD)

Pathology
•
•
•
•

Most autosomal dominant
Type I: Fractures rare at birth
Type II: Most severe form, multiple fractures, lethal
Type III: Multiple fractures at birth, progressive severe
deformity of limbs, spine, skull
• Type IV: Delayed presentation, clinical and
radiographic spectrum between type I and type III

Diagnostic Checklist
• Severe limb shortening with limb and rib fractures,
most likely lethal OJ

ia

• Best imaging tool
o Mid-trimester ultrasound (US)
o 1st trimester endovagina] US in high-risk patients
• Protocol advice
o Measure all long bones/assess for fractures
• Severe shortening in 01 type II
o Look for scapulae
• If visible, campomelic dysplasia unlikely
o Compare chest to abdomina] circumference
• Small chest '* more risk for pulmonary hypoplasia
o Normal ultrasound does not exclude 01 in high-risk
patient

o Mutations in COLlA1, COLlA2 genes of type 1
collagen
o Most autosomal dominant
o Most recurrences of type II attributed to gonadal
mosaicism
• Recurrence risk up to 3%
o Autosomal recessive inheritance proposed in some
cases of type IIC
.
• Epidemiology
o 1/20,000-1/60,000 live births
o Incidence of maternal 01 in pregnancy
1/20,000-1/30,000
• Associated abnormalities
o Dentinogenesis imperfecta
o Hearing loss

I DIFFERENTIAL

Gross Pathologic & Surgical Features

Imaging Recommendations

DIAGNOSIS

• Generalized hypomineralization of all bones
• Fractures uncommon
• Low serum alkaline phosphatase in neonate

• OJ type II (perinatal lethal type)
o Thin cortical bone, sparse trabecular bone
o Increased osteoclasts/osteocytes
o Thin osteoid with thin collagen fibrils
o Patchy mineralization

Achondrogenesis

Staging, Grading or Classification Criteria

•
•
•
•

• Sillence Classification: Based on phenotype
o Type I: Fractures rare at birth
• Blue sclerae
• Type lA, normal teeth; IE with dentinogenesis
imperfecta (60%)
• Hearing loss (35-50%)
• Increased capillary fragility
• Bone fragility improves with adolescence; may
recur after menopause
• Wormian bones
o Type II: Most severe form, multiple fractures, lethal
• IIA with blue sclerae; short, thick tubular bones
• lIB neonatal form of type III
• IIC with blue sclerae, slender/twisted tubular
bones
• Small chest with "beaded" ribs
• Severe limb shortening
• Demineralization of skull

Hypophosphatasia

Spine mineralization absent in type II
Hydrops, cystic hygroma common
Skull ossification variable
Severe micromelia

Campomelic

dysplasia

• Hypoplastic scapulae
• Sharp angulation of femur, tibia/fibula
• Normal skull ossification

Thanatophoric

dysplasia (TO)

• Ossification generally normal
• Severe long bone shortening, bowing may be mistaken
for fractures

I PATHOLOGY
General Features
• Genetics

OSTEOGENESIS
o Type III: Multiple fractures at birth, progressive
severe deformity of limbs, spine, skull
• Detectable by 2nd trimester
• Generalized osteopenia
• Sclerae white or grayish
• Triangular facies
• Severe short stature
• Spinal cord compression
• Pseudarthroses common
• Often non-ambulatory
o Type IV: Delayed presentation, clinical and
radiographic spectrum between type I and type III
• Sclerae white or grayish
• Short stature
• Dentinogenesis imperfecta common
• Hearing loss in later life
• Generalized demineralization
o Types V, VI, VII
• Non-type I collagen defects
• Recognition provisional due to scarce clinical data

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Multiple fractures on mid-trimester ultrasound
o Cases of type III/IV 01 reported with isolated bent
femora in utero
• Other signs/symptoms
o 1st trimester cystic hygroma, increased nuchal
translucency
o Detected as early as 12-14 weeks

IMPERFECTA
• Genetic counseling indicated in all cases
• Biochemical/collagen analysis from chorionic villus
sampling (CVS) or amniocentesis
o Molecular analysis possible in some cases
o Preimplantation genetic diagnosis (PGD) reported in
types I, IV
• Suspected lethal or severe 01
o Pregnancy termination an option
o Confirmation of diagnosis important for genetic
counseling
• Deliver in center with expertise in genetic
fetopathology, skeletal dysplasias
• No benefit from cesarean section
o No increase in survival in lethal 01
o No decrease in perinatal fractures in non-lethal 01
• Autopsy with x-rays if termination or demise
o Tissue for biochemical, molecular confirmation
• Postnatal
o Intramedullary rods to straighten and stabilize long
bones in severe 01
o Cyclic bisphosphonate therapy in severe 01
• Decreases bone turnover and increases bone
density
• Decreases fracture frequency, pain

I DIAGNOSTIC

CHECKLIST

Consider
• Fetal skeletal survey in 3rd trimester

Image Interpretation

Pearls

• Severe limb shortening with limb and rib fractures,
most likely lethal OJ

Demographics
• Age: Tendency towards mildly increased paternal age
in lethal OJ
• Gender: Females> males

I SELECTED
1.

Natural History & Prognosis
• Variable according to type
o Type I, IV: Normal to slightly decreased life span
o Type II: Perinatal lethal
o Type III: Significantly shortened life span
• Pregnancy in women with 01
o Increased uterine atony
o Increased bruising, bleeding tendencies
o Increased ambulation difficulties, back pain
o Preterm delivery
o Respiratory difficulties if very short stature
o Possible association with malignant hyperthermia
with general anesthesia
o 50% risk of fetal transmission
o Cesarean delivery controversial
• Individual considerations
• Maternal pelvic fractures
• Case reports of uterine rupture with vaginal
delivery, attributed to decreased total collagen in
myometrium

Treatment
• No prenatal treatment for fetus
o Experimental bisphosphonate therapy in maternal
01 (preconception)

2.
3.

4.

5.

6.

7.

8.

REFERENCES

McEwing RL et al: First-trimester diagnosis of osteogenesis
imperfecta type II by three-dimensional sonography. J
Ultrasound Med. 22(3):311-4, 2003
Cubert R et al: Osteogenesis imperfecta: mode of delivery
and neonatal outcome. Obstet Gynecol. 97(1):66-9, 2001
Makrydimas Get al: Osteogenesis imperfecta and other
skeletal dysplasias presenting with increased nuchal
translucency in the first trimester. Am J Med Genet.
98(2):117-20, 2001
Byers PH: Osteogenesis imperfecta: perspectives and
opportunities. Curr Opin Pediatr. 12(6):603-9,2000
De Vos A et al: Two pregnancies after preimplantation
genetic diagnosis"for osteogenesis imperfecta type I and
type IV. Hum Genet. 106(6):605-13, 2000
Ries Let al: Prenatal diagnosis of a novel COLlA1
mutation in osteogenesis imperfecta type 1 carried through
full term pregnancy. Prenat Diagn. 20:876-80, 2000
Sarathchandra P et al: A light and electron microscope
study of osteogenesis imperfecta bone samples, with
reference to collagen chemistry and clinical phenotype. J
Pathol. 192:38595, 2000
Gabrielli S et al: Can transvaginal fetal biometry be
considered a useful tool for early detection of skeletal
dysplasias in high-risk patients? Ultrasound Obstet
Gynecol. 13(2):107-11, 1999

OSTEOGENESIS IMPERFECTA
IIMAGE GALLERY
(Left) Sagittal oblique
ultrasound of the chest
shows an irregular, wavy,
beaded appearance of the
ribs (arrows). There was
severe limb shortening with
multiple fractures,
compatible with type /I 0/.
This is the most severe and
uniformly lethal type of 0/.
(Right) Lateral radiograph in
another case of 01 type /I.
There are "beaded" ribs
(arrow) due-to multiple
fractures. There is also
micromelia with a
"crumpled" appearance of
the humerus (open arrow).

(Left) Ultrasound shows
severe bowing (arrows) of
the femur in a mid-trimester
fetus with 0/. Osteopenia is
indicated by poor acoustic
shadowing. (Right)
Anteroposterior radiograph
of the lower extremities
shows poorly ossified bones
with thin cortices in a
newborn with type /V 0/.
Note the healed fracture
(curved arrow) and severe
bowing (arrows).

(Left) Axial ultrasound shows
prominent skull deformation
(arrows) by the usual
pressure of an ultrasound
transducer in a fetus with 0/.
Note the improved
visualization of the near field
of the brain secondary to
poor ossification. Normally
acoustic shadowing would
obscure this area. (Right)
Clinical photograph shows a
mother and infant both
affected with type IV 01.
Note the strikingly dark
sclerae (arrows), triangular
facies (curved arrow) and
pseudarthrosis (open arrow).

SHORT RIB-POLYDACTYLY

Lateral radiograph shows severely shortened
ribs
(arrows) in SRPS Verma-Naumoff type. The vertebral
bodies are small and irregular (curved arrow).

ITERMINOlOGY
Abbreviations

and Synonyms

• Short rib (-polydactyly) syndrome (SRPS)
• Short rib syndrome
• Polydactyly with neonatal chondrodystrophy

Definitions
• Group of rare lethal osteochondrodysplasias
characterized by severe micromelia, short horizontal
ribs, polydactyly, visceral anomalies
o Four subtypes described
• Controversy exists over whether types I and III are
distinct entities or represent a spectrum of same
disorder given very similar radiographic findings

IIMAGING FINDINGS
General Features
• Saldino-Noonan and Verma-Naumoff types (SRPS
types I and III)
o Postaxial polydactyly
o Hydrops
o Cardiac: Septal defects, coarctation, transposition of
great vessels
o Urogenital: Renal cysts, cloacal anomalies, vaginal
atresia, vaginal fistulas

Anteroposterior
radiograph
shows
another
Verma-Naumoff type of SRPS. Note the short horizontal
ribs with broad ends (arrows), protuberant abdomen
and irregular scapulae (open arrow).

o Anorectal: Imperforate anus, cloacal anomalies
o Radiographic findings: Hypoplastic iliac bones with
flattened acetabular roofs, rounded vertebrae with
coronal clefts, long bones with pointed ends/convex
central area with lateral metaphyseal spikes/ragged
appearing ends
• Majewski type (SRPStype II)
o Pre- and postaxial polydactyly
o Hydrops
o Orofacial clefts, often mid-line
o Ambiguous genitalia
o Central nervous system (CNS) abnormalities
o Radiographic findings: Short horizontal ribs, short
tubular bones with smooth ends, short ovoid tibiae
(shorter than fibulae), normal iliac bones
• Beemer-Langer type (SRPStype IV)
o Pre- and postaxial polydactyly in 50%
o Visceral anomalies: Omphalocele, cardiac,
cystic/hypoplastic kidneys, lobulated tongue, oral
frenulae
o Median orofacial cleft
o CNS: Hydrocephalus, holoprosencephaly,
hamartomas
o Ambiguous genitalia
o Radiographic findings: Short horizontal ribs, small
iliac bones, short tubular bones with smooth
metaphyses, bowed radii and ulnae

DDx: Similar Findings In Jeune Syndrome

jeune Syndrome

jeune Syndrome

jeune Syndrome

SHORT RIB-POLYDACTYLY
Key Facts
Pathology

•

ndrod pia ia
m lia, hart h rizontal
mali

ra ic d

I DIFFERENTIAL

trophy)

DIAGNOSIS

•

neti:

uta omal r

Clinical I ues
• Diagn i po ible b 15-16 w ek ge tation ba don
mi romelia, very hart rib
• n id r I t trim t r ndovaginal ultra ound in
at-ri k I r gnancie
• Prenatal/neonatal
I thai

Natural History & Prognosis
• Prenatal/neonatal

Jeune syndrome (asphyxiating thoracic
dystrophy)

Treatment

• Thorax long and narrow with short horizontal ribs
o Thoracic constriction improves with age
• Cystic renal dysplasia
• Polydactyly less common (14%)
• Long bones less severely affected with more normal
tibiae
• Speculation exists that Jeune and SRPS type III are
variants of same disorder

I SELECTED

Ellis van Creveld syndrome
•
•
•
•
•
•
•

Chondroectodermal
dysplasia
Rare; increased incidence in Amish
Less severe thoracic involvement
Cardiac defect in 50%
Postaxial polydactyly
Progressive distal shortening of extremities
Survival with normal intelligence

Mohr-Majewski

syndrome

• Orofacial digital syndrome (OFD) type IV
• Distinction between SRPS and OFD IV is unclear: May
be part of a single spectrum
• Severe tibial involvement, ribs longer
• Neonatal survival possible

I PATHOLOGY

•
•
•
•

1.

2.

3.

4.

5.

lethal

Genetic counseling should be offered
No treatment available
Option of pregnancy termination
Postnatal confirmation of diagnosis crucial for
recurrence risk counseling

REFERENCES

Elcioglu NH et al: Diagnostic dilemmas in the short
rib-polydactyly syndrome group. Am J Med Genet.
111(4):392-400,2002
Viora E et al: Three-dimensional
ultrasound evaluation of
short-rib polydactyly syndrome type II in the second
trimester: a case report. Ultrasound Obstet Gynecol.
19(1):88-91,2002
Krakow D et al: Exclusion of the Ellis-van Creveld region
on chromosome 4p16 in some families with asphyxiating
thoracic dystrophy and short-rib polydactyly syndromes.
Eur J Hum Genet. 8(8):645-8, 2000
Sarafoglou K et al: Short rib-polydactyly syndrome: more
evidence of a continuous spectrum. Clin Genet.
56(2):145-8, 1999
Westvik J et al: Coronal and sagittal clefts in skeletal
dysplasias. Pediatr Radiol. 28(10):764-70, 1998

IIMAGE

GALLERY

General Features
• Genetics: Autosomal recessive
• Etiology: Genetic basis unknown

Microscopic

Features

• Loss of synchrony in cartilage removal and osteogenic
differentiation at all growth plates

ICLINICAL

ISSUES

Presentation
• Diagnosis possible by 15-16 weeks gestation based on
micromelia, very short ribs
o Consider 1st trimester endovaginal ultrasound in
at-risk pregnancies

(Left) Radiograph shows metaphyseal bone spurs (curved arrows) in
Verma-Naumoff SRPS.Acetabular roofs are horizontal (open arrows).
(Right) Radiograph shows postaxial hexadactyly (arrow) of the foot in
a stillborn infant with SRPS. Phalanges are short, rounded (open
arrow) and distal phalanges are hypoplastic (curved arrow).

THANATOPHORIC

Ultrasound shows a normally
ossified, curved
("telephone receiver") femur (arrow), which measured
less than 5th percentile for gestational age. This finding
is classic finding for TO type I.

ITERMINOlOGY
Abbreviations

and Synonyms

• Thanatophoric dysplasia (TD), lethal skeletal dysplasia,
thanatophoric dwarfism, lethal osteochondrodysplasia

Definitions
• Lethal skeletal dysplasia due to mutation of fibroblast
growth factor receptor 3 gene (FGFR3)
• Divided into 2 subtypes based on morphologic
findings
• Thanatophoric is Greek for "death-bearing"

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o TD type I: "Telephone receiver" femur
o TD type II: Kleeblattschadel ("cloverleaf") skull

Ultrasonographic

Findings

• Type I
o Long bones severely affected
• Micromelia
• All measure well below the 5th percentile for
gestational age
• Prominent bowing

DYSPLASIA

Sagittal ultrasound shows a flat mid-face with depressed
nasal bridge (arrow), short upturned nasal tip, and
unusual ("cloverleaf") skull shape (curved arrow) in TO
type 1/.

•
•
•
•

"Telephone receiver" femur
Normal ossification
No evidence of fractures
Progressive shortening observed throughout
gestation
o Head
• Macrocephalic, relatively normal-shaped skull
• Depressed nasal bridge
• Short, upturned nasal tip
• Hypoplastic midface
• Frontal bossing, severe in 3rd trimester
o Thorax
• Small, narrow
• Short horizontal ribs
• Abnormal cardiothoracic ratio
o Spine
• Platyspondyly
• Prominent lumbar kyphosis
• Normal ossification
o Hands
• Very short phalanges
• Trident shaped hands
o Miscellaneous
• Polyhydramnios, often severe
• Limitation in joint mobility noted
• Type II
o Kleeblattschadel ("cloverleaf") skull
o Femurs longer, less curved

DDx: Other Short limb Conditions

01 Type /I

01 Type /II/IV

Achondrogenesis

Achondrogenesis

THANATOPHORIC

DYSPLASIA

Key Facts
Terminology

•

• Lethal kel tal d
growth fa tor r
ptor
• i id d into 2 ubt
finding

•

er

•

(0

Diagnoses

• Achondr g n i
• Homoz ou a hondropla
• amptomelic d plasia

Radiographic Findings
• Fetal skeletal survey
o Performed in 3rd trimester
o Obtain spot films of spine and long bones
• Platyspondyly better seen than on US
• Ossification normal
• Neonatal/postmortem
o Spine
• Notched end plates "H" configuration on frontal
view
• Platyspondyly
• Prominent lumbar kyphosis
o Pelvis
• Hypoplastic with spicules
• Accessory pelvic ossification centers
o Long bones
• Micromelia
• Prominent bowing, especially TD I
• Flared irregular metaphyses
• No fractures

Imaging Recommendations
Measure, assess morphology of all long bones
Carefully assess calvarium shape, profile
Consider fetal skeletal survey in 3rd trimester
3D US may be additive in select cases
o Useful for spatial relationships
o Evaluation of facial dysmorphism
o Relative proportion of appendicular skeletal
elements
o Images aid in counseling parents

I DIFFERENTIAL

•
•
•
•
•
•
•
•

ia

o Platyspondyly less marked
o Other findings similar to TD type I

•
•
•
•

ta (

I)

I w r urrenc ri k
t ommon t pe of I thai

0

t

0

hondr

d

trophy

Clinical Issues

TD type I: "T I phone re iver" f mur
TD type II: Kle blatt chadel (" I
rleaf") kull
Long bon
erelyaff
ted
ormal 0 ification
Trident hap d hand

Top Differential

i imperf

Pathology

Imaging Findings
•
•
•
•
•

teog n

DIAGNOSIS

Achondrogenesis
• Absent spine ossification
• Only skull ossifies well enough to be seen

an b diagno d a early a 14 week
75%
ere polyhydramnio
by lat 2nd trime ter
L thai within fir t few hour -to-da
of lif
Mole ular t ting for F FR3 mutation
utop
important for final pecific diagno i
-ra
n if prenatal ur e perform d
Bone/ artilage biop
Deli r in t rtiary
nter with e perti e in fetal
geneti pathology/ kel tal d pi asia

Homozygous

achondroplasia

• Look at parents
• May not be apparent

Camptomelic

until>

20 weeks

dysplasia

• Hypoplastic scapulae
• Sharp mid-shaft tibial angulation
• Lower extremities more severely affected

Osteogenesis imperfecta

(01)

• Bones acutely angulated from fractures
• Decreased ossification, especially calvarium
• Ribs appear "beaded" due to multiple fractures

Fibrochondrogenesis
• Cloverleaf skull common
• "Dumb bell" shaped long bones
• Hypoplastic posterior vertebrae with clefts

Carpenter
•
•
•
•
•

syndrome

Cloverleaf skull
Polysyndactyly
Cardiac abnormalities
Umbilical hernia
Limbs straight, not as short

I PATHOLOGY
General Features
• General path comments: Defective differentiation of
chondrocytes in cartilage growth plates
• Genetics
o Sporadic, new, dominant mutation of FGFR3 gene
on short arm of chromosome 4
o Identifiable mutation found in all cases
o TD I involves a lysine-to-arginine substitution at
position 248 in approximately 2/3 of cases
o TD II involves a lysine-to-glutamine
substitution at
position 650
o Very low recurrence risk
o Has occurred in monozygous twins
• Discordance for kleeblattschadel skull reported

THANATOPHORIC
o Prenatal Diagnosis
• Ultrasound
• Amniocentesis or chorionic villus sampling (CYS)
for molecular analysis of FGFR3 mutations
• 3rd trimester radiography
• Etiology
o FGFR3 member of tyrosine kinase receptor family
o Tyrosine kinase important in cell growth and
differentiation
o Not due to simple haploinsufficiency
• Epidemiology
o Most common type of lethal
osteochond rodystrop h y
o First described as a distinct entity by Maroteaux in
1967
o 1: 10-40,000 live births in USA
o No ethnic or gender predilection
o Advanced paternal age
• 50% occur with paternal age over 35 years
• Associated abnormalities
o Cleft palate
o Heterotopias
o Polymicrogyria
o Other microscopic central nervous system (CNS)
abnormalities

ICLINICAL

o DNA analysis for FGFR3 mutations
o Bone/cartilage biopsy
o International Skeletal Dysplasia Registry at
Cedars-Sinai Hospital in Los Angeles for variant
cases
• Deliver in tertiary center with expertise in fetal genetic
pathology/skeletal
dysplasia

I DIAGNOSTIC

• Most common signs/symptoms
o Usually found on routine screening ultrasound
o Can be diagnosed as early as 14 weeks
o 1st trimester associations
• Increased nuchal thickness
• Reversed diastolic flow in ductus venosus
• Other signs/symptoms
o May be diagnosed late when polyhydramnios
causes
increased uterine size
o 75% severe polyhydramnios
by late 2nd trimester

Natural History & Prognosis
• Lethal within first few hours-to-days of life
o Small thorax: Pulmonary hypoplasia
o Central apnea also a primary cause of death
o Abnormal skull/spine/small foramen magnum ~
brainstem compression
o Rare survivors beyond infancy have been described

Treatment
• No fetal or neonatal treatment available
• Amniocentesis
o Therapeutic reduction amniocentesis for maternal
symptoms in continuing pregnancy or prior to labor
o Molecular testing for FGFR3 mutations
• Offer pregnancy termination
• If pregnancy progresses and diagnosis certain
o Avoidance of fetal monitoring, cesarean section
o No intervention for preterm labor
o Psychological support for family, perinatal hospice
• If diagnosis unclear and infant liveborn, resuscitation
appropriate until confirmatory tests performed
• Autopsy important for final specific diagnosis
o X-rays even if prenatal survey performed

CHECKLIST

Consider
• Fetal skeletal survey should be performed
trimester

Image Interpretation

in 3rd

Pearls

• Micromelia with normal ossification,
cloverleaf skull

curved femora,

ISELECTED REFERENCES
1.

2.

ISSUES

Presentation

DYSPLASIA

3.

4.

5.
6.

7.

8.

9.

10.
11.

12.

13.

14.

15.

Ferreira A et al: Nuchal translucency and ductus venosus
blood flow as early sonographic markers of thanatophoric
dysplasia. A case report. Fetal Diagn Ther. 19(3):241-5,
2004
Legeai-Mallet L et al: Overexpression of FGFR3, Statl, Stat5
and p21Cip1 correlates with phenotypic severity and
defective chondrocyte differentiation in FGFR3-related
chondrodysplasias.
Bone. 34(1):26-36, 2004
Brodie SG et al: Mouse models orthologous to
FGFR3-related skeletal dysplasias. Pediatr Pathol Mol Med.
22(1):87-103,2003
Krakow D et al: Use of three-dimensional
ultrasound
imaging in the diagnosis of prenatal-onset skeletal
dysplasias. Ultrasound Obstet Gynecol. 21(5):467-72, 2003
Parilla BY et al: Antenatal detection of skeletal dysplasias. ]
Ultrasound Med. 22(3):255-8; quiz 259-61,2003
Cohen MM ]r: Some chondrodysplasias
with short limbs:
molecular perspectives. Am] Med Genet. 112(3):304-13,
2002
Fieni S et al: Ultrasound assessment of biometric trends in
a case of thanatophoric
dysplasia. Gynecol Obstet Invest.
54(2):122-4,2002
Chen CP et al: Prenatal diagnosis and genetic analysis of
type I and type II thanatophoric
dysplasia. Prenat Diagn.
21(2):89-95, 2001
Yamaguchi K et al: Autopsy case of thanatophoric
dysplasia: observations on the serial sections of the brain.
Neuropathology. 21(3):222-8, 2001
Garjian KY et al: Fetal skeletal dysplasia: three-dimensional
US--initial experience. Radiology. 214(3):717-23, 2000
Kuno T et al: Markers for bone metabolism in a long-lived
case of thanatophoric dysplasia. Endocr]. 47 Suppl:S141-4,
2000
Cohen MM ]r: Achondroplasia, hypochondroplasia
and
thanatophoric
dysplasia: clinically related skeletal
dysplasias that are also related at the molecular level. Int]
Oral Maxillofac Surg. 27(6):451-5, 1998
Wilcox WR et al: Molecular, radiologic, and
histopathologic correlations in thanatophoric dysplasia.
Am] Med Genet. 78(3):274-81, 1998
Baker KM et al: Long-term survival in typical
thanatophoric dysplasia type 1. Am] Med Genet.
70(4):427-36, 1997
Bonaventure] et al: Common mutations in the gene
encoding fibroblast growth factor receptor 3 account for
achondroplasia, hypochondroplasia
and thanatophoric
dysplasia. Acta Paediatr Supp!. 417:33-8,1996

THANATOPHORIC
IIMAGE

DYSPLASIA

GALLERY

(Left) Coronal ultrasound
shows a very small thoracic
cavity (arrows) compared to
fetal abdomen. Chest
findings are similar in both
TO type I & /I, with
pulmonary hypoplasia often
being cause of death. (Right)
Axial ultrasound shows an
abnormal skull configuration
with temporal-parietal
prominence (arrows) typical
of a kleeblattschadel or
"cloverleaf" skull in TO type
/I.

(Left) Ultrasound of the hand
(arrow) shows shorl
phalanges and splaying of
the fingers, all of equal
length. This configuration
gives the hand a classic
"trident" appearance.
(Right) Radiograph shows
the curved femur (arrow) of
TO type I. Platyspondyly is
obvious in the lumbar spine
(curved arrow) and the
spiculated appearance of the
iliac wing is shown (open
arrow).

Typical
(Left) Clinical photograph of
TO type I shows marked
frontal bossing with
depressed nasal bridge
(curved arrow) and short
upturned nasal tip. Note the
head is macrocephalic but
normal in shape. (Right)
Clinical photograph of TO
type /I shows unusual skull
shape (kleeblattschadel)
(curved arrows). The chest is
very small (arrow). Note the
typical "trident" hand (open
arrow).

CLUBFOOT

Clinical photograph shows clubfoot. The foot is deviated
medially and foreshortened secondary to plantar flexion.
Talipes equinovarus is the most common type of
clubfoot.

ITERMINOlOGY
Abbreviations

and Synonyms

• Clubfoot (CF)
• Talipes equinovarus

• Location
o 60% bilateral
o 40% unilateral
• Size: Mild or severe angulation

Ultrasonographic

Definitions
• Malformation/malposition
of foot and ankle bones
o Talipes equinovarus
• Most common
• Foot rotated inward (varus)
• Foot plantar flexed (equinus)
o Talipes varus
• Foot rotated inward
• No equinus
o Talipes valgus
• Rare
• Foot rotated outward (valgus)

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Foot medially deviated at ankle
• Long bones of foot lie in same plane as tibia and
fibula
• Must be a consistent finding

DDx: Dysmorphic

Coronal
ultrasound
shows
talipes equinovarus
(clubfoot) in a second trimester fetus. The long axis of
the tibia/fibula (arrows) is in the same plane as the long
axis of the foot and toes (curved arrows).

Findings

• Normal lower extremity orientation
o Coronal axis tibia/fibula (tib/fib) + short axis foot
• Long tib/fib + cross section metatarsals
• Clubfoot
o Talipes varus
• Foot turned inward
• Coronal tib/fib + coronal foot
• Long tib/fib + long metatarsals
o Talipes equinovarus
• Foot plantar flexed and short
• Talipes varus + equina foot
• Equinus = "horse hoof"
o Talipes valgus
• Less common
• Long tib/fib + long metatarsals
• Foot turned outwards
• 60% bilateral
o 75% with other anomalies at time of ultrasound
o 15% false positive rate
• 7% will have normal feet
• 8% will have only unilateral clubfoot
• 40% unilateral

Foot

Ectrodact yly

Amputation.~

- Bands

f

C_L_U_B_F_O_O_T

_

Key Facts
Top Differential Diagno es

Terminology
• Talipe

quin

varu
in am

plan

a tibia and

• R kerb ttom foot
• Ectr da t I
• mni ti band

Pathology
• Epid miology: 1:1,000 Ii e birth

Clinical Issues
und

•
•

•

•

•

•

•

o 62% with other anomalies at time of ultrasound
o 29% false positive rate
• Normal feet
High false negative rates
o 20% clubfoot missed at first ultrasound
o 6% found to have additional anomalies at birth
High false positive rates
o Positional foot
• Foot is against uterine wall
• Look for extended period of time
o Follow-up when isolated finding
Clubfoot and aneuploidy
o 30% with chromosome abnormality
• Same for unilateral as bilateral
o Almost all have associated anomalies
o Trisomy 18 most common
• 23% with clubfoot
• 10% with rockerbottom foot
Associated anomalies common
a Spina bifida
• 24% with clubfoot
• Usually bilateral
o Arthrogryposis
• Fetal akinesia deformation sequence
• Multiple limb contractures
• Intrauterine growth restriction (IUGR)
• Polyhydramnios
o Restricted in utero environment
• Chronic oligohydramnios
important risk factor
• Uterine anomalies
• Any restriction on gestational sac growth
o Intrinsic abnormality of muscle
• Myotonic dystrophy
Association with early amniocentesis (EA)
a Procedure at 11-13 wk is EA
o 4x t risk for clubfoot
• Compared with chorionic villus sampling

Imaging Recommendations
• Best imaging tool
o Routine view of both lower extremities
• Coronal view of tib/fib and foot
o 3D ultrasound may be helpful

•
•
•
•

Do well with treatment
60% ur ler
40l}Oh on r ati
D i ion f r urg r after

months

Diagnostic Checklist
• Look car fully at f et wh n a ociated an mali
• Rem mb r fal po iti e diagno e ar omm n

• Multiplanar imaging advantage
• Allows for meticulous exam
• Protocol advice
o Rule out transient foot position
• Follow-up when isolated finding
o Role for amniocentesis
• Controversial for isolated cases
• Some "isolated" cases show additional
on follow-up

I DIFFERENTIAL

anomalies

DIAGNOSIS

Rockerbottom foot
• "Persian slipper" appearance
o Convex foot on lateral view
o Foot hyperextended
• May be seen with clubfoot
• Rarely isolated
o Strong association with trisomy 18
• 70% bilateral
• Almost always need surgery for repair

Ectrodactyly
• Split hand/foot deformity
o "Lobster-claw" deformity
• Abnormal central ray formation
a Absent middle"fingers/toes
o Deep median cleft
o Fusion of remaining digits
• Isolated or with other anomalies

Amniotic bands
• Entrapment of fetal parts by disrupted amnion
• Amputations
o Missing toes/fingers common
• Constrictions
o Bands around limb
a 2° lymphedema
• Clefts
o Bizarre body wall defects

n

CLUBFOOT
o Severity of associated anomalies

!PATHOlOGY
General Features
• Genetics
o Associated with aneuploidy in 30%
• Trisomy 18
• Trisomy 21
• 47XXY/47XXX

• Etiology
o Persistent embryonic positioning implicated
• Normal early foot position is varus
o Lack of movement from any cause
• Movement starts at 7-8 wks
o Primary hindfoot deformity
• Mostly involving talus and calcaneus
oSpina bifida
• Unopposed muscle group action
• Epidemiology: 1:1,000 live births

Staging, Grading or Classification Criteria
• Talo-calcaneal angle
o Measured on frontal and lateral x-rays
o 3D CT measurements most accurate
o Normal
• Frontal: 35° (or> 35° in children)
• Lateral: 35°
o Clubfoot
• Frontal: < 35°
• Lateral: Talus and calcaneus are parallel
o Used to follow treatment
• Dimeglio score
o 0-20 points based on 4 parameters
• Varus in frontal plane
• Forefoot adduction in frontal plane
• Calcaneo-forefoot rotation around talus
• Equinus in sagittal plane
o Grade I (benign): 1-5 points
• Easily reducible
o Grade II (moderate): 5-10 points
• Reducible but partly resistant
o Grade III (severe): 10-15 points
• Resistant but partly reducible
o Grade IV (very severe): 15-20 points
• Resistant

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Club foot + other anomalies
o Incidentally noted on routine ultrasound

Demographics
• Age
o Advanced maternal age (AMA) at greater risk for
trisomy
• AMA > 35 yrs at time of delivery

Natural History & Prognosis
• Isolated
o Do well with treatment
• Non-isolated
o Depends on karyotype

Treatment
• Clubfoot
o 60% surgery
0:-40% conservative
• Physical therapy (PT)
o Gentle manipulation
• 30 minutes/day
• Baby should never cry during PT
o Progressive reduction of deformity
• Forefoot corrected first
• Hindfoot corrected second
• Equinus corrected last
o Decision for surgery after 3 months
• Flexible splint
o Applied between PT sessions
o Light below-knee splint
• Surgery
o Achilles tendon lengthening
• +/- Posterior tendon release·
• +/- Medial tendon release
o Bone operation
• Usually only in fully-grown foot

I DIAGNOSTIC

CHECKLIST

Consider
• Diagnosis in high-risk fetuses
oSpina bifida
o Arthrogryposis
o Oligohydramnios

Image Interpretation

Pearls

• Look carefully at feet when associated anomalies seen
• Remember false positive diagnoses are common

I SELECTED
1.

2.

3.

4.

5.

6.

7.
8.

9.

REFERENCES

Ippolito E et aI: Validity of the anteroposterior
talocalcaneal angle to assess congenital clubfoot correction.
AJRAm J Roentgenol. 182(5):1279-82, 2004
Mammen Let al: Outcome of fetuses with clubfeet
diagnosed by prenatal sonography. J Ultrasound Med.
23(4):497-500,2004
Philip J et al: Late first-trimester invasive prenatal
diagnosis: results of an international randomized trial.
Obstet Gynecol. 103(6):1164-73,2004
Souchet P et al: Functional treatment of clubfoot: a new
series of 350 idiopathic clubfeet with long-term follow-up.
J Pediatr Orthop B. 13(3):189-96,2004
Bakalis S et al: Outcome of antenatally diagnosed talipes
equinovarus in an unselected obstetric population.Ultrasound Obstet Gynecol. 20:226-9, 2002
van Mulken JM et al: Evalu<\tion of the treatment of
clubfeet with the Dimeglio score. J Pediatr Orthop.
21(5):642-7, 2001
Malone FD et al: Isolated clubfoot diagnosed prenatally: Is
karyotyping indicated? Obstet Gynecol. 95:437-40, 2000
Shipp TD et al: The significance of prenatally identified
isolated clubfoot: Is amniocentesis indicated? Am J Obstet
Gynecol. 178:600-2, 1998
Dimeglio A et al: Classification of clubfoot. J Pediatr
Orthop B. 4(2):129-36, 1995

\

CLUBFOOT
IIMAGE

GALLERY
(Left) Coronal ultrasound
suggests bilateral clubfeet in
a fetus with bladder outlet
obstruction (treated with
bladder shunting). Both feet
are inwardly turned (arrows)
but difficult 10 see. (Right)
Coronal 30 ultrasound
(3D-US) with post-rendering
manipulation better shows
the bony anatomy. The
arrows point to the tibia and
fibula while 5 metatarsals are
seen between the open
arrows. Bilateral club feet
was confirmed at birth.
3D-US can be helpful in
confirming findings.

Typical
(Left) Coronal ultrasound of
a clubfoot. The foot is
medially deviated (arrows).
Also, there is significant
muscle atrophy (curved
arrows). (Right) Sagittal
ultrasound in the same fetus
shows abnormal positioning
of the fetal wrist (curved
arrow) and a clenched hand
(open arrows). This fetus
barely moved and had
multiple joint contractures
and polyhydramnios.
The
findings led to the diagnosis
of arthrogryposis.

(Left) Frontal radiograph in a
baby with clubfoot shows
hindfoot varus as the
calcaneus (open arrow) and
talus (arrow) are
overlapping. A normal
talo-calcaneal angle in an
infant is usually> 3SO. The
forefoot is thus turned
medially. (Right) Lateral
radiograph in the same baby
shows parallel talus (arrow)
and calcaneus (open arrow).
The foot is also
foreshortened
and plantar
flexed, typical of an
equinovarus deformity.

ROCKERBOTTOM FOOT

Sagittal graphic shows the bony anatomy of
rockerbottom foot. The hallmark findings are a vertical
talus (arrows) and hindfoot equinus (open arrows).

ITERMINOLOGY
Abbreviations
•
•
•
•

and Synonyms

Rockerbottom foot
Congenital convex pes valgus
Congenital vertical talus
Congenital convex foot

Definitions
• Dorsolateral dislocation

of midfoot on hindfoot

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o "Persian slipper" foot
• Sole of foot is convex
• Dorsum of foot is concave
• Location
o 70% bilateral
o 30% un i1atera I

Ultrasonographic

• Best imaging tool
o Routine lower extremity evaluation
• Lateral tib/fib + lateral foot
• Coronal axis tib/fib + short axis foot
• Protocol advice
.

• Convex foot on lateral view
o Foot hyperextended
o Convex sole
• Valgus deformity on frontal view

Clubfoot

o Long axis of tibia/fibula (tib/fib) + long axis of foot
o Foot turned away from midline
• Rarely isolated when diagnosed in utero
o 50% isolated in neonatal series
• Common associations
o Clubfoot
• 1:100 with additional rockerbottom morphology
o Trisomy 18
• Rockerbottom foot in 10%
• Clubfoot in 23%
• Other severe anomalies usually also seen
oSpina bifida
• Clubfoot more common (24%)
o Arthrogryposis
• Fetal akinesia deformation sequence
• Multiple limb contractures
• Polyhydramnios
o Restricted in utero environment
• Chronic oligohydramnios
o Intrinsic abnormality of muscle
• Myotonic dystrophy

Imaging Recommendations

Findings

DDx: Dysmorphic

Sagittal ultrasound of a rockerbottom foot in a second
trimester fetus with multiple other anomalies. The foot
resembles a "Persian slipper" as the sole is convex
(arrow) and the toes are upturned (open arrow).

Foot

Ectrodactyly

Amniotic Bands

ROCKERBOTTOM FOOT
Key Facts
Terminology

Top Differential

• ongenital convex pe valgus
• Dor olateral dislocation of midfoot on hindfoot

•

Diagnoses

lubfo t

Clinical Issues

Imaging Findings

• Surgery almost always nece

•
•
•
•
•

• Amniocente i in non-isolated ca e
• Look carefully at feet when as ociated anomali

"Per ian slipper" foot
70% bilateral
Rar Iy isolated when diagnosed in utero
Trisomy 18
Rule out transient foot position

Diagnostic Checklist

o Rule out transient foot position
• Foot up against uterine wall
o Amniocentesis recommended when not isolated

I DIFFERENTIAL

ary

I DIAGNOSTIC

s en

CHECKLIST

Consider
• Amniocentesis in non-isolated cases
• Follow-up on cases which appear isolated
o Rule out transient finding
o Re-evaluate for associated anomalies

DIAGNOSIS

Clubfoot

Image Interpretation

• Talipes equinovarus
o Medial angulation of foot
o Foot abnormally flexed
• More common than rockerbottom

Pearls

• Look carefully at feet when associated anomalies seen

I SELECTED REFERENCES

Ectrodactyly

1.

• Split hand/foot deformity
o "Lobster-claw" deformity
• Absent central ray/rays
o Deep median cleft
o Fusion of remaining digits

2.

3.

Amniotic band syndrome
• Entrapment of fetal parts by disrupted amnion
• Amputations
o Missing fingers/toes
• Constrictions
o 2° lymphedema
• Bizarre body wall defects

4.
5 ..

Levinsohn EM et al: Congenital vertical talus in four
generations of the same family. Skeletal Radiol.
33(11):649-54, 2004
Bakalis S et al: Outcome of antenatally diagnosed talipes
equinovarus in an unselected obstetric population.
Ultrasound Obstet Gynecol. 20:226-9, 2002
Malone FD et al: Isolated'clubfoot diagnosed prenatally: Is
karyotyping indicated? Obstet Gynecol. 95:437-40, 2000
Duncan RD et al: Congenital convex pes valgus. J Bone
Joint Surg Br. 81(2):250-4, 1999
Shipp TO et al: The significance of prenatally identified
isolated clubfoot: Is amniocentesis indicated? Am J Obstet
Gynecol. 178:600-2, 1998

IIMAGE

I PATHOLOGY

GALLERY

General Features
• General path comments
o Dorsal dislocation of talocalcaneonavicular
• Secondary equinus of hindfoot
• Vertical orientation of talus
• Genetics
o High risk of aneuploidy when non-isolated
• Trisomy 18 most common
• Epidemiology: 1:10,000

I CLINICAL

joint

ISSUES

Natural History & Prognosis
• Depends on karyotype and associated anomalies

Treatment
• Surgery almost always necessary
o Often multiple
o Often need further bracing

(Left) Sagittal T2WI MR shows a rockerbottom foot in a fetus with
multiple other anomalies. The typical convex sole is the most obvious
finding (arrows). In addition, this fetus had skin edema (open
arrows).
(Right)
Lateral clinical
photograph
shows isolated
rockerbottom foot in a child. The hindfoot is most severely affected
(arrows) and the sole of the foot is curved. Almost all rockerbottom
feet ne~d surgical correction.

SANDAL GAP FOOT

Clinical photograph
shows sandal gap foot and
syndactyly. Notice the gap (arrows) between the first
and second toes. Soft tissue syndactyly of the other toes
is also seen (curved arrows).

Coronal ultrasound shows sandal gap foot (arrow) in a
normal fetus. The increased space between the first and
second toe was persistent and no other anomalies were
detected.

ITERMINOlOGY
Abbreviations

•

and Synonyms

• Sandal gap foot (SGF)

Definitions
• Big toe angled medially
• Gap between first and second toe

IIMAGING FINDINGS

•

General Features
• Best diagnostic clue: Increased space between first and
second toe
• Location: Unilateral or bilateral

Ultrasonographic

•

Findings

• Routine lower extremity views
o Coronal view of tibia and fibula
o Toes and metatarsals in cross section
• Usually first see gap on cross section view
o Sole view
• Parallel to bottom of foot
• SGF
o Big toe abducted
• Other toes normally positioned
o Most often normal fetus

DDx: Dysmorphic

Ectrodactyly

•

• Often familial
o Rule out positional
SGF and trisomy 21 (T21)
o 45% of fetuses with T21 have SGF
o Look for other markers for T21
• Increased nuchal fold thickness
• Echogenic intracardiac focus
• Echogenic bowel
• Mild renal pelviectasis
• Clinodactyly
SGF and trisomy 18 (TI8)
o Almost never an isolated finding
o Short first metatarsal + SGF
Sandal gap + other foot anomaly common
o Clubfoot
• Foot is turned inward
o Rockerbottom foot
• Toes splayed and upward displaced
• Additional abnormal gaps
SGF and amniocentesis
o Isolated usually idiopathic
• No need for amniocentesis
o Consider amniocentesis only if high risk for T21 or
TI8
• Other anomalies or markers
• Abnormal maternal serum quadruple screen
• Advanced maternal age

Foot

[ctrodactyl'y

Amniotic

Bands

SANDAL GAP FOOT
Key Facts
Terminology

Top Differential

• Big toe angled medially
• ap between first and second toe

• Ectrodactyly
• Syndactyly
• Amniotic band

Imaging Findings
•
•
•
•

Most often normal fetus
45% of fetuses with T21 have SGF
Look for SGF when other markers for T21 seen
As an isolated finding in low-risk patients, no need
for amniocente is

Diagnoses

Diagnostic Checklist
• T21 when other marker pre ent
• Look at other family member's toe
• Examine for an extended period of time to rule out
positional finding

Imaging Recommendations

Treatment

• Protocol advice
o Look for SGF when other markers for T21 seen
o As an isolated finding in low-risk patients, no need
for amniocentesis

• Usually none necessary

I DIAGNOSTIC

CHECKLIST

Consider

I DIFFERENTIAL

• T21 when other markers present
• Look at other family member's toes
• Examine for an extended period of time to rule out
positional finding

DIAGNOSIS

Ectrodactyly
• Split hand/foot deformity
o Lobster claw deformity
• Deficiency of middle phalanx
o Missing fingers/toes

I SELECTED
1.

Syndactyly
• Fusion of adjacent digits
o Soft tissue or bony fusion
o Isolated or part of syndrome
• Apert Syndrome
o Broad first toe, mitten hand

2.

3.

Amniotic bands
• Rupture of amnion with entrapment
• Amputations
o Loss of toes with secondary gaps
• Bizarre body wall/facial defects

4.

of fetal parts

REFERENCES

Devlin L et al: Accuracy of the clinical diagnosis of Down
syndrome. Ulster Med]. 73(1):4-12,2004
Hobbins]C et al: An 8-center study to evaluate the utility
of mid-term genetic sonograms among high-risk
pregnancies.] Ultrasound Med. 22(1):33-8, 2003
Ryu]K et al: Prenatal sonographic diagnosis of focal
musculoskeletal anomalies. Korean] Radiol. 4(4):243-51,
2003
Nicolaides KH et al: Ultrasonographically
detectable
markers of fetal chromosomal abnormalities. Lancet.
340(8821):704-7, 1992

I IMAGE

GALLERY

I PATHOLOGY
General Features
• Genetics
o Usually normal
o T21 (rarely isolated)
o Tl8 (never isolated)
• Epidemiology
o 45% of fetuses with T21
o 2-5% of normal feet

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Routine view of lower extremities
o In association with other anomalies or markers

Natural History & Prognosis
• Excellent prognosis when isolated

(Left) Coronal ultrasound of the foot shows a persistent SCF (arrow)
in a fetus with multiple other anomalies. (Right) Four chamber view
of the heart (arrow) in the same fetus shows a large atrioventricular
septal defect. Note the lack of any central valvular structures. Other
minor markers were present and the amniocentesis results were
trisomy 21.

RADIAL RAY MALFORMATION

Graphic illustrates features of radial ray malformation
(RRM).
The thumb
may
be absent
(arrow),
malpositioned, or triphalangeal. Hand position is often
abnormal and the radius is absent or hypoplastic.

ITERMINOlOGY
Abbreviations

and Synonyms

• Radial ray malformation
• Radial ray hypoplasia
• Radial ray aplasia

(RRM)

Definitions
• Spectrum of anomalies including
hypoplasia of
o Radius
o Radial carpal bones
o Thumb
• +/- Malposition or "fingerization"
(triphalangeal)

absence or

of thumb

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Single forearm bone

Ultrasonographic

Findings

• Grayscale Ultrasound
o Radius is absent or hypoplastic
• Hypoplasia involves distal portion
o Hand position abnormal
• Medial rotation

DDx: Abnormal
"

.

....

• Fixed on prolonged scanning
• Has been detected in first trimester
o Thumb appearance variable
• Absent
• Hypoplastic or mal positioned ("floating")
o Other anomalies/syndromes
common
o Multiple anomalies increase likelihood of
chromosome defect or VACTERL association
• Vertebral anomalies
• Anal atresia
• Cardiovascular anomalies
• Tracheoesophageal fistula, esophageal atresia
• Renal anomalies
• Limb anomalies (radial ray malformation)
o Thrombocytopenia-absent
radius syndrome (TAR)
has normal thumbs but radial aplasia
o Holt-Oram syndrome (heart-hand syndrome)
• Cardiac defect + upper extremity anomalies
including RRM
• 3D
o Useful to show hand position
o Helpful to count digits
o Detail on thumb
• Triphalangeal
• Hypoplastic
o May show facial detail allowing specific syndromal
diagnosis
• Cornelia de Lange syndrome

Hand

:~~~~;:-:.;.,;..
,~~~::

,

....

Endovaginal ultrasound at 72 weeks shows a single
forearm bone (arrow) and a sharply angled, medially
deviated hand (curved arrow) with no thumb. RRM
may be diagnosed in the first trimester.

.:0-..••.. 1.•.

,

~~~~,

~~~t~

Amniotic Band Defect

Arthrogryposis

Adducted Thumbs

RADIAL RAY MALFORMATION
Key Facts
Imaging Findings
•
•
•
•
•
•
•
•
•

Best diagnostic clue: Single forearm bone
Hand position abnormal
Thumb appearance variable
Multiple anomalies increase likelihood of
chromosome defect or VACTERL association
Thrombocytopenia-absent
radius syndrome (TAR) has
normal thumbs but radial aplasia
TAR may involve lower extremities
Cardiac defects common in Holt-Oram
86% of patients with hypoplastic thumbs have other
anomalies
Fetal incidence higher due to trisomies/lethal
syndromes

Top Differential
• Amputation

Diagnoses

Arth rogryposis
Short limbed skeletal dy plasia
X-linked aqueductal stenosis
13q-deletion syndrome

Pathology
• Damage to apical ectoderm of limb bud at 6-12 weeks
• Bilateral in 50%

Clinical Issues
• Detailed clinical evaluation
family members

of liveborn infant and

Diagnostic Checklist
• Syndrome identification important in RRM
• progno is and specific clinical complications vary for
each condition

defects

• Nager syndrome

Imaging Recommendations
• Best imaging tool: Targeted endovaginal ultrasound in
first trimester if positive family history
• Measure all long bones
o Nomograms exist for length
o RRM may be associated with other bone anomalies
• Holt-Oram upper extremity only, asymmetric
• TAR may involve lower extremities
• Fetal echocardiogram recommended in all cases
o Cardiac defects common in Holt-Oram
• Atrial septal defect 34%
• Ventricular septal defect 25%
o VACTERL association: C = cardiac lesion
• Careful search for other structural anomalies
o 86% of patients with hypoplastic thumbs have other
anomalies
o 44% either Holt-Oram or VACTERL
o Fetal incidence higher due to trisomies/lethal
syndromes
• Monitor growth
o Intra-uterine growth restriction
• Chromosome abnormality especially trisomy 18
• Cornelia de Lange syndrome
• Fanconi anemia
• Look for evidence of bleeding
o TAR: Thrombocytopenia
predisposes to bleeding
o Fanconi anemia may also cause thrombocytopenia

I DIFFERENTIAL DIAGNOSIS
Amputation

•
•
•
•

defects

• Look for amniotic bands
• May affect multiple areas

Arthrogryposis
• Abnormal position of hands/feet/extremities
• Bones and digits present

Short limbed skeletal dysplasia
• All long bones affected (to variable degree)

• Usually shortening rather than absence
• Often associated skull or spine abnormalities
• Often abnormal mineralization

X-linked aqueductal
•
•
•
•

stenosis

Adducted thumbs can mimic absence
Forearm bones normal
Severe hydrocephalus
May be family history

13q-deletion

syndrome

• Hypoplastic thumbs
• Syndactyly
• Brain malformation: Syntelencephaly
o Midline interhemispheric
fusion

I PATHOLOGY
General Features
• Genetics
o Autosomal dominant
• Holt-Oram maps to chromosome 12q2, mutation
in TBX5
• Nager syndrome (many cases are new sporadic
mutations)
o Autosomal recessive
• Fanconi anemia
• TAR
o X-linked dominant
o Proven X-linked recessive forms exist but are
extremely rare
o Split hand/split foot syndrome
• Critical region chromosome lOq24
o Aneuploidy
• Trisomy 18, 13
• Diploid/triploid mixoploidy
• Etiology
o Embryology
• Damage to apical ectoderm of limb bud at 6-12
weeks
• Normal hand is fully formed by 14 weeks
o Maternal infection

RADIAL RAY MALFORMATION
o Vascular anomaly
o Maternal diabetes
• 13.3% of infants with dysplastic ears born to
diabetic mothers also had RRM
o Teratogens
• Valproic acid
• Thought to cause defective chondrogenesis
• Epidemiology
o 1:30-80,000 live births
• Bilateral in 50%
o Limb defects (RRM + others) noted in approximately
1/3 of spontaneous 2nd/3rd trimester abortuses with
anomalies
• Associated abnormalities
o Congenital heart disease
o Thrombocytopenia

ICLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Should be detected on routine anatomic survey at
16-18 weeks
• Single forearm bone
• Abnormal hand position
• Absent thumb

• Consider cesarean section
o Risk of dystocia with flexion deformities at elbow
• Some authors suggest platelet transfusion prior to
induction of labor if low platelet count
o TAR, Fanconi anemia
• Detailed clinical evaluation of liveborn infant and
family members
o Require referral to specialist centers for
reconstructive surgery
o Classification system developed to allow
• Tracking of occurrence
• Follow-up of treatment

I DIAGNOSTIC

Image Interpretation

ISELECTED REFERENCES
1.

2.

Natural History & Prognosis
• Depends on associated anomalies
o TAR
• Risk of bleeding
• 40% liveborn die in early infancy
o Fanconi anemia
• Progressive bone marrow failure in childhood
• Depends on underlying cause
o Trisomy 18: Dismal
o Triphalangeal thumb: If isolated, can be surgically
corrected at 1-2 years
• Recurrence risk relates to underlying condition
o Trisomy 18 overall recurrence risk given as 1%
o Autosomal recessive conditions 25%
o Autosomal dominant 50%

Treatment
• Genetic counseling
• Careful maternal history for drug exposure
• Offer karyotype
o Aneuploidy
o Fanconi anemia
• Chromosomes must be studied after exposure to
diepoxybutane
• Exclude maternal diabetes
• Examine parents for subtle defects
o Holt-Oram shows anticipation (increasing severity of
defects in successive generations)
• Consider cordocentesis if family history of TAR
o Thrombocytopenia, aplastic anemia
o Hematologic abnormality must be proven for
specific diagnosis

Pearls

• Syndrome identification important in RRM
o Prognosis and specific clinical complications vary
for each condition
• Look careful for adduction or hypoplasia of thumbs
o May lead to specific diagnoses

Demographics
• Gender: 63% patients with hypoplastic thumbs are
male

CHECKLIST

3.

4.
5.

6.

7.

8.
9.

10.

11.

12.

13.

Le Vaillant C et al: Prenatal diagnosis of a 'minor' form of
Brachmann-de Lange syndrome by three-dimensional
sonography and three-dimensional
computed tomography.
Fetal Diagn Ther. 19(2):155-9,2004
Roscioli T et al: The 10q24-linked split hand/split foot
syndrome (SHFM3): narrowing of the critical region and
confirmation of the clinical phenotype. Am J Med Genet A.
124(2):136-41,2004
Wang R et al: Infants of diabetic mothers are at increased
risk for the oculo-auriculo-vertebral
sequence: A case-based
and case-control approach. J Pediatr. 141(5):611-7,2002
De Kerviler E et al: The clinical and radiological features of
Fanconi's anemia. Clin Radiol. 55:340-5, 2000
Manouvrier S et al: Radioulnar synostosis, radial ray
abnormalities, and severe malformations in the male: a
new X-linked dominant multiple congenital anomalies
syndrome? Am J Med Genet. 90(5):351-5, 2000
Un HJ et al: Omphalocele with absent radial ray (ORR): a
case with diploid-triploid mixoploidy. Am J Med Genet.
75(3):235-9, 1998
Boute 0 et al: Prenatal diagnosis of
thrombocytopenia-absent
radius syndrome. Fetal Diagn
Ther. 11(3):224-30, 1996
James MA et al: Characteristics of patients with hypoplastic
thumbs. J Hand Surg [Am]. 21(1):104-13, 1996
Basson CT et al: Genetic heterogeneity of heart-hand
syndromes. Circulation. 91(5):1326-9, 1995
Sharony R et al: Preaxial ray reduction defects as part of
valproic acid embryofetopathy.
Prenat Diagn.
13(10):909-18, 1993
Brons JT et al: Prenatal ultrasonographic diagnosis of
radial-ray reduction malformations. Prenat Diagn.
10(5):279-88, 1990
Donnenfeld AE et al: Prenatal diagnosis of
thrombocytopenia
absent radius syndrome by ultrasound
and cordocentesis. Prenat Diagn. 10(1):29-35, 1990
Stephens TO et al: A review of limb defects in a large fetus
collection. Am J Hum Genet. 35(3):508-19, 1983

RADIAL RAY MALFORMATION
IIMAGE GALLERY
(Left)

Ultrasound in a fetus
with trisomy 18 shows fixed
medial deviation of the hand
(curved arrow) and a single
forearm bone (arrow).
Second linear echo (open
arrow) is forearm skin.
(Right) Clinical photograph
at autopsy shows the typical
appearance in a similar case
of trisomy 18. Note the hand
position and absent thumb
(finger/ips denoted by
arrows, no thumb present).

(Left)

Ultrasound in a fetus
with Cornelia de Lange
syndrome shows an ulna
(curved arrow) with a small
remnant of the radius
(arrow). The hand was a
small, fused, "flipper-like"
nubbin (open arrow). (Right)
Clinical photograph of the
left upper extremity in the
same case shows fusion
between the arm and
forearm Only one digit
(arrow) is present on the
very hypoplastic hand

(Left) Radiograph of a child
shows the "pouce flottant"
or "floating thumb" (white
arrow) appearance seen in
some forms of radial ray
malformation. There is a
single forearm bone and the
radial carpal bones are
missing (black arrow).
(Right) Clinical photograph
of a neonate with multiple
anomalies including
congenital diaphragmatic
hernia and a ventriculoseptal
defect shows a
malpositioned thumb
(arrow) as part of an
associated RRM.

POLYDACTYLY

Clinical
photograph
shows
bilateral
postaxial
polydactyly in a stillborn with trisomy 73. Multiple other
anomalies, including holoprosencephaly, were present.

ITERMINOLOGY
Definitions
• One or more extra digits or parts of digits
o Most common varieties are postaxial (ulnar, fibular)
or preaxial (radial, tibial)

IIMAGING

FINDINGS

• Best diagnostic clue
o Need to confirm in both axial and coronal views
• Oblique views may give erroneous appearance of
polydactyly
• Location
o Postaxial
• Ulnar or fibular side
• Most common
o Preaxial
• Radial or tibial side
o Central
• Extra digit usually between long and ring finger
o Bilateral in approximately 50%
• Hand more often bilateral than foot
o More often on left when unilateral
• Morphology
o Variable

Meckel-Gruber,

Encep

• Well formed complete digit
• Bifid digit
• Broad digit
• Soft tissue nubbin
o Triphalangeal thumb
• Three defined phalanges
• Long finger-like thumb, "five-finger hand"
• Some consider part of radial ray malformation

Ultrasonographic

General Features

DDx: Syndromal

Ultrasound of the foot in another case of trisomy 73.
The extra digit (arrow) is on the fibular side of the foot
(postaxial). A supernumerary postaxial digit is the most
common type of polydactyly.

Findings

• Extra digit may be small or angulated
• May be fleshy nubbin without bone
o Difficult to see in utero
o Often missed
• Postaxial
o Extra digit in same plane as normal digits
o May attach directly to normal digit (bifid digit)
• Preaxial
o Extra digit proximally located
• Syndactyly may also be present

Imaging Recommendations
• Best imaging tool: 3D ultrasound with surface-mode
reconstruction valuable tool for evaluation of hands
and feet
• Count and recount
o Easy to both under and over diagnose
o Make sure hands (or feet) are not together
• Erroneous appearance of polydactyly

Polydactyly

Short Rib-Polydactyly

Trisomy]],

Iiolopros

Joubert

POLYDACTYLY
Key Facts
Terminology
• One or more extra digit or parts of digits
• Mo t common varieties ar postaxial (ulnar, fibular)
or preaxial (radial, tibial)

Imaging Findings
• Extra digit may be small or angulated
• May be fie hy nubbin without bone
• Best imaging tool: 3D ultrasound with surface-mode
reconstruction valuable tool for valuation of hand
and feet

Top Differential

Diagnoses

• Trisomy 13
• Meck 1- ruber yndrome
• hort rib-polydactyly syndrome
• Ellis-van reveld (chondroectodermal

• Smith-Lemli-Opitz
yndrome
• arp nter syndrome

Pathology
• Triphalang al ("finger-like") thumb con idered part of
preaxial spectrum
• Syndactyly often associated
• Isolated polydactyly is generally autosomal dominant
with variable pen trance
• Maternal diabete ri k factor for preaxial polydactyly
• Isolated postaxial polydactyly lOx more common in
African-American
• More common in male
• Preaxial polydactyly and triphalangeal thumb more
likely to be part of syndrome

dy plasia)

o Confirm in both axial and coronal planes
• Careful scanning for other abnormalities and
syndromes
• Cardiac echo if other abnormalities identified

•
•
•
•
•

I DIFFERENTIAL DIAGNOSIS

Carpenter

Trisomy 13
• Holoprosencephaly
• Facial anomalies
o Proboscis
o Cyclopia
• Cardiac defects
• Intrauterine growth restriction
• Cystic renal disease

Meckel-Gruber
•
•
•
•

(IUGR)

Encephalocele
Renal cystic dysplasia
Polydactyly
Autosomal recessive

syndrome

Jeune syndrome (asphyxiating thoracic
dysplasia)

Disorder of endochondral ossification
Small chest
Polydactyly
Cardiac defects
High incidence in Amish population
Autosomal dominant

syndrome

• Inborn error of cholesterol
• Microcephaly

Majewski syndrome
•
•
•
•

Narrow chest
Micromelia
Polydactyly
Cardiac defects
Genitourinary anomalies
Autosomal recessive

Smith-Lemli-Opitz

• Abnormal cerebellar vermis
• "Molar tooth" sign of cerebellar peduncles
• Autosomal recessive

• Narrow chest
• Long bone shortening
• Autosomal recessive

Ellis-van Creveld (chondroectodermal
dysplasia)
•
•
•
•
•
•

syndrome

Craniosynostosis of multiple sutures
Preaxial polydactyly
Syndactyly
Cardiac defects

Joubert syndrome

syndrome

Short rib-polydactyly
•
•
•
•
•
•

•
•
•
•

Cryptorchidism/abnormal
genitalia
Cardiac defects
Cleft palate
Clench hands, syndactyly, polydactyly
Autosomal recessive

metabolism

Narrow chest
Preaxial and postaxial polydactyly
Cleft lip/palate
Autosomal recessive

Mohr syndrome (oral-facial-digital
syndrome)
• Multiple facial anomalies
o Median clefts
o Malformed nose
o Tongue malformations
• Brain malformations
o Dandy-Walker continuum
o Agenesis of the corpus callosum
• Autosomal recessive

Hypochondroplasia
• Milder form of achondroplasia
• Autosomal dominant

POLYDACTYLY
Bardet-Biedel
•
•
•
•
•

Renal dysplasia
Polydactyly
Mental retardation
Obesity, short stature
Autosomal recessive

Hydrolethalus
•
•
•
•
•

•
•
•
•

syndrome

Hydrocephalus
Cleft lip/palate
Polyhydramnios
Polydactyly
Autosomal recessive

Short rib-polydactyly
]eune syndrome
Ellis-van Creveld
Majewski syndrome

Gross Pathologic & Surgical Features
• Variable amounts of development
o Soft tissue only (skin tag)
o Variable amounts of phalangeal development and
function

IClINICALISSUES
Presentation

I PATHOLOGY
General Features
• General path comments
o Triphalangeal ("finger-like") thumb considered part
of preaxial spectrum
• May be seen with other findings in radial ray
malformation
o Syndactyly often associated
• Usually adjacent to duplicated digit
• More common in feet than hands
• Genetics
o Variable according to syndrome
• Many are autosomal recessive
o Isolated polydactyly is generally autosomal
dominant with variable penetrance
o Chromosomal
• Trisomy 13, 10
• Etiology
o Embryology
• Upper limb buds appear day 24
• Lower limb buds day 26
• Hands and feet begin as paddle-shaped plates
• Digital rays develop in 5 sectors along
anterior/posterior axis
• Separate fingers and toes in eighth week
o Maternal diabetes risk factor for preaxial polydactyly
• Generally affects feet
o Teratogens: Azathioprine, clomiphene, valproic acid
• Epidemiology
o Postaxial
• Isolated postaxial polydactyly lOx more common
in African-Americans
• 1:3,000 Caucasian
• 1:300 African-American
• More common in males
o Preaxial (less common)
• 1:10,000
• No racial predilection
• Associated abnormalities
o Preaxial polydactyly and triphalangeal thumb more
likely to be part of syndrome
o Preaxial polydactyly
• Carpenter syndrome
• Infant of diabetic mother
• Majewski syndrome
• Trisomy 10
o Small chest + polydactyly

• Minor finding with other major malformations
• Incidental finding if isolated
o Often missed prenatally
o Family history usually present

Natural History & Prognosis
• Variable according to syndrome
• Isolated excellent
• In utero "autoamputation" reported
o Digit becomes progressively smaller
o May be born with only a small residual bump

Treatment
•
•
•
•

Karyotype warranted even if isolated
Thorough family history
Genetic counseling regarding syndromes
Resection of extra digit varies in complexity
o Without bone, may be done in nursery
o With bone, often wait until 1-2 years old
• May require joint reconstruction or tendon
transfer

I DIAGNOSTIC

CHECKLIST

Consider
• 3D ultrasound to aid in diagnosis

I SELECTED REFERENCES
1.
2.
3.

4.

5.
6.
7.

8.

Kos M et al: Limb deformities and three-dimensional
ultrasound.]
Perinat Med. 30:40-7, 2002
Bromley B et al: Isolated polydactyly:
Prenatal diagnosis
and perinatal outcome. Prenat Diagn. 20:905-8, 2000
Rodriguez-Pinilla
E et al: Prenatal exposure to valproic acid
during pregnancy and limb deficiencies: a case-control
study. Am] Med Genet. 90(5):376-81, 2000
Zimmer EZ et al: Fetal polydactyly diagnosis during early
pregnancy: Clinical applications.
Am] Obstet Gynecol.
183:755-8, 2000
Castilla EE et al: Associated anomalies in individuals with
polydactyly. Am] Med Genet. 80(5):459-65,1998
Castilla EE et al: Hand and foot postaxial polydactyly: two
different traits. Am] Med Genet. 73(1):48-54, 1997
Slee] et al: Further evidence for preaxial hallucal
polydactyly as a marker of diabetic embryopathy.
] Med
Genet. 34(3):261-3, 1997
Bronshtein M et al: Transvaginal
sonographic
diagnosis of
fetal finger abnormalities
in early gestation. J Ultrasound
Med. 14(8):591-5, 1995

POLYDACTYLY

I IMAGE GALLERY
(Left) Ultrasound shows a
small extra digit (curved
arrow) attached to the
midportion of the 5th finger.
The other fingers are curled
and out of the imaging plane
(arrow - thumb). This was an
isolated finding. When
isolated, polydactyly is most
likely familial and has an
excellent prognosis. (Right)
Clinical photograph of the
hand shows a very similar
configuration with a small
extra digit attached to the
5th finger (arrow). This was
a stillborn with trisomy 73.

(Left) Ultrasound of postaxial
polysyndactyly shows fusion
of toes 2-4 (open arrow), a
great toe (curved arrow),
and two digits (arrows) on
the fibular side of the foot.
(Right) Clinical photograph
of preaxial polysyndactyly in
an infant of a diabetic
mother. There is a bifid great
toe (curved arrow) and
syndactyly of toes 2-3
(arrow).

Typical
(Left) Radiograph of the
hand of an infant with
preaxial polydactyly. The
extra digit (curved arrow) is
on the radial side of the
hand. In addition, there is a
triphalangeal thumb (arrow).
(Right) Clinical photograph
shows a bifid thumb
(arrows) in a neonate with
Carpenter syndrome.
Preaxial polydactyly is less
common than the postaxial
form and is more likely (0 be
associated with a syndrome.

SYNDACTYLY

Ultrasound shows syndactyly of digits 2-] (arrow) and
absence of digits 4-5 (curved arrow) in a mid-trimester
fetus. A shortened radius is present (open arrow) but
the ulna is absent.

!TERMINOlOGY
Abbreviations

and Synonyms

• Syndactyly: Greek for "digits grown together"

Definitions
• Partial or incomplete syndactyly: Affects only
proximal segments of digits
• Complete syndactyly: Affects length of digits to level
of nails
• Polysyndactyly/synpolydactyly:
Combination of
duplicated and fused digits
• Symphalangism: Synostosis of joints of digits
• Zygodactyly: Shallow, membranous webbing of
2nd-3rd toes, most prominent on the plantar surface
• Acrosyndactyly: Soft tissue attachment of distal digits
with non-attached proximal segments

IIMAGING FINDINGS
General Features
• Multiple types of syndactyly exist, characterized by
digits involved
• Phenotypic overlap exists
• Classification centers on 5 subtypes
o Type I: Zygodactyly
• Most common type

Clinical photograph of the same infant at delivery shows
syndactyly with symphalangism of digits 2-] (arrow)
and absence of digits 4-5 (curved arrow). Radiographs
confirmed bilateral ulnar deficiency

• Partial or complete syndactyly of toes 2-3 and
fingers 3-4
o Type II: Synpolydactyly
• Syndactyly of fingers 3-4 with duplication of 3rd
or 4th finger in web
o Type III: Syndactyly of fingers 4-5
• Associated camptodactyly (persistent flexion) of
4th finger to accommodate difference in lengths
of fingers
• This type seen in oculodentodigital syndrome
o Type IV: Complete syndactyly of all fingers
• This type, with craniosynostosis, seen in Apert
syndrome
o Type V: Associated with metacarpal and metatarsal
synostosis
• Very rare

Imaging Recommendations
• Protocol advice
o Careful search for other limb, structural anomalies
• Presence/absence/abnormal
position of thumbs
• Evidence of craniosynostosis
o Examination of hands and feet of parents, siblings
o Consider karyotype if other structural anomalies or
growth restriction are present

DDx: Syndromal Syndactyly

Carpenter

Carpenter

Triploidy

Triploidy

SYNDACTYLY
Key Facts
Terminology
• Syndactyly: Greek for "digits grown together"
• Partial or incomplete syndactyly: Affects only
proximal segments of digits
• Complete yndactyly: Affects length of digits to level
of nails

Imaging Findings
• Multiple types of syndactyly exist, characterized by
digits involved
• Careful search for other limb, structural anomalies
• Examination of hands and feet of parents, siblings

Top Differential

Diagnoses

• on-syndromal syndactyly
• Amniotic bands
• Triploidy

• Apert syndrome
• Carpenter syndrome
• Pfeiffer syndrome

Pathology
•
•
•
•
•
•

Diagnostic Checklist
• Elicit "open hand" view by fetal stimulation
• Syndactyly often missed prenatally due to limitations
of ultrasound

o
o
o
o
o

I DIFFERENTIAL DIAGNOSIS
Non-syndromal

syndactyly

• Type I (zygodactyly) most common
o 2-3 toe syndactyly
o Positive family history common
o May involve hands, feet or both
o Unilateral or bilateral
o May be associated with polydactyly (polysyndactyly)
• Amniotic bands
o Distal digits adherent
o Limb, digital amputations
o Constriction rings
o Bizarre body wall, craniofacial clefts
o Strands of amnion often visible in amniotic fluid

•

Syndromal syndactyly
• Triploidy
o Characteristic 3-4 syndactyly of hands
o Variable syndactyly of feet
o Severe intrauterine growth restriction (IUGR)
o Multiple (variable) structural anomalies
o Associated with partial molar gestation
o Maternal preeclampsia, often in mid-trimester
o Theca lutein cysts of maternal ovaries
• Due to high human chorionic gonadotropin
(hCG) levels
o Lethal, often in utero
• Apert syndrome
o Acrocephalosyndactyly
o "Mitten syndactyly": Partial or complete syndactyly
of fingers, toes
• Complete fusion of digits 2-4 most common
o Broad distal thumbs, halluces in valgus position
o Craniosynostosis with brachyturricephaly (conical
skull shape)
o Mental retardation common
o Autosomal dominant
o Mutations in FGFR2
• Carpenter syndrome
o Brachydactyly, syndactyly of hands
o Broad thumbs, occasional duplication

on-syndromal familial cases are autosomal
dominant
Failure of separation of digital rays
Occurs prior to 6 weeks of development
Mo t common anomaly of the hand
Bilateral in 50%
Syndactyly of toes more common than fingers

•

•

•

Preaxial polydactyly of feet with partial syndactyly
Craniosynostosis of multiple sutures
Shallow orbits
Cardiac defects in 50%
Omphalocele, umbilical hernia
o Hypogenitalism
o Variable intellectual function
o Autosomal recessive
Pfeiffer syndrome
o Acrocephalosyndactyly, Pfeiffer-type
o Craniosynostosis, often severe
o 3 subtypes correlate with prognosis, severity of
cranial abnormality
o Broad distal phalanges of thumb, great toe
o Partial syndactyly of fingers 2-3, toes 2-4
o Autosomal dominant or sporadic
o Some due to mutations in FGFR1,2
Greig cephalopolysyndactyly syndrome
o Syndactyly of fingers 3-4; toes 1-3
o Postaxial polydactyly of hands; preaxial polydactyly
of feet
o Broad thumbs
o Macrocephaly with high forehead
o Due to haploinsufficiency of GLI3 on 7p13
o Allelic to Pallister-Hall syndrome
Oculodentodigital syndrome
o Syndactyly of fingers 4-5; toes 3-4
o Camptodactyly
o Midphalangeal hypoplasia, aplasia of multiple digits
o Microphthalmos
o Microcornea
o Thin hypoplastic alae nasi
o Enamel hypoplasia
o Fine sparse hair
o Normal intellectual function
o Autosomal dominant, variable expressivity
Ectrodactyly-ectodermal dysplasia-c1efting syndrome
o Abnormalities in mid-portion of hands and feet,
ranging from syndactyly to ectrodactyly (absence of
part or all of one or more digits)
o Orofacial clefts
o Nail dysplasia

SYNDACTYLY
o
o
o
o

Hypopigmentation
of skin and hair
Genitourinary anomalies
Anodontia, microdontia
Autosomal dominant with variable expressivity
• Maps to 7q 11.2-21.3
• Split hand-split foot malformation
o Syndactyly most common feature
o Involves central rays of hands, feet
o Presents with syndactyly, median clefting of
hands/feet, hypoplasia/aplasia
of digits
o May involve 1 or both hands without foot
involvement, or all 4 extremities
o Most autosomal dominant with variable penetrance,
or sporadic
• Mild syndactyly in otherwise unaffected
individuals with affected offspring
• 5 loci mapped to 7q21, Xq26, lOq24, 3q27, 2q31
• Mutations p63 gene in some cases of ectrodactyly

I PATHOLOGY
General Features
• Genetics
o Non-syndromal familial cases are autosomal
dominant
• Incomplete penetrance
• Variable expressivity
o Syndromal dependent upon individual syndrome
o Sporadic - amniotic bands
• Etiology
o Failure of separation of digital rays
• Aberrant epidermal growth factor receptor
signaling leading to lack of interdigital apoptosis
o Occurs prior to 6 weeks of development
• Epidemiology
o 1:2,000-3,000 births
o Most common anomaly of the hand
o Bilateral in 50%
o Syndactyly of toes more common than fingers
• Associated abnormalities
o Other limb anomalies
o Clefting, ectodermal dysplasia in
ectrodactyly-ectodermal
dysplasia-clefting syndrome
o Craniosynostosis in FGFR related syndromes
o Other structural anomalies, IUGR in aneuploidy
o Dermatoglyphic abnormalities

Natural History & Prognosis
• Non-syndromal syndactyly usually has good prognosis
• Prognosis in syndromal syndactyly dependent upon
particular syndrome
• Symphalangism associated with significant
impairment due to lack of normal joint formation

Treatment
• Cosmetic versus functional treatment
o Dependent upon which digits involved
o Osseous or soft tissue involvement
o Multiple surgeries, including significant skin graft
procedures, may be required

I DIAGNOSTIC

Image Interpretation

ISSUES

ISELECTED REFERENCES
1.

2.
3.

4.

5.
6.

7.

8.

10.

Presentation
• Most common signs/symptoms
o Fingers appeared "attached" in open hand view on
ultrasound
o Diagnosis of toe syndactyly very difficult on
prenatal ultrasound
• Other signs/symptoms: Other limb, structural
anomalies suggestive of syndromal syndactyly

Demographics
• Age: No association with increased parental age
• Gender: More common in males

Pearls

• Elicit "open hand" view by fetal stimulation
o Persistent inability to visualize spread fingers
concerning for syndactyly
o Syndactyly often missed prenatally due to
limitations of ultrasound

9.

ICLINICAL

CHECKLIST

11.

12.

13.

Johnston JJ et al: Molecular and Clinical Analyses of Greig
Cephalopolysyndactyly
and Pallister-Hall Syndromes:
Robust Phenotype Prediction from the Type and Position
of GLI3 Mutations. Am J Hum Genet. 76(4):609-22,2005
Omi M et al: Studies on epidermal growth factor receptor
signaling in vertebrate limb patterning. Dev Dyn. 2005
Berdon-Zapata V et al: p63 gene analysis in Mexican
patients with syndromic and non-syndromic ectrodactyly.
J Orthop Res. 22(1):1-5, 2004
Dao KD et al: Surgical treatment of congenital syndactyly
of the hand. JAm Acad Orthop Surg. 12(1):39-48, 2004
Wang CK et al: Function of BMPs in the apical ectoderm of
the developing mouse limb. Dev BioI. 269(1):109-22, 2004
van Bokhoven H et al: p63 Gene mutations in eec
syndrome, limb-mammary syndrome, and isolated split
hand-split foot malformation suggest a
genotype-phenotype
correlation. Am J Hum Genet.
69(3):481-92,2001
Cole RJ et al: Classification of ulnar deficiency according to
the thumb and first web. J Hand Surg [Am]. 22(3):479-88,
1997
Prevel CD et al: Acrocephalosyndactyly
syndromes: a
review. J Craniofac Surg. 8(4):279-85, 1997
Cohen MM Jr et al: Hands and feet in the Apert syndrome.
Am J Med Genet. 57(1):82-96, 1995
Schrander-Stumpel CT et al: Type III syndactyly and
oculodentodigital
dysplasia: a clinical spectrum. Genet
Couns. 4(4):271-6, 1993
Winter RM et al: Syndactylies and polydactylies:
embryological overview and suggested classification. Eur J
Hum Genet. 1(1):96-104, 1993
Upton J: Apert syndrome. Classification and pathologic
anatomy of limb anomalies. Clin Plast Surg. 18(2):321-55,
1991
Temtamy Sand McKusick V. The Genetics of Hand
Malformations. BDOAS XIV(3),Alan Liss, Inc.NY. 301-361,
1978

SYNDACTYLY
IIMAGE GALLERY
(Left) Clinical photograph
shows isolated type 11/
syndactyly in a term infant.
Note the 4-5 syndactyly
(arrow) associated with
camptodactyly
of the 4th
digit (curved arrow). (Right)
Ultrasound shows 4-5
syndactyly of the fingers in a
mid-trimester fetus (arrow).
Short limbs are also apparent
(curved arrow).

(Left) Ultrasound of the hand
shows 3-4 syndactyly of the
fingers (arrow). This pattern
of syndactyly can be seen
with triploidy, and a careful
search for other anomalies
including IUCR is warranted.
(Right) Radiograph shows
2-3 and 4-5 syndactyly in a
preterm stillborn (arrows).
Note the digits are also
hypoplastic.

Typical
(Left) Clinical photograph
shows partial syndactyly of
toes 2-3 (arrow) and
complete syndactyly of toes
3-4 (curved arrow) in a 1st
trimester spontaneously
aborted fetus. (Right)
Clinical photograph shows
syndactyly of toes 2-3 seen
especially well from the
plantar surface (arrow).
Postaxial oligodactyly
(curved arrow) is also noted
in this mid-trimester fetus.

CLINODACTYLY

Clinical photograph of a newborn with trisomy 27. The
fingers are short, with fifth finger clinodactyly (curved
arrow) and a simian crease (arrows).

ITERMINOLOGY
Abbreviations

and Synonyms

• Brachymesophalangia

Definitions
• Medial deviation of distal fifth finger
• Small or absent fifth digit middle phalanx (MP)

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Tip of fifth finger turns inward on
open hand view

Ultrasonographic

Findings

• Tip of 5th finger curves towards 4th finger
o Best seen at 18-20 week exam
• Secondary to MP dysplasia
o Delayed ossification
• Fifth digit MP normally last to ossify
o Small 5th digit MP
• Compare with 4th finger MP
o Absent MP (least common)
• Associated with trisomy 21 (T21)
o 60% of T21 have clinodactyly
o T21 detection improved when c1inodactyly is sought

DDx: Abnormal

Coronal ultrasound shows clinodactyly in a second
trimester felUs with T27. The tip of the 5th finger (arrow)
curves towards the 4th finger and all the fingers are
short. Other minor markers for T27 were also seen.

• 10% increased 2nd trimester T21detection
o Often seen with other T21 markers
• t Nuchal fold
• Echogenic intracardiac focus
• Echogenic bowel
• Renal pelviectasis
• Short humerus/femur
• Sandal gap foot
o If 5th MP < 70% length of 4th MP then 70% chance
ofT21
• Trisomy 21 hand
o T21 fetuses more likely to keep hand open
• Poor tone
o All 5 digits are short
• Clinodactyly + short digits more worrisome
• Can use nomograms for 17-26 weeks
o Simian crease
• Single transverse palmar crease
• Can be seen with ultrasound
• 45% of T21 vs. 4% normal
• Isolated c1inodactyly
o 2-4% incidence in normal fetuses
o Amniocentesis only if high risk patient
• Advanced maternal age
• Abnormal maternal serum quadruple screen

Imaging Recommendations
• Best imaging tool: Genetic sonogram

,,~

Digits

..

... '~"',Ji~'...
"1."'
..j
.,\

..·

.......

I .,

Polydactyly (Isolated)

•.

'

'\

'"

I

I,
"
,

Polydactyly (T] 3)

CLINODACTYLY
Key Facts
Imaging Findings

Top Differential

• Be t diagno tic clue: Tip of fifth finger turns inward
on open hand view
• Best een at 18-20 week exam
• Associated with trisomy 21 (T21)
• 60% of T21 have clinodactyly
• If 5th MP < 70% length of 4th MP then 70% chance
ofT21
• linodactyly + short digits more worri ome

• Syndactyly
• Polydactyly

• Protocol advice: Obtain open hand views in 2nd
trimester exam

I DIFFERENTIAL

Diagnoses

Pathology
• 2-4% normal hands

Diagnostic Checklist
• Amnio entesis warranted
high-risk patient

if not isolated or in

Natural History & Prognosis
• Excellent prognosis when isolated

Treatment

DIAGNOSIS

• Rarely needs any treatment
o Physiolysis of MP
• Remove longitudinal physis

Syndactyly
• Fusion of digits
o Bony or soft tissue
o Often with syndromes and aneuploidy
• Triploidy (3rd and 4th digits most common)
• Apert syndrome
o Polysyndactyly (mitten hands)
o Craniosynostosis and other anomalies

I DIAGNOSTIC

CHECKLIST

Consider
• Careful search for other markers of T21
• Amniocentesis warranted if not isolated or in high-risk
patient

Polydactyly
• Extra digits
o Postaxial (extra digit on ulnar side)
o Preaxial (extra digit on radial side)
• Common syndromes and aneuploidy
o Trisomy 13 (Tl3)
o Meckel Gruber syndrome

I SELECTED
1.

2.

I PATHOLOGY

3.

General Features
• Genetics
o Usually normal
o Associated with T21
• Etiology
o Clinodactyly
• Delayed or absent MP ossification
• Abnormal MP longitudinal physis
o Simian crease
• Hands open and close less often than normal
• Leads to one crease instead of normal two
• Epidemiology
o 2-4% normal hands
o 60% of fetuses with T21

4.

REFERENCES

Maymon R et al: All five digits of the hands of fetuses with
Down syndrome are short. Ultrasound Obstet Gynecol.
23(6):557-60,2004
Hobbins JC et al: An 8-center study to evaluate the utility
of mid-term genetic sonograms among high-risk
pregnancies. J Ultrasound Med. 22(1):33-8, 2003
Stempfle N et al: Skeletal abnormalities in fetuses with
Down's syndrome: a radiographic post-mortem study.
Pediatr Radiol. 29(9):682-8, 1999
Kjaer MS et al: Hand development in trisomy 21. Am J Med
Genet. 79(5):337-42, 1998

IIMAGE

GALLERY

I CLINICAL ISSUES
Presentation
• Most common signs/symptoms
o Incidental finding during genetic sonogram
o In conjunction with other anomalies/markers

"

(Left) Coronal ultrasound shows isolated clinodactyly in a normal
fetus. The 5th finger (arrows) curves dramatically towards the 4th
finger. The fingers were otherwise normal in length. (Right) Coronal
ultrasound focused on the 5th finger shows a small middle phalanx
(arrow). A small or misshapen middle phalanx is implicated as the
cause of clinodactyly. Isolated cases carry an excellent prognosis.

ECTRODACTYLY

Clinical
photograph
shows
bilateral
spilt-hand
malformation in an adult. Note asymmetry of defects
(arrows) and distal digital hypoplasia (curved arrows).
(Courtesy M. Bamshad, MO).

o Evaluation of parental hands, feet for subtle
evidence of clefting or syndactyly

!TERMINOlOGY
Abbreviations

Ultrasound shows ectrodactyly
of the foot in a
mid-trimester fetus. Note the median defect (curved
arrow) with syndactyly of the remaining digits (arrows)
resulting in a "lobster claw" appearance.

and Synonyms

• Split hand-split foot malformation
• "Lobster claw"

(SHFM)

I DIFFERENTIAL DIAGNOSIS

Definitions

Split hand-split foot malformation

• Characterized by deficiency/hypoplasia of digits, deep
median cleft and fusion of remaining digits
o Variable syndactyly
• May occur in isolation or as part of a syndrome

• Central ray defect characteristic with deep cleft,
syndactyly of remaining digits
o "Lobster claw" type
o Monodactyly type with radial deficiency, absence of
cleft
• Aplasia/hypoplasia of the phalanges, metacarpals,
metatarsals
• Genetically heterogeneous
o Mutations at 5 different loci

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Cleft appearance of hands and/or
feet with missing digits on mid-trimester ultrasound

Imaging Recommendations
• Best imaging tool
o Endovaginal ultrasound in 1st trimester in high risk
pregnancy
o Should be seen in routine mid-trimester hand/foot
views
• Protocol advice
o Careful evaluation for other limb abnormalities,
clefts, other structural anomalies

Ectrodactyly-ectodermal
syndrome (He)

Amniotic Bands

dysplasia c1efting

• Ectrodactyly of hands and/or feet
• Ectodermal dysplasia
o Hypopigmentation, sparse hair, hypodontia,
dystrophic nails, lacrimal duct abnormalities
• Cleft lip +/- palate
• Genitourinary abnormalities
• Hearing loss

DDx: Distal Extremity Abnormalities

Ulnar Deficiency

(SHFM)

LRD

ECTRODACTYLY
Key Facts
Terminology

Top Differential

•

• Split hand-split foot malformation (SHFM)
• Ectrodactyly-ectodermal
dysplasia clefting yndrome

haracterized by deficiency/hypoplasia
of digits, deep
median cleft and fusion of remaining digits
• May occur in i olation or as part of a syndrome

Imaging Findings
• Best diagnostic clue: Cleft appearance of hands
and/or feet with missing digits on mid-trimester
ultrasound

(EEC)

• Amniotic bands
• Limb reduction defects (LRD)

Pathology
• Genetically heterogeneous

• Epidemiology:

Amniotic bands
• Distal digital amputations/syndactyly,
constriction
rings
• Bizarre craniofacial or body wall clefts

ICLINICAL

• Characterized by transverse terminal deficiency of
limb(s)
• Rudimentary digits often present

• EEC syndrome with multiple complications involving
hearing and visual difficulties; recurrent eye,
respiratory and genitourinary infections
•
•
•
•

• Transverse or intercalary deficiency
o Preaxial = radial; postaxial = ulnar

Syndactyly
• May involve any or all digits of hands or feet

with long bone

• Ectrodactyly often unilateral
• Bilateral absence/hypoplasia
of tibiae most common
• Probable autosomal dominant/reduced
penetrance

Acro-dermato- ungual-Iacri mal-tooth
syndrome (ADULT)

No prenatal treatment
Referral for genetic counseling
Fetal karyotype should be offered
Prenatal syndrome diagnosis possible if linkage or
mutation identified
• Surgical treatment involves improving functionality of
hands, repair of clefts and lacrimal duct abnormalities

I SELECTED REFERENCES
1.

2.

• Phenotypic overlap with EEC
• Ectrodactyly with ectodermal dysplasia features

Limb-mammary

ISSUES

Treatment

Radial-ulnar deficiencies

•
•
•
•

1 in 90,000 births

Natural History & Prognosis

Limb reduction defects (lRD)

Split hand/foot malformation
deficiency (SHFlD)

Diagnoses

syndrome (lMS)

Allelic with ADULT syndrome
Ectrodactyly of hands and/or feet
Hypoplasia/aplasia of mammary gland and nipple
Phenotypic overlap with ulnar-mammary
syndrome
(UMS)
o UMS: Caused by mutations in TBX3 gene
o Ulnar ray defect with apocrine, genital, dental
abnormalities

3.

Brunner HG et al: P63 gene mutations and human
developmental syndromes. Am J Med Genet.
112(3) :284-90, 2002
van Bokhoven H et al: p63 Gene mutations in eec
syndrome, limb-mammary syndrome, and isolated split
hand-split foot malformation suggest a
genotype-phenotype correlation. Am J Hum Genet.
69(3):481-92, 2001
lanakiev P et al: Split-hand/split-foot malformation is
caused by mutations in the p63 gene on 3q27. Am J Hum
Genet. 67(1):59-66, 2000

IIMAGE

GALLERY

I PATHOLOGY
General Features
• Genetics
o Genetically heterogeneous
o Mutations in TP63 have been found in autosomal
dominant ectrodactyly syndromes including EEC,
ADULT, LMS as well as non-syndromic SHFM
• Transcription factor p63 is structurally related to
the pS3 tumor suppressor
o Chromosomal rearrangements involving 7q21

(Left) Clinical photograph shows split-hand malformation in a child.
Note absence of central digits, deep median cleft (arrow). (Courtesy
M. Bamshad, MO).
(Right)
Ultrasound
shows a split-foot
malformation (arrow) in a mid-trimester fetus. Only 3 digits are seen.

ARTHROGRVPOSIS,

Clinical photograph shows severe, symmetrical upper
and lower extremity arthrogryposis. Note the clubfeet
(arrows), wrist contractures (curved arrow) and
camptodactyly (open arrow).

AKINESIA SEQUENCE

Sagittal ultrasound shows hyperextended knees (arrow)
and ankles in a mid-trimester fetus with arthrogryposis.
The legs are held in a persistent "pike" position (curved
arrow).

ITERMINOLOGY

IIMAGING

Abbreviations

General Features

and Synonyms

• Multiple congenital contractures
• Fetal hypokinesia/akinesia
deformation sequence
(FADS)
• Arthrogryposis multiplex congenita (AMe)
• Pena Shokeir phenotype

Definitions
• Arthrogryposis refers to a symptom complex caused by
multiple different etiologies
o Abnormalities related to lack of fetal movement in
utero
• Multiple congenital joint contractures/ankyloses
involving two or more body areas
• Pena Shokeir phenotype
o Heterogeneous group of disorders with
micrognathia, multiple contractures, camptodactyly
(persistent finger flexion), polyhydramnios
o Many are autosomal recessive
o Lethal due to pulmonary hypoplasia
• Distal arthrogryposis
o Subset of non-progressive contractures without
associated primary neurologic or muscle disease

• Best diagnostic clue
o Lack of extremity motion
o Persistent unusual or abnormal

Ultrasonographic

Amyoplasia: Arm

posturing of limbs

Findings

• Lack of extremity motion
o May be seen as early as 1st trimester
o Often progressive over the course of gestation
o In severe conditions only movement may be a
truncal "writhing" motion
o Progressive osteopenia in late gestation
• Unusual or persistent abnormal posturing of limbs
o Persistent "pike" position of lower limbs with
hyperextended knees
o Cross-legged "tailor's position" of lower limbs,
especially in a breech fetus
o Extended elbows with internally rotated, flexed
wrists ( "waiter's tip")
o Clubfeet may be very severe
o Clenched hands never open
• Lack of facial movement
o Open mouth posture
o Recessed chin
• Polyhydramnios: Decreased fetal swallowing
o May be severe in late gestation

DDx: Extremity Contractu res

Trisomy 18: Hand

FINDINGS

Clubfoot

ARTHROGRVPOSIS,

AKINESIA SEQUENCE
Key Facts

Terminology

Top Differential Diagnoses

• Fetal hypokine ia/akinesia deformation sequence
(FADS)
• Arthrogrypo is refers to a symptom complex caused
by multiple diff r nt tiologies
• Abnormaliti
related to lack of fetal movement in
utero
• Multiple congenital joint contractures/ankylo
e
involving two or more body area

•
•
•
•
•

Imaging Findings
• Persistent unusual or abnormal po turing of limbs
• Lack of extremity motion
• In severe condition
only movement may be a
truncal "writhing" motion
• Polyhydramnios: Decreased fetal wallowing
• hort umbilical cord due to lack of fetal movement
• Pulmonary hypoplasia
o Short gracile ribs
o Variable fetal breathing motion
• Short umbilical cord due to lack of fetal movement
• Intrauterine growth restriction (IUGR) in severe cases
• First trimester nuchal edema or cystic hygroma
• Increased skin thickening, hydrops

MR Findings
• Fetal MRI for evaluation of central nervous system
(CNS) in 3rd trimester
o Agenesis of corpus callosum
o Lissencephaly
o Hydrocephalus
o Spinal cord abnormalities

Imaging Recommendations
• Careful survey for associated anomalies
• Evaluation of degree of involvement
o Progressive vs. static
o Generalized vs. focal
o Upper and/or lower extremity involvement
• Is one more severe?
• May provide clue for level of lesion
• Multiple structural anomalies and IUGR
o Increased risk trisomy 18
• Upper extremity in "waiter's tip" position
o Amyoplasia
• "Whistling" face with pursed lips on profile
o Freeman-Sheldon syndrome
• Risk of respiratory difficulties at birth increased with
o Polyhydramnios
o Micrognathia
o Generalized decreased fetal movement
o Hydrops

I DIFFERENTIAL

DIAGNOSIS

Trisomy 18
• Multiple structural anomalies,
• lUGR

Trisomy 18
Distal arthrogryposi
Amyoplasia
Multiple pterygium
lubfeet

(DA)
yndrome

Pathology
• Destruction of anterior horn cells may be an
underlying cau e
• ffected muscle replaced by fat, fibrou tissue
• Evidence of hypoxic-i
hemic damage in spinal cord,
brain

Diagnostic Checklist
• Progressive generalized lack of fetal movem
hydrops predict high ri k of lethality

nt with

• "Classic" finger position (clenched hand with
overlapping index finger)

Distal arthrogryposis (DA)
• Most common cause of multiple congenital
contractu res
• Normal growth parameters
• Distal arthrogryposis type lA (DAIA)
o Overlapped fingers with abnormal digital flexion
creases
o Talipes equinovarus and vertical talus
• Freeman-Sheldon syndrome (FSS)
o Distal arthrogryposis type 2A (DA2A)
o "Whistling" face: Mouth may be only few mm in
diameter
o Ulnar deviation of fingers with camptodactyly
o Hypoplastic thumbs

Amyoplasia
• Extended elbows with internally rotated shoulders and
flexed wrists ("waiter's tip")
• Symmetric contractures involving all 4 extremities
• Round face with micrognathia
• Midline facial hemangioma
• Generally good prognosis

Multiple pterygium syndrome
• Severe contractures with webbing across joints
• Cystic hygroma
• Prenatal or neonatal lethal

Spinal muscular atrophy (SMA)
• 2nd most common recessive disorder in Caucasians
with carrier frequency of 1/50
• Heterogeneous group of (often) lethal neuromuscular
disorders
• Loss/destruction of anterior horn cells
• > 95% due to homozygous deletions of exons 7 & 8 in
survivor motor neuron (SMNl) gene

Acetylcholine receptor (AChR) antibodies
including

cardiac

• Myasthenia gravis
o Acetylcholine receptor (AChR) antibodies
of patients with myasthenia gravis

in - 85%

ARTHROGRVPOSIS,
o AChR antibodies cross placenta and block
neuromuscular transmission in fetus
o Neonatal myasthenia in 12% of affected mothers
o Occasional stillbirth
• AChR clustering protein rapsyn
o Early onset: Severe arthrogryposis
o Late onset: Weakness, features similar to
seronegative myasthenia gravis

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Lack of fetal movement and abnormal extremity
position on 1st or 2nd trimester ultrasound
o Polyhydramnios

Natural History & Prognosis

Restrictive dermopathy
•
•
•
•

AKINESIA SEQUENCE

• Depends on
o Number and severity of contractures
o Associated anomalies/chromosomal
disorders
• Ventilator dependence at birth => poor prognosis

Tight rigid skin with erosions
Micrognathia, small mouth
Severe arthrogryposis
Perinatal lethal

Gaucher type 2: Perinatal lethal type

Treatment

• Absent lower spine
• Lower extremity contractu res

• Genetic counseling: Offer karyotype
• Deliver at tertiary center
o Risk of respiratory failure
o Expertise in genetics, fetopathology
• Mode of delivery
o Vaginal delivery may be compromised by fixed
extremity position
o Fracture risk due to osteopenia
• Complete autopsy in cases of fetal or neonatal death
o Evaluation of brain, spinal cord, muscle, peripheral
nerves

I PATHOLOGY

I DIAGNOSTIC

• Lysosomal storage disease due to glucocerebrosidase
deficiency
• Hepatosplenomegaly
• Hydrops and arthrogryposis

Clubfeet
• Other joints move freely

Caudal regression sequence

CHECKLIST

General Features

Image Interpretation

• Genetics
o Chromosomal abnormality in - 2%
• Trisomy 18, mosaic trisomy 8
o Autosomal dominant
• Distal arthrogryposis: Caused by mutations in
genes encoding fast-twitch contractile proteins
o Autosomal recessive
• Pena Shokeir
• Spinal muscular atrophy
• Restrictive dermopathy
• Scandinavian lethal congenital contractures
• Fowler syndrome: Proliferative vasculopathy,
hydranencephaly, akinesia
o Sporadic
• Teratogen exposure: 1st trimester misoprostol
• Etiology
o Destruction of anterior horn cells may be an
underlying cause
o Maximum sensitivity to hypoxia at 8-14 weeks
gestation
• Epidemiology: 1:3,000 live births
• Associated abnormalities
o Absent flexion creases
o Skin dimples over affected joints

• Progressive generalized lack of fetal movement with
hydrops predicts high risk of lethality

Gross Pathologic & Surgical Features

I SELECTED REFERENCES
1.

2.

3.

4.

5.

6.

7.

8.

• Affected muscles replaced by fat, fibrous tissue

Microscopic

Features

• Anterior horn cell depletion
• Evidence of hypoxic-ischemic
brain
• Proliferative vasculopathy

9.

damage in spinal cord,

Pearls

Burke G et al: Rapsyn mutations in hereditary myasthenia:
distinct early- and late-onset phenotypes. Neurology.
61(6):826-8, 2003
Sung SS et al: Mutations in genes encoding fast-twitch
contractile proteins cause distal arthrogryposis syndromes.
AmJ Hum Genet. 72(3):681-90,2003
Sung SS et al: Mutations in TNNT3 cause multiple
congenital contractures: a second locus for distal
arthrogryposis type 2B. Am J Hum Genet. 73(1):212-4,
2003
Witters I et al: Fetal akinesia deformation sequence: a study
of 30 consecutive in utero diagnoses. Am J Med Genet.
113(1):23-8, 2002
Hausmanowa-Petrusewicz I: Phenotype and genotype
correlation in childhood spinal muscular atrophy. Neurol
Neurochir Pol. 35 Suppl 3:29-35, 2001
Witters I et al: Cystic hygroma colli as the first echographic
sign of the fetal akinesia sequence. Genet Couns.
12(1):91-4,2001
Coelho KE et al: Misoprostol embryo toxicity: clinical
evaluation of fifteen patients with arthrogryposis. Am J
Med Genet. 95(4):297-301, 2000
Krakowiak PA et al: Clinical analysis of a variant of
Freeman-Sheldon syndrome (DA2B). Am J Med Genet.
76(1):93-8, 1998
Bamshad M et al: A revised and extended classification of
the distal arthrogryposes. Am J Med Genet. 65(4):277-81,
1996

ARTHROGRVPOSIS,

AKINESIA SEQUENCE

IIMAGE GALLERY
(Left) Ultrasound shows a
hyperextended
knee (arrow)
and flexed ankle (curved
arrow) in a mid-trimester
fetus with severe
arthrogryposis. Mild
polyhydramnios
is also
present. (Right) Coronal
ultrasound shows persistently
extended legs and bilateral
clubfeet (arrows). No lower
extremity movement
was
seen during the exam.

Typical
(Left) Sagittal ultrasound
shows micrognathia (arrow).
The wrist is flexed and hands
are held in a clenched
position (curved arrow).
(Right) Coronal oblique
ultrasound shows a
persistently open mouth
(arrow) and recessed chin
(curved arrow) in a 3rd
trimester fetus with hydrops
and severe arthrogryposis.

(Left) Coronal ultrasound
shows abnormal upper
extremities with flexed
elbows and wrists (arrow)
and extended fingers (curved
arrow) that did not move
during prolonged
observation. (Right) Clinical
photograph of a neonate
with asymmetric
arthrogryposis limited to the
lower extremities. Both knees
are flexed. Note the severe
right clubfoot (arrow) and
the dimple over the knee
(curved arrow).

MULTIPLE PTERYGIUM SYNDROME

Graphic shows multiple limb contractures with soft
tissue webbing involving the neck, elbows and popliteal
areas of a fetus with lethal multiple pterygium
syndrome.

Radiograph shows a stillbirth with lethal multiple
pterygium syndrome (curved arrows). A collapsed
cystic hygroma is noted (arrow) as well as a clubfoot
and camptodactyly (open arrow).

ITERMINOlOGY

Imaging Recommendations

Abbreviations

• Protocol advice: Consider 3D ultrasound to evaluate
joint spaces for pterygia

and Synonyms

• Escobar syndrome
• Multiple pterygium syndrome
• Lethal multiple pterygium syndrome

I DIFFERENTIAL

Definitions
• Heterogeneous group of syndromes characterized by
multiple limb contractures with soft tissue webbing
across joints
• Lethal type also with associated cystic hygroma,
hydrops and pulmonary hypoplasia

IIMAGING

FINDINGS

Multiple pterygium syndrome (Escobar
syndrome)
•
•
•
•
•

Significantly small stature
Multiple pterygia of neck, axillae, elbows, knees
Micrognathia
Digital hypoplasia, camptodactyly, syndactyly
Scoliosis

Multiple

General Features
• Best diagnostic clue
o Fixed joint contractures, abnormal posture of fetus
on 1st or 2nd trimester scan
• More difficult to see in 3rd trimester because of
crowding
• Association of cystic hygroma +/- hydrops and joint
contractures in a fetus at risk is confirmatory
• Pterygia may not be seen on prenatal imaging

DIAGNOSIS

•
•
•
•
•
•

pterygium syndrome (lethal type)

Prenatal growth restriction
Flexion contractures of limbs
Multiple extensive pterygia
Cystic hygroma
Hydrops
Hypoplastic lungs

Popliteal pterygium syndrome
• Contractures with soft tissue webbing of popliteal
fossae
• Cleft lip and palate
• Syndactyly

DDx: Soft Tissue Webs

Pterygium Colli

Arthrogryposis

Popliteal Pterygium

MULTIPLE PTERYGIUM SYNDROME
Key Facts
Terminology

• Pterygia may not be seen on prenatal imaging

• Heterogeneous group of syndromes characterized by
multiple limb contractu res with soft tissue webbing
across joints
• Lethal type also with associated cystic hygroma,
hydrops and pulmonary hypoplasia

Top Differential

Pathology

Imaging Findings
• Fixed joint contractures, abnormal
1st or 2nd trimester scan

posture of fetus on

• Clubfeet

• Lethal multiple pterygium may be phenotype
resulting from early onset severe fetal akinesia

Treatment

Pterygium colli
• Soft tissue webbing at lateral neck/base of neck
• Secondary to resolution of a cystic hygroma
o Commonly seen in Turner, Down and Noonan
syndromes

Arthrogryposis
•
•
•
•
•

Diagnoses

• Multiple pterygium syndrome (E cobar syndrome)
• Multiple pterygium syndrome (lethal type)
• Popliteal pterygium syndrome

multiplex congenita

Multiple fixed joint contractures
Clubfeet
May be associated with fetal akinesia/hypokinesia
Lethal when severe
Normal intelligence in survivors

•
•
•
•

No prenatal treatment
Referral for genetic counseling
Multiple surgeries often required
Mixed results with resection of pterygia, which often
grow back
• Lengthening of Achilles tendon may improve ability
to ambulate
• Removal of ophthalmic pterygia may save vision

I SELECTED REFERENCES
1.

Isolated pterygia
• Soft tissue webbing associated with joint contracture(s)

I PATHOLOGY

2.

3.

General Features
• Genetics
o Escobar syndrome and lethal multiple pterygium:
Autosomal recessive
o Rare reports of X-linked recessive cases of lethal
multiple pterygium syndrome
o Popliteal pterygium syndrome: Autosomal dominant
• Etiology
o Unknown pathogenesis
o Lethal multiple pterygium may be phenotype
resulting from early onset severe fetal akinesia

4.

Cox PM et al: Diversity of neuromuscular pathology in
lethal multiple pterygium syndrome. Pediatr Dev Pathol.
6(1):59-68, 2003
Hertzberg BS et al: Lethal multiple pterygium syndrome:
antenatal ultrasonographic diagnosis. ] Ultrasound Med.
19(9):657-60,2000
Froster UG et al: Lethal multiple pterygium syndrome:
suggestion for a consistent pathological workup and review
of reported cases. Am] Med Genet. 68(1):82-5, 1997
Anthony] et al: Lethal multiple pterygium syndrome. The
importance of fetal posture in mid-trimester diagnosis by
ultrasound: discussion and case report. Ultrasound Obstet
Gynecol. 3(3):212-6, 1993

IIMAGE GALLERY

Gross Pathologic & Surgical Features
• Variable histopathologic features including evidence
of myopathy, neuromuscular disease and rarely
storage disease

I CLINICAL

ISSUES

Natural History & Prognosis
• Multiple pterygium (lethal type) uniformly lethal in
perinatal period due to pulmonary hypoplasia
o Most are stillborn
• Escobar syndrome
o Progressive (severe) scoliosis is common and may
result in restrictive lung disease
o Pterygia involving the oral cavity may obstruct
airway and impair nutrition

(Left) Clinical photograph shows multiple axillary pterygia (arrows) in
a mid-trimester fetus. Webbing of the jaw and anterior chest (open
arrow) is also seen. (Courtesy of}. Comstock, MO). (Right) Clinical
photograph shows a severely growth restricted fetus with multiple
pterygia (open arrows). Note the micrognathia
(curved arrow),
syndactyly (white arrow) and clubfoot (black arrow).

SECTION 11: Umbili(:al Cord

Introduction and Overview
Normal Umbilical Cord & Doppler

11-2

Umbilical Cord
Abnormal Cord Doppler
Single Umbilical Artery
Umbilical Cord Cyst
Umbilical Cord Aneurysms
Persistent Right Umbilical Vein
Vasa Previa
Nuchal Cord

11-6
11-10
11-14
11-18
11-22
11-24
11-26

NORMAL UMBiliCAL

3D ultrasound shows a normal fetal profile and several
loops of cord against the uterine wall. The coiling of the
cord vessels (arrows) is clearly evident deep to the cord
covering.

ITerminology
Abbreviations
•
•
•
•
•

Umbilical artery (UA)
Umbilical vein (UV)
Peak systolic velocity (PSV)
End diastolic velocity (EDV)
Time averaged velocity (TAV):Average flow velocity
over a complete cardiac cycle

Ilmaging Anatomy
Ultrasound
• Normal cord has 3 vessels encased in Wharton jelly
o Two arteries carry deoxygenated blood to placenta
o One vein brings oxygenated blood back to fetus
• Cord coiled
o Arteries coil around vein
• Connections
o Abdominal wall insertion surrounded by intact skin
o Placental insertion normally centered on placental
disc

IAnatomy-Based

Imaging Issues

Imaging Protocols
• AlUM guidelines
o Abdominal wall
• Axial image at cord insertion to show intact skin
on each side
o 3 vessel cord
• Image cross section of free floating loop of cord
• Axial section at level of bladder: UA seen on either
side of bladder
• Evaluation of placental insertion site not part of
guidelines but useful
o Marginal and velamentous insertions may have
complications
o Placental insertion is preferred site for intervention
as not influenced by fetal movement

CORD & DOPPLER

Color Doppler ultrasound shows normal coiling of the
cord.
The two arteries (curved
arrows)
taking
deoxygenated blood to the placenta, coil around the
vein (arrow).

• Cordocentesis/intrauterine
transfusion
• Assess cord length
o Short cord
• Akinesia sequence
• Trisomy 21
• Body stalk anomaly
o Long cord
• Hyperactivity
• Increased likelihood of true cord knot
• Doppler
o Best to evaluate UA flow in a free floating loop of
cord
o Use of ratios overcomes angle dependence of
velocity measurements
• Flow ratios used in evaluation of UA signal
o Systolic to diastolic ratio (SD) ratio
• PSV/EDV
o Pulsatility index (PI)
• PSV-EDV/TAV
o Resistive index (RI)
• PSV-EDV/PSV
o Waveform of umbilical vein
• Should be "flat" (Le. constant flow back to fetus)
• If pulsatile check for timing of pulse in relation to
cardiac cycle
• Regular pulse at end-diastole concerning for
elevated right heart pressure
• If not timed to end-diastole likely fetal breathing,
should normalize when breathing stops
• Multiple fetuses
o Doppler at abdominal cord insertion site to allow
comparable serial measurements
o Cords may fuse close to placenta in monoamniotic
twins
a Conjoined twins may have> 3 vessels in cord

Imaging Pitfalls
• Ultrasound
o Fetal extremities
• May mimic herniated loops of bowel
• May obscure skin of anterior abdominal wall
o Vasa previa
• Fetal vessels in membranes

NORMAL UMBiliCAL

CORD & DOPPLER

Key Facts
Anatomy
• :\orlllal cord has 3 vessels: Two arteries, one vein
• Fully formed by 9 weeks gestation
• lIV is the only conduit for oxygenated blood to
rdurn to fetus
• Single UA associated with growth restriction
o If additional anomalies ~ t risk for aneuploidy

Doppler Assessment
• Umbilical artery should have low resistance flow
• Middle cerebral artery should have high resistance
flow
Rl'\ersal of this pattern = "head sparing effed" seen
\\i Ih h\'P0.\ia
• Umbilical vein should have continuous non-pulsatile
flow

• Check carefully for this with
multiples/succenturiate
lobe
• Endovaginal scan with color Doppler to identify
vessels
• Pulsed Doppler shows fetal rate in arteries; cannot
differentiate maternal from fetal veins
o Two vessel cord
• Even if two UA around bladder may be single UA
in free floating cord
• Carries same risks as when one seen at bladder
• Doppler
o Fetal breathing
• Highly variable PSV
• UV pulsation linked to respiration not cardiac
cycle
o Resistance is highest close to abdominal wall/lowest
at placental insertion site
o Do not Doppler normal fetuses
• All outcome data based on UA velocimetry is in
high-risk pregnancy
• Cannot be applied to general population
o Arrythmia
• Bradycardia ~ prolonged cycle ~ diastolic flow
decreased over time ~ EDV low ~ SD ratio
spuriously high
• Tachycardia ~ shortened cycle ~ inadequate time
for diastolic run off t<;)occur ~ EDV high ~ SD
ratio spuriously low
o Absent end-diastolic flow (AEDF)
• Pitfall: Tendency to measure "something"; if flow
reaches the baseline before systolic upstroke then
diastolic flow is absent
• AEDF is normal in early pregnancy before
placental circulation fully developed
• AEDF/reversed end diastolic flow (REDF) may
occur intermittently in multiples due to cord
compression; does not have saIne prognostic
implications as in singletons

• Ductus venosus has triphasic waveform reflecting
cardiac cycle with continuous forward flow
.
• Technique
o Best to sample in free-floating loops of cord
o Take multiple measurements and avoid sampling
during fetal breathing
n In multiple gestations salllple at abdoll1inal cord
insertion site to allow for reliable serial
Illeasu renlL'nts

Clinical Importance of Doppler
• Evaluation of flow in Ul\!UVjDV assesses fdal
henllldynamic stalus in Illultipll' conditions
, Placental insufficiency
" Anemia
Arrythmia
n Complications
of twinning

• Cord length: Average 50-60 em (range 30-90 em)
• Cord circumference: Average 1-2 em

I Pathologic

Issues

General Pathologic Considerations
• Placental insufficiency major cause of abnormal
Doppler
o t Placental vascular resistance ~ ~ forward flow in
UA ~ ~ diastolic flow
o SD ratio, PI and RI all increase
o Eventually diastolic flow reaches zero = AEDF
• Further increase in placental vascular resistance causes
flow reversal in diastole = REDF
,. 0 Right ventricle works harder to overcome this
increased resistance
o Eventual decompensation ~ tricuspid regurgitation
o Reversal of flow in inferior vena cava/ductus
venosus (DV) ~ pulsatile flow in UV
• Cord knot
o True
• Fetus swims through loop of cord: May cause
restriction of flow/thrombosis
• Major cause of morbidity/mortality in
monoamniotic twins
o False
• Vessels are longer than the cord length so may
"kink" as they spiral
• No clinical significance
• Nuchal cord: Only clinically significant if it impairs
cerebral blood flow
• Reversed direction of flow in UA seen in twin reverse
arterial perfusion
o Anomalous twin perfused by deoxygenated blood
from co-twin
o No placental perfusion

Normal Measurements

I Embryology

• SD ratio
o < 3 after 30 weeks
0<2 at term

• Day 14

Embryologic Events

NORMAL UMBiliCAL

Transabdominal ultrasound shows a nine-week embryo
inside the thin-walled amniotic sac (curved arrows)
apparently suspended by it's umbilical cord (arrow).
Cord length approximates that of the embryo.

•

•

•

•

•

o Connecting stalk develops from extraembryonic
mesoderm: Connects embryo to chorion
o Bilaminar embryo lies between primary yolk sac (YS)
and amnion
Days 16 to 22
o Allantois arises as outpouching of secondary YS
o Allantois and it's vessels extend partly into
connecting stalk
o Longitudinal folding of embryo incorporates part of
YSto form foregut
o Allantois and residual extraembryonic YSextend
into connecting stalk mesenchyme
Days 28 to 40
o Amniotic sac enlarges rapidly
o Embryo folds laterally and longitudinally
o Eventually allantois/connecting
stalk fuse into
narrow umbilical cord
o Allantoic vessels => umbilical vessels
o Amnion fuses with cord to form its epithelial
covering
• Amnion densely fused to cord: Provides turgor
• Turgor protects vessels/increases cord tensile
strength
Umbilical vein
o Initially two UVs arise from allantoic veins
o Drain to sinus venosus
o Fuse to single vessel in cord
o Right UV + section left UV between liver and sinus
venosus degenerate as hepatic bud enlarges in 6th
week
o Remaining left UV anastomoses with left portal vein
and ductus venosus
Umbilical arteries
o Arise from allantoic arteries
o 96% anastomose within 1.S cm placental surface
allowing uniform distribution of blood to placenta
o One artery often larger than the other, may have
single UA
Cord growth
o Lengthens as embryo prolapses into amniotic sac
o Further growth is thought to relate to fetal
movement

CORD & DOPPLER

Color Doppler ultrasound shows the spiraling vessels in
the cord at ten week three days gestational age. The
cord is fully formed by nine weeks gestation. It
lengthens progressively during the rest of the pregnancy.

• Cord coiling
o Well established by 9 weeks, thought to strengthen
cord
• Bowel herniation
o Bowel grows rapidly: Volume greater than embryo
therefore herniates into base of cord
o Bowel rotates and returns to peritoneal cavity by
11.2 weeks gestation

I Clinical Implications
Clinical Importance
• UV is the single conduit for oxygenated blood to
return from placenta to fetus
o Umbilical vein thrombosis => hydrops/intrauterine
fetal demise
• SUA associated with intrauterine growth restriction
(IUGR) even if isolated
o SUA + anomalies => increased risk of aneuploidy
• Doppler studies vital in management of IUGR
• Doppler used in grading twin twin transfusion
syndrome
• Abnormal Doppler may impact timing of delivery in
monoamniotic twins
• Perinatal mortality
o AEDF 9%
o REDF 36%

I Related
1.

2.

3.

References

Oi Salvo ON et al: Sonographic evaluation of the placental
cord insertion site. AJRAm J Roentgenol. 170(5):1295-8,
1998
Sherer OM et al: Prenatal ultrasonographic morphologic
assessment of the umbilical cord: a review. Part II. Obstet
Gynecol Surv. 52(8):515-23, 1997
Lacro RV et al: The umbilical cord twist: origin, direction,
and relevance. AmJ Obstet Gynecol. 157(4 Pt 1):833-8,
1987

NORMAL UMBiliCAL

CORD & DOPPLER

IIMAGE GALLERY
(Left) Sagittal color Doppler
ultrasound shows the normal
course of the umbilical vein
(arrow) through the ductus
venosus (open arrow) into
the heart. The descending
aorta (curved arrow) is also
seen in this view. (Right)
Axial oblique color Doppler
ultrasound shows the two
umbilical arteries (arrows)
flanking the bladder then
coursing anteriorly and
cephalad to enter the
umbilical cord (open arrow).

(Left) Pulsed Doppler
ultrasound shows continuous
forward umbilical arterial
flow in diastole (arrows) due
to low-resistance placental
circulation. Venous flow
(open arrow) is constant
throughout the cardiac
cycle. (Right) Pulsed
Doppler ultrasound shows a
normal tracing from the
middle cerebral artery in a
third trimester fetus. Flow is
high resistance with almost
no antegrade flow in diastole
(arrows). This pattern
changes to low resistance
with hypoxia.

(Left) Pulsed Doppler
ultrasound shows a normal
ductus venosus (DV)
waveform. Flow should
always be forward. Two
peaks mark ventricular
systole (5) and diastole (0),
with decreased flow during
atrial systole (arrow). (Right)
Pulsed Doppler ultrasound
shows dramatic variations
(arrows) in UA peak systolic
velocity during fetal
breathing. Umbilical vein
flow (open arrow) is also
phasic. The tracing was
normal after breathing
stopped.

ABNORMAL CORD DOPPLER

Pulsed Doppler ultrasound shows absent end-diastolic
flow in the umbilical artery (arrows). This implies
increased placental vascular resistance. The umbilical
vein flow (curved arrow) is normal.

o Intrauterine growth restriction (IUGR) may be
present
• Abdominal circumference lags behind other
biometric parameters
• Poor growth/weight gain
• Oligohydramnios
o May see features of cardiac decompensation
if severe
t placental resistance
• Cardiomegaly
• Tricuspid regurgitation
• Pulsed Doppler
o SD ratio should be < 3 after 30 weeks
0< 2 at term
o High resistance flow is normal in early gestation
• Placental vascular bed not fully formed
• AEDF is normal < 16 weeks gestation

ITERMINOLOGY
Abbreviations
•
•
•
•

and Synonyms

Absent end-diastolic flow (AEDF)
Reversed end-diastolic flow (REDF)
Peak-systolic velocity (PSV)
End-diastolic velocity (EDV)

Definitions
• Abnormalities of velocity ± direction of flow in
o Umbilical artery (UA)
o Umbilical vein (UV)
o Ductus venosus (DV)
o Middle cerebral artery (MCA)
• Systolic-diastolic (SD) ratio
o PSV/EDV
o Use of ratios overcomes angle dependence of
velocity measurements

Imaging Recommendations

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Diminished

Ultrasonographic

diastolic flow in UA

Findings

• Grayscale Ultrasound

DDx: Abnormal

Axial ultrasound in the same fetus shows cardiomegaly
right atrial (RA) enlargement, pericardial effusion
(arrow) and oligohydramnios. UV flow remained
normal despite clear cardiac compromise.

• Evaluate cord flow in consistent location
o Fetal insertion site: Highest resistance
o Placental insertion site: Lowest resistance
o Best to measure in free floating loop
• In multifetal gestations
o Verify chorionicity and amnionicity
• Monochorionic twins at risk for twin-twin
transfusion
• Monoamniotic twins at risk for cord
entanglement

UA Doppler
VI
V2
RI

S/O

0.273m/s
0.061
0.78

m/s

4.46

kAJ~.L.t
-..

Fetal Breathing

Vt,4"';"'\'~

Nt Early Pregnancy

Thrombosed

UA

ABNORMAL CORD DOPPLER
Key Facts
Imaging Findings
• Best diagnostic clue: Diminished diastolic flow in UA
• Intrauterine growth restriction (lUGR) may be present
• May see features of cardiac decompensation if severe
t placental resistance
• SD ratio should be < 3 after 30 weeks
• High resistance flow is normal in early gestation
• Decreased MCA resistance implies shunting of blood
to brain

Top Differential Diagnoses
• Fetal breathing
• Cord compression

Clinical Issues
• Perinatal mortality AEDF: 9%
• Perinatal mortality REDF: 36%

o Check placental cord insertion sites
• Velamentous insertion of cord increased risk for
IUGR
o Place sample volume at fetal insertion site
• Different recommendation than for singleton
• Prevents confusion between umbilical cords
• Ensures reliable serial measurements in individual
fetuses
o If anomalous fetus
• Check direction of flow in UA
• Reversed flow (Le. arterial flow toward abnormal
fetus) diagnostic of twin reversed arterial perfusion
• If UA flow abnormal, measure SD ratio in middle
cerebral artery (MCA)
o Decreased MCA resistance implies shunting of blood
to brain
o "Head-sparing" flow in attempt to protect brain from
hypoxia
o Severe/prolonged hypoxia ~ cerebral edema
o MCA flow may become more "normal" (Le. high
resistance) with cerebral edema
o Beware apparent improvement in "head-sparing"
flow unless associated with better UA tracing
• Venous Doppler also reflects cardiovascular response
to increased placental resistance
o t Cardiac work required to perfuse abnormally
resistive placenta
o Right ventricle is the fetal systemic ventricle
o RV decompensation ~ tricuspid regurgitation
o Tricuspid regurgitation ~ increased right atrial
pressure
o t Right atrial pressure transmitted to venous
structures
o Inferior vena cava (lVe)
• Normal cyclical waveform reflects cardiac cycle
• t Right atrial pressure ~ t retrograde flow in IVC
o DV
• Normal flow is continuously forward
• Pulses reflect cardiac cycle
• Nadir of flow "Awave" at atrial contraction
• As heart decompensates right atrial pressures are
sufficient to prevent continuous forward flow

• REDFassociated with fetal demise within 1-7 days

Diagnostic Checklist
• UA Doppler is the "tip of the iceberg" with respect to
fetal hemodynamic state
• Addition of venous Doppler ~ more information on
fetal response to adverse conditions
• Management decisions not based on Doppler alone
• Do not do Doppler in fetuses with normal growth
• All management data based on high-risk pregnancies
• Beware apparent improvement in "head-sparing"
pattern
• Hypoxia •• cerebral edema •• t intracranial pressure
~ t resistance in MCA
• Real improvement occurs only when changes are in
bothUA and MCA circulations

• With further decompensation retrograde flow
occurs during atrial contraction
o UV

• Normal flow is continuous, forward, non-pulsatile
• Regular pulse at end-diastole reflects elevated right
heart pressure
• t Right heart pressure transmitted IVC -. DV -.
UV

• Pulsations not timed to end-diastole likely relate
to fetal breathing activity
• Tracing will normalize when breathing stops
• Pulsatile UV flow signifies advanced cardiac
decompensation

I DIFFERENTIAL

DIAGNOSIS

Fetal breathing
• Variable peak systolic velocity
• Umbilical vein phasicity not linked to end diastole
• Tracings return to normal when breathing stops

Cord compression
• Intermittent abnormal tracings in multiple gestations
• Cord compressed by crowding of fetal parts or
maternal position
• Tracings return to normal with change in position
• No other features of concern for fetal compromise

I PATHOLOGY
General Features
• Etiology
o Normal placentation
• 1st trimester: Mesenchymal villi ~ 1°,2°, 3° stem
villi
• 2nd trimester: Branching angiogenesis '* 10-15
generations intermediate villi
• 3rd trimester: Non-branching angiogenesis '*
many terminal villi sprout from intermediate villi
o Failed/abnormal branching '* small muscular
arteries

ABNORMAL CORD DOPPLER
• Increased placental resistance
o Maternal connective tissue disease
• Immune complex deposition
• Vasculitis
• Placental infarction/thrombosis
• Epidemiology
o Abnormal Doppler may occur with lUGR
• By definition 10% of all pregnancies meet criteria
for lUGR

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Placental insufficiency presents in second trimester
• lUGR
• Oligohydramnios
• Other signs/symptoms
o Twin-twin transfusion syndrome
• Doppler evaluation part of grading criteria
• Grade at diagnosis does not correlate with
prognosis
• Change in grade during gestation does have
prognostic implications
• Serial evaluation important in timing and choice
of fetal intervention
o Monoamniotic twins
Cord e~nglement
is major source of morbidity
and mortality
• Cord Doppler may be used to determine need for
delivery

• Addition of venous Doppler ~ more information on
fetal response to adverse conditions
• Management decisions not based on Doppler alone
o Gestational age
o Interval growth and amniotic fluid volume
o Non-stress testing and biophysical profile
o Maternal factors

Image Interpretation

I SELECTED
1.

2.

t< ·

Natural History & Prognosis

3.

4.

• Depends on gestational age at which changes are
observed

Treatment

5.

• > 30 weeks
o Abnormal Doppler contributes to decision to deliver
• In second trimester
o Weigh risks of hostile intrauterine environment vs.
risks of extreme prematurity
• AEDF
o Bed rest, aggressive management of maternal disease
• 30% improve within 48 hrs
o Improvement supports continuation of pregnancy
in second trimester
o Perinatal mortality AEDF: 9%
• REDF
o Quantified by ratio highest amplitude forward flow
(A)/maximum reverse flow (B)
o A/B ratio> 4.3 without venous pulsation in free loop
may support expectant management in second
trimester
o Perinatal mortality REDF: 36%
o REDFassociated with fetal demise within 1-7 days

I DIAGNOSTIC

CHECKLIST

Consider
• VA Doppler is the "tip of the iceberg" with respect to
fetal hemodynamic state

Pearls

• Do not do Doppler in fetuses with normal growth
o All management data based on high-risk
pregnancies
o Cannot be applied to general population
• Beware apparent improvement in "head-sparing"
pattern
o Hypoxia ~ cerebral edema ~ t intracranial pressure
~ t resistance in MCA
• Real improvement occurs only when changes are in
both VA and MCA circulations

6.

7.

8.

9.

10.
11.

12.

13.

REFERENCES

Baschat AA: Doppler application in the delivery timing of
the pre term growth-restricted fetus: another step in the
right direction. Ultrasound Obstet Gynecol. 23(2): 111-8,
2004
Baschat AA et al: Venous Doppler in the prediction of
acid-base status of growth-restricted fetuses with elevated
placental blood flow resistance. Am J Obstet Gynecol.
191(1):277-84,2004
Bellotti M et al: Simultaneous measurements of umbilical
venous, fetal hepatic, and ductus venosus blood flow in
growth-restricted human fetuses. Am J Obstet Gynecol.
190(5):1347-58, 2004
Olutoye 00 et al: Abnormal umbilical cord Doppler
sonograms may predict impending demise in fetuses with
sacrococcygeal teratoma. A report of two cases. Fetal Diagn
Ther. 19(1):35-9, 2004
Spinillo A et al: Interaction between risk factors for fetal
growth retardation associated with abnormal umbilical
artery Doppler studies. Acta Obstet Gynecol Scand.
83(5):431-5,2004
Harman CR et al: Comprehensive assessment of fetal
wellbeing: which Doppler tests should be performed? Curr
Opin Obstet Gynecol. 15(2):147-57,2003
Raio Let al: Umbilical cord morphologic characteristics
and umbilical artery Doppler parameters in intrauterine
growth-restricted fetuses. J Ultrasound Med. 22(12):1341-7,
2003
Weiner Z et al: Assessment of uterine placental circulation
in thrombophilic women. Semin Thromb Hemost.
29(2):213-8, 2003
Wee LYet al: The twin-twin transfusion syndrome. Semin
Neonatol. 7(3):187-202,2002
Arbeille P: Fetal arterial Doppler-IUGR and hypoxia. Eur J
Obstet Gynecol Reprod BioI. 75(1):51-3, 1997
Kingdom JC et al: Pathology and clinical implications of
abnormal umbilical artery Doppler waveforms. Ultrasound
Obstet Gynecol. 9(4):271-86, 1997
Divon MY: Umbilical artery Doppler velocimetry: clinical
utility in high-risk pregnancies. Am J Obstet Gynecol.
174(1 Pt 1):10-4, 1996
Marsal K: Rational use of Doppler ultrasound in perinatal
medicine. J Perinat Med. 22(6):463-74, 1994

ABNORMAL CORD DOPPLER
IIMAGE GALLERY
(Left) Pulsed Doppler
ultrasound shows reversed
end-diastolic flow (arrows)
in the umbilical artery (UA).
This implies that placental
resistance is 50 high that
blood flows away from the
placenta back into the
umbilical arteries during
diastole. (Right) Pulsed
Doppler ultrasound of the
middle cerebral artery
(MCA) shows increased
diastolic flow (arrow) (i.e.
decreased resistance)
indicating shunting of
oxygenated blood to the
brain (i. e. "head-sparing").

(Left) Axial transabdominal
ultrasound shows a dilated
IVC in a third-trimester fetus
with severe placental
insufficiency. The IVC is
larger in caliber than the
aorta (arrow). Also note
severe oligohydramnios
(Right) Pulsed Doppler
ultrasound shows AEDF
(arrows) and associated UV
pulsation (curved arrows)
indicating cardiac
decompensation.

(Left) Pulscd Doppler
ultrasound shows reversal of
flow in the ductus venosus
with flow below the baseline
(arrows) during atrial systole
(A wave). This signifies
significant elevation of right
heart pressure. (Right) Axial
color Doppler ultrasound
shows the UAs in the pelvis.
Thc bladder should he seen
bc/ween the UAs (arrows).
As placental resistance
increases, the fetus shunts
blood to the brain
decreasing renal perfusion.
Urine production decreases
and oligohydramnios
ensues.

SINGLE UMBiliCAL

Long axis clinical photograph of the umbilical cord
shows a SUA (arrows). The UA is almost the same size
as the Uv. In a normal 3 vessel cord, with two UAs,
each UA is much smaller than the Uv.

ARTERY

Long axis color Doppler ultrasound shows an isolated
SUA (arrows) in an otherwise normal pregnancy. The
umbilical cord is well coiled in this case but there are
only two vessels throughout.

!TERMINOLOGY

Ultrasonographic

Abbreviations

• Normal umbilical cord
o Free loop cross section view
• 2 UA + 1 UV
• "Mickey Mouse" appearance on cross section
• UA diameter is < 50% UV diameter
o Longitudinal view
• Arteries coil around vein
• Cord is fully coiled by end of 1st trimester
• 40 coils/cord
o Color Doppler transverse fetal pelvis view
• One UA on each side of bladder
• UAs insert into iliac arteries
• SUA diagnosis
o Free loop shows SUA + UV
o Within fetal pelvis
• SUA travels around bladder
• Inserts into right or left iliac artery
• Best way to determine which UA missing
o 8% false positive diagnosis
• 3 vessel cord at delivery
• SUA is larger than normal UA
o SUA diameter is > 50% diameter of UV
o All blood volume in SUA
• Normal is 1/2 blood volume in each UA
• SUA cord less coiled than normal
o Long axis view of cord

and Synonyms

• Single umbilical artery (SUA)
• Two vessel cord
• Absent umbilical artery

Definitions
• Absence of right or left umbilical artery (UA)
o Cord with 1 UA and 1 umbilical vein (UV)
• Normal cord has 2 UA and 1 UV

IIMAGING

FINDINGS

General Features
• Best diagnostic clue
o Free loop of cord with 2 vessels
• Seen best on cross section
o Color Doppler of fetal pelvis
• Transverse view of bladder
• Only 1 UA adjacent to fetal bladder
• Location
o 70% absent left UA
o 30% absent right UA
• Size: SUA is larger than 3 vessel cord UA
• Morphology: SUA cord less coiled

DDx: Abnormal

UA Thrombus

Umbilical Vessels

UV Thrombus

Findings

SINGLE UMBiliCAL

ARTERY

Key Facts
Terminology

Top Differential

• Two vessel cord

• Fused umbilical arteries
• Umbilical vessel thrombosis
• Excessive Wharton jelly

Imaging Findings
•
•
•
•
•
•
•

•
•
•
•

Free loop of cord with 2 vessels
Seen best on cross section
Only 1 UA adjacent to fetal bladder
70% absent left UA
SUA is larger than normal UA
15% develop IUGR
t Systolic/diastolic ratios suggest t IUGR risk
ot as ociated with trisomy 21
Hypoplastic UA within spectrum of SUA
Best imaging tool: Color Doppler transver e pelvis
image shows SUA around bladder
Look for additional fetal anomalies when SUA seen

• UA and UV parallel
• Right vs. left SUA
o Same outcome
o Same incidence of associated anomalies
• SUA and intrauterine growth restriction (IUGR)
o 15% develop IUGR
• May be related to poor coiling
o SUA cord Doppler
• Same values as for normal cord
• t Systolic/diastolic ratios suggest t IUGR risk
• Nonisolated SUA
o 50% aneuploidy rate
o Trisomy 18 (T18)
• Cardiac defects
• Extremity anomalies
• Choroid plexus cysts
• Early severe IUGR
o Trisomy 13 (T13)
• Holoprosencephaly
• Midline cleft lip/palate
• Cardiac defects
• Polydactyly
o Unilateral renal agenesis
• Difficult diagnosis
• Color Doppler shows single renal artery
o Sirenomelia
• Fused lower extremities
• Bilateral renal agenesis
• Always with SUA
• SUA inserts directly into aorta
o Velamentous cord origin
• Cord originates from membranes
• Higher incidence of SUA
o Twin reversed arterial perfusion sequence
• Arterial placental anastomosis between twins
• Acardiac twin receives blood from pump twin
• 2/3 of acardiac twins have SUA
• SUA and amniocentesis
o Isolated SUA
• Amniocentesis not indicated
• Not associated with trisomy 21
o Nonisolated SUA

Diagnoses

Pathology
•
•
•
•
•

Usually normal with isolated SUA
50% aneuploidy rate if SUA + other anomalies
Trisomy 18
Tri omy 13
1-2% second and third trimester fetuses

Diagnostic Checklist
•
•
•
•

Follow-up exam for IUGR
Amniocentesis if not an isolated finding
Routinely document number of vessels in cord
Look for hypopla tic UA on routine views

• Amniocentesis indicated
• 50% aneuploidy rate
• Hypoplastic UA within spectrum of SUA
o Small right or left UA
• > 50% difference in size between UAs
o More difficult diagnosis than SUA
o Doppler abnormalities in small UA
• Increased resistance
• Higher systolic/diastolic ratio
• Can not use same nomograms as normal cord

Imaging Recommendations
• Best imaging tool: Color Doppler transverse pelvis
image shows SUA around bladder
• Protocol advice
o Look for additional fetal anomalies when SUA seen
• Cardiac (consider echocardiogram)
• Renal
• Anomalies of T18 and T13
o Serial ultrasound exams for growth
• 15% develop IUGR

I DIFFERENTIAL DIAGNOSIS
Fused umbilical arteries
• Often within 3cm of placenta
• Longer fused segments mimic SUA
o Look for 2 UAs in fetal pelvis
• Not associated with other abnormalities
• Not associated with aneuploidy

Umbilical vessel thrombosis
• UV or UA thrombosis
o Rare
o Echogenic thrombus in UV or one UA
• Two patent + 1 thrombosed vessel
• Mimics a two vessel cord
o Doppler helps identify vessels
• Maternal thrombophilia
association
o Acquired
• Antiphospholipid
syndrome common
o Inherited

SINGLE UMBiliCAL
• Protein C deficiency common
• Complication of interventional procedure
o UV sampling
• High fetal mortality

Excessive Wharton jelly
• Excessive gelatinous stroma
o Thick umbilical cord
• Umbilical vessels displaced from each other
• Associated with T21
o t Risk in 1st trimester

ARTERY

o SUA + lUGR

Natural History & Prognosis
• Isolated SUA
o Excellent prognosis
o Possible lUGR
• SUA + anomalies
o Prognosis related to severity of anomalies
o Amniocentesis indicated

Treatment
• Not necessary for isolated SUA

I PATHOLOGY
General Features
• Genetics
o Usually normal with isolated SUA
o 50% aneuploidy rate if SUA + other anomalies
• Trisomy 18
• Trisomy 13
• Etiology
o UA atrophy
• 40% show muscular remnant of missing UA
o UA agenesis
• One UA never forms
o Persistent vitelline artery (VA)
• Sirenomelia most common example
• VA should regress with yolk sac
• VA connects directly to aorta
• UAs never form
• Lower extremity fusion may be from UA agenesis
• Epidemiology
o 3% first trimester
o 1-2% second and third trimester fetuses
o 0.63% newborn infants
• Associated abnormalities
o lUGR in 15%
o Anomalies commonly seen with T18
o Anomalies commonly seen with T13

Staging, Grading or Classification Criteria
• Type I SUA
o 1 UA + 1 UV
o Most common (98%)
• Type II SUA
o Persistent VA + UV
o Almost always with sirenomelia
• Type III SUA
o lUA (or VA) + UV + persistent right umbilical vein
o Associated with renal and venous anomalies
o Rare
• Type IV SUA
o 1 UA (or VA) + persistent right umbilical vein
o Usually die early in pregnancy
o Extremely rare

I CLINICAL ISSUES
Presentation
• Most common signs/symptoms
o Routine cord view
o SUA + other anomalies

I DIAGNOSTIC

CHECKLIST

Consider
• Follow-up exam for IUGR
o Into 3rd trimester
o Can use cord Doppler values
• Same Doppler nomograms as for normal cords
• Amniocentesis if not an isolated finding
• Repeat ultrasound at 22-24 weeks
o 8% false positive rate
o Better evaluation of fetal anatomy

Image Interpretation

Pearls

• Routinely document number of vessels in cord
o Cross section view of 2 UA and 1 UV
• Use color Doppler in fetal pelvis to document number
and size of UAs
• Look for hypoplastic UA on routine views
o Same associations as SUA
o Hypoplastic UA will have higher resistance flow

I SELECTED
1.

2.
3.

4.

5.

6.

7.

8.

REFERENCES

Prucka S et al: Single umbilical artery: what does it mean
for the fetus? A case-control analysis of pathologically
ascertained cases. Genet Med. 6(1):54-7, 2004
Gornall AS et al: Antenatal detection of a single umbilical
artery: does it matter? Prenat Diagn. 23(2):117-23, 2003
Rembouskos G et al: Single umbilical artery at 11-14 weeks'
gestation: relation to chromosomal defects. Ultrasound
Obstet Gynecol. 22(6):567-70, 2003
Gamzu R et al: Type II single umbilical artery (persistent
vitelline artery) in an otherwise normal fetus. Prenat
Diagn. 22(11):1040-3, 2002
Budorick NE et al: The single umbilical artery in a high-risk
patient population: what should be offered? J Ultrasound
Med. 20(6):619-27; quiz 628, 2001
Degani S et al: Early second-trimester low umbilical coiling
index predicts small-for-gestational-age
fetuses. J
Ultrasound Med. 20(11):1183-8, 2001
Chow JS et al: Frequency and nature of structural
anomalies in fetuses with single umbilical arteries. J
Ultrasound Med 17:765-8, 1998
Persutte WH et al: Single umbilical artery: a clinical enigma
in modern prenatal diagnosis. Ultrasound Obstet Gynecol.
6(3):216-29, 1995

SINGLE UMBiliCAL

ARTERY

I IMAGE GALLERY
(Left) Axial ultrasound shows
only two vessels in the
umbilical cord. The UA
(curved arrow) has a thicker
wall than the UV (arrow).
The increased diameter of
the SUA is most apparent on
cros.s section views. (Right)
Axial color Doppler
ultrasound through the fetal
pelvis shows a SUA (arrow)
adjacent to the fetal bladder
(curved arrow). The UA
arises into the iliac artery
(open arrow). Normally, the
bladder is flanked by 2 UAs.

(Left) Sagittal ultrasound of
the fetal face shows a two
vessel cord (arrow) and a
proboscis (curved arrows).
This fetus also had
holoprosencephaly
and
other anomalies.
Amniocentesis
revealed
trisomy 73. (Right) Axial
ultrasound of the cord
insertion site shows an
omphalocele
containing
small bowel (curved arrow)
and a SUA (arrows). Other
anomalies were also seen
and amniocentesis
results
revealed trisomy 78.

Variant
(Left) Axial ultrasound shows
a hypoplastic umbilical
artery (arrow). Compare the
diameter of the normal
umbilical artery (curved
arrow) with the hypoplastic
artery and the other cases of
SUA. (Right) Axial power
Doppler ultrasound within
the fetal pelvis shows the
small UA (arrow) compared
to the normal UA (curved
arrow). Hypoplastic UAs
have higher resistive indices
(increased systolic/diastolic
ratio) on Doppler
interrogation.

UMBILICAL CORD CYST

Sagittal ultrasound shows a large allantoic cyst (arrows)
at the fetal end of the umbilical cord. A patent urachus
was not seen prenatally, but was suspected, given the
size and location of this umbilical cord cyst (UCC).

ITERMINOLOGY
Abbreviations
•
•
•
•
•

and Synonyms

Umbilical cord cyst (ueC)
Umbilical cord pseudocyst
Allantoic cyst
Urachal cyst
Omphalomesenteric
duct cyst

Definitions
• eyst or cysts associated with umbilical cord (UC)

IIMAGING FINDINGS
General Features
• Best diagnostic clue: ue with one or more cysts
• Location
o Paraxial (60%)
• Eccentrically located cyst
• ue vessels not displaced
o Axial (40%)
• eyst centrally located in ue
• ue vessels splayed by uee
o Seen anywhere along length of cord
• 28% at fetal insertion
• 33% at placental origin
• 39% at mid ue

Clinical photograph of the same newborn shows a urine
filled UCc. A patent urachus was diagnosed with a
voiding cystourethrogram procedure and was surgically
treated.

• Size
o First trimester
• Median diameter of 3 mm
o 2nd and 3rd trimester
• Variable
• Morphology
o Round
o Oval
o Thin walled

Ultrasonographic

DDx: Umbilical Cord Cyst

-,---

~"
.. ,:'

tf-:
..
::--

~

i

«-

]1

..•.~~

~

,«-

-.

..

71

... '/

UA Aneurysm

Findings

• uee general features
o Thin walled cyst or cysts
• Usually anechoic
• Rarely with minimal internal echoes
o Single or multiple
• Multiple cysts often cluster
o Doppler
• Differentiates uee from vessels
o Pseudocyst vs. true cysts
• Look identical on ultrasound
• Pseudocyst without epithelial wall
• True cyst with epithelial wall
• First trimester uee
o 2% prevalence
• Between 7-14 wks
o Usually form at 8-9 wks
• Same time as ue coiling

Yolk Sac With VA

UMBiliCAL CORD CYST
Key Facts
Terminology

Top Differential

•

• ormal yolk ac
• Umbilical cord aneury m

yst or cysts as ociated with umbilical cord (U

Imaging Findings
• Paraxial (60%)
• e n anywhere along length of cord
• Thin walled cyst or cysts
• Usually an choic
• 2<r6 prevalence
• Mo toft n transient finding
• Mo tare p eudocysts
• Multiple U
with increa ed risk of anomalies and
an uploidy
i near fetal end of
• Look at fetal bladder if U
umbilical cord
• Allantoic cysts can grow

• Associated with physiologic bowel herniation
o Pseudocyst
• Most common UCC
• Fluid accumulation within Wharton jelly
o 75% single UCC
• Not associated with poor outcome
o 25% multiple UCC
• 2/3 with aneuploidy or anomalies
• Associated with increased nuchal translucency
• 7.6x increased risk of poor outcome
o Most often transient finding
• Resolve by 2nd trimester
• Better prognosis if cysts resolve
• 2nd and 3rd trimester UCC
o Most are pseudocysts
• Higher incidence of aneuploidy
• Variable but stable size
• Usually paraxial
o Allantoic cyst
• True cyst
• 2° to patent urachus (bladder connected to UC)
• May grow and compress cord (contains urine)
• Always near fetal insertion
o Omphalomesenteric
duct cyst
• True cyst
• Rarest cause of UCC
• 2° to omphalomesenteric
duct remnant
• + Abdominal wall anomalies
• + Intra abdominal mesenteric cysts
• + Other severe anomalies
• t Trisomy 21 (T21) risk in nonisolated cases
• 2nd trimester UCC and aneuploidy
o Multiple tiny cysts in thickened cord
• Abnormal Wharton jelly
• Mucoid degeneration
o Trisomy 18 (T18) and trisomy 13 (T13) association
• May be an isolated finding in first trimester
• Not an isolated finding in second trimester
• Rarely single cyst
o UCC and T21
• No increased risk if isolated finding
• UCC and Doppler

Diagnoses

Pathology
• Genetics: T18 and Tl3 association
• 2° mucoid or cy tic degeneration of Wharton
• Embryonic duct remnant

jelly

Clinical Issues
• Excellent progno i if transient
• ingle U
better prognosis than multiple U

Diagnostic Checklist
een
• First trimester geneti screening when U
• Second trimester gen tic ultra ound
• Look carefully at abdominal wall and fetal bladder

o Helps differentiate UCC from UC vessels
a Used to rule out vessel anomaly/compression

Imaging Recommendations
• Best imaging tool
o Transvaginal ultrasound in first trimester
• Best visualization of anatomy
o Routine evaluation of UC
• Document 2 umbilical arteries and 1 umbilical
vein
• Document cord insertion at fetal end
• Look for cord origin at placenta
• Scan through free loops of cord
• Protocol advice
o Look carefully for other anomalies
• Multiple UCC with increased risk of anomalies
and aneuploidy
o Look at fetal bladder if UCC is near fetal end of
umbilical cord
• Allantoic cyst
• May see patent urachus
o Follow-up to see if UCC resolves
• Allantoic cysts can grow

I DIFFERENTIAL DIAGNOSIS
Normal yolk sac
• Yolk sac is extra-amniotic
o Connected to vitelline artery (VA) not UC
• UCC is intra-amniotic sac
a Connected to UC, not vitelline artery
• Transvaginal ultrasound helpful

Umbilical cord aneurysm
• Aneurysmal dilatation of umbilical vein (varix) or
artery (UA)
• Can look exactly like UCC on gray scale imaging
• Doppler helpful to differentiate from UCC
• t Risk thrombosis
o Associated with fetal demise

UMBiliCAL CORD CYST
• Rare
• 2° to cord trauma
o Usually from cordocentesis
• Hematoma appearance changes with time
o Echogenic '* cystic

• Omphalomesenteric
cysts
o Prognosis related to associated anomalies
• Omphalocele
• Mesenteric cyst
• Hernia
• Spina bifida
• Cardiac defects

UC supernumerary

Treatment

Resolving UC hematoma

•
•
•
•

vessels

More than 3 vessels in UC
Very rare
Usually seen with conjoined twins
Doppler differentiates from UCC

I PATHOLOGY
General Features
• Genetics: TI8 and T13 association
• Etiology
o Pseudocyst
• Form at time of UC coiling and midgut herniation
• Increased UC hydrostatic pressure
• 2° mucoid or cystic degeneration of Wharton jelly
• Single> multiple
o True cysts
• Embryonic duct remnants
• Allantoic duct
• Omphalomesenteric
duct
• Vitelline duct
o Abnormal Wharton jelly
• Abnormal extracellular matrix
• Results in multiple pseudocysts
• Found in T18 and T13
• Epidemiology
o 2% in first trimester
• Most resolve without sequelae

Microscopic

Features

• True cysts are lined by epithelium
• Pseudocysts are not lined by epithelium

I CLINICAL

• None necessary for isolated UCC
• Growing cyst
o May compromise cord
o Early delivery considered
o Cyst drainage considered
• Ultrasound guided drainage

I DIAGNOSTIC
Consider

• First trimester genetic screening when UCC seen
o Nuchal translucency + maternal serum screen
• Assess maternal risk for aneuploidy
o Increased risk for aneuploidy with multiple UCC
• TI8 most common
• Second trimester genetic ultrasound
o Markers for TI8
o Markers for T13
• Look carefully at abdominal wall and fetal bladder
o Abdominal wall hernia
o Patent urachus from bladder to umbilical cord

Image Interpretation

I SELECTED REFERENCES
1.

• Most common signs/symptoms
o Incidentally noted during first trimester scan
o Second trimester
• Isolated most common
• Associated with other anomalies

2.

3.

4.

Demographics
• Age
o Advanced maternal age associated with TI8 and T13
• ~ 35 yrs at time of delivery

Natural History & Prognosis
• First trimester
o Excellent prognosis if transient
• Single UCC better prognosis than multiple UCC
• Allantoic cysts
o May grow if patent urachus
o Often need surgery
o Postnatal work up necessary

Pearls

• Careful evaluation of umbilical cord in all first
trimester cases
o Identify yolk sac separate from suspected UCC
• Color Doppler of umbilical cord when diagnosis
suspected

ISSUES

Presentation

CHECKLIST

5.
6.

7.
8.

Emura T et al: Omphalocele associated with a large
multilobular umbilical cord pseudocyst. Pediatr Surg Int.
20(8):636-9, 2004
Kilicdag EBet al: Large pseudocyst of the umbilical cord
associated with patent urachus. J Obstet Gynaecol Res.
30(6):444-7, 2004
Ghezzi F et al: Single and multiple umbilical cord cysts in
early gestation: two different entities. Ultrasound Obstet
Gynecol. 21(3):215-9, 2003
Kiran H et al: Pseudocyst of the umbilical cord with
mucoid degeneration of Wharton's jelly. Eur J Obstet
Gynecol Reprod BioI. 111(1):91-3,2003
Sepulveda W: Beware of the umbilical cord 'cyst'.
Ultrasound Obstet Gynecol. 21(3):213-4, 2003
Sepulveda W et al: Pseudocyst of the umbilical cord:
prenatal sonographic appearance and clinical significance.
Obstet Gynecol. 93(3):377-81, 1999
Sepulveda W et al: Cliniclll significance of first trimester
umbilical cord cysts. J Ultrasound Med. 18:95-9, 1999
Sepulveda Wet al: Prenatal diagnosis of umbilical cord
pseudocyst. Ultrasound Obstet Gynecol. 4:147-50, 1994

UMBiliCAL CORD CYST
I IMAGE GAllERY
Typical
(Left) Sagittal ultrasound of a
first trimester cord shows an
UCC (arrows). Isolated UCC
are often seen at the same
time as physiologic bowel
herniation (curved arrow).
(Right) Coronal ultrasound in
another first trimester case
shows a UCC (arrows) near
the placental origin. The
cord is normally coiled
(curved arrow) and not
thickened. Both of these
cysts were pseudocysts
and
resolved without sequelae.

(Left) Axial ultrasound shows
multiple large UCCs (arrows)
at placental end of UC in a
second trimester fetus.
Although multiple UCCs are
often associated with other
abnormalities, these UCCs
were isolated and fetal
outcome was normal. (Right)
Axial color Doppler
ultrasound in another second
trimester fetus with multiple
UCC (arrows) shows how
Doppler can help
differentiate cysts from UC
vessels. This fetus also had a
cardiac defect and
hydrocephalus.

Variant
(Left) Axial ultrasound shows
a thickened cystic umbilical
cord (arrows) and an
omphalocele
containing
small bowel (curved arrow)
in this second trimester fetus
with trisomy 78. (Right) Long
axis ultrasound of the
umbilical cord in the same
fetus shows innumerable
small cysts (arrows). This
appearance is from mucoid
degeneration of abnormal
Wharton jelly.

UMBiliCAL

CORD ANEURYSMS

Coronal transabdominal ultrasound shows the increased
diameter of the varix (curved arrow) compared to the
intrahepatic portion of the umbilical vein (arrow).

o UA aneurysm usually near placental end of cord

ITERMINOlOGY
Abbreviations

Pulsed Doppler ultrasound shows venous flow in the
varix. The elongated nature of the varix (arrow) is better
seen on oblique scan planes, as it extends from the
abdominal wall to the inferior liver edge.

Ultrasonographic

and Synonyms

• Umbilical vein varix (UV varix, UVV)
• Umbilical artery aneurysm (UA aneurysm)

Definitions
• UV varix: Focal dilatation of umbilical vein> 9 mm
diameter
o Alternate definition: Varix diameter 50% >
intrahepatic portion of umbilical vein
• UA aneurysm: Aneurysmal dilatation of umbilical
artery

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o UV varix: Cyst-like space in upper abdomen with
venous flow on Doppler
• UV varix in free floating loops of cord is much
harder to see
o UA aneurysm: Saccular dilatation of umbilical artery
with arterial flow
• Location
o UV varix usually intra-abdominal but extrahepatic
• May also occur in free-floating loops of cord

Imaging Recommendations
• Protocol advice
o Measurement technique of UV varix:

DDx: Cystic Mases Simulating Umbilical Cord Aneurysms

Cord

Cyst

Choledochal

Cyst

Findings

• UV varix
o Upper abdominal "cyst"
• Oval or elongated shape
• Thin walled
• Anechoic
o May occur in association with persistent right
umbilical vein
o May be large
o Must show continuity of "cyst" with UV and
presence of blood flow to make this diagnosis
o Runs between abdominal cord insertion site and
inferior edge of liver
• Oblique orientation
• UA aneurysm
o Cord "cyst" near placental origin
o Arterial malformation not venous
o May have arteriovenous fistula to umbilical vein
o Associated with single umbilical artery
o Wall may be calcified
o Associated with multiple anomalies
• Trisomy 18
o Much more rare than UV varix

Ovarian

Cyst

UMBiliCAL

CORD ANEURYSMS
Key Facts

Terminology

Top Differential

• UV varix: Focal dilatation of umbilical vein> 9 mm
diameter
• Alternate definition: Varix diameter 50% >
intrahepatic portion of umbilical vein

• Abdominal cysts
• Umbilical cord cysts

Imaging Findings
• UV varix: Cy t-like space in upper abdomen with
venous flow on Doppler
• UA aneurysm usually near placental end of cord
• UA aneurysm strongly associated with multiple
anomalies and trisomy 18
• Increasing turbulence in varix/aneury m concerning
for impending thrombosis
• Failure of entire varix/aneurysm to fill with color on
Doppler concerning for thrombus

o

o

o

o
o

• Axial image of fetal abdomen immediately
cephalad to umbilical vein insertion
• Measure UV from outer edge to inner edge
(leading edge to leading edge)
Careful search for other anomalies
• Significant adverse impact on prognosis if present
• UA aneurysm strongly associated with multiple
anomalies and trisomy 18
UV varix may be first manifestation of elevated
venous pressure
• Formal fetal echocardiogram should be performed
Monitor for signs of impending hydrops
• Measure ratio of heart to chest circumference
• Look for tricuspid regurgitation
• Check ductus venosus waveform
• Look for end-systolic umbilical vein pulsation
Monitor for anemia
• Middle cerebral artery peak systolic velocity
Use color Doppler
• Increasing turbulence in varix/aneurysm
concerning for impending thrombosis
• Failure of entire varix/aneurysm to fill with color
on Doppler concerning for thrombus

I DIFFERENTIAL
Normal fluid-filled

Pathology
• UV varix may be first manifestation of abnormal
venous pressure
• Expanding varix in cord may compre s umbilical
artery

Clinical Issues
• Karyotype if other anomalies
• lose fetal monitoring
• Consider early delivery for UV varix

Diagnostic Checklist
• UV varix in differential

of an intra-abdominal

cyst

o Female fetus
o No flow
o Complex appearance if torsion or hemorrhage
• Duplications cyst
o Small bowel duplication cysts
o Layered wall = gut signature
o May be associated with polyhydramnios
• Urachal cyst
o Midline
o Between dome of bladder and cord insertion site
o No flow

Umbilical cord cysts
• Allantoic cyst
o Persistent communication
from bladder to cord
o Cystic dilatation of extra-embryonic allantois
o Cyst at base of cord (near fetal insertion)
o Umbilical vessels separated by cyst
• Cysts and pseudocysts other than allantoic
o Displace cord vessels rather than separate them
(paraxial location)
o No internal flow

I PATHOLOGY
DIAGNOSIS
structures

• Stomach
• Gallbladder

Abdominal

Diagnoses

cysts

• Choledochal cyst
o No flow
o Right upper quadrant, associated with liver
• Meconium pseudocyst
o No flow
o Usually associated with bowel perforation
• Echogenic bowel
• Dilated loops of bowel
• Ascites
• Peritoneal calcifications
• Ovarian cyst

General Features
• Genetics
o Sporadic if isolated
o If part of multiple anomaly complex
• Trisomy 18
• Triploidy
• Etiology
o Intra-abdominal,
extrahepatic UV is the least
supported portion
• Increased venous pressure => focal dilatation in
this segment
o Association with cardiomegaly and hydrops
• UV varix may be first manifestation of abnormal
venous pressure
• May signify increased risk of cardiac
decompensation
• Epidemiology

UMBiliCAL

CORD ANEURYSMS

o True in utero incidence VV varix unknown
• 3.8% of cord malformations in series of perinatal
deaths
• Variceal thrombosis ~ stillbirth
o M:F = 2:1
o VA aneurysm: Scattered case reports, extremely rare
• Embryology
o Normal umbilical vein increases in size with
advancing gestational age
• 3 mm at 15 weeks
• 8 mm at term

Gross Pathologic & Surgical Features
• Expanding varix in cord may compress umbilical
artery
o Intrauterine growth restriction
o Hypoxia ~ abnormal non-stress test and biophysical
profile
• Enlarging VA aneurysm ~ VV compression ~ fetal
compromise
• VV is sole conduit for returning oxygenated blood
o Demise in otherwise structurally normal fetuses
attributed to acute circulatory disturbance from
thrombosis
• UA aneurysm thrombosis ~ similar acute circulatory
disturbance if associated with single umbilical artery

o Rarer than intra-abdominal
o May bleed through amniotic
• Fetal exsanguination

sheath

Treatment
• Karyotype if other anomalies
o 12% incidence aneuploidy for VV varix
• Close fetal monitoring
o Death tends to occur rapidly after abnormal
non-stress test
• Attributed to thrombosis of varix
• Consider early delivery for VV varix
o Some authors advise as early as 34 weeks
o At lung maturity
o If any signs fetal distress

I DIAGNOSTIC

CHECKLIST

Consider
• VV varix in differential of an intra-abdominal
o Must be in continuity with umbilical vein
o Color Doppler allows rapid diagnosis
• UA aneurysm much rarer
o High association with anomalies

cyst

ISELECTED REFERENCES
ICLINICAL

ISSUES

1.

Presentation
• Most common signs/symptoms
o UV varix: Cyst-like lesion in fetal abdomen
• Flow on color Doppler
• Pulsed Doppler shows venous signal
o UA aneurysms: Cyst-like lesion in cord
• Flow on color Doppler
• Pulsed Doppler shows arterial signal

2.

3.
4.
5.

Natural History & Prognosis
• Variable outcomes reported with intra-abdominal
UV
varix
o Isolated VV varix
• Intrauterine fetal demise (IUFD) in 1:7 cases
despite close surveillance
o 10 year experience single institution, all cases with
UV varix
• 48% normal outcome
• 13% preterm delivery
• 35% other anomalies
o Literature review 42 cases
• 24% IUFD
• 12% chromosomal abnormality
• 5% hydrops
• Secondary schistocytic hemolytic anemia
o Turbulent flow in varix ~ red cell destruction
o Anemia may cause hydrops
• Thrombosis of UV varix
o Hydrops
o IVFD
• Early diagnosis (second trimester) may correlate with
worse outcome
• If truly isolated, UV varix prognosis generally good
• UV varix of intra-amniotic segment

6.

7.

8.
9.
10.

11.

12.

13.

Valsky DV et al: Adverse outcome of isolated fetal
intra-abdominal
umbilical vein varix despite close
monitoring. Prenat Diagn. 24(6):451-4, 2004
Viora E et al: Anomalies of the fetal venous system: a
report of 26 cases and review of the literature. Fetal Diagn
Ther. 19(5):440-7,2004
Zachariah M et al: Umbilical vein varix thrombosis: a rare
pathology. J Obstet Gynaeeal. 24(5):581, 2004
Viora E et al: Thrombosis of umbilical vein varix.
Ultrasound Obstet Gynecol. 19(2):212-3, 2002
Rahemtullah A et al: Outcome of pregnancy after prenatal
diagnosis of umbilical vein varix. J Ultrasound Med.
20(2):135-9, 2001
Batton DG et al: Fetal schistocytic hemolytic anemia and
umbilical vein varix. J Pediatr Hematol Oneal.
22(3):259-61, 2000
Ami MB et al: Prenatal sonographic diagnosis of persistent
right umbilical vein with varix. J Clin Ultrasound.
27(5):273-5, 1999
Allen SL et al: Thrombosing umbilical vein varix. J
Ultrasound Med. 17(3): 189-92, 1998
Sepulveda W et al: Fetal prognosis in varix of the intrafetal
umbilical vein. J Ultrasound Med. 17(3):171-5, 1998
Babay ZA et al: A case of varix dilatation of the umbilical
vein and review of the literature. Fetal Diagn Ther.
11(3):221-3, 1996
White SP et al: Prenatal diagnosis and management of
umbilical vein varix of the intra-amniotic portion of the
umbilical vein. J Ultrasound Med. 13(12):992-4, 1994
Estroff JA et al: Fetal umbilical vein varix: sonographic
appearance and postnatal outcome. J Ultrasound Med.
11(3):69-73, 1992
Mahony BS et al: Varix of the fetal intra-abdominal
umbilical vein: comparison with normal. J Ultrasound
Med. 11(2):73-6, 1992

UMBiliCAL

CORD ANEURYSMS

IIMAGE GALLERY
(Left) Axial ultrasound of the
fetal abdomen shows the
typical location of an
umbilical vein varix (arrow)
adjacent to the cord
insertion site (curved arrow).
(Right) Ultrasound with
correlative gross photograph
of umbilical vein thrombosis
(arrows). Thrombosis is a
potential serious
complication of an umbilical
vein varix, often with fatal
outcome.

Typical
(Left) Axial ultrasound
through the fetal abdomen
shows a cystic-appearing
mass within the abdomen
(arrows). (Right) Axial color
Doppler ultrasound through
this "cystic mass" shows
flow, confirming its vascular
etiology. Note that the entire
structure fills on color
interrogation. This fetus had
no adverse consequences.

Typical
(Left) Pulsed Doppler
ultrasound at the placental
end of the cord shows an
arterial waveform (arrow) in
one of the UA aneurysms
(curved arrows). Multiple
fetal anomalies were also
present. (Right) Cross
pathology shows the two UA
aneurysms (arrows),
adjacent to the placental
cord insertion. There is a
single umbilical artery and
this fetus had trisomy 78.
Both of these conditions are
associated with UA
aneurysms.

PERSISTENT

RIGHT UMBILICAL VEIN

Graphic shows a PRUV (arrows) entering the liver
lateral to the gallbladder (open arrows). Within the liver,
it hooks towards the stomach as it joins the left portal
vein (curved arrow).

!TERMINOLOGY
Abbreviations

and Synonyms

• Persistent right umbilical vein (PRUV)

Definitions
• Embryologic right umbilical vein (RUV) remains open

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Intrahepatic portion of umbilical
vein (UV) curves towards stomach
• Location
o Intrahepatic PRUV (most common)
o Extrahepatic PRUV

Ultrasonographic

Findings

• Intrahepatic PRUV (72%)
o PRUV passes to right of gallbladder (GB)
• GB medially displaced
• GB transversely oriented
o PRUV fuses with left portal vein
• Left curve of UV instead of right
• UV hooks towards stomach instead of liver
o Typically seen on transverse view through liver
• Coronal view helpful for confirmation

Coronal ultrasound shows an intrahepatic
PRUV
(arrows). The umbilical vein enters the liver and hooks
towards the stomach (curved arrow) instead of towards
the right lobe of the liver.

o Normal portal venous connections
• Normal ductus venosus
o Often isolated finding
• Extrahepatic PRUV (18%)
o PRUV bypasses liver and portal system
• Extrahepatic PRUV runs anterior to liver
o Abnormal venous connections
• PRUV drains into systemic veins
o Extrahepatic PRUV associated with other anomalies
and aneuploidy
• Trisomy 18 (TI8)
• Noonan syndrome
• Cardiovascular anomalies
• Central nervous system anomalies
• Gastrointestinal anomalies
• Intrauterine growth restriction
o Single umbilical artery in almost all cases
• Color Doppler and 3D ultrasound
o Helps show course and connections of PRUV

Imaging Recommendations
• Best imaging tool: Abdominal circumference (AC) view
• Protocol advice
o Look at position of UV curve in all cases
o Consider amniocentesis when other anomalies seen

DDx: Persistent Right Umbilical Vein

UV varix

UV Varix

Normal UV

PERSISTENT

RIGHT UMBILICAL VEIN
Key Facts

Terminology
• Embryologic right umbilical vein (RUV) remains open

Top Differential

Imaging Findings
• Best diagnostic clue: Intrahepatic portion of umbilical
vein (UV) curves towards stomach
• Intrahepatic PRUV (72%)
• Extrahepatic PRUV (18%)
• Extrahepatic PRUV runs anterior to liver

I DIFFERENTIAL

• Extrahepatic PRUV associated with other anomalies
and aneuploidy

DIAGNOSIS

Diagnoses

• or mal umbilical vein
• Umbilical vein varix (UV varix)

Clinical Issues
• Intrahepatic PRUV usually an isolated finding

I DIAGNOSTIC

CHECKLIST

Normal umbilical vein

Consider

• Left UV patent
• UV curve is towards liver
• Gallbladder is lateral to uv

• PRUV in cases of abnormal-appearing

Umbilical vein varix (UV varix)
•
•
•
•

Intraabdominal varix most common
Extrahepatic portion of UV focally dilated
May be associated with IUGR and aneuploidy
May be associated with PRUV

Image Interpretation

I SELECTED

I PATHOLOGY
2.

General Features

I CLINICAL

Pearls

• Diagnosis often missed
o Abnormal direction of UV hook not noticed
• Look for additional anomalies when PRUV seen

1.

• Genetics: Extrahepatic variant associated with T18
• Etiology
o Normal embryology
• Early placenta has 2 umbilical veins
• Right normally obliterates by 7th week
• Left connects to portal veins and ductus venosus
o Intrahepatic PRUV
• Left UV occludes instead of right
• PRUV provides normal flow
• Does not alter blood distribution to fetus
o Extrahepatic PRUV
• PRUV drains into systemic veins
• Right atrium, superior vena cava most often
• Epidemiology: 1:526 fetuses

gallbladder

3.

4.
5.

REFERENCES

Nakstad B et al: Abnormal systemic venous connection
possibly associated with a persistent right umbilical vein; a
case report. BMC Pediatr. 4(1):7, 2004
Wolman I et al: Persistent right umbilical vein: incidence
and significance. Ultrasound Obstet Gynecol. 19(6):562-4,
2002
De Catte L et al: Persistent right umbilical vein in trisomy
18: sonographic observation. J Ultrasound Med.
17(12):775-9,1998
Ariyuki Y et al: Antenatal diagnosis of persistent right
umbilical vein. J Clin Ultrasound. 23(5):324-6, 1995
Hill LM et al: Persistent right umbilical vein: sonographic
detection and subsequent neonatal outcome. Obstet
Gynecol. 84(6):923-5, 1994

IIMAGE

GALLERY

ISSUES

Presentation
• Most common signs/symptoms
o Incidentally noted on routine AC view
o Seen in association with other anomalies

Natural History & Prognosis
• Intrahepatic variant
o Excellent prognosis
o Intrahepatic PRUV usually an isolated finding
• Extrahepatic variant
o Prognosis related to chromosome results
• T18 most common aneuploidy
o Prognosis related to associated anomalies

(Left) Axial ultrasound shows an intrahepatic PRUV The UV (arrow)
turns left and towards the stomach (curved arrow) instead of towards
the right lobe of the liver (open arrow). (Right) Axial ultrasound in the
same fetus shows a medially displaced
gallbladder
(arrow). The
umbilical vein (curved arrow) passes to the right of the gallbladder.
Normally, the umbilical vein inserts between
the stomach and the
gallbladder.

VASA PREVIA

Graphic of vasa previa shows velamentous cord
insertion (A) and succenturiate lobe (B). In B, fetal
vessels travel between the main placenta (curved
arrow) and the accessory lobe (arrow).

ITERMINOLOGY
Definitions
• Submembranous

IIMAGING

fetal vessels cross cervical os

FINDINGS

General Features
• Best diagnostic clue
o Pulsed Doppler shows fixed fetal vessels overlying
cervical os
o Associated with succenturiate lobe and velamentous
cord insertion

Ultrasonographic

Sagittal color Doppler ultrasound shows vasa previa.
Fetal umbilical vessels (arrows) overly the cervix (open
arrows). The vessels are submembranous. Cervical
dilatation would lead 10 fetal hemorrhage.

• Vessels within 2 cm of internal cervical os
• Transvaginal ultrasound (TVUS) + Doppler required
o Color Doppler shows crossing vessels
o Pulsed Doppler proves fetal vascularity
• Umbilical arterial flow
• Document fetal heart rate

Imaging Recommendations
• Best imaging tool: TVUS + color Doppler + pulsed
Doppler
• Protocol advice
o Careful surveillance of entire uterus
• Identify succenturiate lobe
o Doppler TVUS in all low lying placenta
o Identify placental Cl when suspicious of diagnosis

Findings

• Vasa previa from succenturiate lobe
o Most common etiology
o Main placenta + accessory placenta
• Low lying placenta common
o Communicating
vessels between lobes
o Vessels traverse internal cervical os
• Carry fetal blood
• Vasa previa from velamentous cord insertion
o Placental cord insertion (CI) is velamentous
• CIon membranes
• Usually adjacent to placenta
o Low lying placenta + velamentous CI

I DIFFERENTIAL

Marginal sinus previa
• Variant of marginal placenta previa
• Maternal veins from placenta near cervix
o Normal placental CI
• Bleeding is maternal not fetal

Cord presentation
• Umbilical cord is presenting part at labor
• Free loop of cord in front of cervix
• t Risk for cord accident

DDx: Vessels Near Cervix

Presenting Cord

DIAGNOSIS

Marginal Sinus Previa

VASA PREVIA
Key Facts
Top Differential

Terminology
• Submembranous

fetal vessels cross cervical os

Imaging Findings
• Associated with succenturiate lobe and velamentous
cord insertion
• Best imaging tool: TVUS + color Doppler + pulsed
Doppler
• Identify placental CI when suspicious of diagnosis

• Often incidental

finding if patient not in labor

Uterine vessel near cervix
• Incidental finding
• Placenta not near cervix

I PATHOLOGY
General Features
• Etiology
o Vasa previa and succenturiate placenta
• Normal placenta originally present
• Partial atrophy results in ~ 2 placentae
• Vessels travel between lobes
• Fetal vessels cross cervical os
o Vasa previa and velamentous CI
• Originally placenta previa
• Partial atrophy from poor decidual vascularity
• CI ends up submembranous near cervix
• Epidemiology: 1:3,500 deliveries
• Associated abnormalities
o Monochorionic twins
• t Velamentous CI incidence
o Maternal uterine anomalies
• t Abnormal placentation

Gross Pathologic & Surgical Features
• Submembranous vessels are extremely fragile
o No placental tissue support

Staging, Grading or Classification Criteria

Diagnoses

• Marginal sinus previa
• Cord presentation

Pathology
• Epidemiology:

1:3,500 deliveries

Clinical Issues
• 60-80% fetal mortality if diagnosis missed
• Cesarean section before onset of labor

I DIAGNOSTIC

CHECKLIST

Consider
• Rule out vasa previa if succenturiate lobe seen
• Rule out vasa previa if marginal placenta previa seen

Image Interpretation

Pearls

• Have a high index of suspicion
• Use color Doppler with transvaginal ultrasound
o May not see vessels with grayscale alone
• Use pulsed Doppler if crossing vessels seen
o Determine fetal vessels vs. maternal vessels

ISELECTED REFERENCES
1.

2.

3.

4.

Oyelese Y et al: Vasa previa: the impact of prenatal
diagnosis on outcomes. Obstet Gynecol. 103(5 Pt
1):937-42,2004
Stafford IP et al: Abnormal placental structure and vasa
previa: confirmation of the relationship. J Ultrasound Med.
23(11):1521-2, 2004
Robert JA et al: Fetal exsanguination from ruptured vasa
previa: still a catastrophic event in modern obstetrics. J
Obstet Gynaecol. 23(5):574, 2003
Sepulveda W et al: Prenatal detection of velamentous
insertion of the umbilical cord: a prospective color Doppler
ultrasound study. Ultrasound Obstet Gynecol. 21(6):564-9,
2003

IIMAGE GALLERY

• Type 1: Vasa previa from velamentous CI
• Type 2: Vasa previa from succenturiate lobe

ICLINICALISSUES
Presentation
• Most common signs/symptoms
o Incidental finding with succenturiate lobe
o Incidental finding with placenta previa
o 2nd/3rd trimester bleeding
o Vessel palpation over intact membranes

Natural History & Prognosis
• 60-80% fetal mortality if diagnosis missed

Treatment
• Cesarean section before onset of labor

(Left) Sagittal ultrasound of the lower uterus shows a succenturiate
lobe. A small anterior placenta (curved arrows) and a low lying larger
posterior
placenta
(open arrows)
are seen. (Right) Sagittal
endovaginal ultrasound in the same case, performed in the third
trimester, shows a crossing vessel in front of the cervical os (arrow).
Pulsed Doppler
shows fetal arterial
flow. The fetal vessels
communicating between the two placental lobes cross in front of the
cervix in this case of vasa previa.

NUCHAL CORD

Transverse color Doppler ultrasound shows multiple
loops of umbilical cord wrapped around the fetal neck.
Four complete loops were noted at delivery.

ITERMINOlOGY
Definitions
• One or more complete loops of umbilical cord around
fetal neck

Sagittal ultrasound shows a nuchal cord creating a
"divot" sign (arrow). There is also oligohydramnios.
These findings are associated with a greater risk of
complications. (H - head, C - chest).

o Growth
o Amniotic fluid
• Oligohydramnios increases risk of complication
o Umbilical cord Doppler flow
o Fetal movement

IIMAGING FINDINGS

I DIFFERENTIALDIAGNOSIS

General Features

Cord adjacent to neck

• Best diagnostic clue
o Must see in both sagittal and transverse planes to
rule out false positive diagnosis
• 3D ultrasound may be more accurate in making
diagnosis

• Will not form complete loop around neck
o Not present in both sagittal and transverse views
• Changes during course of exam or on follow-up

Ultrasonographic

Findings

Cystic hygroma
• Multiseptated mass
• No Doppler flow

• Obvious flow with color Doppler
• Compressive effects on fetal skin (divot sign)
• May spontaneously unwind

I PATHOLOGY

Imaging Recommendations

General Features

• Look for vascular compromise
o Increased systolic to diastolic (SID) ratio
o Early diastolic notching
o If umbilical artery flow is abnormal, interrogate
middle cerebral artery
• Follow-up ultrasound with attention to

• Etiology
o Cords with less vascular coiling are more pliable and
at greater risk
o Longer cords at increased risk
• Epidemiology
o Prevalence 8-30%
• Increases with advancing gestational age

DDx: Cystic Neck Mass

Cystic Hygroma

Cystic Hygroma

Hygroma And Hydrops

NUCHAL CORD
Imaging Findings

Key Facts
Pathology

• Must see in both sagittal and transverse planes to rule
out false positive diagnosis
• Obvious flow with color Doppler
• Compressive effects on fetal skin (divot sign)
• Look for vascular compromise
• Oligohydramnios
increases risk of complication

• Cords with less vascular coiling are more pliable and
at greater risk

Top Differential Diagnoses

• Multiple loops and evidence of pressure effects at
greater risk of complications

• Cord adiacent to neck

o
o
o

o
o

• 6% at 20 weeks
• 29% at 42 weeks
More common in males
• Longer cords
Single loop 10.6%
Double loop 2.5%
Triple loop 0.5%
Quadruple loop 0.1 %

Clinical Issues
• Most reduced during delivery without consequence

Diagnostic Checklist

• Consider non-stress test (NST) and biophysical profile
for tight or multiple loops
• Patient should be made aware of importance of
decreased fetal movement
• Early delivery for deteriorating status

I DIAGNOSTIC

CHECKLIST

Gross Pathologic & Surgical Features

Consider

• Type A
o Umbilical end of cord passes over the placental end
o Can spontaneously unwind
• Type B
o Umbilical end of cord passes under the placental
end
o "Locking" type
o Greater risk for stillbirth
o May move down cord to form knot
• 10% fetal mortality rate with knot

• Including in every report
o Controversial, no standardized reporting practice
o Some feel low risk makes reporting unnecessary

Image Interpretation

I SELECTED REFERENCES
1.

ICLINICAL

ISSUES

2.

Presentation
• Most common signs/symptoms
o Incidental finding
o Rarely fetal distress

Natural History & Prognosis
• Vast majority are of no consequence
o Excellent outcome
• Reported associations (usually not associated with
long-term sequelae)
o Growth restriction
o Intrapartum fetal distress
o Low Apgar scores
o Meconium staining
o Lower umbilical artery pH
o Assisted ventilation « 30 min)
• Rare serious complications
o Developmental delay, spastic quadriplegia, stillbirth
• Factors increasing risk
o Multiple loops
o Tightness of loops
o Oligohydramnios

Treatment
• Most reduced during delivery without consequence

Pearls

• Multiple loops and evidence of pressure effects at
greater risk of complications

3.
4.

Callen PW: Categorical Course in Diagnostic Radiology:
The umbilical cord looks funny: What does that mean?
Chicago, RSNA . 9-20, 2002
Sherer OM et al: Prenatal ultrasonographic diagnosis of
nuchal cord(s): Disregard, inform, monitor, or intervene?
Ultrasound Obstet Gynecol, 14:1-8, 1999
Collins JH: Nuchal cord type A and type B. Am J Obstet
Gynecol. 177:94, 1997
Larson JD et al: Multiple nuchal cord entanglements and
intrapartum complications. Am J Obstet Gynecol.
173(4):1228-31,1995

IIMAGE GALLERY

(Left) Axial ultrasound shows the umbilical cord wrapped around the
fetal neck (arrows). Note the cord does not show the normal coiling.
which is felt to be a risk factor. (Right) Coronal color Doppler
ultrasound quickly confirms that the cystic mass on grayscale is.
indeed. the umbilical cord.

SECTION 12: Pla«:enta & Membranes

Introduction

and Overview

Placenta & Membranes

12-2

Placenta & Membranes
Placental Sonolucencies
Chorioamniotic Separation
Placenta Previa
Velamentous Cord
Placental Abruption
Succenturiate Lobe
Circumvallate Placenta
Battledore Placenta
Placentomegaly
Placenta Accreta Spectrum
Chorioangioma
Complete Hydatidiform Mole
Invasive Mole
Choriocarcinoma

12-6
12-10
12-12
12-16
12-18
12-22
12-24
12-26
12-28
12-30
12-34
12-38
12-42
12-44

PLACENTA & MEMBRANES

Graphic shows how chorionic villi are initially evenly
distributed (arrows) within the chorionic sac. By 10
wks, the chorionic frondosum (curved arrow) is formed
while other villi atrophy

I Imaging Anatomy
Ultrasound
• First trimester gestational sac (5-7 wk)
o Diffusely echogenic ring
• Chorionic ring of tissue
• First trimester placenta (8-13 wks)
o Chorionic frondosum
• Focal chorionic thickening
o Placentation site now determined
o Umbilical cord inserts in center of chorionic
frondosum
• Second trimester placenta
o Uniformly echogenic structure
o Occasional sonolucencies if> 20 wks
• Placental lakes, intervillous thrombus
• Third trimester placenta
o More heterogeneous
o Sonolucencies common
o Occasional calcifications
• Normal placental location
o Fundal to mid uterus
o Low-lying placenta often resolves by 3rd trimester
o Trophotropism
• Areas of placenta atrophy as other areas grow
• Placental cord insertion site
o Initially central
o Often eccentric at term
• 2° to trophotropism
• Membranes
o Amnion attached to early embryo
• Amnion expands
• Embryo/fetus becomes intra-amniotic
o Chorion attached to trophoblasts
o Chorionic cavity (extraembryonic coelom space)
• Fluid between amnion and chorion
• Yolk sac is in chorionic cavity
o Amnion fuses with chorion at 14-16 wks

MRI
• May help determine placental location
o Posterior placenta, obese patient, twins

Graphic shows placental circulation. Maternal blood
enters and leaves the intervillous space (arrows). The
main stem villus (open arrows) arises from the umbilical
cord and contains fetal blood.

• Abnormal placental invasion
o Accreta/percreta
• Intact vs. disrupted myometrium

IAnatomy-Based Imaging Issues
Key Concepts or Questions
•
•
•
•
•
•

Where has placenta implanted?
Is placenta detaching (abruption)?
Does placenta appear prematurely heterogeneous?
Is placental cord insertion normal?
Are membranes fused?
Is amnion intact?

Imaging Approaches
• Transabdominal ultrasound usually adequate
o Full survey of placenta recommended
• Transvaginal ultrasound (TVUS)
o Lower uterine segment assessment
• Doppler ultrasound
o To assess placental function

Imaging Protocols
• American Institute of Ultrasound in Medicine (AlUM)
o Document placental location
o Relationship to internal cervical os
• TVUS may be necessary
o Placental appearance
• Thickness
• Presence of sonolucencies/calcifications
• Placenta "grading" to assess maturity
o Not required by guidelines
o Grade 0 « 18 wk): Uniform echogenicity
o Grade 1 (18-29 wk): Occasional parenchymal Ca++
o Grade 2 (> 30 wks): Occasional basal Ca++
• Minimal chorionic plate indentation
o Grade 3 (> 39 wks): Significant basal Ca++
• Significant chorion to basal indentation
• Individual cotyledons easily seen
o Early grade 3 appearance considered abnormal
• t Risk for placental insufficiency
• Placental cord insertion assessment

PLACENTA & MEMBRANES
Key Facts
Imaging Issues
• Determine placental implantation anatomy
Rule out placenta previa
• false positive diagnosi if full maternal bladder
Rule out implantation on fibroid
Look for extra lobes (succenturiate)
• Evaluate placental attachment
Abruption if premature detachment
• Evaluate placenta morphology
Early maturation may be abnormal
ormal placental thickness < 4 cm
• Determine normal placental cord insertion
Branching vessels on placenta parenchyma
Velamentou placental cord insertion associated
with fetal morbidity
• Evaluate membranes

o Not required by guidelines
o May be eccentric later in pregnancy
o Rule out velamentous insertion
• Doppler assessment of placental function
o Uterine artery waveform
• High-resistance flow early in pregnancy
• Low-resistance flow established by 16-18 wks
o Umbilical artery waveform
• Always with antegrade diastolic flow
• Systolic/diastolic ratio < 3 after 30 wks

Imaging Pitfalls
• Full maternal bladder
o Anterior uterine wall approximates posterior wall
• Falsely elongated lower uterine segment
o Normal placenta appears low-lying
o Must re-image with less full bladder
• Focal myometrial contraction
o Can mimic fibroid or thick placenta
o Resolves with time
• Succenturiate lobe
o 1 or more accessory placentas
o May be missed if uterus not fully scanned
• Acute placental hemorrhage
o Acute blood isoechoic to placenta
o Power Doppler to identify avascular hematoma
• Uterine synechiae
o 2 to uterine scar
o May mimic amniotic bands
o No fetal entrapment or anomalies
0

Normal Measurements
• Placenta thickness t with gestation
o 10 mm at 10 wks
o 20 mm at 20 wks
o 30 mm at 30 wks
o > 40 mm considered abnormally thick
• Placental thickness measurement
o Subplacental venous complex to amniotic fluid
junction
• Myometrium not included
• Mature placenta at term
o 250-550 grams, 16-20 cm diameter

Amnion fuses with chorion at 14-16 wk

Clinical Importance

Of Doppler

• Abnormal uteroplacental Doppler
Suggestive of pia ental insufficiency
• Uterine artery Doppler
Should be low re istance by early second trimester
Abnormal uterine artery Doppler finding
• Delayed "normalization"
• Presence of post ystolic notch
o Associated with placental in ufficiency
• IUGR, preeclampsia, oligohydramnios
• Umbilical artery Doppler
ormally low re i tive flow
Absent or reversed diastolic flow abnormal
o Flow changes occur later than in uterine artery

o Chorionic plate (fetal surface)
o Basal plate (maternal surface)

I Embryology
Embryologic Events
• First trimester placentation
o Blastocyst implants by menstrual day 28
• Outer trophoblasts => placenta & membranes
• Chorionic sac diffusely covered by villi
o Villi adjacent to endometrium proliferate
• Form chorionic frondosum
o Villi adjacent to uterine cavity atrophy
• Establishment of uteroplacental circulation
o Trophoblasts invade uterine spiral arteries
• Partial plugs lead to "percolating blood"
• t Flow pressure into early placenta
• t Pressure would cause detachment
o Spiral artery remodeling
• Musculo-elastic layers disappear
• Low pressure intervillous flow established
• Spiral artery loses "arterial" qualities by 10 wks
o Myometrial colonization at 14-18 wks
• Myometrial spiral arteries invaded
• Uterine artery waveform changes to t resistive
flow
• Chorionic villi branch to 50-60 cotyledons
o 1 primary stem villus per cotyledon
o Supplied by 1 branches of umbilical vessels
• Trophotropism
o Dynamic process of placentation
o Parts of placenta atrophy as other parts grow
o Growth in areas with good uterine vascularity
• Membrane formation
o Chorion attached to outer trophoblasts
o Amnion originates from cytotrophoblasts
• Initially attached to embryonic disk
o Amnion and chorion fuse at 14-16 wks
0

Practical Implications
• Abnormal uteroplacental circulation
o Associated with fetal and maternal morbidity

PLACENTA & MEMBRANES

Cross pathology of a term placenta, fetal surface, shows
a normal placental cord insertion site (arrow). Many
branching vesselsarise from the cord. The amnion and
chorion cover this surface.

• Intrauterine growth restriction (IUGR)
• Pre-eclampsia
• Placental abruption and previa
• Abnormal membrane formation
o Amniotic membrane rupture
• Amniotic bands
o Delayed chorioamnionic
fusion
• Associated with aneuploidy

Clinical Implications
Clinical Importance
• Placenta previa
o Marginal placenta previa
• Edge of placenta within 2 cm of internal os
o Complete placenta previa
• Placenta covers internal os
o Maternal hemorrhage
o Cesarean section often necessary
• Placental abruption
o Early placental detachment
o Marginal abruption most common
• From edge of placenta
o Retroplacental abruption
• Mimics thick placenta
o Preplacental abruption most rare
• Hematoma at fetal surface
• May compress cord
• Placenta accreta spectrum
o Placental invasion beyond endometrium
o Accreta: Placenta adherent to myometrium
o lncreta: Placenta invades myometrium
o Percreta: Placenta invades beyond myometrium
o Higher risk if multiple cesarean sections
• Velamentous cord insertion
o Membranous placental cord insertion
o Submembranous fetal vessels are fragile
• Hemorrhage is fetal blood
o If placental cord insertion is low then vasa previa
may be present
• Vasa previa

Cross pathology of the maternal surface shows multiple
placental lobes, or cotyledons (arrows). The lobes
served as an intervillous space for maternal-fetal nutrient
and gas exchange.

o 2° to succenturiate lobe
• Fetal vessels traveling between placentae cross
internal os
o 2° to low-lying velamentous cord insertion
• Placental masses
o Gestational trophoblastic neoplasia
o Chorioangioma
• Delayed chorioamnionic
fusion
o Most fused by 14-16 wks
o Delayed fusion associated with aneuploidy
o Most worrisome for trisomy 21
• Amniotic bands
o Amnion rupture
o Entanglement of fetus with "slash" defects

Function- Dysfunction
• Abnormal uterine artery waveform
o Resistive indices> 0.66 after 16-18 wks
o Post-systolic notch
o May be earliest indicator of placental dysfunction
o Low dose aspirin treatment often successful if done
early
• Facilitate myometrial spiral artery conversion
• Abnormal umbilical artery waveform
o Absent or reversed diastolic flow
o Late manifestation of placental dysfunction
• Abnormally mature placenta
o Grade 3 placenta seen before term
• Associated with smoking, hypertension, diabetes

Related References
1.
2.
3.

Lobos H et al: The natural history of fetal growth
restriction in women with abnormal uterine artery
Doppler. Prenat Diagn. 25(4):331-2, 2005
Kurdi W et al: Delayed normalization of uterine artery
Doppler waveforms is not a benign phenomenon. Eur]
Obstet Gynecol Reprod BioI. 117(1):20-3, 2004
Carbillon Let al: Uteroplacental circulation development:
Doppler assessment and clinical importance. Placenta.
22(10):795-9,

4.

2001

Kennedy A et al: Obstetric ultrasonography: the placenta.
Abdom Imaging. 22(6):602-10,1997

PLACENTA & MEMBRANES
IMAGE GALLERY
(Left) Sagittal endovaginal
ultrasound shows the
amniotic membrane (arrows)
at 70 wks gestation. The
embryo is within the
amniotic.cavity and the
chorionic cavity (curved
arrow) lies between the
amnion and gestational sac.
(Right) Sagittal ultrasound
shows the amnion at near 74
wks gestation. The amniotic
membrane (arrows) lies very
close to the uterine wall (and
the chorion). The
membranes are normally
fully fused by 76 wks.

(Left) Sagittal ultrasound
shows a full bladder (arrow)
causing a false positive
placenta previa (curved
arrows). TVUS (lower
image), done after the
patient voided, shows a
normal cervix (open arrows)
and no previa. (Right) 3D
ultrasound with color
Doppler shows a normal
second trimester placenta.
Occasional sonolucencies
(arrow), subplacental veins
(open arrow) and a normal
placental cord insertion
(curved arrow) are routinely
seen.

(Left) Sagittal ultrasound
shows a grade 3 placenta in
a near term pregnancy.
Extensive basal calcifications
(arrows) and chorionic plate
indentation (curved arrows)
are seen. Fetal growth was
normal. (Right) Pulsed
Doppler ultrasound of a
normal (upper) and
abnormal (lower) uterine
artery Doppler waveform in
two different second
trimester fetuses. There is
high resistive flow (little
diastolic flow) and a post
systolic notch (arrows) in the
abnormal tracing.

12
5

PLACENTAL SONOLUCENCIES

Sagittal ultrasound shows a single large placental lake
(arrows) in a third trimester placenta. On the realtime
grayscale ultrasound exam, slow-flowing blood was
seen in the sonolucency

ITERMINOLOGY
Abbreviations
•
•
•
•
•

and Synonyms

Placental sonolucencies
Placental lakes (PL)
Placental caverns
Venous lakes
Intervillous thrombus (IVT)

Sagittal ultrasound shows multiple sonolucencies
(arrows). One of the lesions (curved arrow), did not
have visible flow and is consistent with an intervillous
thrombus. Pregnancy outcome was normal.

• Fetal surface of placenta
• Bulge into amniotic cavity
• Size
o Variable
• > 1 cm for diagnosis
• May be very large
o Often changes size during scan
• Morphology: Can mimic placental mass

Definitions

Ultrasonographic

• Discrete sonolucent or hypoechoic lesions in placenta
• Enlarged intervillous vascular spaces
o Initially with blood flow
• Placental lake
o With thrombus
• Intervillous thrombus
o Eventual fibrin deposition

• Homogeneous sonolucencies in placenta
o > 1 cm diameter
o Multiple lesions common
o Surrounded by otherwise normal placenta
o Most often considered a normal finding
• Swirling streams of blood in PL
o Seen best with real time grayscale imaging
• Color Doppler often negative
• Flow is extremely slow
o Blood is maternal
o Occasional fluid-fluid level seen
• RBC settle in serum
• PL shape and size may change during exam
o Change in maternal position
o 2° to uterine contraction
• Intervillous thrombus
o Thrombosis of PL
• IVT and PL often seen together in same placenta

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Single or multiple hypoechoic
lesions in placenta
• Location
o Within placenta parenchyma
• Surrounded by normal placenta
o Subchorionic

DDx: Placental Masses

..
. '.';

..~_

:;'.

.. ~
...

..

'~'\"

~;

'~':

Findings

t.

.. •.•..•••

"

.,

.

1/.

"'. '1:':;
t -'.
Complete Mole

Chorioangioma

Abruption

PLACENTAL SONOLUCENCIES
Key

Facts

Terminology

Pathology

• Placental lakes (PL)
• Intervillous thrombus

• ontain only maternal blood
• Fibrin deposition after thrombosi
• 2-18% of placentas have sonolucencies

(IVT)

Imaging Findings
•
•
•
•
•

Most often considered a normal finding
Swirling streams of blood in PL
PL shape and ize may change during exam
IVT and PL often seen together in same placenta
Early, numerous and large sonolucencies may be
ignificant
• "Swiss cheese" placenta variant

Top Differential

Diagnoses

• Gestational trophoblastic
• Chorioangioma
• Placental abruption

neoplasia (GT

• No flow
• Does not change size
o Hypoechoic more likely than sonolucent
o May lead to fibrin deposition
• Sonolucencies more often seen in thick placentas
o Placenta> 3 cm is 6x more likely to have
sonolucencies
o Both findings are usually incidental
• Early, numerous and large sonolucencies may be
significant
0< 20-25 wks
o > 3 lesions
o >2cm
• "Swiss cheese" placenta variant
o Patchy placenta from diffuse fibrin deposition
o Diffusely heterogeneous by ultrasound
• Innumerable sonolucencies
• Placentomegaly
o Mimics gestational trophoblastic neoplasia (GTN)
• Genetic testing necessary
o t Fetal morbidity and mortality

MR Findings
• TIWI
o MR can differentiate between PL and IVT
o Placental lake: + Intensity
• Turbulent flow
o IVT: t Intensity
• T2WI
o Placental lake: Isointense
• Turbulent flow
o IVT: Isointense

Imaging Recommendations
• Best imaging tool: Complete evaluation of placenta on
routine ultrasound exam
• Protocol advice
o Look carefully for swirling blood in sonolucencies
• Helps differentiate PL from other masses
o Most often a normal finding
• Third trimester placenta
• Occasional lesions
• Normal fetal growth

at 15-34 wks

Clinical Issues
• t Risk for placental

insufficiency

Diagnostic Checklist
• Follow-up ultrasound if extensive (> 3), large (> 2 cm)
or if present before 20-25 wks
• Look for signs of placental insufficiency
• Rule out more significant placental lesions
• Amniocentesis may be necessary to rule out GT
• Real time grayscale imaging is best way to diagno e
placental lakes
• Increase gain to ee swirling blood

• Normal amniotic fluid
• Follow-up not necessary
o Diffuse or early sonolucencies considered abnormal
• Consider amniocentesis to rule out GTN
• Rule out intrauterine growth restriction (IUGR)
o Umbilical artery Doppler if extensive number of
lesions
• High resistance umbilical artery flow, t placental
resistance

I DIFFERENTIAL DIAGNOSIS
Gestational trophoblastic

neoplasia (GTN)

• Complete mole
o Paternal chromosomes
o No fetus or embryo
o Diffusely cystic placenta
• Partial mole
o Triploid karyotype
o Abnormal fetus
• Severe IUGR +/- anomalies
o Variable placenta
• Often cystic
• Placenta may appear normal
• Coexistent mole
o Complete mole + normal twin
o Two placentas are present
• Normal placenta with normal fetus
• Cystic placenta without fetus

Chorioangioma
• Benign vascular tumor
o Flow easily seen with Doppler
• Unlike slow flow in PL
• Solitary circumscribed solid mass
o Hypoechoic or hyperechoic
• Often near umbilical cord origin

Placental abruption
• Preplacental abruption can mimic PL
o Bulges into amniotic cavity
o No blood flow

PLACENTAL SONOLUCENCIES
• Marginal and retroplacental abruption more common
o Marginal from edge of placenta
o Retroplacental behind placenta
• Old blood becomes hypoechoic/sonolucent
• Symptomatic patients
o Painful bleeding
o Preterm labor

I PATHOLOGY
General Features
• General path comments
o Placental lakes
• Islands of red blood cells in lake of serum
• Contain only maternal blood
o Intervillous thrombus
• Thrombosis of PL
o Fibrin deposition after thrombosis
• Subchorionic
• Along basal plate
• Genetics: Not associated with fetal aneuploidy
• Etiology
o Role of placental lakes in normal pregnancy
• PLs regulate placental pressure
• t Intervillous space helps equalize pressure
o Multiple or large lesions often abnormal
• t Adjacent villous infarction
• Epidemiology
o Variable incidence reported prenatally
• 2-18% of placentas have sonolucencies at 15-34
wks
o Postnatal placenta
• Intervillous thrombi in 40%
• Associated abnormalities
o More common if extensive involvement of placenta
• IUGR
• Oligohydramnios
• Antiphospholipid syndrome
• Preeclampsia
• Elevated maternal serum alpha-fetoprotein (AFP)
• Placental abruption

Gross Pathologic & Surgical Features
• Fibrin deposition with extensive thrombosis
o Subchorionic
o Basal
• May lead to maternal floor infarction

Microscopic

Features

• Intervillous thrombus
o Villus free focus of coagulated blood

I CLINICAL

• Other signs/symptoms
o Elevated maternal serum AFP
o IUGR

Natural History & Prognosis
• Most often a normal finding
o Occasional PL or IVT
o Third trimester placenta
o Excellent prognosis
• Extensive sonolucencies may be abnormal
o t Risk for placental insufficiency

Treatment
• If associated placental insufficiency then early delivery
may be necessary
• Treatment for anti phospholipid syndrome
o Heparin, aspirin
o Prednisone
o Immunoglobulin

I DIAGNOSTIC
Consider

• Follow-up ultrasound if extensive (> 3), large (> 2 cm)
or if present before 20-25 wks
o Look for signs of placental insufficiency
• IUGR
• Oligohydramnios
• Abnormal Doppler
• Rule out more significant placental lesions
o Abruption, GTN
• Amniocentesis may be necessary to rule out GTN

Image Interpretation

Pearls

• Real time grayscale imaging is best way to diagnose
placental lakes
o Increase gain to see swirling blood
• Change maternal position
o Size of PL may change
o May see fluid-fluid level shift

I SELECTED
1.

2.

3.

4.

ISSUES

Presentation
• Most common signs/symptoms
o Incidentally noted in normal pregnancy
o Preeclampsia
o Antiphospholipid
syndromes
• Autoimmune disorder
• Circulating anti phospholipid antibodies
• 2° placental thrombosis and infarction

CHECKLIST

5.
6.

REFERENCES

Morikawa M et al: Magnetic resonance image findings of
placental lake: report of two cases. Prenat Diagn.
25(3):250-2, 2005
Reis NS et al: Placental lakes on sonographic examination:
correlation with obstetric outcome and pathologic
findings. J Clin Ultrasound. 33(2):67-71, 2005
Van Horn JT et al: Histologic features of placentas and
abortion specimens from women with antiphospholipid
and antiphospholipid-like syndromes. Placenta.
25(7):642-8, 2004
Moldenhauer JS et al: The frequency and severity of
placental findings in women with preeclampsia are
gestational age dependent. Am J Obstet Gynecol.
189(4):1173-7,2003
Thompson MO et al: Are placental lakes of any clinical
significance? Placenta. 23(8-9):685-90, 2002
Harris RD et al: Sonography of the placenta with emphasis
on pathologic correlation. Semin Ultrasound CT MRI.
17:66-8, 1996

PLACENTAL SONOLUCENCIES
IIMAGE

GALLERY
(Left) Sagittal ultrasound
shows multiple subchorionic
placental lakes (arrows)
bulging into the amniotic
cavity. The placenta appears
thickened. Their
echogenicities vary from
sonolucent to almost
isoechoic to placenta.
(Right) Axial ultrasound
shows placental lakes
(arrows) without any
detectable flow on color
Doppler imaging. However,
with realtime grayscale
ultrasound, slow swirling
flow was easily seen.

(Left)

Axial ultrasound shows

a single, large subchorionic

placental lake (arrows).
(Right) Axial ultrasound Of
the same lake later in the
exam, and after maternal
position change, exemplifies
the dynamic nature of the
lesion. The lake is larger
(arrows) and contains a
fluid-fluid level (open
arrows). The appearance is
secondary to maternal red
blood cells settling within the
serum of the lake.

Variant
(Left) Ultrasound shows
innumerable sonolucencies
in a "swiss cheese"
appearing placenta.
Oligohydramnios and IUGR
were also present. While the
appearance is suspicious for
GTN, amniocentesis results
were normal. (Right) Gross
pathology of the basal
surface (left) and
cross-section (right) of a
placenta with extensive,
tannish fibrin deposition
(arrows) and diffuse
thrombosis. Several lakes
without thrombosis (curved
arrows) are also seen.

CHORIOAMNIOTIC

Graphic
shows
amniocentesis. The
is stripped off the
separation is usually

chorioamniotic
separation
from
amniotic membrane (open arrows)
chorion (arrow). This type of 0\
minimal and benign.

SEPARATION

Axial ultrasound
shows
complete
chorioamniotic
separation at 75 wks. The free floating thin amnion
(arrows) is seen adjacent to the uterine wall. Karyotype
results were normal in this case.

ITERMINOLOGY
Abbreviations

and Synonyms

• Chorioamniotic separation (CA separation)
• Delayed amniochorionic fusion
• Persistent coelom cavity

Definitions

•
•

• Persistent unfused amnion and chorion> 14-16 wks
• May be primary non-fusion or secondary to
amniocentesis

IIMAGING

•

FINDINGS

General Features

•

• Best diagnostic clue
o Free floating amniotic membrane in > 14-16 wk
gestation
• Amnion normally fuses with chorion at 12-14 wks
• Size
o Descriptions vary in literature
• > 1 mm separation along> 1/2 uterine cavity
• > 3 mm separation involving 3 sides of amnion
• 10 mm separation at any single point

Ultrasonographic

Findings

•

o Thin membrane best seen perpendicular to beam
o Incomplete fusion (most common)
o Complete nonfusion
• Attached only at placental cord insertion site
CA separation after 14 wks considered delayed
o Definitive diagnosis after 16 wks
Association with aneuploidy
o 12% in high-risk pregnancies with CA separation
• Advanced maternal age (AMA)
• Prior abnormal fetus
• CA separation + fetal anomaly
o Trisomy 21 most common
Associated with anomalies (normal karyotype)
o Genitourinary anomalies
o Oligohydramnios from any cause
Transient finding
o Fusion eventually occurs even if fetus is abnormal
CA separation secondary to amniocentesis is common
(up to 25% incidence)
o Often minimal and not seen unless sought
o Most often without sequelae

Imaging Recommendations
• Protocol advice
o Look carefully for markers of aneuploidy
o Follow-up to look for additional anomalies

• Amniotic membrane separate from uterine wall

DDx: Intrauterine

Amniotic Bands

Membranes

Uterine Synechia

CHORIOAMNIOTIC

SEPARATION

Key Facts
Terminology

Top Differential

• Per istent unfused amnion and chorion> 14-16 wks
• May be primary non-fusion or econdary to
amniocente i

• Amniotic bands
• Uterine synechia

Imaging Findings

• 120Al of high-risk pregnancies with CA separation
have aneuploidy
• 4% aneupl idy rate if isolated finding> 14 wks
• 25% of fetuses with aneuploidy have A separation

• Amniotic membrane separate from uterine wall
• Definitive diagno is after 16 wks
• A separation econdary to amniocentesis is
common (up to 25% incidence)

I DIFFERENTIAL

Diagnoses

Pathology

o Aneuploidy, premature rupture of membranes,
preterm delivery, growth restriction

DIAGNOSIS

Amniotic bands

Treatment

• Rupture of amniotic membrane
• Entanglement of fetal parts
o Amputations, body wall defects
• Not associated with aneuploidy

• Because membranes are not fused, chorionic villus
sampling rather than amniocentesis often needed for
karyotype

Uterine synechia
• Uterine scar from prior endometrial
• Bridging band in uterus
o From one wall to another
• Synechia is thicker than amnion
• No fetal entanglement

trauma

First trimester pregnancy
• Normal fusion at 12-14 wks
• Yolk sac in chorionic space
• Chorionic fluid more echogenic than amniotic fluid

I DIAGNOSTIC

Image Interpretation
• Look for CA separation
aneuploidy

I SELECTED
1.

2.

I PATHOLOGY

3.

General Features
• Etiology
o Iatrogenic
• Amniocentesis needle strips amnion from chorion
o Associated aneuploidy
• Trisomy 21 > 13 > 18
• Epidemiology
o 12% of high-risk pregnancies with CA separation
have aneuploidy
o 4% aneuploidy rate if isolated finding> 14 wks
o 46% aneuploidy rate if non isolated finding
o 25% of fetuses with aneuploidy have CA separation
o Mean fetal age at diagnosis: 15.8 wks

I CLINICAL

CHECKLIST

4.

Pearls
in patients at-risk for

REFERENCES

Abboud P et al: Chorioamniotic separation after 14 weeks'
gestation associated with trisomy 21. Ultrasound Obstet
Gynecol. 22(1):94-5, 2003
Bromley B et al: Amnion-chorion separation after 17 weeks'
gestation. Obstet Gynecol. 94(6):1024-6, 1999
Ulm Bet al: Unfused amnion and chorion after 14 weeks of
gestation: associated fetal structural and chromosomal
abnormalities. Ultrasound Obstet Gynecol. 13(6):392-5,
1999
Levine D et al: Chorioamniotic separation after
second-trimester genetic amniocentesis: importance and
frequency. Radiology. 209(1):175-81,1998

IIMAGE

GALLERY

ISSUES

Presentation
• Most common signs/symptoms
o Incidentally noted
• Usually when evaluating for amniocentesis
o Noted in association with other fetal anomalies

Natural History & Prognosis
• Majority resolve by 18 wks without sequelae
• Complete separation with worse prognosis

(Left) Sagittal ultrasound shows CA non-fusion (arrows) and nuchal
fold thickening (open arrow) in a fetus with trisomy 27. (Right)
Sagittal ultrasound shows CA separation (arrow), distended fetal
bladder (curved arrow), and skin edema (open arrow) in a fetus with
trisomy 78. The amniotic membrane is draped over the fetal face.

PLACENTA PREVIA

Sagittal ultrasound shows symmetric, complete placenta
previa. The placenta is implanted in the lower uterus,
directly over the cervix (calipers). This type of previa will
not resolve with advancing pregnancy.

Sagittal
complete
placenta
(calipers).

ITERMINOLOGY
Abbreviations

and Synonyms

• Placenta previa (PP)

Definitions

•

• Placenta implants in lower uterine segment (LUS)
• Placenta crosses or lies close to internal os (10) of
cervix

IIMAGING

FINDINGS
•

General Features
• Best diagnostic clue: Transvaginal ultrasound (TVUS)
shows placental edge near or covering 10
• Location
o Complete placenta previa
• Placenta completely covers 10
o Partial placenta previa
• Placenta partially covers 10
o Marginal placenta previa
• Placental edge within 2 cm of 10

Ultrasonographic

•

Findings

• Placenta previa diagnosis in 2nd trimester
o Routine sagittal LUS image
• TVUS may be necessary for adequate view

•

translabial ultrasound
shows
asymmetric
placenta previa. A small portion of the
(arrows) extends anterior to the cervix
Open arrows point to the vagina.

• Show fluid or fetus in direct contact with 10
o Low placenta on routine view
• Placental edge within 2 cm of 10
o Often asymptomatic
o Many marginal PP resolve
Placenta previa diagnosis in 3rd trimester
o More likely to present with vaginal bleeding
o Transabdominal view
• Increased soft tissue between cervix and fetus
• Nonengaged, "floating" presenting fetal part
o TVUS almost always necessary for diagnosis
• Perform careful TVUS to avoid 10 disruption
Complete placenta previa
o Placenta completely covers 10
o Symmetric complete placenta previa
• Placenta centrally implanted on cervix
• Will not resolve with advancing pregnancy
o Asymmetric complete placenta previa
• Small part of placenta crosses 10
• May resolve with advancing pregnancy
• If> 15 mm crosses 10 then less likely to resolve
Marginal placenta previa
o Inferior edge of placenta within 2 cm of 10
• Does not cover os
o Often resolves with advancing pregnancy
• Follow-up at 34 wks
Partial placenta previa
o Edge of placenta partially covers internal os

DDx: Low-Lying Placenta

Full Maternal Bladder

Full Maternal Bladder

Contraction

Abruption

PLACENTA PREVIA
Key Facts
Terminology
• I'lacenta implants in lower uterine segment (LUS)
• Placenta crosses or lies close to internal os (10) of
cervix

Imaging Findings
• Best diagnostic clue: Transvaginal ultrasound
shows placental edge near or covering 10
• Complete placenta previa
• Marginal placenta previa
• Partial placenta previa
• Marginal sinus placenta previa
• SOlo of placenta previa have associated
accreta/percreta

Top Differential

(TVUS)

Diagnoses

• Focal myometrial contraction
• Placental abruption

Pathology
• 5% between 15-16 wks
• 0.5% at term

Clinical Issues
• Painless bleeding
• Often presents in 3rd trimester
• Majority of partial and marginal placenta previa
resolve
• Placenta crossing> 15 mm over 10 less likely to
resolve
• Excellent prognosis with appropriate management
• Cesarean section delivery in vast majority

• Full maternal bladder

•

•

•

•

o Difficult to differentiate from marginal PP
o Same prognosis as marginal PP
Marginal sinus placenta previa
o Placental veins near or cross 10
• Maternal veins, not fetal
• Do not confuse with vasa previa
o Placental parenchyma may be> 2 cm from 10
o Same prognosis as marginal PP
Low-lying placenta
o Preferred term if < 20 wks and TVUS not done
o Asymptomatic
o Often resolve by 34 wks
Placenta previa associated with accreta/percreta
spectrum
o Abnormal placenta grows through endometrium
• Adheres to myometrium or beyond
o 5% of placenta previa have associated
accreta/percreta
• t Risk for accreta if prior cesarian section +
anterior PP
• t Risk with t number of prior cesarean sections
• 67% risk if previa and > 4 cesarean sections
o Look for intact subplacental myometrial zone
• Hypoechoic line between bladder and placenta
• Should be contiguous
o Color Doppler and MR helpful
Placenta previa and vasa previa
o Velamentous cord insertion
• Low-lying placenta + abnormal placental cord
insertion
• Fetal vessels cross 10
o Succenturiate lobe
• Low-lying accessory placenta
• Fetal vessels travel between placentas
• Fetal vessels cross 10
o Use Doppler TVUS
• Color Doppler shows crossing vessels
• Pulsed Doppler to diagnose fetal vessels
• Must differentiate from maternal vessels

Imaging Recommendations
• Best imaging tool: Transvaginal
inferior placental edge

ultrasound

to identify

• Protocol advice
o Obtain routine lower uterine segment (LUS) image
• Sagittal plane of LUS and cervix
• Show internal cervical os free of placental tissue
o TVUS often necessary
• Scan while carefully inserting probe
• Find midline sagittal plane
• Identify inferior edge of placenta
• Measure distance between placenta and 10
• Measure cervical length
o Transperineal/translabial
technique
• Use only if TVUS not possible
• Elevate maternal hips to minimize bowel artifact
• Place probe on perineum (labia minora)
• Collapsed vagina is acoustic window to cervix
• Measure distance between placental edge and 10

I DIFFERENTIAL DIAGNOSIS
Full maternal bladder
• Approximates anterior and posterior uterine wall
o Normally implanted placenta appears low
• Falsely elongates cervix
• Have patient void and repeat exam

Focal myometrial

contraction

• Contraction can cause approximation of uterine walls
o Similar to maternal full bladder
• May mimic placenta
o Can appear mass-like and echogenic
• Resolves with time
• TVUS can often differentiate cervix from contraction
o Slip of fluid seen at 10

Placental abruption
• Premature placental detachment
o Often with accompanying clot
• Acute clot often isoechoic to placenta
o Mimics PP if clot located near 10
• Power Doppler helpful
o Shows no flow in clot

PLACENTA PREVIA
I PATHOLOGY
General Features

o Maternal transfusion if necessary
o Cesarean section delivery in vast majority
• Asymptomatic placenta previa ~ 34 wks
o Cervical rest
o Cesarean section delivery in vast majority
• Minority of marginal PP may be delivered vaginally
o Fetal head compresses placenta during delivery
o "Double set-up" vaginal delivery
• Room set up for emergency cesarean section

• Etiology
o Endometrial damage
• Blastocyst implants low
o Low placenta may resolve 2° to trophotropism
• Atrophy in areas of poor blood supply (Le., LUS)
• Growth in areas of better blood supply
o Low placenta may resolve as LUS grows
• LUS "stretches" later in pregnancy
o Placental "migration" rate
• Approximately 5 mm/wk
• Epidemiology
o ~ Incidence as pregnancy advances
• 5% between 15-16 wks
• 0.5% at term
o t Incidence with t parity
o 1:1,500 in nulliparous patients
o High-risk patients
• Prior placenta previa
• Prior cesarean section
• Prior suction curettage
• Multiparity
• Smoking
• Cocaine use
• Associated abnormalities: 5% with associated accreta

I SELECTED REFERENCES

Staging, Grading or Classification Criteria

1.

• Complete placenta previa
o Symmetric
o Asymmetric
• Partial placenta previa
• Marginal placenta previa
• Marginal sinus previa

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Painless bleeding
• Often presents in 3rd trimester
o Incidental finding on routine ultrasound
• Often resolves

Demographics
• Age
o t Risk with advanced maternal age (AMA)
• ~ 35 yo at time of delivery

Natural History & Prognosis
• Majority of partial and marginal placenta previa
resolve
o PP after 34 weeks not likely to resolve
• Some complete PP will resolve
o Placenta crossing> 15 mm over 10 less likely to
resolve
• Excellent prognosis with appropriate management
o Maternal mortality < 1%

Treatment
• Bleeding placenta previa
o Bed rest +/- hospitalization

I DIAGNOSTIC

CHECKLIST

Consider
• TVUS to rule out PP in all patients with bleeding in
2nd/3rd trimester
• Posterior PP if posterior myometrium appears thick
o May be from unsuspected succenturiate lobe

Image Interpretation

Pearls

• Beware false positive PP from full maternal bladder
oRe-image after patient voids
• Use TVUS color Doppler when placenta is low
o Rule out marginal sinus previa
o Rule out vasa previa

Shukunami K et al: A small-angled thin edge of the
placenta predicts abnormal placentation at delivery. J
Ultrasound Med. 24(3):331-5, 2005
2. Bhide A et al: Recent advances in the management of
placenta previa. Curr Opin Obstet Gynecol. 16(6):447-51,
2004
3. Chama CM et al: From low-lying implantation to placenta
praevia: a longitudinal ultrasonic assessment. J Obstet
Gynaecol. 24(5):516-8, 2004
4. Moodley J et al: Imaging techniques to identify morbidly
adherent placenta praevia: a prospective study. J Obstet
Gynaecol. 24(7):742-4, 2004
5. Weerasekera DS: Placenta praevia and scarred uterus - an
obstetrician's dilemma. J Obstet Gynaecol. 20(5):484-5,
2000
6. Sunna E: Transvaginal and transabdominal ultrasound for
the diagnosis of placenta praevia. J Obstet Gynaecol.
19(2):152-4, 1999
7. Ziadeh A T Abu-Heija M F EI-Jallad M: Placental praevia
and accreta: an analysis of two-years' experience. J Obstet
Gynaecol. 19(6):584-6, 1999
8. Smith RSet al: Transvaginal ultrasonography for all
placentas that appear to be low-lying or over the internal
cervical os. Ultrasound Obstet Gynecol. 9:22-4, 1997
9. Laurie MR et al: The use of second-trimester transvaginal
sonography to predict placenta previa. Ultrasound Obstet
Gynecol. 8:337-40, 1996
10. Wing DA et al: Management of symptomatic placenta
previa; a randomized, controlled trial of inpatient versus
outpatient expectant management. Am J Obstet Gynecol.
175:806-11, 1996

PLACENTA PREVIA
I IMAGE GAllERY
(Left) Sagittal endovaginal
ultrasound shows partial
placenta previa. The edge of
the posterior placenta
(arrows) is located at the 10
(curved arrow). Color
Doppler clearly
demonstrates the
subplacental vessels. (Right)
Sagittal ultrasound
performed later in the same
pregnancy shows that the
partial previa has resolved.
The edge of the placenta
(arrow) is now at a
significant distance from the
10 (curved arrow). This
patient never had bleeding.

Typical
(Left) Sagittal ultrasound
shows marginal sinus previa.
While the placenta
parenchyma (arrows) is at
some distance from the
cervix (calipers), prominent
placental vessels (open
arrows) are located near the
10. (Right) Sagittal
endovaginal ultrasound in
another patient with
bleeding shows a placental
vessel (arrow) located
directly over the 10. Pulsed
Doppler demonstrates
maternal venous flow.

Variant
(Left) Sagittal ultrasound
shows a low-lying
succenturiate lobe (arrows,
lower image) detected
during routine second
trimester ultrasound. The
majority of the placenta is
located anteriorly (open
arrows, upper image).
(Right) Sagittal endovaginal
ultrasound performed in the
3rd trimester confirms a
marginal placenta previa of
the succenturiate lobe. The
inferior edge of the placenta
(arrow) is within 2 em of the
10 (curved arrow).

VELAMENTOUS CORD

Ultrasound shows a velamentous cord insertion in a 3rd
trimester pregnancy. The umbilical vessels (arrows) are
splayed and insert upon the membranes at the placental
edge.

• Some or all vessels on membranes
o Color Doppler best for diagnosis
• Nearly 100% sensitive for finding CI site
• Vasa previa from velamentous CI
o Placenta previa + velamentous CI
o Fetal vessels within 2 cm of cervical os
• Complications of velamentous CI
o Intrauterine growth restriction
o Cord thrombosis and rupture
o Twin-twin transfusion syndrome (TTTS)

ITERMINOlOGY
Abbreviations

and Synonyms

• Submembranous cord insertion (CI)

Definitions
• Umbilical vessels insert on membranes

IIMAGING

Clinical photograph
in the same case confirms a
velamentous cord insertion. An umbilical artery (arrow)
is seen traversing the membranes
(curved arrows)
before inserting upon the placenta (open arrow).

FINDINGS

General Features

Imaging Recommendations

• Best diagnostic clue: Color Doppler shows
velamentous CI adjacent to placenta
• Location: Fixed submembranous vessels

• Best imaging tool: Color Doppler evaluation of cord
insertion site
• Protocol advice
o Identify cord insertion in all high-risk patients
• Placenta previa
• Monochorionic twins
o When placenta is posterior
• Gently move fetus
• Place patient in lateral position
o Rule out vasa previa in high-risk patients
• Doppler transvaginal ultrasound

Ultrasonographic

Findings

• Normal placental CI
o Cion placental mass
• Found easily with grayscale ultrasound
o All branching vessels located on placenta
• Seen best with color/power Doppler
• Velamentous CI
o Umbilical cord inserts on membranes
• Often adjacent to placenta
o Cord vessels are dilated
• Lack placental support
o Vessels sepflrated at CI site

I DIFFERENTIAL

DIAGNOSIS

Battledore placenta
• Eccentric cord insertion

DDx: Abnormal

Battledore Placenta

Placental/Cord

Vascularity

Battledore Placenta

Marginal Sinus Previa

Marginal Sinus Previa

VELAMENTOUS CORD
Key Facts
Top Differential

Terminology
•

ubmembranou

Diagnoses

• Battledore placenta
• Marginal inu previa

cord in ertion ( I)

Imaging Findings

Pathology

• Best diagnostic clue: olor Doppler hows
velamentou
I adjacent to placenta
• Ve els separated at I site
• orne or all ve el on membranes
• Identify cord insertion in all high-ri k patients

•
•
•
•
•

Trophotropism re ult in shifting placenta
Epidemiology: ] <}bof deliveri s
64% of twins with TITS have a velamentou
Subm mbranou ve sels are extremely fragile
Type 1 va a pr via is secondary to velamentous

I DIAGNOSTIC

• Cord inserts at margin of placenta
o Within 10 mm of edge
o Branching vessels all on placenta
• More common than velamentous cord
o 2-10% incidence
• Usually without morbidity

CHECKLIST

Image Interpretation

Pearls

• Use color Doppler to identify cord insertion
o Differentiate from eccentric cord insertion
• Branching vessels within placental mass
• Find both CI sites in monochorionic
twins
• Rule out vasa previa when placenta is low-lying
o Document CI

Marginal sinus previa
• Marginal placenta previa
o Maternal vessels overly cervical os
• Normal placental cord insertion
o Use color Doppler
• Outcome same as for marginal previa

I SELECTED
1.

I PATHOLOGY

2.

General Features
• Etiology
o Trophotropism results in shifting placenta
• CI originally normal
• Parts of placenta grow while parts atrophy
• CI becomes membranous
• Epidemiology: 1% of deliveries
• Associated abnormalities
o Monochorionic twins
• 10% incidence of velamentous CI
• 13x t risk for TITS
• 64% of twins with TITS have a velamentous
o Maternal uterine anomalies
• t Incidence of abnormal placentation

3.

4.

REFERENCES

Stafford IP et al: Abnormal placental structure and vasa
previa: confirmation of the relationship. J Ultrasound Med.
23(11):1521-2,2004
Sepulveda W et al: Prenatal detection of velamentous
insertion of the umbilical cord: a prospective color Doppler
ultrasound study. Ultrasound Obstet Gynecol. 21(6):564-9,
2003
Hanley ML et al: Placental cord insertion and birth weight
discordancy in twin gestations. Obstet Gynecol.
99(3):477-82, 2002
Fries MH et al: The role of velamentous cord insertion in
the etiology of twin-twin transfusion syndrome. Obstet
Gynecol. 81(4):569-74, 1993

IIMAGE GALLERY
CI

Gross Pathologic & Surgical Features
• Submembranous vessels are extremely fragile
o No placental tissue or cord membrane support

Staging, Grading or Classification Criteria
• Type 1 vasa previa is secondary to velamentous

I CLINICAL

CI

ISSUES

Natural History & Prognosis
• Cord rupture during placental extraction
• Vasa previa from velamentous CI
o 60-80% fetal mortality if diagnosis missed
o Minimal blood loss results in fetal death

Treatment
• Careful placental extraction
• Cesarean section for vasa previa

(Left) Axial color Doppler ultrasound in monochorionic twins, shows
a velamentous CI for twin B. The CI (arrows) is seen arising from the
membranes adjacent to the placenta (open arrows). (Right) Pulsed
Doppler ultrasound of the umbilical artery shows absent diastolic
flow (arrows). Twin B, with the velamentous CI, was the smaller twin
in this pregnancy complicated by twin-twin transfusion. syndrome.

PLACENTAL ABRUPTION

Graphic shows placental abruption sites. Marginal
abruption (arrows) occurs at the placental edge.
Retroplacental (curved arrow) and preplacental
hemorrhage (open arrow) are less common.

Sagittal ultrasound shows a second trimester marginal
abruption (arrows). The edge of the placenta (curved
arrow) is lifted off the uterus. Also, the placenta is
implanted upon a leiomyoma (open arrow).

ITERMINOlOGY
Abbreviations

and Synonyms

• Abruptio placenta
• Subchorionic hemorrhage

•

Definitions
• Premature separation of placenta from uterus
•

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Hypoechoic blood clot near or
behind placenta
• Location: Abruptions may be marginal (most
common), retroplacental or preplacental
• Size: Extremely variable
• Morphology: Often crescentic

Ultrasonographic

•

Findings

• Ultrasound (US) appearance varies with age and size of
hematoma
o Small abruptions often not detectable by US
• Acute hematoma
o Echogenic blood
• Isoechoic to placenta
o May appear as a thick placenta

•

• Mimics placentomegaly
o Power Doppler helpful in diagnosis
• Differentiate clot from placenta/uterus
• No flow in hematoma
Subacute hematoma
o More heterogeneous than acute
• May contain fluid-fluid level
• Septations common
o Easier to resolve clot vs. placenta
Resolving hematoma
o Liquefying blood
• Eventually sonolucent
o May mimic amniotic fluid
Intraamniotic blood common
o Echogenic debris in fluid
o Acute
• Large hemorrhage traverses amnion
o Resolving hemorrhage
• Clot proteins diffuse into fluid
o Associated with fetal echogenic bowel
• From ingestion of debris
Marginal abruption
o Most common type of abruption
• 91% < 20 weeks are marginal
• 67% > 20 weeks are marginal
o Hemorrhage from edge of placenta
• Can see raised edge in 50%
o Adjacent hematoma

DDx: Placental Mass-Like Lesions
.,.

•
J~

4..

-"""

.

'

"c.~

.

__

~"

.:P

~;.
~..... ~

~~.~
__

Leiomyoma

-

1li.

Leiomyoma

•••

Contraction

Chorioangioma

PLACENTAL ABRUPTION
Key Facts
Terminology
• Premature

eparation

of placenta from uterus

• Placenta previa
• Chorioangioma

Imaging Findings

Pathology

• Best diagno tic clue: Hypoechoic blood clot near or
behind placenta
• Location:
bruptions may be marginal (most
common), retroplacental or preplacental
• May appear as a thick placenta
• Estimate amount of placenta detached
• 50% of abruptions have no US finding
• Look for abruption in all cases with 2nd/3rd trimester
vaginal bleeding
• Evaluate fetal heart rate

• 1% of all pregnancies
• 17x t ri k if prior abruption

Top Differential

Diagnoses

Clinical Issues
•
•
•
•
•

80% pre ent with vaginal bleeding
20% with pain and no bleeding
7x t risk if motor vehicle accident
Excellent prognosis if small
> 50% placental detachment ha > 50% fetal death
rate
• Retroplacental abruption most worrisome
• Poor outcome when fetal bradycardia present

• Leiomyoma

•

•

•

•

• Curvilinear clot near placenta
o Remote hematoma
• Hemorrhage dissects under chorionic membrane
• Clot at a distance from placenta
• Look in front of cervical os
o Estimate amount of placenta detached
o Look for accompanying cervical change
• Cervical effacement/funneling
• Transvaginal US required
Retroplacental abruption
o Second most common
o Central hematoma between placenta and uterus
o Large detachment more likely than with marginal
abruption
• t Risk of fetal morbidity
o Appears acutely as "placentomegaly"
• Isoechoic blood behind placenta
• Direct hemorrhage into placenta
o Power Doppler helpful
• Delineates clot from placenta
Preplacental abruption
o Rare
o Hematoma on fetal surface of placenta
• Subchorionic or subamniotic space
o Clot may compress cord
• Find placental cord insertion
• Use Doppler to evaluate flow
o May mimic placental mass
• Chorioangioma
• Large venous lake
Twins and abruption
o Rare hematoma between membranes
• Bizarre intra-amniotic mass without flow
Abruption and negative US
o 50% of abruptions have no US findings
• More likely marginal and small
• Hematoma has passed before US is performed
o Better prognosis if negative US

Imaging Recommendations
• Best imaging tool
o Grayscale US to detect clot
o Power Doppler in acute setting

• Protocol advice
o Look for abruption in all cases with 2nd/3rd
trimester vaginal bleeding
o Use power Doppler when apparent "placentomegaly"
seen
o Quantify amount of placental detachment
o Evaluate fetal heart rate
o Follow-up US in all cases
• Fetal growth (intrauterine growth restriction
potential complication)
• Recurrent abruption

I DIFFERENTIAL

DIAGNOSIS

leiomyoma
• Hypoechoic uterine wall mass
• Placenta may implant upon myoma
o Mimic retroplacental abruption
o Increased risk for abruption
• Leiomyoma has blood flow

Placenta previa
• Complete placenta previa
o Placenta covers internal cervical os
• Marginal placenta previa
o Edge within 2 cm of internal os
• Often present with painless bleeding
• Previa + abruption common
o Abnormal placentation in low uterus

Focal myometrial

contraction

• Transient myometrial thickening
o Normal phenomenon
• Appears mass-like
• Inner myometrium affected more than outer
• Will resolve with time

Chorioangioma
• Vascular placental mass
o Doppler essential for diagnosis
• Can mimic preplacental abruption
surface of placenta

if located on fetal

PLACENTAL ABRUPTION

I PATHOLOGY
General Features
• Etiology
o Initial spiral artery bleed
• Arteries without trophoblast invasion
• More prone to hemorrhage
o Hemorrhage into decidua basalis layer
• Hematoma splits decidua
o Placenta detaches as bleed grows
• Epidemiology
o 1% of all pregnancies
o 17x t risk if prior abruption
• Associated abnormalities
o Placenta previa
o Leiomyoma

Gross Pathologic & Surgical Features

• Poor outcome when fetal bradycardia present
o Emergency cesarean section if viable fetus
• Abruption and placental insufficiency
o Large and recurrent abruptions
o Serial US necessary
• Look for intrauterine growth restriction
• Oligohydramnios
o Cord Doppler
• Look for t systolic/diastolic ratio

Treatment
• Expectant management
o Usually self limited process
• Vaginal delivery in stable patients
• Cesarean section in acute distress
• Early delivery if placental insufficiency

• Clot in subchorionic space

I DIAGNOSTIC

Staging, Grading or Classification Criteria

Consider

• us classification

in all gestations> 20 wks and vaginal
bleeding
• Retroplacental abruption if acutely tender uterus with
or without vaginal bleeding

based on location

o Marginal
o Retroplacental
o Preplacental

CHECKLIST

• us for abruption

Image Interpretation

IClINICALISSUES
Presentation
• Most common signs/symptoms
o Abruption is a clinical diagnosis
• Most common in 3rd trimester
o 80% present with vaginal bleeding
• +/- Pain
• Blood is maternal
o 20% with pain and no bleeding
• Often from retroplacental abruption
• Preterm labor
• Blood is irritating to uterus
o High-risk patients
• Prior history of abruption (17x t risk)
• Thrombophilia
• Maternal hypertension
• Cocaine use (related to hypertension)
• Smoking
• Increased parity
• Advanced maternal age
• Leiomyoma (2.6x t risk)
o Abruption and trauma
• 7x t risk if motor vehicle accident
• Regardless of other maternal injury

Natural History & Prognosis
• Excellent prognosis if small
o < 30% placenta detached
• Poor prognosis if large
o > 50% placental detachment has> 50% fetal death
rate
• Retroplacental abruption most worrisome
o Increased risk of fetal morbidity
o Often delayed diagnosis
• No vaginal bleeding
• Blood isoechoic to placenta

• Use power Doppler
• Evaluate fetal heart
• Rule out abruption
vehicle accident
o Perform US even

I SELECTED
1.

Pearls

in cases of placental thickening
rate when abruption seen
in all women involved in motor
if no maternal injuries

REFERENCES

Ananth CV et al: Placental abruption in the United States,
1979 through 2001: temporal trends and potential
determinants. Am J Obstet Gyneco!. 192(1):191-8,2005
2. Hoffman R et al: Thrombophilia related issues in women
and children. Semin Thromb Hemost. 31(1):97-103, 2005
3. Schiff MA et al: Pregnancy outcomes following
hospitalization for motor vehicle crashes in Washington
State from 1989 to 2001. Am J Epidemio!. 161(6):503-10,
2005
4.
Broers T et al: The occurrence of abruptio placentae in
Canada: 1990 to 1997. Chronic Dis Can. 25(2):16-20, 2004
5.
Toivonen S et al: Obstetric prognosis after placental
abruption. Fetal Diagn Ther. 19(4):336-41,2004
6. Kayani SI et al: Pregnancy outcome in severe placental
abruption. BJOG. 110(7):679-83, 2003
7.
Glantz C et al: Clinical utility of sonography in the
diagnosis and treatment of placental abruption. J
Ultrasound Med. 21(8):837-40, 2002
8. Sheiner E et al: Incidence, obstetric risk factors and
pregnancy outcome of preterm placental abruption: a
retrospective analysis. J Matern Fetal Neonatal Med.
11(1):34-9, 2002
9. Kramer MS et al: Etiologic determinants of abruptio
placentae. Obstet Gyneco!. 89:221-9, 1997
10. Nyberg DA et al: Sonographic spectrum of placental
abruption. AJR. 148:161-4, 1987

PLACENTAL ABRUPTION
IIMAGE GALLERY
Typical
(Left) Axial ultrasound shows
an acute retroplacental
abruption. The placenta
appears heterogeneous and
thickened (arrows). A
discrete blood c/ot is difficult
to discern. Color Doppler
imaging should always be
performed in this situation.
(Right) Axial ultrasound in
the same case, performed 3
weeks later, now shows a
hypoechoic blood c/ot
(arrows) beneath the
placenta (open arrows).
With time, blood becomes
more hypoechoic and finally
anechoic.

(Left) Sagittal color Doppler
ultrasound shows
preplacental hemorrhage. A
complex fluid collection
(arrows) is seen along the
fetal surface of the placenta.
The hematoma is adjacent
to, but does not compress,
the cord insertion site (open
arrow). (Right) Clinical
photograph shows a large
preplacental hemorrhage
(arrows) located near the
cord insertion.

Typical
(Left) Sagittal ultrasound
shows an isoechoic, acute
hematoma (arrows) adjacent
to an otherwise well
attached placenta (curved
arrow). Sometimes, the
hematoma is located at a
distance from the placenta.
(Right) Sagittal ultrasound
performed 7 week later,
shows the hematoma
(arrows) has traveled
inferiorly and now overlies
the internal cervical os
(curved arrow). Also, the
blood is now almost
sonolucent.

SUCCENTURIATE LOBE

Axial ultrasound shows a posterior succenturiate lobe
(arrows). The main placental mass is anterior (curved
arrow) and contains the cord insertion. The presence of
2 placentas, one large and one small, is typical.

o Placenta cord insertion (Cl) usually on main
placenta
• May be marginal or velamentous
o Bilobate placenta
• Variant of SL
• 2 equal placental masses with central thinning
• Placental cord insertion (PCI) is on thinned area
• Color Doppler
o Helps to identify communicating
vessels
• Submembranous fetal vessels
• Communicating
vessels more prone to injury
o Vasa previa type 2
• Communicating
vessels cross internal cervical os
• SL is most common cause of vasa previa
• Bleeding from vasa previa is fetal blood

!TERMINOlOGY
Abbreviations

and Synonyms

• Succenturiate lobe (SL)
• Accessory placenta

Definitions
• 1 or more accessory placental lobes
o Separate from main placenta
o Connected by placental vessels

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Two separate placentas seen on
routine ultrasound
• Location: Anywhere in uterus, including previa
• Size: SL is smaller than primary lobe

Ultrasonographic

Findings

• Grayscale Ultrasound
o Two separate placental masses
• SL has same echogenicity as main placenta
o SL diagnosis often missed
• Uterus not completely scanned
o SL may be low-lying or cross internal os
• Transvaginal ultrasound (TVUS) necessary

DDx: Extraplacental

Acute Abruption

Cross pathology of a placenta with a succenturiate lobe.
Large communicating
vessels (open arrows) are seen
traveling between the main placenta (curved arrow)
and the succenturiate lobe (arrows).

Imaging Recommendations
• Best imaging tool
o Gray scale ultrasound to identify accessory placenta
o Color Doppler to identify communicating vessels
o TVUS
• Rule out SL previa
• With Doppler to rule out vasa previa
• Protocol advice
o View entire uterus before assigning placental
location
o TVUS and color Doppler US for all SL cases
• Rule out vasa previa and velamentous CI

Uterine Echogenicity

Acute Abruption

SUCCENTURIATE LOBE
Key Facts
Terminology

Top Differential

• 1 or more accessory placental lobes
• onnected by placental vessel

• Acute placental abruplion
• Focal myometrial contraction

Imaging Findings

Clinical Issues

• ize: SL is smaller than primary lobe
• SL may be low-lying or cross internal 0
• L is most common cau e of vasa previa
• View entire uterus before as igning placental location
• Rule out va a previa and velamentou
I

• Increased risk for retained placenta

o TVUS for all patients with unexplained
bleeding to rule out unsuspected SL

I DIFFERENTIAL

vaginal

DIAGNOSIS

Acute placental abruption
• Acute blood isoechoic to placenta
• Color Doppler shows no flow in hematoma

Focal myometrial

contraction

Diagnoses

Diagnostic Checklist
• Use color Doppl r to rule out complication

• SL + velamentous cord insertion
o t Risk for cord rupture during labor
o t Risk for intrauterine growth restriction

I DIAGNOSTIC

CHECKLIST

Consider
• Posterior SL previa in cases of unexplained
bleeding

Image Interpretation

• Use color Doppler to rule out complications
o Vasa previa
o Velamentous CI

I PATHOLOGY

I SELECTED REFERENCES

• Etiology
o Trophotropism
• Placenta grows in areas with good decidua
• Atrophy occurs in areas of poor vascularity
o Fetal vessels connect main placenta and SL
• More susceptible to injury
o Placental CI may end up velamentous or marginal
• CI marks original implantation site
• Epidemiology: SOlo of pregnancies
• Associated abnormalities
o Velamentous cord
o Vasa previa

1.

2.

3.

4.

vaginal

Pearls

• Distorts inner myometrium more than outer
o Can mimic succenturiate lobe
• Often more hypoechoic than placenta
• Resolves with time

General Features

of SL

of SL

Stafford IP et al: Abnormal placental structure and vasa
previa: confirmation of the relationship. J Ultrasound Med.
23(11):1521-2,2004
Shukunami K et al: Placenta previa of a succenturiate lobe:
a report of two cases. Eur J Obstet Gynecol Reprod BioI.
99(2):276-7, 2001
Chihara H et al: Prenatal diagnosis of succenturiate lobe by
ultrasonography and color Doppler imaging. Arch Gynecol
Obstet. 263(3):137-8, 2000
Hata K et al: Succenturiate placenta diagnosed by
ultrasound. Gynecol Obstet Invest. 25(4):273-6, 1988

I IMAGE

GALLERY

IClINICALISSUES
Presentation
• Most common signs/symptoms: Usually an incidental
finding on routine ultrasound
• Other signs/symptoms
o Second or third trimester vaginal bleeding
• SL previa
• Vasa previa

Natural History & Prognosis
• Increased risk for retained placenta
o Post partum hemorrhage
o Post partum infection
• SL + vasa previa
o 60-80% fetal mortality if not diagnosed prenatally

(Left) Sagittal ultrasound shows an anterior succenturiate lobe
(arrows). In addition, the larger posterior plaCenta (curved arrows) is
low-lying (calipers measure the distance to the internal cervical as).
(Right) Sagittal endovaginal ultrasound with Doppler, performed later
in the pregnancy, shows vasa previa. Fetal arterial blood flow is
documented within the vessels that communicate between the two
placental lobes.

CIRCUMVALLATE PLACENTA

Cross pathology shows a circumvallate placenta. The
placental membranes are attached superficially to the
fetal surface of the placenta (arrows) rather than at the
placental margin.

Axial ultrasound shows the placental edge (curved
arrows) raised off the uterine wall (arrow). The lack of
marginal villous attachment results in this ultrasound
appearance of circumvallate placenta.

• Placenta membranes attach to fetal surface of placenta
o Membranes normally attach to villous margin
• Circumvallate placenta
o Placenta margin elevated along with membranes
• Circummarginate placenta
o Placenta margin not deformed
• Only membranes involved
• Usually not an ultrasound diagnosis

o Margin becomes fibrosed with time
• Peripheral echogenic rim
• May be only finding in 3rd trimester
• Placental "marginal shelf"
o Short bands of tissue
• 2-3 mm thick
o Shelf attaches on placenta
• Within 3 cm of margin
• Does not attach to uterine wall
o Shelf extends around placenta
• 100% involvement rare
• > 2/3 margin involvement more likely symptomatic
o Placental abruption
o Premature rupture of membranes (PROM)
o Intrauterine growth restriction (JUGR)
o Pre term labor

IIMAGING

• Protocol advice: Carefully scan placental margin

ITERMINOlOGY
Abbreviations

and Synonyms

• Circumvallate placenta
• Circummarginate placenta
• Extrachorial placenta

Definitions

Imaging Recommendations

FINDINGS

General Features
• Best diagnostic clue: Margin of placenta is elevated off
uterine wall
• Location: Complete or partial margin elevation

Ultrasonographic

Findings

• Elevated placental margin
o Infolding margin is towards cord insertion site

I DIFFERENTIAL DIAGNOSIS
Synechia (amniotic sheets)
• Caused by uterine scar
• 2-3 mm bands or sheets
o Often see triangular attachment point
• Attach to uterine wall, not placenta
o Placenta may abut or adhere to synechia

DDx: Uterine Bands/Membranes

Synechia

Synechia

Uterine Septum

CIRCUMVALLATE PLACENTA
Key Facts
Imaging Findings

Pathology

•
•
•
•
•

•
•
•
•

Elevated placental margin
Peripheral echogenic rim
Short band of tissue
Shelf attache on placenta
> 2/3 margin involvement

Top Differential

more likely symptomatic

Diagnoses

• Synechia (amniotic sheets)
• Amniotic band

Oi crepant size between chorion and basal plates
If placental tissue involved then circumvallate
If only membranous then circummarginate
Circumvallate: 1-2% pregnancies

Diagnostic Checklist
• When intrauterine membrane
attachment points

Amniotic bands

I DIAGNOSTIC

• 2° to amniotic membrane rupture
• Amnion entraps fetus
• Fetal malformations
o Amputation, body wall defects

Consider

Septate uterus
• Uterine duplication anomaly
• Septum in fundus
• Placenta may implant on septum

I PATHOLOGY
General Features
• Etiology
o Discrepant size between chorion and basal plates
• Results in raised membranes (chorion and
amnion)
• If placental tissue involved then circumvallate
• If only membranous then circummarginate
• Epidemiology
o Circumvallate: 1-2% pregnancies
o Circummarginate: 20% pregnancies
• Associated abnormalities: Placental hemorrhage

Gross Pathologic & Surgical Features
• Pale yellow to white peripheral ring
o Complete ring vs. partial ring
• Fibrinoid degeneration of villi between membranes
o Occurs later in pregnancy

I CLINICAL

een, look carefully at

CHECKLIST

• Follow-up ultrasound
margin involved

for fetal growth when>

Image Interpretation

2/3 of

Pearls

• When intrauterine membrane seen, look carefully at
attachment points
o Circumvallate placenta if membranes attach only on
placenta ("marginal shelf")
o Synechia if membranes attach to uterine wall
o Amniotic bands if membranes attach to fetus

I SELECTED REFERENCES
1.

2.
3.

4.

Harris RD et al: Accuracy of prenatal sonography for
detecting circumvallate placenta. AJRAm J Roentgenol.
168(6):1603-8, 1997
McCarthy Jet al: Circumvallate placenta: sonographic
diagnosis. J Ultrasound Med. 14(1):21-6, 1995
Sistrom CL et al: Abnormal membranes in obstetrical
ultrasound: incidence and significance of amniotic sheets
and circumvallate placenta. Ultrasound Obstet Gynecol.
3(4):249-55, 1993
Bey M et al: The sonographic diagnosis of circumvallate
placenta. Obstet Gynecol. 78(3 Pt 2):515-7, 1991

IIMAGE

GALLERY

ISSUES

Presentation
• Most common signs/symptoms
o Pathologic diagnosis after delivery most often
o Incidental finding during ultrasound
• Other signs/symptoms
o Vaginal bleeding
o PROM
o IUGR
o Preterm labor/delivery

Natural History & Prognosis
• Usually excellent prognosis when partial

(Left) Sagittal ultrasound shows the lifted placental margin (arrows).
(Right) Axial color Doppler ultrasound in the same case shows a
placental "marginal shelf" (arrows). The short bands of tissue attach
on the placenta, not the uterus, and therefore can be differentiated
from synechia.

BATTLEDORE PLACENTA

Sagittal ultrasound shows a marginal cord insertion
(battledore placenta).
The umbilical cord (arrows)
inserts within 2 cm of the placental edge (open arrow).
In addition, there is a two vessel cord (curved arrow).

!TERMINOlOGY
Abbreviations

and Synonyms

• Marginal placental cord insertion
• Eccentric cord insertion

Definitions
• Battledore placenta: Umbilical cord inserts within 2
cm of placental edge
o All subsequent branching vessels within placenta
• No submembranous vessels
• Battledore means racquet
o Battledore was a precursor game to badminton

IIMAGING FINDINGS

o Branching vessels seen on fetal surface
• Marginal PCI vs. velamentous cord insertion (CI)
o May be difficult to differentiate
• Branching vessels within placenta in marginal PCI
• Submembranous vessels with velamentous CI
o 3D ultrasound
• Multiplanar capability helpful
• Surface rendered views lack resolution
o Marginal PCI may rarely evolve into velamentous
cord

Imaging Recommendations
• Protocol advice
o Document cord insertion site on placenta
• PCI found in 99% of cases < 30 wks
o Scan 360 around PCI
o Look for any accompanying velamentous vessels
o Follow-up ultrasound to rule out progression to
velamentous CI
0

General Features
• Best diagnostic clue: Color Doppler shows cord
insertion site within 2 cm of placental edge
• Morphology: Placenta often thicker than usual

Ultrasonographic

Clinical photograph shows a battledore placenta. The
placenta is heart-shaped, as it partially splits at the cord
insertion site. All the vessels are within the placental
mass.

Findings

• Grayscale ultrasound to first find placental cord
insertion (PCI)
o More difficult if> 30 wks
• Color Doppler confirms marginal PCI
o Cord insertion within 2 cm of placental edge

I DIFFERENTIALDIAGNOSIS
Velamentous

cord insertion

• Umbilical cord inserts upon membranes not placenta
o Incidence of 1:100
• Submembranous vessels are extremely fragile
• t Risk of poor outcome compared with marginal PCI

DDx: Eccentric Cord Insertion

Velamentous Cord

Velamentous Cord

Adjacent Cord

Adjacent Cord

BATTLEDORE PLACENTA
Key Facts
Terminology

Top Differential

• Battledore placenta: Umbilical cord inserts within 2
cm of placental edge

• Velamentous cord insertion
• Adjacent cord

Imaging Findings

Pathology

• Branching vessels seen on fetal surface
• Marginal PCI may rarely evolve into velamentous
cord
• Scan 360 around PCI

• Epidemiology:

0

o t Incidence
(IUGR)
o t Incidence
o t Incidence
• 13x t risk
o t Incidence

of intrauterine

growth restriction

of preterm labor
of monochorionic
twin complications
for twin-twin transfusion
of cord rupture at delivery

Diagnoses

2-10% marginal PCI at delivery

Clinical Issues
• t Incidence
•

0

in monochorionic
twins
increased likelihood of IUGR or preterm labor

I DIAGNOSTIC

CHECKLIST

Consider
• Document cord insertion site in high-risk pregnancies
o IUGR, monochorionic
twins, placenta previa
o Rule out vasa previa and velamentous cord

Adjacent cord

Image Interpretation

• Free loop of cord adjacent to placenta surface
• No branching vessels with color Doppler
• Find true PCI

• Look for velamentous vessels at time of diagnosis
• Follow-up ultrasound
o Assess evolution into velamentous cord

I PATHOLOGY

I SELECTED

General Features

1.

• Etiology
o Trophotropism results in shifting placenta
• Cord insertion marks original implantation site
• Parts of placenta grow while parts resorb
• Cord insertion ends up marginal
o Marginal PCI evolution into velamentous CI
• Further resorption of placental margin
• Fetal vessels now submembranous
• Epidemiology: 2-10% marginal PCI at delivery
• Associated abnormalities
o Monochorionic twins
• t Morbidity if velamentous cord
o Single umbilical artery (SUA)
• 18% SUA with marginal PCI
• 9% SUA with velamentous CI

2.

3.

4.

Pearls

REFERENCES

Sepulveda W et al: Prenatal detection of velamentous
insertion of the umbilical cord: a prospective color Doppler
ultrasound study. Ultrasound Obstet Gynecol. 21(6):564-9,
2003
Uu CC et al: Sonographic prenatal diagnosis of marginal
placental cord insertion: clinical importance. J Ultrasound
Med. 21(6):627-32, 2002
Di Salvo DN et al: Sonographic evaluation of the placental
cord insertion site. AJRAm J Roentgenol. 170(5): 1295-8,
1998
Pretorius DH et al: Placental cord insertion visualization
with prenatal ultrasonography. J Ultrasound Med.
15(8):585-93, 1996

I IMAGE

GALLERY

Gross Pathologic & Surgical Features
• "Heart-shaped placenta"
o Placenta partially split where cord inserts

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Incidentally noted during routine ultrasound
o t Incidence in monochorionic
twins

Natural History & Prognosis
• Excellent prognosis when isolated
o No increased likelihood of IUGR or preterm labor
• May progress to velamentous cord

Treatment
• Usually none necessary

(Left) Axial ultrasound shows marginal cord insertion incidentally
noted during a second trimester ultrasound. The cord appears to
insert upon the placental edge (arrows). (Right) Axial color Doppler
ultrasound in the same case proves that the CI is marginal. All
branching vessels were within the placenta. Since velamentous CI
can evolve from marginal placental CI, follow-up ultrasound is
indicated.

PLACENTOMEGALY

Axial ultrasound shows placentomegaly in a pregnancy
complicated
with maternal hypertension,
IUCR and
5 cm
oligohydramnios.
The placenta
measures
(calipers) and is heterogeneous.

ITERMINOLOGY
Definitions
• Abnormally thick placenta

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Placenta thickness> 4 cm
• Location: More common with lateral placenta
• Morphology
o Normal morphology but thick
• Often with t sonolucencies
o Globular morphology
• Small placental attachment area

Ultrasonographic

Findings

• Exclude myometrium in placental measurement
o Measure from subplacental veins to amniotic fluid
junction
• Placenta thickness correlates with menstrual age
o 1 mm/wk growth considered normal (placental
thickness roughly equal to gestational age in wks)
• 10 wk placenta = 10 mm
• 20 wk placenta = 20 mm
• 30 wk placenta = 30 mm
• Thick placenta

DDx: Thickened

Abruption

Pulsed Doppler ultrasound shows absent diaslolic flow
in the umbilical artery (arrows) and increased diastolic
flow in the fetal MCA (open arrow). The pattern
suggests fetal "brain sparing" physiology

o Thickness significantly> 1 mm/wk rule
• > 4 cm always considered abnormal
o Related to placental attachment area
• t Sonolucencies common with placentomegaly
o Sonolucencies normally rare < 20 wks
o Placental lakes
o Intervillous thrombus
o Fibrin deposition and infarction
• "Jelly-like" placental variant
o Thick heterogeneous placenta
• Patchyechogenicity
• Sonolucent spaces
o Quivers like jelly with abdominal pressure
o 60-75% have IUGR
o t Association with short femur
• Related to abnormal fibroblasts
• Placentomegaly is nonspecific diagnosis
o Seen with maternal and fetal disorders
o t Risk for placental insufficiency regardless of cause
• t Intrauterine growth restriction (IUGR)
o Doppler waveforms often abnormal
• t Umbilical artery (UA) resistance
• ~ Middle cerebral artery (MeA) resistance
• t Maternal uterine artery resistance
• Abnormal ductus venosus flow
o Also associated with fetal macrosomia
• Often in diabetic patients

Placenta

Abruption

Myoma

PLACENTOMEGALY
Key Facts
Imaging Findings

Top Differential

• Best diagnostic clue: Placenta thickness> 4 em
• 1 mm/wk growth considered normal (placental
thickness roughly equal to gestational age in wks)
• "Jelly-like" placental variant
• Placentomegaly is nonspecific diagnosis
• Seen with maternal and fetal disorders
• t Risk for placental insufficiency regardless of cause
• Also associated with fetal macrosomia

• Placental abruption
• Subplacental myoma
• Gestational trophoblastic

• Best imaging tool
o Routine evaluation of placenta
o Doppler of fetal-placental circulation
• Protocol advice
o Measure placenta if noticeably thick
o Careful fetal growth assessment

I DIFFERENTIAL

helpful

DIAGNOSIS

Diagnostic Checklist
• Exclude myometrium

in measurements

ISSUES

• Depends on associated findings

Treatment
• Early delivery may be necessary for IUGR

I DIAGNOSTIC

CHECKLIST

Consider

• Acute retroplacental abruption
o Isoechoic blood mimics placenta
• Color Doppler helpful
o Differentiate hematoma from placenta

myoma

• Placenta implants upon myoma
o Myoma often hypoechoic to placenta
• Placenta appears focally thick

Gestational trophoblastic

• Early delivery may be necessary for IUGR

Natural History & Prognosis

Placental abruption

Subplacental

neoplasia (GT

Clinical Issues

I CLINICAL

Imaging Recommendations

Diagnoses

• Careful evaluation

Image Interpretation

I SELECTED
1.

2.

3.

I PATHOLOGY
General Features
• Etiology
o Abnormal trophoblast invasion of spiral arteries
o 2° compensatory hypertrophy
• Areas without defective invasion grow thicker
o Most thick placentas weigh < 10th percentile after
delivery
• Reflects fact that many have small attachment
area so overall volume of placenta is small
• Does not apply to thick placenta in setting of
hydrops
• Epidemiology: 1-8%
• Associated abnormalities
o Hydrops from any cause
o Maternal hypertension, anemia, diabetes
o Placental mosaicism
o Intrauterine infection
o Beckwith-Wiedemann
syndrome

circulation

Pearls

• Do not confuse subplacental focal myometrial
contraction for placentomegaly
• Exclude myometrium in measurements

neoplasia (GTN)

• Diffusely cystic placenta
• Complete mole without fetus
• Triploidy with abnormal fetus

of fetal-placental

REFERENCES

Raio Let al: The thick heterogeneous (jellylike) placenta: a
strong predictor of adverse pregnancy outcome. Prenat
Diagn. 24(3):182-8, 2004
Elchalal U et al: Sonographically thick placenta: a marker
for increased perinatal riskna prospective cross-sectional
study. Placenta. 21(2-3):268-72, 2000
Kennedy A et al: Obstetric ultrasonography: the placenta.
Abdom Imaging. 22(6):602-10, 1997

I IMAGE GALLERY

(Left) Sagittal ultrasound shows a markedly thickened, echogenic
placenta (arrows) in a pregnancy complicated by fetal hydrops.
Placentomegaly, in this case, is secondary to placental edema. (Right)
Axial ultrasound in the same case shows severe skin' edema (arrows)
and cystic hygroma (open arrows) in this syndromic fetus.
Placentomegaly is often seen with hydrops, regardless of cause.

PLACENTA ACCRETA SPECTRUM

Sagittal graphic shows a placenta previa with percreta.
Placental tissue breaches the anterior myometrium and
invades the bladder (arrow). Decidua is absent at the
site of abnormal placental invasion.

ITERMINOlOGY
Definitions
• Abnormal penetration of placental tissue beyond
endometrial lining of uterus
• Three variants of the spectrum collectively termed
"placenta accreta"
o Placenta accreta vera (80%)
• Attaches to myometrium without muscular
invasion
o Placenta increta (15%)
• Chorionic villi invade the myometrium
o Placenta percreta (5%)
• Penetration of chorionic villi through uterus
• May also invade rectum and bladder

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Loss of subplacental hypoechoic zone
o Irregular placental vascular lacunae

Ultrasonographic

Findings

• Normal subplacental hypoechoic zone ("clear space")
o Comprised of decidua basalis and myometrium
o Should be present over entire placental surface

Sagittal ultrasound
shows
multiple
large vessels
extending through the bladder wall (arrows) from the
placenta in this case of placenta percreta. Note the
nodular appearance of the inner bladder wall.

o First visualized in week 12
o Decreased visualization in anterior placentas
• Clear space may be lost in near field
• Use high-resolution transducer if placenta anterior
o Normal bladder mucosa is highly echogenic reflector
• Findings associated with placental invasion
o Placenta previa in almost all cases
• 5% of placenta previa cases will have associated
accreta
o Loss of subplacental hypoechoic zone
• High false positive rate if this sign used in
isolation
o Thinning of subplacental hypoechoic zone ::5 2 mm
o "Swiss cheese" or "moth-eaten" placenta
• Multiple, hypoechoic placental vascular lacunae
• Better positive predictive value than loss of "clear
space"
• Seen as early as 15 weeks
o Interruption of bladder wall-uterine interface
• Dashed rather than continuous echolucent line
• More specific but less sensitive sign
o Anterior myometrium thinner than posterior
• Best seen in early pregnancy
• Endovaginal ultrasound to better evaluate if
placenta previa present
o Findings associated with placenta percreta
• Loss of bladder mucosal reflector

DDx: Placental Abnormalities
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Placenta Previa

Placenta Previa

~"-

,..

Placental Lucencies

Molar Pregnancy

PLACENTA ACCRETA SPECTRUM
Key Facts
Terminology

Top Differential

• Abnormal penetration of placental tissue beyond
endometrial lining of uterus
• Placenta accreta vera (80%)
• Placenta increta (15%)
• Placenta percreta (5%)

• Uncomplicated placenta previa
• Placental sonolucencies

Imaging Findings
•
•
•
•

Loss of subplacental hypoechoic zone
Irregular placental vascular lacunae
Placenta previa in almost all cases
Large vessels extending through myometrium +/- into
bladder
• MRI and US: Poor predictive value for all type (better
for percreta)
• Can progre
from accreta to percreta

• Large vessels extending through myometrium +/into bladder
• Exophytic or nodular mass extending through
bladder wall
• Rarely gestational sac may penetrate through
myometrium as well

MR Findings
• T2WI
o Loss of normal low signal myometrium
o Extension of intermediate signal placental tissue
beyond uterine margins
o Loss of fat planes between uterus/pelvic organs
• Gadolinium enhancement
o Gadolinium crosses placenta
o Generally avoided in pregnancy
o Proponents argue risk/benefit ratio acceptable in
life-threatening condition
• MR technique
o Place pelvic coil low so that optimal coverage is in
lower uterine segment/bladder interface
• Most accretas occur low, over site of cesarean
section scar
o May require body coil for fundal/posterior
placenta
o Bladder full to better evaluate for invasion
o Consider surgilube as vaginal contrast
o Angled scan planes to best evaluate
placenta/uterine/bladder
interface
o Fast scan techniques avoid fetal motion artifact

Imaging Recommendations
• MRI and US: Poor predictive value for all types (better
for percreta)
o Sensitivity MR 38%, US 33%
o Must have high index of suspicion in at-risk patient
• Use high resolution linear transducer to assess
abdominal wall, myometrial thickness
o Better resolution of near-field hypoechoic zone
• Use endovaginal ultrasound for previa/anterior
placenta
• Serial ultrasound scans
o Can progress from accreta to percreta
• MRI better for posterior placenta in at-risk patient

Diagnoses

Pathology
• 5% of patients with placenta previa have accreta
• Present in 10% of patients with> 4 cesarean sections
and no previa
• Present in 67% of patients with placenta previa and>
4 cesarean sections

Clinical

Issues

• High morbidity from hemorrhage
• Manage for worst case scenario
• esarean ection with hysterectomy
• onsider delivery of infant only (placenta left in
uterus)

o Prior myomectomy
o Hysteroscopic resection of uterine septum
• Pre-operative MRI for extrauterine extent
o Cannot reliably diagnose accreta/increta

I DIFFERENTIAL DIAGNOSIS
Uncomplicated

placenta previa

• Intact subplacental

hypoechoic

zone

Placental sonolucencies
• Subplacental hypoechoic zone intact
• Intact bladder/uterine interface

Gestational trophoblastic

disease

• Partial mole
o Diffusely cystic placenta
o Triploid karyotype
o Abnormal fetus with severe intra-uterine growth
restriction
• Complete mole with twin pregnancy
o Two placentas: One cystic and one normal

I PATHOLOGY
General Features
• General path comments
o Abnormal placentation may predispose to bleeding
diathesis
• Disseminated intravascular coagulation
• Pulmonary and cerebral embolization of
trophoblastic tissue during cesarean section
o Sites at risk for abnormal placental penetration
• Uterine scars (cesarean section most common)
• Submucosal fibroid
• Lower uterine segment
• Rudimentary horn
• Uterine cornua
• Etiology
o Deficiency of decidua basalis
o Prior uterine instrumentation
or surgery

PLACENTA ACCRETA SPECTRUM
o Multiparity
o History of manual placental extraction
o Endometriosis
o Advanced maternal age
o Usually several risk factors are present
• Epidemiology
o 1:1,000 to 3,000
• Variability largely based on cesarean section rates
o 5% of patients with placenta previa have accreta
o Prior cesarean section and accreta
• Present in 10% of patients with> 4 cesarean
sections and no previa
• Present in 67% of patients with placenta previa
and> 4 cesarean sections
• Risk higher if cesarean section occurred prior to
onset of labor
o Increased incidence with advanced maternal age

Microscopic

Features

• Decidua basalis replaced with loose connective tissue
• Chorionic villi penetrate/invade myometrium

I CLINICAL

ISSUES

Presentation
• Classical presentation
o Uncontrollable hemorrhage in 3rd stage of labor
• Placenta previa
o Must do a directed careful search
o Close follow-up as may progress
• First trimester low sac position < 10 weeks ~ increase
suspicion
• Maternal serum alpha-fetoprotein may be elevated

Natural History & Prognosis
• Risk of bleeding high, even if spontaneous abortion or
intrauterine demise
o Placenta fails to separate after fetus delivered
o Uncontrollable hemorrhage described at dilatation
and curettage
• Significant risk maternal and fetal demise
• High morbidity from hemorrhage
o 90% require transfusion
• 40% ~ 10 units
o 28% post-operative infection
• 7% mortality
• 15% uterine rupture with placenta percreta
o Can occur as early as 10 weeks

Treatment
• Increased awareness ~ active search in patients at-risk
o Careful monitoring in 2nd and 3rd trimester
• Pre-operative planning
• Pre-operative storage of blood products
• Manage for worst case scenario
• Consider hospitalization from 30 weeks
• Deliver at 34-35 weeks
o Hemorrhagic complications increase markedly> 36
weeks
• Cesarean section with hysterectomy
o Most common indication of perinatal hysterectomy
• Consider delivery of infant only (placenta left in
uterus)

o Post-operative chemotherapy
• Methotrexate
o Post-operative embolization
o Delayed hysterectomy theoretically safer than at
time of delivery
• Reduction in uterine blood flow
o At risk for postpartum hemorrhage
• Consider pre-operative placement of arterial occlusion
catheters
o Anecdotal reports of effective control of bleeding
• Additional teams on standby for bladder/ureter/bowel
invasion or injury

I DIAGNOSTIC

CHECKLIST

Consider
• Careful attention to placenta and uterine wall in 1st
trimester in at-risk patient
• Endovaginal ultrasound with placenta previa or at-risk
patient
• MR if posterior placenta or ultrasound inconclusive

Image Interpretation

Pearls

• Have high index of suspicion for accreta in setting of
placenta previa or prior cesarean section with
placental implantation over scar
o Very high suspicion if both are present

I SELECTED REFERENCES
Bhide A et al: Recent advances in the management of
placenta previa. Curr Opin Obstet Gynecol. 16(6):447-51,
2004
2. Comstock CH et al: Sonographic detection of placenta
accreta in the second and third trimesters of pregnancy.
Am] Obstet Gynecol. 190(4):1135-40,2004
3. Esmans A et al: Placenta percreta causing rupture of an
unscarred uterus at the end of the first trimester of
pregnancy: case report. Hum Reprod. 19(10):2401-3,2004
4.
Kim]A et al: Magnetic resonance imaging with true fast
imaging with steady-state precession and half-Fourier
acquisition single-shot turbo spin-echo sequences in cases
of suspected placenta accreta. Acta Radiol. 45(6):692-8,
2004
5.
Taipale P et al: Prenatal diagnosis of placenta accreta and
percreta with ultrasonography, color Doppler, and
magnetic resonance imaging. Obstet Gynecol.
104(3):537-40,2004
6.
Comstock CH et al: The early sonographic appearance of
placenta accreta.] Ultrasound Med. 22(1):19-23; quiz 24-6,
2003
7.
Buetow MP: Sonography of placenta percreta during the
first trimester. A]R Am] Roentgenol. 179(2):535, 2002
8. Conrad]A et al: Placenta Percreta: Magnetic resonance
imaging and temporary bilateral internal iliac artery
balloon occlusion. Journal of Women's Imaging. 4:139-44,
2002
9.
Son in AI: Nonoperative treatment of placental percreta:
Value of MR imaging. A]R 177:1301-3, 2001
10. Zaki ZM et al: Risk factors and morbidity in patients with
placenta previa accreta compared to placenta previa
non-accreta. Acta Obstet Gynecol Scand. 77(4):391-4, 1998
11. O'Brien] et al: The management of placenta percreta:
Conservative and operative strategies. Am] Obstet
Gynecol. 175:1632-8, 1996
1.

PLACENTA ACCRETA SPECTRUM
IIMAGE

GALLERY
(Left) Sagittal ultrasound
shows placenta previa with
loss of the subplacental
hypoechoic zone in a case of
placenta accreta. The
placental margin abuts the
echogenic bladder reflection
(arrow). (Right) Placental
ultrasound in a case of
percreta shows multiple,
large, irregular vascular
lacunae, giving the placenta
a "swiss chess" appearance.

(Left) Sagittal T2WI MR of a
placenta percreta shows
obvious placental invasion
into the bladder (arrows).
(Right) Intra-operative
photograph from a different
case of placenta percreta
shows serosal irregularity
(open arrow) at the site of
placental invasion. Note the
dramatically dilated blood
vessels (arrows) on the
surface of the uterus. Serious
and potentially catastrophic
hemorrhage is a significant
risk for the placenta accreta
spectrum.

(Left) Sagittal T2WI MR in a
case of placenta previa
(curved arrow) shows a thin
but intact uterine wall
(arrows). Although this
excludes percreta,
accretalincreta
can not be
ruled out. (Right)
Hysterectomy
was
performed for other reasons
and the intact uterus
scanned. The uterine wall
subjacent to the placenta
(arrows) is thinned but
intact. Pathology showed a
placenta increta. A fetal
subdural hematoma (curved
arrow) is also seen.

CHORIOANGIOMA

Color Doppler ultrasound shows marked vascular flow
in a large placental chorioangioma. The pregnancy was
complicated by fetal hydrops and polyhydramnios.

ITERMINOLOGY
Abbreviations

and Synonyms

• Chorioangioma
• Placental hemangioma

• Morphology
o Encapsulated masses
o Usually solitary but may be multiple
(chorioangiomatosis)

Ultrasonographic

Definitions
• Benign, vascular placental tumor
o Most common placental tumor

IIMAGING

Four chamber view of the fetal heart in the same case
shows marked cardiomegaly (arrow) with enlargement
of all four chambers.

FINDINGS

General Features
• Best diagnostic clue: Hypoechoic, vascular placental
mass
• Location
o Most common on fetal side of placenta, near cord
insertion
o Less common locations
• Maternal surface, replacing a lobule
• Pedunculated mass surrounded by membranes
• May involve umbilical cord
• Size

o Majority are small and incidentally noted at delivery
• Most < 5 em
• Those> 5 em more likely to be diagnosed
prenatally

Findings

• Grayscale Ultrasound
o Generally hypoechoic
• May be more heterogeneous if areas of
hemorrhage, infarction or degeneration with
hyaline deposition
o Well-defined
o Infrequently calcify
• Color Doppler
o Essential for making diagnosis
o Amount of flow in mass is quite variable
o Greater arterial flow increases risk of developing
hydrops
• Flow through mass is from fetal circulation
• At risk for high-out cardiac failure and hydrops
o May see increased flow around mass even if mass
itself is hypovascular
• 3D

o Vascularity may be better defined
o Useful for helping to differentiate from other masses

MR Findings
• Not necessary for diagnosis

DDx: Placental Masses

Leiomyoma

Preplacental Abruption

Teratoma

Teratoma

CHORIOANGIOMA
Key Facts
Terminology

Top Differential

• Placental hemangioma
• Benign, a ular placental tumor

• Venou lake
• lntervillou thrombi
• Placental abruption/hemorrhage
• ubmucosal fibroid

Imaging Findings
• Most common on fetal side of placenta, near cord
in ertion
• Gen rally hypoechoic
• Well-defined
• > 5 cm more likely to have complication
• Va cularity may be more important than ize for
predicting outcome
• Polyhydramnio
common with large ma e
• Hydrops from arteriovenou
hunting or from fetal
anemia secondary to hemoly i

Diagnoses

Pathology
• Mo t found in women>

30 yr

Clinical Issues
• Mo t often diagno ed after 20 week
• Excellent prognosi without hydrops
• enerally no treatm nt nece ary
• Amnior duction for polyhydramnio
• onsider intervention f r impending

fetal hydrop

o Consider performing for large masses prior to
intervention
• TlWI
o Isointense to placenta
o May have high signal rim from hemorrhage
• T2WI
o Heterogeneous, high signal intensity
o May have low signal rim from hemorrhage

I DIFFERENTIAL

Imaging Recommendations

Intervillous thrombi

• Measure mass
o < 5 cm unlikely to have complications
o > 5 cm more likely to have complications
• Described in up to 50% of cases
• Document vascularity
o Vascularity may be more important than size for
predicting outcome
o Vascularity may either increase or decrease as
gestation progresses
• Follow every 2-3 weeks for size, vascularity and fetal
assessment
• Evaluate for complications
o Polyhydramnios common with large masses
• Etiology uncertain but may be transudate from
leaky tumor vessels, compressed venous return
from masses by umbilical cord or association with
fetal hydrops
o Hydrops from arteriovenous shunting or from fetal
anemia secondary to hemolysis
• Initial hypertrophic cardiomyopathy
~ dilated
cardiomyopathy
from progressive cardiac
decom pensation
• Pleural effusion
• Pericardial effusion
• Ascites
• Skin thickening
o Fetal anemia
• Hemolysis of red blood cells
• Evaluate flow in middle cerebral artery to
determine need for transfusion

• No flow
• Surrounded by normal placental parenchymal
o Does not change placental contour

o Intrauterine growth restriction

DIAGNOSIS

Venous lakes
• Look for subtle motion
o Pooling venous blood
o Changing patient position may make more obvious
• Flow too slow to be seen with Doppler
o Better seen with grayscale

Placental abruption/hemorrhage
• No flow with Doppler
• Will evolve over time

Submucosal fibroid
• Uterine wall mass

Teratoma (rare)
• Arises between amnion and chorion
• Heterogeneous mass with cystic and solid components
• Calcifications may be present

Gestational trophoblastic

disease

• Complete hydatidiform mole
o No fetus
o Heterogeneous, cystic endometrial mass
• Triploidy
o Three complete sets of chromosomes
o Fetus is abnormal
• Multiple anomalies
• Severe growth restriction
o Placental appearance varies according to extra set of
chromosomes
• Large and cystic if extra set is paternal (diandry)
• Normal or small if extra set is maternal (digyny)
• Invasive mole/choriocarcinoma
o Placental invasion into myometrium or metastatic

disease

CHORIOANGIOMA
• Likely from polyhydramnios
all cases
o Rarely, preeclampsia reported

Placental metastases (rare)
• Maternal
o Melanoma
• May metastasize to fetus
o Breast, lymphoma
• Fetal
o Neuroblastoma
• Large tumors
• Hydrops usually present

Natural History & Prognosis
• Excellent prognosis without hydrops
• Poorer if hydrops present
o At risk for perinatal death

Treatment

I PATHOLOGY
General Features
• Etiology
o Unclear
o Not seen in first trimester abortuses so unlikely from
defective villous angiogenesis
• Acquired lesion latter in pregnancy
• Epidemiology
00.6-1% of placentas at delivery
• Most too small to visualize by ultrasound
• Many microscopic
o Most found in women> 30 yrs
o Fetuses are more often female (72% in one study)
o More common in women living at higher elevation
• Associated abnormalities
o Fetal hemangiomas
• Cutaneous and liver
o Beckwith-Wiedemann
syndrome
o Single umbilical artery

Gross Pathologic & Surgical Features
• Encapsulated, firm masses
• Color varies from purple-red to tan depending
cellular make-up

Microscopic

Features

• 3 types
o Angiomatous
• Numerous blood vessels
• Most likely to cause complications
o Cellular
• ompacted endothelial cells
• Few vessels
o Degenerated
• Myxoid and hyaline deposition
• Mass will become more echogenic and less
vascular by US

ICLINICALISSUES
Presentation
• Most common signs/symptoms
o Incidental finding
• Most often diagnosed after 20 weeks
• Other signs/symptoms
o Large masses
• Elevated maternal serum alpha-fetoprotein
• Polyhydramnios
• Rarely, fetal hydrops
o Preterm labor

but does not explain

on

• Generally no treatment necessary
• Amnioreduction for polyhydramnios
o Reduce likelihood of premature delivery
• Consider intervention for impending fetal hydrops
o Transfusion for anemia
o Vessel ligation, laser coagulation, alcohol injection
and microcoil embolization all described
• Variable results

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Always evaluate placental masses with Doppler
• Close follow-up as size and vascularity may change
with advancing gestation

I SELECTED

REFERENCES

Quarello E et al: Prenatal laser treatment of a placental
chorioangioma. Ultrasound Obstet Gynecol. 25(3):299-301,
2005
Bakaris S et al: Case of large placental chorioangioma
2.
associated with diffuse neonatal hemangiomatosis.
Pediatr
Dev Pathol. 7(3):258-61, 2004
power
3. Shih JC et al: Quantitative three-dimensional
Doppler ultrasound predicts the outcome of placental
chorioangioma. Ultrasound Obstet Gynecol. 24(2):202-6,
2004
4.
Wehrens XH et al: Fetal cardiovascular response to large
placental chorioangiomas. J Perinat Med. 32(2):107-12,
2004
insights into a
5. Guschmann M et al: Chorioangioma--new
well-known problem. I. Results of a clinical and
morphological study of 136 cases. J Perinat Med.
31(2):163-9,2003
Hamill
et al: Prenatal diagnosis and management of fetal
6.
anemia secondary to a large chorioangioma. Obstet
Gynecol. 102(5 Pt 2):1185-8, 2003
Sepulveda W et al: Perinatal outcome after prenatal
7.
diagnosis of placental chorioangioma. Obstet Gynecol.
102(5 Pt 1):1028-33, 2003
8. Bashiri A et al: Twelve cases of placental chorioangioma.
Pregnancy outcome and clinical significance. Arch Gynecol
Obstet. 266(1):53-5, 2002
9.
Jauniaux E et al: Color Doppler imaging in the diagnosis
and management of chorioangiomas.
Ultrasound Obstet
Gynecol. 15:463-7, 2000
10. Kawamotoa S et al: Chorioangioma: antenatal diagnosis
with fast MR imaging. Magn Reson Imaging. 18(7):911-4,
2000
11. Reshetnikova OS et al: Increased incidence of placental
chorioangioma in high-altitude pregnancies: hypobaric
hypoxia as a possible etiologic factor. Am J Obstet Gynecol.
174(2):557-61,1996
12. Bromley B et al: Solid masses on the fetal surface of the
placenta: Differential diagnosis and clinical outcome. J
Ultrasound Med. 13:883-6, 1994
1.

CHORIOANGIOMA
IIMAGE GALLERY
Typical
(Left) Color Doppler
ultrasound shows a
well-defined, vascular,
hypoechoic mass (arrow) on
the fetal surface of the
placenta. This is the typical
appearance of a
chorioangioma. There are
other hypoechoic areas
(open arrow), which could
represent other smaller
masses. (Right) Cross
pathology from a different
case shows small
chorioangiomas (arrows) on
the placental surface.

(Left) Ultrasound shows a
large mass (arrows) within
the placenta. It has a
well-defined rim and mild
internal heterogeneity.
Despite its large size, there
was little flow within the
mass and the pregnancy was
uncomplicated. (Right)
Cross pathology shows the
chorioangioma (open
arrows) extending almost the
entire thickness of the
placenta. The yellow areas
(arrows) represent regions of
infarction and hyaline
deposition.

Variant
(Left)

t;':
',I

Pulsed Doppler
ultrasound of a
pedunculated, hypoechoic,
placental mass shows both
arterial and venous flow.
(Right) Ultrasound of the
same mass shows that it is
covered by a membrane
(arrows). The inset shows
the gross appearance at
delivery. Pathology
confirmed a pedunculated
chorioangioma.
I . ~

V•.

(..•.

"

\I

f

COMPLETE HYDATIDIFORM

Sagittal ultrasound shows a heterogeneously echogenic
mass with variable-sized cysts (arrows), completely
filling the uterine cavity. This appearance is classic for
complete hydatidiform mole (CHM).

•
•
•
•
•

Cross pathology shows a hysterectomy specimen with
CHM. The molar mass, comprised of trophoblastic
hydropic villi, distends the uterine cavity without
invading the myometrium (arrows).

• Location
o Intrauterine mass
• No myometrial invasion
• Size: Variable-sized cysts

ITERMINOLOGY
Abbreviations

MOLE

and Synonyms

Complete hydatidiform mole (CHM)
Complete mole
Classic mole
Molar pregnancy
Gestational trophoblastic neoplasia

Ultrasonographic

Definitions
• Most common type of gestational trophoblastic
neoplasia
• Proliferative growth of trophoblastic tissue
• May become invasive and metastasize
o Invasive mole
o Choriocarcinoma

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Enlarged uterus with "swiss cheese" endometrium
• "Snowstorm" older term used before technology
was capable of discerning individual cysts
o Bilateral complex ovarian cysts
• Theca lutein cysts
o No fetus or embryo

Findings

• "Swiss cheese" endometrium
o Heterogeneous, echogenic intrauterine mass
• Hyperechoic + cystic elements
• Completely fills uterine cavity
o Individual cysts can be seen
• Cysts vary in size
• Hydropic placenta
o No embryo or fetus
• Doppler findings
o Mass is vascular
• Color Doppler easily shows flow
o High-velocity, low-impedance flow
• Mean resistive index (RI) of 0.55
o Normally uterine arcuate artery flow is low-velocity
until 3rd trimester
• Normal RI often> 0.66 if < 20 wks
• Ovarian theca lutein cysts
o Bilateral multi septated cysts
o Only in 50% of all CHM
o Ovarian hyperstimulation
• i Human chorionic gonadotropin
(hCG) hormone
• First trimester CHM

DDx: Placental Cysts

Pseudomo/e

Trip/oidy

COMPLETE HYDATIDIFORM MOLE
Key Facts
Terminology
• Most common
neoplasia

type of gestational

trophoblastic

Pathology

Imaging Findings
• Hyperechoic + cystic elements
• Cysts vary in size
•
0 embryo or fetus
• High-velocity, low-impedance flow
• Ovarian theca lutein cysts
• Only 56% with classic findings if < 13 wks
• 12-15% become invasive mole
• 5-8% become choriocarcinoma
• Look for signs of invasion

Top Differential

• Placental sonolucencies/pseudomole
• Triploidy

Diagnoses

• Placental hydropic degeneration

o Variable ultrasound appearance
o Only 56% with classic findings if < 13 wks
• Echogenic cystic endometrium
o 44% with other findings
• Anembryonic gestational sac
• Heterogeneously thick endometrium
• Echogenic fluid-fluid level
o Can look identical to anembryonic gestation
• GS > 10 mm without yolk sac
• GS > 18 mm without living embryo
o Doppler may be helpful for diagnosis
• Vascular mass
• t Velocity, ~ impedance flow
o Theca lutein cysts rare < 13 wks
• HCG not extremely elevated yet
• Coexistent mole and fetus
o Dizygotic twin pregnancy
• One normal fetus, one CHM
• Normal fetus has a normal placenta
o Must differentiate from partial mole (triploidy)
• Triploid karyotype
• Abnormal fetus
• +/- Cystic placenta
• CHM often associated with hemorrhage
o Adjacent sonolucent hematoma
• Mimics perigestational hemorrhage
o Hemorrhage within mass
• Disrupts typical appearance
• Progression cif tumor
o Invasive mole
• 12-15% become invasive mole
o Choriocarcinoma
• 5-8% become choriocarcinoma
o Often suspected clinically
• t hCG levels after CHM treatment
• Symptoms of metastasis
o MR may be helpful
• Myometrial mass
• Variable signal intensity
• Enhancement with gadolinium
o Imaging often negative if HCG levels low

• 100% paternal genetic makeup
• 46,XX karyotype most common
• Recurrence risk 1-2%

Clinical Issues
• Vaginal bleeding
• Hyperemesis
• t hCG levels
• Excellent progno i

Diagnostic Checklist
• ormal hCG levels do not rule out CHM if < 13 wks
• CHM can look identical to anembryonic pregnancy

Imaging Recommendations
• Best imaging tool: Careful endometrial assessment in
threatened abortion cases
• Protocol advice
o Think of CHM in anembryonic gestation
• Look for cystic placenta
• Use Doppler to evaluate flow
• Send tissue for histology
o Look for signs of invasion
• Myometrial vascular cystic spaces

I DIFFERENTIAL DIAGNOSIS
Placental hydropic degeneration
• Hydropic change without proliferation
• Seen after pregnancy failure
o Embryonic demise
o Anembryonic gestation
• Can look identical to CHM
o Need histologic diagnosis
• Less vascular than CHM
o ~ Velocity, ~ impedance
• Low HCG levels

Placental sonolucencies/pseudomole
• Often normal finding> 25 wks
o Placental lakes
o Intervillous thrombus
• "Swiss cheese" variant mimics CHM
o Pseudomole
o Often with placentomegaly
• Associated with maternal/fetal morbidity
o Preeclampsia
o Intrauterine growth restriction (IUGR)
• Not associated with aneuploidy

Triploidy
• Three complete sets of chromosomes
o 2 paternal + 1 maternal (diandry)
• Placenta is cystic
• Most likely to be confused with CHM

COMPLETE HYDATIDIFORM MOLE
o 2 maternal + 1 paternal (digyny)
• Placenta normal or small
• Fetus is abnormal
o Severe IUGR
o Multiple anomalies
• Must differentiate from twin pregnancy with one
CHM
o Normal fetus + CHM

I PATHOLOGY
General Features
• General path comments: Abnormal trophoblast
proliferation
• Genetics
o 100% paternal genetic makeup
o 46,XX karyotype most common
• Sperm fertilizes ovum with inactive nucleus
• Haploid sperm duplicates to diploid
• Cell division progresses
o 47,XY karyotype
• 23X + 23Y sperm fertilization
• Ovum with inactive nucleus
• Cell division progresses
• Etiology
o Molar pregnancy
• Autonomous trophoblast growth
• Size of villi t as gestation progresses
o Theca lutein cysts
• Ovarian hyperstimulation by t hCG
• Only present in 50%
• Rare < 13 wks
• Epidemiology
o 0.5:1,000 in United States
o 8:1,000 in Asia
o Recurrence risk 1-2%

Gross Pathologic & Surgical Features
• Cystic villi
o Cluster of grapes
• No fetal tissue

Microscopic

Features

• Trophoblastic hyperplasia
• Hydropic villi

I CLINICAL

ISSUES

Demographics
• Age
o t Risk with advanced maternal age (AMA)
• ~ 35 year old at time of delivery
• Ethnicity: t Risk for Asian women

Natural History & Prognosis
• Excellent prognosis
o Evacuation often curable
• Invasive disease may develop
o Invasive mole in 12-15%
o Choriocarcinoma in 5-8%
o Excellent prognosis even with metastasis

Treatment
• Suction evacuation of mass
• Curettage of endometrium
o Helps determine myometrial invasion
• Serial hCG levels
o 1 year surveillance
o Chemotherapy for invasive disease
• Methotrexate
• Actinomycin D
• Etoposide

I DIAGNOSTIC
Consider
•
•
•
•

CHM with atypical anembryonic gestation
Rule out CHM when hCG levels are t
Normal hCG levels do not rule out CHM if < 13 wks
Careful evaluation for invasive disease
o Color Doppler of myometrium
o MRI

Image Interpretation

Pearls

• Repeat imaging if hCG levels t after treatment
o Ultrasound to look for myometrial vascular cysts
o MRI
• CHM can look identical to anembryonic pregnancy

I SELECTED
1.

2.

Presentation
• Most common signs/symptoms
o Most CHM present in first trimester
o Vaginal bleeding
• May cause anemia
o Rapid uterine enlargement
o Hyperemesis
o t hCG levels
• hCG may not be elevated < 13 wks
o Preeclampsia
• Other signs/symptoms
o Enlarged ovaries
• Theca lutein cysts

CHECKLIST

3.

4.

5.

6.

REFERENCES

Zhou Q et al: Sonographic and Doppler imaging in the
diagnosis and treatment of gestational trophoblastic
disease: a 12-year experience. J Ultrasound Med.
24(1):15-24,2005
Garner EI et al: Subsequent pregnancy experience in
patients with molar pregnancy and gestational
trophoblastic tumor. J Reprod Med. 47(5):380-6, 2002
Matsui H et al: Outcome of subsequent pregnancy after
treatment for persistent gestational trophoblastic tumour.
Hum Reprod. 17(2):469-72, 2002
Benson CB et al: Sonographic appearance of first trimester
complete hydatidiform moles. Ultrasound Obstet Gynecol.
16:188-91,2000
Jauniaux E et al: Early ultrasound diagnosis and follow up
of molar pregnancies. Ultrasound Obstet Gynecol. 9:17-21,
1999
Lazarus E et al: Sonographic appearance of early complete
molar pregnancies. J Ultrasound Med. 18(9):589-94; quiz
595-6, 1999

COMPLETE HYDATIDIFORM
IIMAGE

MOLE

GALLERY
(Left) Coronal endovaginal
ultrasound shows an
enlarged ovary with theca
lutein cysts. The cysts cause
a multiseptated appearance,
are often bilateral and are
associated with high
maternal serum hCC levels.
(Right) Clinical photograph
shows bilateral enlarged
ovaries (arrows) from theca
lutein cysts. The ovaries are
as large as the enlarged
uterus. Theca lutein cysts are
present in only 50'Y<,of CHM
cases and are rarely seen
before 73 wks gestation.

(Left) Sagillal endovaginal
ultrasound shows an
anembryonic gestational sac.
Histology from this failed
pregnancy was diagnostic of
CHM. It is important to be
aware, only 56% of 1st
trimester CHMs present with
classic findings of a cystic
mass. Consider performing
Doppler, which would show
high-velocity,
low-impedance flow. (Right)
Ultrasound shows
hemorrhage (arrows), a
common finding, adjacent to
a CHM (open arrows).

Variant
(Left) Axial ultrasound shows

a normal fetus with
coexistent mole. The normal
twin (open arrow) and
placenta (curved arrows) are
seen adjacent to a CHM
(white arrows). A thick
membrane (black arrows)
separates the two. (Right)
Color Doppler ultrasound
with pulsed Doppler shows
the vascularity of CHM.
Uterine vessels (arrow), and
vessels within the mass
(curved arrows) show a
high-velocity,
low-impedance (open
arrow) flow pattern.

INVASIVE MOLE

Sagittal endovaginal ultrasound with and without color
Doppler, shows invasive mole. A heterogeneously
echogenic endometrial mass (curved arrows) invades
the myometrium (arrows). The mass is very vascular.

ITERMINOlOGY
Abbreviations

and Synonyms

• Invasive mole
• Chorioadenoma

destruens

Definitions
• Invasive gestational trophoblastic neoplasia
o Often from complete hydatidiform mole (CHM)

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Echogenic cystic mass invading
myometrium
• Location
o Local invasion
o Metastasis possible
• Invade uterine veins then carried elsewhere
• Not same pathology as choriocarcinoma

Ultrasonographic

Findings

Percreta

• Less common
• Abnormal placenta + invasion + abnormal fetus
o Invasive mole after CHM or triploidy treatment
• t Human chorionic gonadotropin (hCG) levels
• Focal heterogeneous myometrial mass
• Imaging often negative if hCG < 700 mIU/mL
• Color Doppler
o Cystic vascular mass
o Resolves with treatment
• Pulsed Doppler
o High-velocity, low-impedance flow
• Lower resistive indices (RI) than CHM
• RI of 0.28 with invasive mole vs. 0.55 with CHM

MR Findings
• Myometrial mass
o Heterogeneous intermediate signal
• Disruption of uterine zonal anatomy on T2WI
• Tumor enhances with gadolinium
o Can assess depth of invasion

Imaging Recommendations
• Protocol advice
o Transvaginal ultrasound to evaluate for myometrial
invasion
o Foci of invasive tumor "light up" with color Doppler
o Negative ultrasound or MR does not rule out
invasive mole
• Sensitivity is < 70%

• Grayscale Ultrasound
o Myometrial invasion by CHM
• Echogenic cystic mass fills uterus
• Mass extends into myometrium
o Myometrial invasion in triploidy

DDx: Abnormal

Cross pathology shows myometrial invasion (black
arrows) of a large endometrial mass (white arrows).
Most invasive moles are secondary to complete moles
which invade beyond the confines of the endometrium.

Placentation

RPOC

RPOC

Subplacental Myoma

INVASIVE MOLE
Key Facts
Terminology

Top Differential

• Inva ive g tational trophobla tic neoplasia
• Often from complete hydatidiform mole ( HM)

• Retain d products of conception
• Placenta accreta/percreta

Imaging Findings

Pathology

• Myometrial invasion by HM
• Focal heterogeneou
myometrial ma
• Foci of in a ive tumor "light up" with color Doppler
• egative ultra ound or MR does not rule out invasiv
mole

• 12-15°1() of

o Must follow hCG levels

I DIFFERENTIAL

Clinical Issues
• Excellent progno is with treatment
• ombination chemotherapy

CHECKLIST

Consider

DIAGNOSIS

Retained products of conception

(RPOC)

• Heterogeneous material within endometrial
• Never invades myometrium

cavity

Placenta accreta/percreta

• Invasive mole or choriocarcinoma when hCG levels
persist after treatment of CHM or triploidy

Image Interpretation

Pearls

• Color Doppler helpful in identifying
invasion

small foci of

or beyond

I SELECTED
1.

Subplacental

myoma

• Heterogeneous

myoma may mimic invasion
2.

I PATHOLOGY

3.

General Features
• Genetics: Most often diploid (100% paternal genes)
• Etiology: CHM with t polymorphic trophoblasts, more
likely to invade
• Epidemiology
o 12-15% of CHM progress to invasive mole
o Triploidy less common cause of invasive mole

Microscopic

(RP

HM progre s to in asive mole

I DIAGNOSTIC

• Normal placenta invades myometrium
• Associated with prior cesarean section
• Placenta previa often present

Diagnoses

4.

Zhou Q et al: Sonographic and Doppler imaging in the
diagnosis and treatment of gestational trophoblastic
disease: a 12-year experience. J Ultrasound Med.
24(1):15-24,2005
Oguz S et al: Doppler study of myometrium in invasive
gestational trophoblastic disease. lnt J Gynecol Cancer.
14(5):972-9, 2004
Li HW et al: Current understandings of the molecular
genetics of gestational trophoblastic diseases. Placenta
23:20-31,2002
Cohn D et al: Gestational trophoblastic disease: ew
standards for therapy. Current opinion in Oncology
12:492-6, 2000

IIMAGE

Features

REFERENCES

GALLERY

• Trophoblast hyperplasia + hydropic villi
• Invades myometrium or uterine vessels

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Vaginal bleeding
o t hCG levels despite treatment

of CHM

Natural History & Prognosis
• Excellent prognosis with treatment
o Cure rates of > 90%
• Bleeding can be life-threatening
o Embolization may be necessary
• Hysterectomy seldom necessary

Treatment
• Combination chemotherapy
o Methotrexate + others
• Monitor hCG levels

(Left) Sagittal color Doppler ultrasound of a retroflexed uterus shows
heterogeneous, vascular, trophoblastic tissue (arrows) with invasion
into the myometrium (curved arrows). (Right) Sagittal T2WI MR of
the same case, shows a retroflexed uterus with some intracavitary,
trophoblastic tissue (arrows) and a large invasive component (curved
arrow), within the anterior myometrium.

CHORIOCARCINOMA

Sagittal T2WI MR and T7WI with contrast shows a
heterogeneous myometrial mass (arrows) in a patient
who failed therapy for CHM. Nodular enhancement of
the inferior margin (open arrow) suggests viable tumor.

shows a large, necrotic, myometrial
An area of viable choriocarcinoma
with central hemorrhage is seen,
the area of enhancement on MRI.

o Often very small
• 2-8 mm focus in uterus
• May not be detectable with imaging
o Size not related to presence of metastases

ITERMINOlOGY
Abbreviations

Gross pathology
tumor (arrows).
(open arrows)
corresponding to

and Synonyms

• Choriocarcinoma

Definitions

Ultrasonographic

• Malignant tumor from abnormal proliferation of
trophoblastic tissue
• Type of gestational trophoblastic neoplasia (GTN)
o Benign GTN
• Complete hydatidiform mole (CHM)
• Triploidy
o Malignant GTN
• Invasive mole
• Choriocarcinoma

• Uterine findings quite variable
o There may be no detectable uterine mass
• Patient presents with metastases
o Small tumors common « 10 mm)
o Heterogeneous intrauterine mass
• Infiltrating heterogeneous mass
• Often invading myometrium and beyond
• Cystic areas from necrosis
• Heterogeneity from hemorrhage
• Enlarged cystic ovaries (theca lutein cysts)
o 2° to t levels of human chorionic gonadotropin
(hCG) hormone
• Color Doppler
o Helpful for identifying foci of myometrial invasion
• Can not differentiate from invasive mole
• Pulsed Doppler
o High-velocity, low-impedance flow
• CC resistive indices lower than CHM
• CC RI of 0.25 vs. 0.55 for CHM
o Doppler waveform similar to invasive mole

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Metastatic disease +/- uterine
mass in patient with GTN
• Location
o Local extension
• Myometrial invasion
• Parametrial extension
o Distant metastases common
• Size

Findings

MR Findings
• Tl WI: t Signal from hemorrhage

DDx: Uterine Mass Associated With Pregnancy

Invasive Mole

RPOC

RPOC

CHORIOCARCINOMA
Key Facts
Terminology

Top Differential

• Malignant tumor from abnormal proliferation of
trophoblastic tissue
• Type of gestational trophobla tic neopla ia (GT )

• Retained products of conception (RP
• Invasive mole
• Other hemorrhagic brain meta ta e

Diagnoses

Imaging Findings

Pathology

• Be t diagnostic clue: Meta tatic disease +/- uterine
mas in patient with GTN
• Lung, brain, liver metasta es common
• Uterine finding quite variable
• There may be no detectable uterine ma s
• Small tumor common « 10 mm)
• Enlarged cystic ovaries (theca lutein cyst)
• Suspect choriocarcinoma
if t h G after GT or any
pregnancy
• h G < 700 mlU/ml often with negative imaging

• 50% originate from molar pregnancy
• 25% occur after failed pregnancy
• 25% occur after normal pregnancy

• T2WI
o Uterus
• Intermediate heterogeneous signal
• Loss of uterine zonal anatomy
• Tumor may extend beyond uterus
• Flow voids from t vessels
o Brain
• Hemorrhagic masses
• Vasogenic edema
• T1 C+
o t Enhancement

with gadolinium
• Helps detect active foci of tumor

CT Findings
• NECT
o Hemorrhagic brain metastasis
• High density on NECT
• CECT
o Best for metastasis detection
• Lung, brain, liver metastases common
• Bone uncommon
• Metastases often large and heterogeneous
o Brain
• Detect additional masses
• Vasogenic edema
o Pelvis
• Look for parametrial extension

Imaging Recommendations
• Best imaging tool
o Transvaginal ultrasound with color Doppler
• Look for small foci of tumor
o CTand MR
• Local invasion
• Metastases
• Protocol advice
o Suspect choriocarcinoma if t hCG after GTN or any
pregnancy
o Start with pelvic ultrasound
• May be negative
o CT/MRI for staging
o hCG < 700 mIU/ml often with negative imaging

Clinical Issues
• Per i tent t h G
• Symptoms from metasta es
• Choriocarcinoma
originating from
prognosis
• ear 100% cure with chemotherapy
• Hysterectomy necessary in 1/3

I DIFFERENTIAL

HM ha be

t

DIAGNOSIS

Retained products of conception

(RPOC)

• Intrauterine tissue after normal delivery or abortion
• Most often present with excessive bleeding
• Heterogeneous mass in endometrial cavity
o Never invades myometrium
• Low hCG levels compared to GTN

Invasive mole
• May look identical to choriocarcinoma
• Can metastasize
• Less aggressive tumor
o Less hemorrhagic
o Less necrotic
• Pathology often necessary to differentiate from
choriocarcinoma
o Hydropic villi present
• Differentiation from choriocarcinoma often does not
affect treatment
o Multiple agent chemotherapy
• Excellent prognosis

Other hemorrhagic
•
•
•
•

brain metastases

Melanoma
Renal cell carcinoma
Lung cancer
None have t hCG levels

I PATHOLOGY
General Features
• General path comments: Aggressive, necrotic,
hemorrhagic tumor
• Genetics
o Aneuploidy common
o Choriocarcinoma
from CHM
• Diploid
• Exclusive paternal DNA
o Choriocarcinoma
from triploidy
• Mixed DNA (maternal and paternal)
• Etiology

CHORIOCARCINOMA
o Genomic imbalance compared to benign GTN
• t Oncogenes
• ~ Tumor suppressor genes
• Epidemiology
o CHM progression to choriocarcinoma
• Worldwide: 5% of CHM progress to
choriocarcinoma
• United States < 2% of CHM progress to
choriocarcinoma
o 50% originate from molar pregnancy
• Usually from CHM
• Uncommonly triploidy
o 25% occur after failed pregnancy
• Ectopic pregnancy
• Spontaneous abortion
o 25% occur after normal pregnancy

• Other signs/symptoms
a Symptoms from metastases
• Dyspnea
• Cough
• Headache
• Seizure
• Abdominal pain

Gross Pathologic & Surgical Features

Treatment

• Rapidly growing aggressive tumor
o Extensive necrosis
o Hemorrhage
• Early vascular invasion common

Microscopic

Features

• Sheets of trophoblasts with anaplastic features
o Cytotrophoblasts
o Syncytiotrophoblasts
o Minimal intermediate trophoblasts
• No chorionic villi
o Helps differentiate from other GTN
• Triploidy, CHM, invasive mole

Staging, Grading or Classification Criteria
• International Federation of Gynecology and Obstetrics
(FIGO staging)
o Stage 1: Confined to uterus
o Stage 2: Limited to pelvis
o Stage 3: Lung metastases
o Stage 4: Other metastases
• Prognostic scoring index subclassifies FIGO staging
o If score is ::5 7 or then substage is A
o If score is ~ 8 then substage is B
• Scoring index based on many factors
o Maternal age (worse prognosis if > 40 yr)
o Prior pregnancy history
• Choriocarcinoma
following CHM with better
prognosis than those following failed or normal
pregnancy
o Interval of time to start of chemotherapy
• Longer time interval -+ worse prognosis
a HCG level (> 100,000 with worse prognosis)
o Tumor size (> 5 em with worse prognosis)
o Site of metastases
a Number of metastases (> 8 with worse prognosis)
o Prior chemotherapy for treatment of CHM
• Prior use of multiple agents with worse prognosis

Demographics
• Ethnicity:

Natural History & Prognosis
• Choriocarcinoma originating from CHM has best
prognosis
o Near 100% cure with chemotherapy
• 75% remission even with extensive metastatic disease
and poor prognostic scoring index
• Multiple chemotherapy agents
o Methotrexate
o Actinomycin D
o + Other agents
• Hysterectomy necessary in 1/3
o For cure in selected group
• Extensive parametrial invasion
• Non-responsive tumor
o Secondary to bleeding
• Embolization often attempted first

I DIAGNOSTIC

• Choriocarcinoma
if t hCG
treatment
o Dilatation and curettage
• Choriocarcinoma
diagnosis
patients with hemorrhagic

Image Interpretation
• Negative pelvic ultrasound

I SELECTED
1.

2.

3.

4.

ISSUES
6.

Presentation
• Most common signs/symptoms
o Persistent t heG
• Most commonly occurs after treatment

of CHM

CHECKLIST

Consider

5.

ICLINICAL

16x t risk for GTN in Asian population

levels after initial GTN
of benign GTN
in young, parous female
brain lesions

Pearls
does not rule out CC

REFERENCES

Lurain JR et al: Secondary chemotherapy for high-risk
gestational trophoblastic neoplasia. Gynecol Oncol.
97(2):618-23, 2005
Zhou Q et al: Sonographic and Doppler imaging in the
diagnosis and treatment of gestational trophoblastic
disease: a 12-year experience. J Ultrasound Med.
24(1):15-24,2005
Oguz S et al: Doppler study of myometrium in invasive
gestational trophoblastic disease. Int J Gynecol Cancer.
14(5):972-9, 2004
Li HW et al: Current understandings of the molecular
genetics of gestational trophoblastic diseases. Placenta
23:20-31,2002
Cohn D et al: Gestational trophoblastic disease: New
standards for therapy. Current opinion in Oncology.
12:492-6, 2000
Preidler KW et al: Magnetic resonance imaging in patients
with gestational trophoblastic disease. Invest Radiol.
31(8):492-6,1996

CHORIOCARCINOMA
I IMAGE GALLERY
Typical
(Left) Sagittal ultrasound
shows a normal uterus
(arrows - endometrium)
in a
patient with metastatic
choriocarcinoma.
She
presented with abdominal
pain and distension 3
months after a spontaneous
abortion. She had extensive
liver metastases and very
high hCG levels. (Right)
Endovaginal ultrasound
examination of her ovaries
showed bilateral
enlargement with multiple,
complex, theca lutein cysts
(arrows).

Typical
(Left) Axial CECT shows a
pulmonary metastasis from
choriocarcinoma.
A large,
hilar lung mass (arrows) and
pleural effusions (open
arrows) are seen. (Right)
Axial CECT shows multiple
liver metastases (arrows).
The lung and liver are the
most common sites for
metastasis. Both of these
patients presented with
symptoms from their
metastases and had normal
uterine ultrasounds.

(Left) Axial NEeT shows
hemorrhagic brain
metastases (arrows) in a
patient 7 month after
delivery of a normal baby.
This patient presented
acutely with confusion.
(Right) Axial T2WI MR in
another patient with
metastatic choriocarcinoma
shows a mass (arrows) with
a fluid-fluid level (open
arrow) and hemosiderin
deposit (curved arrow) from
hemorrhage. Significant
vasogenic edema is present
in both cases.

SECTION 13: Multiple Gestations

Dichorionic Diamniotic Twins
Monochorionic Diamniotic Twins
Monochorionic Monoamniotic Twins
Discordant Twin Growth
Twin-Twin Transfusion Syndrome
Twin Reversed Arterial Perfusion
Conjoined Twins
Triplets and Beyond

13-2
13-6
13-10
13-14
13-18
13-22
13-26
13-30

DICHORIONIC DIAMNIOTIC TWINS

Graphic of
membrane
of amnion
(pink line).

dichorionic twins. There is a thick inter-twin
(white arrows) composed of two thin layers
(white line) and two thick layers of chorion
The placentas (black arrows) are separate.

Endovaginal
two, thick,
surrounding
determining

ultrasound (EV) in the first trimester shows
echogenic, chorionic sacs (arrows) each
an embryo. This case illustrates the ease of
chorionicity with EV sonography

ITERMINOLOGY

Ultrasonographic

Abbreviations

• First trimester
o Best time for determination of chorionicity and
amnionicity
o Thick echogenic chorion completely surrounds each
sac
o Two yolk sacs
• Specific sign of diamniotic gestation
• Dichorionic (DC) twins must be diamniotic
• Second trimester
o Fetal genders may be different in DZ
• Will be same in MZ even when DC
o Two placentas but may be difficult to prove
• Adjacent implantation sites
• Placental fusion
• Late presentation
o Thick inter-twin membrane
• Subjective
• No finite measurement
• All membranes look thin in third trimester
• Count layers with high resolution transducer, if >
2 must be DC
o "Twin peak" or Lambda sign
• Chorionic tissue extends into inter-twin
membrane at placenta
• Chorion forms echogenic triangle

and Synonyms

• Dichorionic diamniotic twins (DDT)
• Fraternal twins
o Non-identical twins if dizygotic (DZ)
• Identical twins if monozygotic (MZ)

Definitions
• Two fetuses in separate chorionic sacs
o Two amniotic sacs
o Two yolk sacs

IIMAGING

FINDINGS

General Features
• Best diagnostic clue
o First trimester
• Thick echogenic chorion completely surrounds
each embryo
o Second trimester
• "Twin peak" sign: Wedge of chorionic tissue
extending into base of inter-twin membrane
o Third Trimester
• Different gender is most specific sign of DZ twins
• MZ twins will be same gender but may still be
dichorionic

DDx: Dichorionic

Oiamniolic Twins

Findings

Twins

Oiamniolic Twins

Monoamniolic Twins

Monoamniolic Twins

DICHORIONIC DIAMNIOTIC TWINS
Key Facts
Terminology
• Two f tu

Pathology
in eparate chorioni

a

Imaging Findings
• Thick echogenic chorion completely urround each
mbryo
• "Twin peak" ign: Wedge of chorionic lis ue
extending into base of inter-twin membrane
• Different gender i mo t specific sign of DZ twins
• Thick inter-twin membrane
• Growth r triction more common in multipl
• erum creening Ie effective in multiple, therefore
genetic onogram assumes greater importance

Top Differential
• Monochorionic
• Monochorionic

Diagnoses
diamniotic twin (MDT)
monoamniotic
twin (MMT)

• Triangle base on placental surface, apex fades into
inter-twin membrane
• Reliable indicator of dichorionicity
o Absent "twin-peak"
• Membrane abuts placental surface without
triangle of chorionic tissue
• Described as "T" sign
• Does NOT exclude dichorionicity

MR Findings
• May be of benefit to evaluate anomalies
o Incidence of anomalies increased in twins
o Acoustic access may be limited by co-twin

Imaging Recommendations
• Monitor growth
_
o Growth restriction more common in multiples
• Look for anomalies
o 2-3 x more common in twins than singletons
o Monozygotic 50% > dizygotic
o Serum screening less effective in multiples, therefore
genetic sonogram assumes greater importance
• Watch for signs of crowding
o Clubfoot
• Make sure amniotic fluid volume is symmetric
o Amniotic fluid index (AFI) difficult in twins
o Use single deepest pocket
• Sagittal scan plane
• Transducer perpendicular to floor not maternal
abdomen
• Consider cervical length measurement
o Endovaginal (EV) transducer
o Gentle technique - avoid compressing cervix
o Document shortest length
o Prolonged scan period for dynamic changes
• Assess placental implantation sites
o Increased risk of placenta previa
o Increased risk vasa previa
• Fetal vessels crossing the internal os
• Pulsed Doppler will differentiate fetal from
maternal arterial vessels
• Cannot reliably differentiate fetal from maternal
veins

• Twin 1:90 pr gnancie in U
• Twins account for 101).\) perinatal morbidity and
mortality (P M)

Clinical Issues
•

ge related risk of an uploidy in MZ twins equal to
singleton rate
• Age related risk of an uploidy in DZ twin higher
than singleton rate
> ingleton pregnancy
• Maternal complication

Diagnostic Checklist
• E U in the first trimester i the be t modality for
determination of chorioni ity and amnioni ity
• Twin pr gno i relate to chorionicity not zygocity

• Rupture in labor ~ fetal exsanguination
• If confirmed on imaging, elective caesarian
section performed

I DIFFERENTIAL DIAGNOSIS
Monochorionic

diamniotic

twins (MDT)

• Must be same gender
• Single placental mass
• Thin inter-twin membrane

Monochorionic

monoamniotic

twins (MMT)

• Must be same gender
• No inter-twin membrane
• Cord entanglement

I PATHOLOGY
General Features
• Genetics
o Dizygotic twinning increased with maternal family
history of twins
o Paternal history not relevant
• Etiology
o Embryology
• Zygote divides within 3 days of conception
• Complete duplication of cell lines
• Two chorions
• Two amnions
• Two embryos
o Later division of cell mass results in monochorionic
(MC) twinning
• Epidemiology
o Twins
• 70% are dizygotic
• 30% are monozygotic
o Of monozygotic twins
• 30% DDT
• 60-65% MDT
• 5-10% MMT
• < 1% con joined

DICHORIONIC

DIAMNIOTIC TWINS

o Twins 1:90 pregnancies in USA
• Twins account for 10% perinatal morbidity and
mortality (PNM)
• PNM monochorionic>
dichorionic twins
o Assisted reproduction
• MZ twinning with assisted reproduction 3.8 x
general population rate
• However most multiples with assisted
reproduction are dizygotic
o Dizygotic twins
• 7-11 per 1,000 births in USA ( geographic
incidence varies)
• Increased with maternal age
• Increased with maternal parity
• Increased with maternal family history
• No increase with paternal family history
• Rate varies with race
• African-American> Caucasian> Asian
o Monozygotic twins
• 4 per 1,000 births in USA
• Rate independent of race/age/parity

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Size> dates
o Hyperemesis gravidarum
• Other signs/symptoms
o Hyperreactio luteinalis may occur
• Syndrome akin to hyperstimulation
syndrome
occurring in response to normal pregnancy
• Bilateral theca lutein cysts may cause confusion
with ovarian tumors
• Presence of ascites/pleural effusion may further
increase suspicion for neoplasm
• ~ human chorionic gonadotropin (~-hCG) may be
dramatically elevated
• ~-hCG levels cause confusion with gestational
trophoblastic disease
• Hyperandrogenism
~ maternal and occasional
fetal virilization
• Almost always benign and self limited

• Maternal complications>
singleton pregnancy
o Hypertension
o Preeclampsia
o Antenatal hemorrhage
• Placenta previa
• Placental abruption
• Other causes
o Postpartum hemorrhage
• Perinatal mortality reported 10%
o Preterm delivery
• Median gestational age (GA) twins at delivery 36
weeks
o Intrauterine growth restriction
o Anomalies

Treatment
• Monthly scans for growth
• Monitor fluid volume
o Deepest pocket for each twin
• Cervical measurements controversial
o Preterm delivery increased in twins
o Short cervix may be a predictor for pre term delivery
• Dynamic cervix may be more sensitive than short
o Cervical length > 35 mm at 23 weeks identifies
group at low-risk for preterm delivery
o Impact on management unclear
• No definitive therapeutic measures to prevent
early delivery

I DIAGNOSTIC

Image Interpretation

Pearls

• EV us in the first trimester is the best modality for
determination of chorionicity and amnionicity
• Twin prognosis relates to chorionicity not zygocity

I SELECTED
1.

2.
3.

Natural History & Prognosis
• Probability of delivering two live infants if normal US
at 6 weeks
o MC 39%, DC 75.8%
• Probability of delivering two live infants if normal US
at 12 weeks
o MC 74.4%, DC 95.8%
• Age related risk of aneuploidy in MZ twins equal to
singleton rate
• Age related risk of aneuploidy in DZ twins higher than
singleton rate
o Risk of one fetus being affected: 2x singleton risk
o Risk of both fetuses being affected: (Singleton risk)2
o Maternal serum screening less reliable in multiples
• DC twin loss rate within 4 weeks of amniocentesis>
that for singletons
o 2.7% DC twins with amniocentesis
o 0.6% control singletons with amniocentesis

CHECKLIST

4.

5.

6.

7.

REFERENCES

Cleary-Goldman J et al: Management of single fetal demise
in a multiple gestation. Obstet Gynecol Surv. 59(4):285-98,
2004
Rao A et al: Obstetric complications of twin pregnancies.
Best Pract Res Clin Obstet Gynaecol. 18(4):557-76,2004
Sherer OM: Adverse perinatal outcome of twin pregnancies
according to chorionicity: review of the literature. Am J
Perinatal. 18(1):23-37,2001
Skentou C et al: Prediction of preterm delivery in twins by
cervical assessment at 23 weeks. Ultrasound Obstet
Gynecol. 17(1):7-10,2001
Kiely JL: What is the population-based risk of preterm birth
among twins and other multiples. Clin Obstet Gynecol
41:3-11, 1998
Bajoria R et al: The case for routine determination of
chorionicity and zygosity in multiple pregnancy. Prenat
Oiagn. 17(13):1207-25, 1997
Ouenhoelter JH: Survival of twins after acute fetal
hemorrhage from ruptured vasa previa. Obstet Gynecol.
73(5 Pt 2):866-7, 1989

DICHORIONIC DIAMNIOTIC TWINS
IIMAGE GAllERY
Typical
(Left) Transabdominal
ultrasound shows a thin
amniotic membrane (white
arrow), which eventually
fuses to the thicker chorionic
membrane. An early "twin
peak" sign (black arrow) and
embryo (open arrow) are
also present. (Right)
Transabdominal ultrasound
(TA) shows a later first
trimester pregnancy with a
thick inter-twin membrane
(arrow) composed of two
layers of chorion. The thin
amnion is not usually
resolved separately on TA
scans.

Typical
(Left) Ultrasound shows the
typical appearance of the
"twin peak" sign. A triangle
of echogenic tissue based on
the placental surface
(arrows) extends into the
inter-twin membrane
(curved arrow). (Right)
Ultrasound shows the thick
inter-twin membrane (arrow)
with two clearly visible
chorionic layers even in the
second trimester. Fluid
distribution is symmetric
about the membrane.

Typical
(Left) Ultrasound shows a
thick inter-twin membrane
(arrow) meeting the placenta
in a "T" configuration. The
twins were different genders
so had to be dizygotic.
Absent "twin peak" does not
exclude dichorionicity.
(Right) Ultrasound shows
two separate placentas
(arrows) in second trimester
DOT. Differentiating
placentas becomes more
difficult later in pregnancy.
There is also a thick
inter-twin membrane
(curved arrow).

MONOCHORIONIC

DIAMNIOTIC TWINS

Graphic of monochorionic
diamniotic twins. A thin
membrane forms from two layers of amnion (white
arrows). There is a single chorionic sac (curved arrow)
and single placenta (black arrow).

• Single placental mass
• Twins must be same gender
• Thin inter-twin membrane
• No "twin peak" (lambda sign)
o Thin inter-twin membrane is subjective
• No specific measurement
• Difficult in 3rd trimester: All membranes look thin
• Color Doppler
o Use during endovaginal (EV) sonography of cervix
for possible associated vasa previa
• Pulsed Doppler for heart rate identifies fetal vs.
maternal arterial vessels
• Cannot differentiate maternal and fetal venous
flow

ITERMINOLOGY
Abbreviations

and Synonyms

• Monochorionic diamniotic twins (MDT)
• Identical twins

Definitions
• Two fetuses in single chorionic sac
o Two amniotic sacs
o Two yolk sacs

IIMAGING

FINDINGS

General Features

MR Findings

• Best diagnostic clue
o First trimester
• Two yolk sacs in single chorionic sac
o Second trimester
• Thin inter-twin membrane

Ultrasonographic

Findings

• Grayscale Ultrasound
o First trimester
• Two yolk sacs (YS)
• Number YS = number amnions but YSeasier to see
early in gestation
o Second trimester

DDx: Monochorionic

Dichorionic Twins

Diamniotic

Endovaginal ultrasound shows a single chorionic sac
with two embryos, yolk sacs (black arrows), and
amnions (white arrows). Note the ease of assessing
chorionicity and amnionicity in the first trimester.

• Use to evaluate brain injury
o Intervention contraindicated if hypoxic brain injury
already present
o Intervention carries risk of subsequent brain injury
o Manifests 10-14 days after injury
• Intracranial hemorrhage
• Encephaloclastic changes
• Porencephalic cyst formation
• May be helpful to clarify anomalies
o Family may chose selective reduction
o Intervention contraindicated if both fetuses
anomalous

Twins

DOT Absent Twin Peak

DOT Twin Peak

Monoamniotic Twins

MONOCHORIONIC DIAMNIOTIC TWINS
Key Facts
Terminology

Pathology

• Two fetuses in single chorionic sac
• Two amniotic sacs

• MZ twins 4:1,000 births in USA
• 60% of MZ twins are monochorionic

Imaging Findings

Clinical Issues

• Number YS = number amnions but YSeasier to see
early in gestation
• Single placental mass
• Twins must be same gender
• Thin inter-twin membrane
• Monochorionic twin anomaly rate 3-5x that of
singletons or dichorionic twins

• Perinatal morbidity and mortality of MC twins 3-5x
that of DC twins

Top Differential Diagnoses
• Dichorionic diamniotic twins (DDT)
• Monochorionic monoamniotic twins (MMT)

Imaging Recommendations
• Best imaging tool: EV scan in first trimester
• Evaluate nuchal translucency (NT) in first trimester: If
abnormal
a Increased risk of aneuploidy
a Increased incidence of twin-twin transfusion
syndrome (TITS)
• Risk of TITS particularly if ductus venosus flow
also abnormal
• Look for anomalies
a Monochorionic twin anomaly rate 3-Sx that of
singletons or dichorionic twins
• Anencephaly
• Holoprosencephaly
• Hydrocephalus
• Sacrococcygeal teratoma
• Consider fetal echocardiography
a Prevalence congenital heart disease increased
• Attempt to identify placental cord insertion sites
a Increased incidence of marginal cord insertion
• Unequal placental sharing
• Increased risk for discordant growth
a Increased risk velamentous cord insertion
• Associated with 13 fold increase risk discordant
birth weights
a Increased incidence of vasa previa
• Fetal vessels cross internal os
• Labor ~ vessels tear ~ fetal exsanguination
• Monitor growth
a Growth restriction more common in multiples
• Discordant growth
a > 20% difference in estimated fetal weight (EFW)
a > 20 mm difference in abdominal circumference
(Ae)
o By convention "discordant" only used when one
twin has intrauterine growth restriction (IUGR)
o If neither twin IUGR, use asymmetric/disparate
growth (terminology convention)
• Check for symmetric amniotic fluid volume
o Asymmetric distribution important sign of TITS
o If discordant growth, smaller twin may have
oligohydramnios

Diagnostic Checklist
• Check chorionicity and amnionicity in every
multiple gestation
• Prognosis in twins depends on chorionicity not
zygocity
• Amniotic fluid discordance most important single
predictor of poor outcome

a Oligohydramnios in one sac may imply anomaly
• Look for specific complications of monochorionic
twinning
o TITS
o Twin reverse arterial perfusion sequence (TRAP)
o Twin embolization syndrome (TES)

I DIFFERENTIAL DIAGNOSIS
Dichorionic diamniotic twins (DDT)
• Fused placentas may appear as one
• Twin peak sign usually present
o Best seen when US beam perpendicular to
membranes
o Scan in multiple planes
• Inter-twin membrane thicker
• Inter-twin membrane composed of four layers
a Chorion and amnion from each fetus
a High resolution transducer may show multiple
layers
o Most useful in late presentation
• Fetal gender may differ in dizygotic twins

Monochorionic

monoamniotic twins (MMT)

• No inter-twin membrane
• Cord entanglement common
o Cord entanglement can occur in diamniotic twins if
inter-twin membrane ruptures

I PATHOLOGY
General Features
• General path comments
o Monochorionic (MC) placentation ~ vascular
connections between fetuses: Risk of
• TITS
• TRAP
• Twin embolization syndrome
o Twin embolization syndrome; Older hypothesis
• Twin demise ~ tissue necrosis
• Embolization to live twin

MONOCHORIONIC DIAMNIOTIC TWINS
o Twin embolization syndrome: Current theory
• Twin demise => loss of peripheral resistance
• Vascular anastomoses between twins due to
monochorionic placentation
• Abrupt drop in peripheral resistance secondary to
demise
hypotension in live twin
o End result is "hypoperfusion" lesions of brain and
kidneys
• Intraventricular hemorrhage
• Porencephaly
• Periventricular leukomalacia
• Renal infarction
• Genetics: Risk aneuploidy in MDT equals singleton
risk
• Etiology
o Embryology
• MDT occur when inner cell mass of blastocyst
splits between 4th and 8th day post conception
• Chorion already formed
• Division results in formation of two amnions and
two embryos
• Division after 8th day => monoamniotic twins
• Epidemiology
o MZ twins 4:1,000 births in USA
o 60% of MZ twins are monochorionic
o Rate of MZ twinning independent of
• Race
• Maternal age
• Family history
o MZ twinning rate in assisted reproduction is 3.8x
general population rate
• Most multiples in chemically induced pregnancies
are dizygotic

'*

I CLINICAL

I DIAGNOSTIC
Consider

• Check chorionicity and amnionicity in every multiple
gestation
o Always easier in early pregnancy
• Prognosis in twins depends on chorionicity not
zygocity

Image Interpretation

Pearls

• In first trimester count yolk sacs per chorionic sac
o YS can be seen before amnion is visible
o Two YSimplies two amnions
• Thin inter-twin membrane best sign after first
trimester
• Check fetal gender
o If different cannot be MC gestation
• Amniotic fluid discordance most important single
predictor of poor outcome

I SELECTED
1.

3.

REFERENCES

Fieni S et al: Very-early-onsetdiscordant growth in
monochorionic twin pregnancy. Obstet Gynecol. 103(5 Pt
2):1115-7,

2.

2004

LewiL et al: Monochorionic diamniotic twins:
complications and management options. Curr Opin Obstet
Gynecol. 15(2):177-94,2003
Hanley MLet al: Placental cord insertion and birth weight
discordancy in twin gestations. Obstet Gynecol.
99(3):477-82,2002

4.

5.

ISSUES
6.

Natural History & Prognosis
• Early demise (10-14 weeks) of one twin may occur
o Described in 6% dichorionic (DC) twins
• Generally no adverse impact on surviving twin
o Described in 3% monochorionic twins
• Early MC twin demise indicates poor prognosis
• Spontaneous abortion occurred in all cases in one
study
• Perinatal morbidity and mortality of MC twins 3-Sx
that of DC twins
o Relates to specific MC complications
o Preterm delivery

CHECKLIST

7.

Fukuda Yet al: Prenatal confirmation of periventricular
leukomalacia in a surviving monochorionic-diamniotic
twin after death of the other fetus: a case report. Tohoku]
ExpMed. 190(1):61-4,2000
Gaziano APet al: Diamniotic monochorionic twin
gestations: An overview.] Matern FetalMed. 8:89-96, 2000
Lin IJet al: Infants of twin pregnancies with one twin
demise in the uterus: a retrospective study. ActaPaediatr
Taiwan. 40(2):92-6, 1999
Sutherland RS:Diamniotic twin gestation discordant for
renal dysplasia and oligohydramnios. Urology.54(6):1097,
1999

8.

KrauseHG et al: Cord entanglement in monochorionic
diamniotic twins. Aust N Z] Obstet Gynaecol. 38(3):341-2,

9.

Hill LMet al: Sonographic determination of first trimester
twin chorionicity and amnionicity. ] Clin Ultrasound.

1998

24(6):305-8,
10.

1996

BromleyBet al: Using the number of yolk sacsto
determine amnionicity in early first trimester
monochorionic twins.] Ultrasound Med. 14(6):415-9, 1995
Maier RFet al: Acute and chronic fetal hypoxia in
monochorionic and dichorionic twins. Obstet Gynecol.

Treatment

11.

• Monthly scans for growth and fluid
• Careful watch for complications
o Discordant/disparate growth
o Anomalies
o TTTS
o TRAP
• Improved outcome with early diagnosis allowing for
o Aggressive monitoring
o Early hospitalization

12. Chen SEet al: Antepartum rupture of diamniotic
membranes separating monozygotic twins. Acase report. ]
ReprodMed. 39(1):67-70, 1994
13. Chou YHet al: Multicystic encephalomalacia in a surviving
monochorionic twin. Zhonghua Min Guo Xiao Er KeYi
Xue Hui Za Zhi. 34(6):474-9, 1993
14. FinbergH]:The "twin peak" sign: reliable evidence of
dichorionic twinning.] Ultrasound Med. 11(11):571-7,

86(6):973-7,

1995

1992
15.

BurkeMS:Singlefetal demise in twin gestation. Clin
Obstet Gynecol. 33(1):69-78, 1990

MONOCHORIONIC DIAMNIOTIC TWINS
I IMAGE GALLERY
Typical
(Left) Ultrasound of a twin
gestation shows two male
fetuses with no obvious
inter-twin membrane.
The
membrane is thin and often
difficult to identify in MDT. A
careful search is necessary to
rule out a monoamniotic
gestation. (Right) Ultrasound
of the same case shows a
thin membrane (arrow)
inserting directly onto a
single placenta (curved
arrow). The membrane is
composed of two layers of
amnion with no chorionic
tissue.

Typical
(Left) T2WI MR shows a
single placenta (arrow), two
fetuses, and a thin inter-twin
membrane
(curved arrow).
This patient had TTTS and
had undergone a successful
laser ablation of anastomotic
vessels. (Right) Ultrasound
shows MDT gestation
complicated
by TTTS. A
single placenta (curved
arrow) and thin inter-twin
membrane
(arrow) contlrm
MDT. Note the asymmetric
fluid distribution about the
membrane.

Typical
(Left) Color Doppler
ultrasound shows one twin's
cord inserting centrally into a
single placental mass
(arrow). This is a MDT
pregnancy complicated by
unequal placental sharing
and growth discordance.
(Right) Color Doppler
ultrasound in the same case
shows the co-twin has a
marginal cord insertion
(arrow). Such unequal
placental sharing oilen
causes discordant growth as
in this case.

MONOCHORIONIC MONOAMNIOTIC TWINS

Graphic of monoamniotic twins shows a single chorion
(curved arrow), single amnion (arrow) and single
placenta. Note the cord originsare close and the cords
are entangled (open arrow).

• Single YSis reliable predictor of monoamnionicity
on endovaginal scans> 7 weeks
o Second trimester
• No inter-twin membrane
• Single placental mass
• Same gender
o Umbilical cord entanglement
• Described as early as 10 weeks gestational age (GA)
• Cord appears to branch
• Mass of vessels with differing fetal heart rates
• Side by side placental insertion may increase risk
o Umbilical cord fusion
• Each twin has cord
• Cords fuse at short distance from placental
insertion
• V-shaped or forked appearance
• Not branching entanglement as seen with cord
knot
• Color Doppler
o Majority of cases have cord entanglement
• Apparent branching of cord vessels seen with
color
• Hard to differentiate knot from coils of single cord
on grayscale imaging
• Pulsed Doppler
o End systolic notch in umbilical artery abnormal
• May reflect hemodynamic alterations in vessels
narrowed by knot

ITERMINOlOGY
Abbreviations

and Synonyms

• Monochorionic monoamniotic
• Identical twins

twins (MMT)

Definitions
• Two fetuses in single sac
o Single chorion
o Single amnion
o Single yolk sac

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o First trimester
• Single yolk sac
o Second trimester
• Cord entanglement

Ultrasonographic

Findings

• Grayscale Ultrasound
o First trimester
• Count yolk sacs (YS)
• If single YSearly, follow-up in one week

DDx: Monoamniotic

Conjoined Twins

3D ultrasound image of a 70 week monochorionic
monoamniotic twin gestation. Both embryos are easily
identified (arrows) within a single sac. No intervening
membrane was present.

Twins

"Stuck" Twin

Membrane Rupture

MONOCHORIONIC MONOAMNIOTIC TWINS
Key Facts
Terminology

Pathology

• Two fetuses in single sac

• < 1% of monozygotic twinning

Imaging Findings

Clinical Issues

•
•
•
•
•
•

• Cord entanglement described as early as 10 weeks
• High perinatal mortality (PNM)
• MMT rare yet account for significant percentage of
twin pregnancies with bad outcome
• Consider selective termination for discordant major
anomaly
• Timing and mode of delivery are controversial

Single yolk sac
No inter-twin membrane
Single placental mass
Same gender
Majority of cases have cord entanglement
3D is most accurate imaging method in early first
trimester

Top Differential Diagnoses

Diagnostic Checklist

• Conjoined twins
• Diamniotic twins with "absent" inter-twin membrane

• Single YS at > 7 weeks GA on endovaginal scan is
diagnostic
• Cord knot implies fetuses in same sac

• 3D
o 3D is most accurate imaging method in early first
trimester
o Can exclude conjoined twins by 6 weeks GA

MR Findings
• Use to evaluate brain injury
o Intervention contraindicated if hypoxic brain injury
already present
o Risk of hypotension during intervention with
resultant brain/renal injury
o Manifests 10-14 days after event
• Intracranial hemorrhage
• Encephaloclastic changes
• Porencephalic cyst formation
• May be very helpful to clarify anomalies
o Family may choose selective reduction
o Intervention contraindicated if both twins
anomalous
o Influences mode of delivery

CT Findings
• Consider CT amniogram if sonographic visualization
is poor (e.g. maternal obesity)
• Single injection of contrast medium into amniotic
fluid
o If contrast seen in both fetal stomachs must be
monoamniotic gestation

Imaging Recommendations
• Count YS
o Number YS = number amnions
o YSeasier to see than amniotic membrane
• Check fetal gender
o If different must be dizygotic twins
• Assess umbilical cord
o Insertion sites
o Entanglement
o Spectral analysis
• Careful search for anomalies
o MMT higher discordance rate for anomalies
• 25% discordant for major anomaly
• Anomalies often lethal

o Renal agenesis particularly difficult
• No oligohydramnios: Amniotic fluid produced by
normal co-twin
• Fetal adrenals may be mistaken for kidneys
• Bladder should be seen to change in volume if
normal urine production
• Evaluate for twin-twin transfusion syndrome (TTTS)
o Polyhydramnios
o Hydrops in one fetus
o Small/absent bladder in other fetus
o Donor oligohydramnios cannot be assessed
• No inter-twin membrane
• Amniotic fluid from normal twin surrounds both
fetuses

I DIFFERENTIAL

DIAGNOSIS

Conjoined twins
• Contiguous skin covering at same anatomic plane
• Cords may be fused but do not appear knotted
o Short segment cord fusion adjacent to placenta may
be mildest presentation of conjoined twins

Diamniotic twins with "absent" inter-twin
membrane
• Twin-twin transfusion syndrome
o Recipient twin larger, polyhydramnios +/- hydrops
o Donor twin smaller, in fixed position ("stuck" twin)
o Cardiac activity present in "stuck" twin
o Membrane "shrink-wrapped" around fetus
• Difficult to see -+ called absent .
• Twin demise
o Anhydramnios in sac of dead twin
o Membrane closely applied to dead fetus
• Difficult to see -+ called absent
o Dead co-twin in fixed position with no cardiac
activity
• Twin anomaly
o Renal agenesis/sirenomelia in one twin
• Premature rupture of membranes
o Anhydramnios around presenting twin

MONOCHORIONIC

MONOAMNIOTIC TWINS

• Intrauterine membrane rupture
o Failure to see membrane after earlier documentation
o Infection
o Developmentally abnormal membrane
o Trauma
• Serial amniocenteses for treatment of TITS
increases risk of membrane rupture

I PATHOLOGY
General Features
• Epidemiology
o < 1% of monozygotic twinning
• Rare therefore true incidence uncertain
o May be up to 5% monochorionic twins
o M<F

• Embryology
o MMT occur when embryo splits after 8th post
conception day
• Chorion and amnion already forming therefore
two embryos develop within a single sac
o Split in first 3 days '* dichorionic diamniotic twins
(DDT)
o Split between 4th and 8th days '* monochorionic
diamniotic twins (MDT)
o After 13th day '* conjoined twins

Gross Pathologic & Surgical Features
• Cord insertion sites on placenta closer than in MDT
o Mean inter cord distance 5 cm MMT
o Mean inter cord distance 17.5 em MDT
• MMT placental vascular connections differ from MDT
o MMT 100% arterioarterial connections
o Similar venovenous connections to MDT
o Less opposing arteriovenous connections than MDT
• TITS less common in MMT than MDT

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Cord entanglement described as early as 10 weeks
o Absent inter-twin membrane

Natural History & Prognosis
• High perinatal mortality (PNM)
o Reported PNM rates 28-68%
o Highest loss rate (68%) in series with first trimester
diagnosis
• Outcome data from 2nd trimester diagnosis
discounts early losses
• MMT rare yet account for significant percentage of
twin pregnancies with bad outcome
o < 1% of monozygotic twins are monoamniotic
o In a series of 86 twin deaths 20% were MMT
• Factors influencing PNM
o Prematurity
o Growth restriction
o Anomalies
o Cord accidents
o Vascular anastomoses
o Twin-twin transfusion

• Less common than in MDT as more bidirectional
shunts in MMT placentas
• Old data suggested double (both twins) survival rare
• Modern management '* double survival more likely

Treatment
• Monthly scans to assess
o Growth
o Polyhydramnios
o TITS
• Consider selective termination for discordant major
anomaly
o Common circulation contraindicates methods such
as intracardiac potassium
o Must also transect cord to prevent entanglement
o Harmonic scalpel: Simultaneous coagulation/cutting
• Minimally invasive: One trocar, US guidance
• In case of twin demise
o Increased risk of brain/renal hypoxic injury in
survivor
o Immediate delivery does not prevent hypoxic tissue
damage
• Adds risks of prematurity to existing risks of
hypoxia
• Intensive monitoring
o Daily nonstress testing (NST) from 26 weeks
• Increasing frequency of decelerations may herald
serious cord compression
o Continuous heart monitoring if variable
decelerations increase in frequency or severity
o Biophysical profile for nonreactive NST
• Timing and mode of delivery are controversial
o Elective delivery at 34 weeks after maternal
corticosteroid administration or
o Deliver at lung maturity
• Cesarean section preferred to avoid cord accident
o Successful vaginal delivery described
o At least one series shows no increase in
complication with vaginal delivery

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Single YSat > 7 weeks GA on endovaginal scan is
diagnostic
• Cord knot implies fetuses in same sac

I SELECTED REFERENCES
1.

2.

3.

4.

5.

Narine LH et al: Mode of conception, placental
morphology and perinatal outcome of twin gestations. J
Perinat Med. 31(2):99-104, 2003
Umur A et al: Monoamniotic-versus
diamniotic-monochorionic
twin placentas: anastomoses
and twin-twin transfusion syndrome. Am J Obstet
Gynecol. 189(5):1325-9,2003
Sherer DM et al: Diagnosis of umbilical cord entanglement
of monoamniotic twins by first-trimester color Doppler
imaging. J Ultrasound Med. 21(11):1307-9, 2002
Su LL: Monoamniotic twins: Diagnosis and management.
Acta Obstet Gynecol Scand 81:995-1000, 2002
Seibre NJ et al: First trimester diagnosis of monoamniotic
twin pregnancies. Ultrasound Obstet Gynecol 16:223-5,
2000

MONOCHORIONIC MONOAMNIOTIC TWINS
IIMAGE GAllERY
Typical
(Left) Ultrasound of a first
trimester pregnancy shows
side-by-side placental cord
insertion sites (arrows). This
increases risk for cord
entanglement. Vascular
anastomoses are also more
likely. (Right) Gross
pathology shows term
placenta with side-by-side
cord insertions (white
arrows). This increases the
risk for cord entanglement.
Note that the cords are
entwined but not knotted
(curved arrow).

Typical
(Left) Axial ultrasound shows
twins in single sac with no
inter-twin membrane. Note
smaller size of lower twin
due to discordant growth.
Skin covering is not
contiguous excluding
conjoined twins. (Right) CT
amniogram of an obese
woman in whom the
membrane could not be
assessed by ultrasound. Both
fetuses are within a single
contrast opacified amniotic
sac. Note swallowed
contrast within fetal stomach
(arrow).

Typical
(Left) Axial oblique color
Doppler ultrasound shows
cord entanglement. This is
best appreciated by looking
for a "branching"
appearance of the umbilical
vessels (arrow). (Right)
Gross pathology shows
entangled umbilical cords.
This resulted in thrombosis of
one cord (arrow) and
subsequent fetal demise.
Cord accidents are a major
contributing factor to the
high perinatal mortality in
MMT.

DISCORDANT

Ultrasound shows a monoamniotic twin gestation with
the twins lying side by side (arrows - stomach bubbles).
Abdominal circumference of the superior twin is visibly
larger than that of the inferior twin.

ITERMINOlOGY
Definitions
• Twins of different sizes
o By convention discordant only used when estimated
fetal weight (EFW) of one twin < 10th percentile
o If twins differ in size but both within normal range
called asymmetric/disparate twin growth
o May occur in monochorionic or dichorionic
pregnancies
• Monochorionic more common

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Discordant growth
• One twin with intrauterine growth restriction
(IUGR) Le. EFW < 10th percentile
• Abdominal circumference (AC) difference> 20
mm

• EFW difference> 20%

Ultrasonographic

Findings

• Grayscale Ultrasound
o Crown rump length disparity in first trimester
predictor for discordant birthweight

DDx: Discordant Growth

.~

..

.

••

TWIN GROWTH

Gross pathology of the placenta from a discordant twin
gestation. The cord of the twin with normal growth
(curved arrow) is normal in size, whereas the cord of
the growth restricted twin is small (arrow).

• Series dichorionic pregnancies with
demise/anomalies excluded
• Crown rump length (CRL) difference> 3 days at
11-14 weeks gestational age (GA)
• Likelihood ratio of 5.9 for discordant birthweight
o Oligohydramnios about smaller twin
• Sign of placental insufficiency
• May also occur with anomaly or aneuploidy
'*
• Placental insufficiency/anomaly/aneuploidy
impaired growth
• Twin-twin transfusion syndrome (TITS) unlikely
unless monochorionic twins and polyhydramnios
around other fetus
• Color Doppler
o Useful to assess for placental cord insertion site
o Velamentous cord insertion associated with 13x
increase in discordant birth weight
o Marginal cord insertion increases suspicion for
unequal placental sharing
• Pulsed Doppler
o Growth restriction may be secondary to abnormal
resistance in maternal spiral arteries
• Resistive index measured within 5 cm radius of
placental cord insertion site
• Elevated RI not seen in concordant twins or
discordance in presence of TITS
o Systolic/diastolic (SD) ratio in umbilical artery (UA)
may help to predict discordance

DISCORDANT
Terminology

TWIN GROWTH

Key Facts
Top Differential Diagnoses

• Twins of different sizes
• By convention discordant only used when estimated
fetal weight (EFW) of one twin < 10th percentile
• If twins differ in size but both within normal range
called asymmetric/disparate twin growth
• May occur in monochorionic or dichorionic
pregnancies

Imaging Findings
• Oligohydramnios about smaller twin
• Systolic/diastolic (SD) ratio in umbilical artery (VA)
may help to predict discordance
• Velamentous cord insertion associated with 13x
increase in discordant birth weight
• Discordant growth may be result of anomalies or
aneuploidy in one fetus
• Significant difference in SD ratio> 15% between
twins
• 92% sensitivity for birthweight difference> 15%
• 70% specificity for birthweight difference> 15%
• Sensitivity and specificity similar to that of
estimated fetal weight
o SD ratio difference> 0.4 between twins has also
been used to predict discordance
• 75% sensitivity for birthweight difference> 25%
• 69% specificity for birthweight difference> 25%
• 3D

o May be helpful to assess placental volume in early
pregnancy
o If asymmetric placental volumes consider chorionic
villus sampling
• May be indicator of triploidy

Imaging Recommendations
• Protocol advice
o Assess chorionicity and amnionicity in all multiple
gestations
o Look for unequal placental sharing
• Where are the cord insertion sites?
• Marginal cord
• Velamentous cord
o Evaluate for poor placentation
• Placenta implanted on septum/fibroids
o Meticulous survey for anomalies
• Discordant growth may be result of anomalies or
aneuploidy in one fetus
o Vse Doppler to monitor smaller fetus
• SD ratios: VA > middle cerebral artery implies
"head-sparing" effect
• Reversed or absent end diastolic flow VA implies
abnormal placental resistance
• Reversed flow in ductus venosus implies cardiac
decompensation
• Pulsatile venous flow in umbilical vein implies
impending heart failure
• In multiple gestations measure SD ratio at
abdominal cord insertion site for reproducibility

• Twin demise
• Twin-twin transfusion syndrome (TITS)

Clinical Issues
• Discordant pairs have worse perinatal outcomes
within each gestational age category
• Management decisions should not be based on EFW
differences alone

Diagnostic Checklist
• Discordant twin growth may present as early as the
first trimester
• Risk of neurologic impairment in discordant twins is
at least as great as that in TITS

I DIFFERENTIAL

DIAGNOSIS

Twin demise
• Should be obvious: Absent cardiac activity
• Anhydramnios
• Overlapping skull bones sonographic equivalent of
Spalding sign

Twin-twin transfusion syndrome (TTTS)
• Type specific complication of monochorionic
twinning secondary to placental vascular anastomoses
• Donor twin
o Poor growth
o Hypoxia/anemia
o Oligohydramnios
• Recipient twin
o Well grown
o Plethoric
o Polyhydramnios
o May be hydropic

I PATHOLOGY
Gross Pathologic & Surgical Features
• Placental abnormalities
o Immature villi, shortage of terminal villi
o Hypoxic areas with alteration and destruction of
villi
o Avascular villi
• Massive perivillus fibrin deposition (maternal floor
infarction)

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Twin discordance described as early as first trimester
o Most commonly presents late 2nd or early 3rd
trimester

DISCORDANT
Natural History & Prognosis
• Multiple case reports of first trimester discordance
persisting and deteriorating
o Series of 5 twins with first trimester discordance (5
day difference CRL) and live birth for both
o Major anomalies in all smaller twins
• Diaphragmatic hernia
• Ventriculomegaly
• Schizencephaly
• Critical aortic stenosis
• Sacral agenesis
• Growth discordance does not correlate with late fetal
death
o 1.6% of 3,019 twin gestations complicated by
stillbirth of one or both fetuses
o Only 15% of dead twins were small for GA
• Discordant pairs have worse perinatal outcomes
within each gestational age category
• Discordant monochorionic
twins risk neurological
impairment
o 60% if co-twin demise
o 42% if discordant
o 37% if TITS
• 8% risk neurological impairment in concordant
monochorionic twins

Treatment
• Even first trimester discordance should be worked up
• Nuchal translucency measurements predict
aneuploidy and risk for TITS
• Offer genetic counseling +/- karyotype
o Chorionic villus sampling (CVS) allows early
diagnosis of aneuploidy
o Selective termination easier to perform
• Risks of 2nd trimester amniocentesis higher in twins
than singletons
o Loss rate 2.7% in twins following amniocentesis
o Loss rate 0.6% in singletons following amniocentesis
• Selective termination for anomalous or aneuploid
fetus
o If MC placentation co-twin at risk for vascular
compromise => neurological damage, even death
• Radiofrequency ablation of cord vessels
• Laser ablation shunt vessels
o If monoamniotic,
cord transection essential to
prevent entanglement
• Follow-up for growth
o Every 4 weeks for concordant twins
o Discordant twins followed more frequently
• Some authors suggest growth assessment every 2
weeks
o Monitor twins with velamentous cord insertion
closely
• 13 fold increased risk of discordant birthweight
• Controversy surrounds ability to predict actual
birthweight discordance accurately
• Management decisions should not be based on EFW
differences alone
o Multiple factors in decision to deliver
• Fluid volume
• Doppler measurements
• Non-stress test
• Biophysical profile

TWIN GROWTH
• With early onset discordant growth and deteriorating
well being of small fetus
o Consider conservative non-intervention
to avoid
risks of prematurity for normally grown twin
o Co-twin demise has no adverse sequela for survivor
in dichorionic gestation

I DIAGNOSTIC

CHECKLIST

Consider
• Fetal MRI
o Clarify anomalies
o Evaluate placental relationship
septa/fibroids

Image Interpretation

to uterine

Pearls

• Discordant twin growth may present as early as the
first trimester
• Risk of neurologic impairment in discordant twins is
at least as great as that in TITS
• Twins may be discordant for anomalies as well as
growth

I SELECTED
1.

2.

REFERENCES

Adegbite ALet al: Neuromorbidity in preterm twins in
relation to chorionicity and discordant birth weight. AmJ
Obstet Gynecol. 190(1):156-63, 2004
Blickstein I et al: Neonatal mortality rates among
growth-discordant twins, classified according to the birth
weight of the smaller twin. Am J Obstet Gynecol.
190(1):170-4,2004

3.

Fieni S et al: Very-early-onset discordant growth in
monochorionic twin pregnancy. Obstet Gynecol. 103(5 Pt
2):1115-7,2004

4.

5.

Gupta N et al: Massive perivillous fibrin deposition
associated with discordant fetal growth in a dichorionic
twin pregnancy. J Obstet Gynaecol. 24(5):579-80, 2004
Branum AM et al: The effect of birth weight discordance on
twin neonatal mortality. Obstet Gynecol. 101(3):570-4,
2003

6.

7.

Gassner R et al: Triploidy in a twin pregnancy: small
placenta volume as an early sonographical marker. Prenat
Diagn. 23(1):16-20, 2003
Kalish RBet al: First trimester prediction of growth
discordance in twin gestations. Am J Obstet Gynecol.
189(3):706-9,2003

8.

9.

Hartley RSet al: Size-discordant twin pairs have higher
perinatal mortality rates than non discordant pairs. AmJ
Obstet Gynecol. 187(5): 1173-8, 2002
Matijevic R et al: Non-invasive method of evaluation of
trophoblast invasion of spiral arteries in monochorionic
twins with discordant birthweight. Placenta. 23(1):93-9,
2002

10. Scher AI et al: The risk of mortality or cerebral palsy in

twins: a collaborative population-based study. Pediatr Res.
52(5):671-81,

2002

DISCORDANT

TWIN GROWTH

I IMAGE GALLERY
Typical
(Left) Growth curves (or
discordant, but otherwise
normal, dichorionic twins.
The smaller twin had an EFW
< 70th percentile and the
clinical decision was made
to deliver at 35 weeks
gestational age. (Right)
Photograph o( the twins at
one month o( age. The
smaller twin required initial
tube feeds but was otherwise
normal. At 77 months, there
is a Sib weight difference but
both boys are healthy and
developmentally
normal.

(Left) Transabdominal
ultrasound shows discordant
dichorionic twins (arrows) in
first trimester. Crown rump
length measurements
are
compatible with 10.2 and
77.3 weeks gestation. There
is increased risk for
discordant birth weight, as
well as anomalies in smaller
twin. (Right) T2WI MR
shows monoamniotic
twins
discordant in size by US
criteria. They are also
discordant (or anomalies
with the smaller twin having
multiple anomalies including
a neural tube defect (arrow).

Typical
(Left) Color Doppler
ultrasound shows a marginal
cord insertion (curved
arrow) onto the placenta
(arrow). The biometry
showed a size discrepancy of
4 weeks. (Right) Pulsed
Doppler ultrasound of the
umbilical cords shows
abnormal flow in the growth
restricted fetus (twin A) with
reversal of end diastolic flow.
The normally grown fetus
(twin B) has a normal cord
Doppler waveform and
systolic/diastolic
ratio.

TWIN-TWIN TRANSFUSION

Graphic shows discordant twins with an arteriovenous
shunt (arrow) on the placental surface. Deoxygenated
blood from the donor twin mixes with oxygenated
blood returning to recipient via the umbilical vein.

ITERMINOlOGY
Abbreviations

and Synonyms

• Twin-twin transfusion
• Twin oligohydramnios
(TOPS)

syndrome (TTTS)
polyhydramnios
sequence

Definitions
• Monochorionic (Me) twinning
• Artery-to-vein anastomoses in placenta
• Donor twin partly perfuses recipient twin

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Monochorionic twins with
asymmetric fluid distribution and growth

Ultrasonographic

Findings

• Grayscale Ultrasound
o First trimester
• Measure nuchal translucency (NT)
• If abnormal consider evaluation of ductus venosus
(OV) flow
• Abnormal NT + abnormal OV flow may predict
cases most at risk for TTTS
o Single placental mass

SYNDROME

Ultrasound shows marked asymmetry of fluid
distribution and discordant twin size. The membrane
(white arrow) was closely adherent to the smaller
"stuck" twin (black arrow) and could be easily missed.

o Twins same gender
o Thin inter-twin membrane in monochorionic
diamniotic twins (MDT)
o Asymmetric distribution of fluid about inter-twin
membrane
• Polyhydramnios defined as deepest pocket ~ 8 cm
• Oligohydramnios
defined as deepest pocket::; 2
cm
o "Stuck twin" describes severe oligohydramnios with
a fixed position of smaller twin
o Twin growth usually asymmetric with ~ 20%
difference in estimated fetal weight
• Lesser degrees of discrepancy do not exclude
diagnosis
• Severe discordance suggests unequal placental
sharing or anomaly in smaller twin
o Echogenic bowel described as sign of hypoxia in
donor
o TTTS can occur in monochorionic
monoamniotic
twins (MMT)
• Rarer than in MDT and harder to diagnose
• Can't see asymmetry of fluid as no inter-twin
membrane
• Look for high output +/- hydrops in one twin
• Absent bladder in other twin
• Differential includes discordant anomalies
• Look for shunt vessels on placenta with color
Doppler to prove TTTS

DDx: Stuck Twin

Renal Agenesis

lUG R-Oligohydramnios

TWIN-TWIN TRANSFUSION

SYNDROME

Key Facts
Terminology

Top Differential

• Artery-to-vein ana tomoses in placenta
• Donor twin partly perfu es recipient twin

• Premature rupture of membranes
• Twin demise
• Anomalou twin causing" tuck" appearance

Imaging Findings
• Best diagnostic clue: Monochorionic twins with
asymmetric fluid di tribution and growth
• Echogenic bowel described as ign of hypoxia in
donor
• ongenital heart di ease ( HD) more prevalent in
TTTS than in uncomplicated MDT
• tage 1: Donor bladder visible, normal Doppler
• tage 2: Donor bladder empty, normal Doppler
• Stage 3: Donor bladder empty, abnormal Doppler
• tage 4: Hydrops in recipient
• Stage 5: Demi e of one or both

o Congenital heart disease (CHD) more prevalent in
TTTS than in uncomplicated MDT
• Uncomplicated MDT: 2.3%
• Recipient twin in TTTS: 11.9%
• Color Doppler
o Useful to identify arteriovenous anastomoses
o "Nose-to-nose" appearance of vessels on placental
surface
• Normally artery and vein enter placental
cotyledon side by side
• Pulsed Doppler
o Criteria for abnormal Doppler
• Umbilical artery (UA): Absent or reversed end
diastolic flow
• Umbilical vein: Pulsatile flow
• Ductus venosus (DV): Reversed flow
• Inferior vena cava (IVC): Reversed flow

MR Findings
• Used to confirm normal brain structure prior to
intervention
• Follow for adverse sequelae of laser coagulation of
shunt vessels
o Intracranial hemorrhage
o Encephaloclastic changes
o Porencephalic cyst formation

Imaging Recommendations
• Stage twin-twin transfusion syndrome (TTTS)
o Stage 1: Donor bladder visible, normal Doppler
o Stage 2: Donor bladder empty, normal Doppler
o Stage 3: Donor bladder empty, abnormal Doppler
o Stage 4: Hydrops in recipient
o Stage 5: Demise of one or both
• Fetal echocardiography
for functional problems
relating to TTTS in recipient
o Cardiac enlargement
o Tricuspid regurgitation
o Impaired ventricular function
o Biventricular hypertrophy
o Right ventricular outflow tract obstruction
• Described in as many as 9% recipients
o Donor twins without CHD have normal function

Clinical

Diagnoses

Issues

• Progressive disorder> 90% mortality if untreated
• Stage at presentation does not correlate with outcome
• hange of tage during treatment alter prognosis

Diagnostic Checklist
• Search carefully for membrane in apparent MMT
• evere oligohydramnios
of recipient twin
~"shrink-wrap" membrane which is difficult to detect
~ mistaken diagnosis MMT
• Treatment and prognosis differ for MMT and TTTS
therefore accurate diagnosis i important

• Fetal echocardiography
also important for detection
CHD: Increased in MDT with TTTS
• Recent reports of pulmonary artery calcification in
recipient twins
o May progress to pulmonary atresia
o May require postnatal instrumentation
or surgery
• If TTTS treated with serial amnioreduction
monitor
membranes
o Chorioamniotic
separation
o Membrane rupture
• Inter-twin membrane rupture creates functional
monoamniotic
state
o Risk of cord accident
o Increased morbidity and mortality
• Fetal MRI after laser coagulation
o Wait at least 10-14 days from intervention
o If scanned too soon significant pathology may be
missed

I DIFFERENTIAL DIAGNOSIS
Premature rupture of membranes
•
•
•
•

If known dichorionic pregnancy TTTS excluded
Ask the patient: Gush of fluid or blood
Test for ferning, fetal fibronectin
Oligohydramnios usually about leading twin

Twin demise
• Absent cardiac activity in oligohydramnios

sac

Anomalous twin causing "stuck" appearance
•
•
•
•
•
•
•

Renal agenesis
Sirenomelia
Bilateral multicystic dysplastic kidneys
Autosomal recessive polycystic kidney disease (ARPKD)
Po:;terior urethral valves
Severe intrauterine growth restriction of one twin
Normal co-twin will not have high-output state in any
of these conditions

TWIN-TWIN TRANSFUSION

I PATHOLOGY
General Features
• General path comments: Often marginal insertion of
donor cord
• Etiology
o ~ 1 arteriovenous (AV) anastomoses within a
monochorionic placenta
• Unidirectional flow: Donor to recipient
• Transfusion occurs within placental cotyledon
• Vessels enter and leave cotyledon via common
foramen
• "Nose-to-nose" appearance different from normal
paired vessels
• "Nose-to-nose connections" readily seen at
fetoscopy
• Abnormal connection can be identified
sonographically to guide selective laser
coagulation
o +/- Absence of bidirectional (to and from both
fetuses) arterioarterial anastomoses
• Direct luminal contact on placental surface
• Found in most MC placentas
• Generally no net shunt
• May be protective against TITS: Compensate for
unbalanced donor to recipient shunt in AV
anastomosis
o Hormonal factors recently implicated in
pathogenesis
• Discordant renin angiotensin expression
• Endothelin
• Natriuretic peptide
o Natriuretic peptide
• Elevated brain levels in recipients correlate with
severe cardiac dysfunction
• Cardiac levels NP do not correlate with cardiac
function
o Shunt leads to significant inter-twin hematocrit
differences at cordocentesis
• Mean hemoglobin difference 4.8 g/dl (range
1.8-8.1g/dl)
• Mean hematocrit difference 18.3%
• Epidemiology: Complicates 10-20% of monochorionic
pregnancies

I CLINICAL

ISSUES

Presentation
• Twins with asymmetric fluid and growth
• May resolve spontaneously
• Shunt direction may change
o Donor becomes recipient

Natural History & Prognosis
• Progressive disorder> 90% mortality if untreated
• Stage at presentation does not correlate with outcome
• Change of stage during treatment alters prognosis
o Decreased stage: 94% survival
o Increased stage: 27% mortality
• Morbidity common in survivors
o Neurological: 5-23% especially if co-twin demise

SYNDROME

o Cardiac: Most functional
months

changes resolve within 6

Treatment
• Stage TITS at time of diagnosis
• Monitor closely
o Growth every three weeks
o Fluid volume weekly or more frequently
o Stage at diagnosis may not reliably predict outcome
o Deteriorating stage is associated with adverse
outcome
• May precipitate aggressive management such as
referral for laser coagulation
• United Kingdom approach
o Serial amnioreduction/septostomy
for early stage
disease
o Laser coagulation of shunt vessels reserved for more
severe cases
• Risk procedure-related fetal loss
• USA: Multi-center study currently enrolling patients to
determine
o If fetoscopic laser coagulation =>improved survival
of twins with severe TITS vs. serial amnioreduction
o If fetoscopic laser coagulation =>improved cardiac,
neurological and developmental outcomes of twins
with severe TITS vs. serial amnioreduction
o Complex protocol requiring serial scans, Doppler,
echocardiography, and MRI

I DIAGNOSTIC

CHECKLIST

Consider
• Postnatal echocardiography
o 50% of surviving recipient twins had persistent
abnormalities>
28 days of life

Image Interpretation

Pearls

• Search carefully for membrane in apparent MMT
o Severe oligohydramnios
of recipient twin
=>"shrink-wrap" membrane which is difficult to
detect =>mistaken diagnosis MMT
o Treatment and prognosis differ for MMT and TITS
therefore accurate diagnosis is important

I SELECTED
1.
2.
3.

4.

5.

6.

REFERENCES

Jain V et al: The twin-twin transfusion syndrome. Clin
Obstet Gynecol. 47(1):181-202, 2004
Quintero RA:Twin-twin transfusion syndrome. Clin
Perinatol. 30(3):591-600, 2003
Saxena A et al: Pulmonary artery calcification in recipient
twins of twin to twin transfusion syndrome: a report of
three cases. Pediatr Cardiol. 24(1):80-3, 2003
Bajoria R et al: Natriuretic peptides in the pathogenesis of
cardiac dysfunction in the recipient fetus of twin-twin
transfusion syndrome. Am J Obstet Gynecol. 186(1):121-7,
2002
Karatza AA et al: Influence of twin-twin transfusion
syndrome on fetal cardiovascular structure and function:
prospective case-control study of 136 monochorionic twin
pregnancies. Heart. 88(3):271-7, 2002
Lougheed J et al: Acquired right ventricular outflow tract
obstruction in the recipient twin in twin-twin transfusion
syndrome. J Am Coli Cardiol. 38(5):1533-8, 2001

TWIN-TWIN TRANSFUSION

SYNDROME

IIMAGE GALLERY
(Left) Color Doppler
ultrasound through the pelvis
of a donor twin shows flow
in the umbilical arteries. The
bladder should be seen as a
fluid-filled structure between
these vessels. "Absent"
bladder with normal Doppler
is stage 2 TTTS. (Right)
Sagittal ultrasound shows
skin thickening and ascites
(arrow) indicating hydrops
of a recipient twin in the
second trimester. This
implies stage 4 TTTS.

Typical
(Left) Ultrasound of
umbilical cords in a TTTS
case shows a marked
difference in cord size.
Cursors demarcate the donor
cord (curved arrow) which is
about one third the area of
the recipient cord (white
arrows). (Right) Pulsed
Doppler ultrasound of the
UA shows reversed end
diastolic flow in the donor
twin. Demise occurred
within 2 days of this scan.
The recipient had a normal
brain on a fetal MRI
examination and was normal
at birth.

(Left) Axial ultrasound
through the abdomen of a
donor twin shows echogenic
bowel (arrows) with
echogenicity as great as
bone. This appearance
correlates with ischemic
bowel secondary to
intrauterine hypoxia. (Right)
Coronal ultrasound of the
brain on day one of life
shows severe cystic
encephalomalacia
(arrows),
another sequela of
intrauterine hypoxia.

TWIN REVERSED ARTERIAL PERFUSION

Craphic depicts a normal twin perfusing an abnormal
co-twin via artery (deoxygenated blood) to artery
placental anastomosis (arrow). Abnormal circulation
impairs development of heart, head and torso.

Ultrasound shows an acardiac twin with well-formed
lower extremities (white arrow) but no cranial structures
(curved arrow). Note edema of torso (black arrows).
The pump twin (open arrow) was structurally normal.

ITERMINOLOGY
Abbreviations

o

and Synonyms

• Twin reversed arterial perfusion (TRAP)
• Cardiac regression sequence
• Acardiac monster

Definitions
• Monochorionic placentation
• Arterioarterial anastomosis in placenta
• Acardiac twin perfused by deoxygenated blood from
"pump" twin
• Blood enters fetus via umbilical artery
o Reversed perfusion
• Normal perfusion: Oxygenated blood from
placenta enters fetus via umbilical vein

IIMAGING

FINDINGS

o

(HC/CC)

General Features
• Best diagnostic clue: Flow in umbilical artery (UA) of
abnormal twin is toward fetus

Ultrasonographic

o
o

• May be monoamniotic
or diamniotic
• Thin inter-twin membrane if diamniotic
Acardiac twin dysmorphic with edema and cyst
formation in soft tissues
• No cardiac structures or activity
• Often no identifiable cranial structures
• Presence and structure of upper extremities
extremely variable
• Usually recognizable torso and lower extremities
• Lower extremities move spontaneously
Single umbilical artery in 66% of acardiac twins
Polyhydramnios
• Strong correlation with presence of renal tissue in
acardiac twin
• Increases risk for premature labor
Echocardiography of pump twin
• At risk for hydrops secondary to high output state
• Measure ratio heart to chest circumference

Findings

• Grayscale Ultrasound
o Must be monochorionic gestation
• Single placental mass

• Myocardial thickening
• Tricuspid regurgitation
• Color Doppler
o Occasionally single UA of acardiac twin connects
directly to cord of pump twin
o Beware "twinkle" artifact after ablation
• Color does not equal flow
• Use pulsed Doppler to verify waveform
• Pulsed Doppler

DDx: Twin Reverse Arterial Perfusion

Twin Demise

Cystic Hygroma

Anencephaly

TWIN REVERSED ARTERIAL PERFUSION
Key Facts
• Twin demise

Terminology
• Arterioarterial anastomosi in placenta
• Acardiac twin perfused by deoxygenated blood from
"pump" twin

Imaging Findings
• Best diagnostic clue: Flow in umbilical artery (UA) of
abnormal twin is toward fetus
• Must be monochorionic gestation
• Acardiac twin dy morphic with edema and cy t
formation in soft tissues
• Ratio of EFW of acardiac to pump twin> 70% confers
bad prognosis

Top Differential

Diagnoses

• Anomalous twin mimicking acardiac twin
• Conjoined twins

o Reversed flow in UA pathognomonic
o Doppler shunt vessel
• Usually on placental surface
• Artery to artery anastomoses pulsatile flow
• Vein to vein non-pulsatile flow in opposite
direction
o Look for signs of impending hydrops in pump twin
• Reversed flow in ductus venosus (DV)
• Reversed flow in inferior vena cava (IVC)
• Pulsatile umbilical vein (UV) flow

MR Findings
• May be used prior to intervention
o Confirm normal brain in pump twin
o Exclude anomalies in pump twin
• Post intervention used to monitor adverse effects on
pump twin
o Intracranial hemorrhage
o Encephaloclastic changes
o Porencephalic cyst formation

Imaging Recommendations
• Careful search for anomalies of pump twin
• Monitor size of acardiac twin
o Measure longest linear dimension
o Weight in grams = -1.66 x length + 1.21 x length2
o Rapid growth of acardiac twin associated with poor
prognosis
• Monitor growth of pump twin especially estimated
fetal weight (EFW)
• Ratio of EFW of acardiac to pump twin> 70% confers
bad prognosis
o Preterm delivery 90%
o Polyhydramnios 40%
o Pump twin hydrops 30%

I DIFFERENTIAL DIAGNOSIS
Anomalous twin mimicking acardiac twin
• Anencephaly or destructive process like amniotic
bands
o Cardiac structures present

Pathology
• Acardiac twin has no placental circulation: Blood
supply is from pump twin
• 1% of monochorionic pregnancies

Clinical Issues
• Acardiac twin anomalies are lethal
• Untreated reported pump twin mortality 50-75%
• Pump twin survival improves to 76% with
intervention
• Intra fetal radiofrequency (RF) ablation seems better
than cord occlusion

Diagnostic Checklist
• You will never miss this diagnosis if you check
direction of umbilical artery flow in anomalous twins
o Flow in umbilical artery away from fetus
• Cystic hygroma
o Normal cranium and presence of cardiac activity

Conjoined

twins

• Contiguous external skin contour
o Acardiac twin is separate from pump twin
• No inter-twin membrane
o Use with care: TRAP can occur in monoamniotic
pregnancy

Twin demise
• Should be anhydramnios in sac of dead twin if
diamniotic
• No flow in dead twin cord

I PATHOLOGY
General Features
• Genetics
o Not hereditary
o No recurrence risk
• Etiology
o Acardiac twin has no placental circulation: Blood
supply is from pump twin
o Reverse perfusion from artery-to-artery placental
anastomoses
• Acardiac twin perfused with deoxygenated blood
from pump twin
• Reverse perfusion allows continued but abnormal
development
• Deoxygenated blood ~ arrested development in
early embryogenesis
• Deoxygenated blood ~ hypoxic damage to
developing tissues
• Umbilical arteries ~ iliac arteries ~ selective
perfusion of lower torso
• Upper body maldevelopment more apparent than
lower
• "Form follows function": Absence of normal
circulation impairs cardiac development
o Primary defect in cardiac embryogenesis

TWIN REVERSED ARTERIAL PERFUSION
• Alternate theory that cardiac malformation
primary event
• Does not explain associated structural
abnormalities as well as reversed perfusion
• Epidemiology
o 1% of monochorionic pregnancies
o 1:35,000 births

is the

Gross Pathologic & Surgical Features
• Broad spectrum of anomalies: 4 subtypes described
o Acardius acephalus
• Commonest
• Well-developed pelvis, lower extremities
o Acardius anceps
• Rudimentary cranial structures
o Acardius amorphous
• No identifiable human features
o Acardius acormus
• Rarest
• Head develops without body
• Pseudoacardius
o Malformed twin with remnants of cardiac structures

I CLINICAL

•

•

•

ISSUES

Presentation
• Most common signs/symptoms: Grossly anomalous
twin with no cardiac activity and reversed UA flow
• Described in first trimester
• Case reports of cardiac activity in both twins
o Subsequent loss of cardiac activity in one fetus
o Reverse perfusion allows continued but abnormal
growth
o Cardiac development ceases after shunt flow directs
perfusion to umbilical artery

Natural History & Prognosis
• Spontaneous closure of shunt vessels reported
• Acardiac twin anomalies are lethal
• Untreated reported pump twin mortality 50-75%
o Mortality increased with
• Hydrops
• Polyhydramnios
• Developed arms, ears, kidneys in acardiac twin
• Preterm delivery
• Goal of intervention is to interrupt blood supply to
acardiac twin
o Acardiac twin ceases to grow
o High output state for pump twin resolved
• Pump twin survival improves to 76% with
intervention
o Intrafetal radiofrequency (RF) ablation seems better
than cord occlusion
• Later gestational age at delivery
• Longer interval from intervention to delivery
• Lower technical failure rate
• Lower rate premature rupture membranes
• Lower rate preterm labor

Treatment
• Offer termination
• Offer karyotype
o 33% abnormal

•

o Trisomies commonest
• Usually associated structural anomalies seen
Conservative nonintervention
o Successful outcome reported if
• Acardiac twin smaller than pump twin
• Pump twin without signs cardiac compromise
• No polyhydramnios
Intervention indicated with
o Impending hydrops in pump twin
o Risk of extreme prematurity
Interventional techniques
o Radiofrequency ablation of intraabdominal
umbilical artery
• Color Doppler allows easy identification of vessels
• No special expertise required as US guidance
routinely used for other fetal intervention
o Endoscopic laser coagulation of shunt vessels < 24
weeks
• Fetoscopy more invasive
• Requires specialist expertise in tertiary referral
center
• Technical issues limit performance to early
pregnancy
o Ligation of acardiac umbilical cord after 24 weeks
• Endoscopic or sonographic guidance
• Risk of inadvertent ligation of pump twin's cord
• Series of 16 cases with perinatal mortality 38%
and preterm delivery 70%
Other reported treatments
o Intrafetal alcohol ablation
o Hysterotomy with selective delivery of acardiac twin
o US-guided embolization of acardiac umbilical artery
o Indomethacin for polyhydramnios
o Digoxin for hydrops

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• You will never miss this diagnosis if you check
direction of umbilical artery flow in anomalous twins

I SELECTED
1.

2.

3.

4.

5.

REFERENCES

Hirose M et al: Successful intrauterine treatment with
radiofrequency ablation in a case of acardiac twin
pregnancy complicated with a hydropic pump twin.
Ultrasound Obstet Gynecol. 23(5):509-12, 2004
Kamitomo M et al: First-trimester findings associated with
twin reversed arterial perfusion sequence. Fetal Diagn Ther.
19(2):187-90,2004
Weisz B et al: Tailored management of twin reversed
arterial perfusion (TRAP)sequence. Ultrasound Obstet
Gynecol. 23(5):451-5, 2004
Gimenez-Scherer JA et al: Malformations in acardiac twins
are consistent with reversed blood flow: liver as a clue to
their pathogenesis. Pediatr Dev Pathol. 6(6):520-30, 2003
Tan TY et al: Acardiac twin: a systematic review of
minimally invasive treatment modalities. Ultrasound
Obstet Gynecol. 22(4):409-19, 2003

TWIN REVERSED ARTERIAL PERFUSION
IIMAGE GALLERY
(Left) Sagittal ultrasound at
76 weeks shows a torso
(white curved arrow), upper
(arrow) and lower
extremities (black curved
arrow) with a soft tissue
"mass" (open arrow) in
place of normal cranium.
(Right) Cross pathology of
same case shows the lack of
normal craniofacial
structures. There is a stoma
(curved arrow) but neither
nose nor orbits. Note excess
skin folds secondary to
edema (open arrows).

Typical
(Left) Sagittal ultrasound
shows massive edema
(arrows) of an acardiac torso
with cyst formation (curved
arrow). Moving lower
extremities were present but
there were no upper
extremities and no cranium.
(Right) Color Doppler
ultrasound at 74 weeks
gestation shows umbilical
arterial flow from the normal
pump twin (arrow) toward
the abnormal, edematous
acardiac twin (curved
arrow).

Typical
(Left) Axial ultrasound image
through an acardiac twin
chest shows massive edema
of the torso (arrows). This is
the scan plane for the 4
chamber view but no
cardiac structures are seen
within the chest. (Right)
Axial ultrasound shows
cardiomegaly (arrow) in the
pump twin. Progressive
cardiomegaly and tricuspid
regurgitation required
intervention. RF ablation was
successful with a term
delivery of a normal infant.

CONJOINED TWINS

Coronal ultrasound of dicephalus twins shows two
cranial vaults (arrows), inseparable faces and a single
chest. The diaphragm (curved arrow) appears intact
above a single abdominal cavity.

Cross pathology
shows
thoraco-omphalopagus
conjoined twins. The fetuses face each other with their
spines hyperextended. Chest and abdomen are fused
with cord inserted on common omphalocele (arrow).

ITERMINOlOGY

IIMAGING FINDINGS

Abbreviations

General Features

and Synonyms

• Conjoined twins
• Siamese twins
o First Siamese twins "exhibited" in America in 1829
o Chang and Eng born in Thailand, came to USA at
age 18
o Lived long and productive lives despite being
conjoined

Definitions
• Fetal fusion of variable degree
• Nomenclature
o Site of fusion + suffix "pagus"
• Thoracopagus: Fused at chest
• Omphalopagus: Fused xiphoid to umbilicus
• Thoraco-omphalopagus: Extensive chest and
abdominal fusion
• Pygopagus: Fused at buttocks
• Ischiopagus: Fused at hips
• Craniopagus: Fused at cranial level
o Prefix "Di" + completely separate parts
• Dicephalus: Conglomerate mass with two
identifiable heads
• Diprosopus: Conglomerate skull vault with two
faces, variable extremities
• Janiceps: Synonym for diprosopus

DDx: Conjoined

Monoamniotic

Twins

• Best diagnostic clue: Contiguous skin covering
between fetuses

Ultrasonographic

Findings

• Grayscale Ultrasound
o Fetuses inseparable
o Monochorionic twinning
• Single placental mass
o No inter-twin membrane
o Variable presentation does not exclude diagnosis
• Fused tissue may be pliable, relative position not
always constant
o Often hyperextension of cervical spines
o Unusual limb positioning
o Fused umbilical cord
• 2 to 7 vessels
o Omphalopagus
• 80% share liver
• 30% incidence congenital heart disease (CHD)
o Thoracopagus
• 90% share pericardium
• 75% share heart
o Fetal echocardiography
• High incidence CHD
• Cardiac anomaly may require emergent separation

Twins

Membrane Rupture

TRAP

CONJOINED TWINS
Key Facts
Terminology

Top Differential

•
•
•
•

• Twin reverse arterial perfusion (TRAP)
• Monoamniotic twin

•
•
•
•

Fetal fusion of variable degree
Thoracopagus: Fu ed at chest
Omphalopagu : Fu ed xiphoid to umbilicus
Thoraco-omphal
pagus: Extensive che t and
abdominal fu ion
Pygopagus: Fu ed at buttocks
Ischiopagus: Fused at hips
Dicephalus:
onglomerate mass with two identifiable
heads
Dipro opu:
onglomerate skull vault with two face,
variable extremitie

Diagnoses

Pathology
• 1:50,000 to 1:100,000 births

Clinical Issues
• 40% stillborn
• 75% die within first 24 hours of life
• Ex utero intra partum lr atment (EXIT) proc dure can
be planned if prior knowledge of need for mergent
eparation

Imaging Findings

Diagnostic Checklist

• Fetuses inseparable
• Look for different heart rates

• Mu t be contiguous
conjoined twins

• Better acoustic access in utero than post delivery
• Color Doppler
o May be very helpful in craniopagus
o Complete craniopagus implies shared brain
substance
• Vessels seen coursing between brains
• Precludes separation
o Partial craniopagus when brains separate, cranium
shared
• Separate circulations
• Separation can be attempted
• Separation requires extensive reconstruction of
cranial vault
o If arachnoids separate but shared dura
• Venous sinus anatomy determines feasibility of
separation
o Color also very useful in evaluation liver blood
supply
• Common portal vein precludes separation
• Evaluate number and orientation of hepatic veins
• M-mode
o Look for different heart rates
• Proves separate circulations
• 3D
o Easier for parents to understand
o Better surface views
o 2D and Doppler better to determine degree of organ
sharing

MR Findings
• Pre-surgical planning
o Fetuses stable on placental support
o No sedation required
o Defines degree of organ sharing
o T2WI excellent for brain/renal/chest
detail
o Tl WI for additional bowel and liver information
• Clarify anomalies
o Either fetus may have lethal anomaly in addition to
being conjoined
o Information may influence management
• Termination of pregnancy
• Requirement for emergent separation
• Mode of delivery

skin covering for diagnosis

CT Findings
• Reported use for confirmation
• MRI now preferred modality

I DIFFERENTIAL

in difficult cases

DIAGNOSIS

Twin reverse arterial perfusion (TRAP)
• Umbilical arterial flow is toward abnormal fetus
• Acardiac fetus has no cardiac activity
• Fetuses are separate in TRAP

Monoamniotic

twins

• Fetuses in same sac but no contiguous skin covering
• No inter-twin membrane
• Two cords
o Cords may have common origin
o Y shaped confluence close to placental insertion site
o If cords knotted, vessels are entangled and appear
branched
• Conjoined twins inseparable so cannot tangle
cords

I PATHOLOGY
General Features
• General path comments
o Embryology
• Incomplete cleavage embryonic disc after 13th
post-conception day
• Cell lines committed to amnion and chorion
• Variable amount of embryonic development
already complete
• Non-duplicated structures shared
• Duplication of some structures occurs after
incomplete cleavage
o Parasitic conjoined twins
• Embryonic demise one twin of conjoined pair
• Residual body parts of dead twin perfused by
survivor

CONJOINED TWINS
o Thoracopagus associated with complex cardiac
malformation
o Omphalopagus
• Liver fusion common
• Often unequal liver sharing
• Biliary anomalies especially common if shared
duodenum
o Pygopagus associated with complex genitourinary
malformations
• 50% fused rectum
• Imperforate anus
• Rectovaginal fistulae
• Vaginal atresia
• Etiology
o Increased incidence in women with prolonged oral
contraceptive use
• Ovulatory dysfunction (especially in underweight
women)
• Abnormal calcium metabolism delays
implantation
• Epidemiology
o 1:50,000 to 1:100,000 births
o Craniopagus 1:2,500,000
o 70% female

IClINICALISSUES
Presentation
• Can be diagnosed in first trimester
• May occur within higher order multiple gestation

Natural History & Prognosis
•
•
•
•

Majority deliver pre term
40% stillborn
75% die within first 24 hours of life
If live to separation
o 50% survive neonatal separation
o 90% survive separation at > 4 months of age
• Bigger, stronger baby
• Placement of skin expanders prior to definitive
surgery
• Long term morbidity from associated defects
o Unequal sharing of limbs
o Incomplete pelvic girdle
o Incomplete chest wall
o Skull vault reconstruction
o Perineal reconstruction
• Vaginoplasty
• Urethroplasty
• Anoplasty
o Short bowel syndromes
o Biliary atresia/stenoses
• First successful separation reported in 1689

Treatment
• Offer termination
• If pregnancy continues
o Fetal echocardiogram
o Consider fetal MRI to assess degree of organ sharing
o Deliver at tertiary center
• Cesarean section required
o Mechanical obstruction precludes vaginal delivery

• Cesarean section in third trimester requires "classical"
(vertical) uterine incision
o Increased immediate maternal morbidity
• Longer recovery
• Increased risk of infection
o Increased risk in future pregnancies
• Uterine rupture
• Placenta accreta spectrum
• Classical caesarian section precludes vaginal
delivery in subsequent pregnancy
• Not an indication for early delivery
o Morbidity and mortality increase with low birth
weight
o Problems of prematurity add to those of being
conjoined
• Separation requires multidisciplinary team
o Outcome improved in small series utilizing
advanced imaging techniques
o 3D CT/MRI/MRA
o Barium studies required for bowel sharing
o Complex biliary anomalies are associated with
duodenal fusion
• Nuclear medicine studies may be misleading
• Consider MRI with cholangiopancreatography
(MRCP)
• Delayed separation preferred
• Emergent separation required if
o One twin with rudimentary heart
o Demise of one twin
o Lethal anomaly of one twin
• Ex utero intra partum treatment (EXIT) procedure can
be planned if prior knowledge of need for emergent
separation
• If lethal anomaly sacrificed twin may act as tissue
donor to survivor
• Huge ethical and legal dilemmas for parents and teams
involved in care of conjoined twins

I DIAGNOSTIC

CHECKLIST

Consider
• Fetal MRI to evaluate degree of organ sharing

Image Interpretation

Pearls

• Must be contiguous skin covering for diagnosis
conjoined twins
• Variable presentation does not exclude the diagnosis
• 3D US very helpful in early first trimester

I SELECTED
1.
2.

3.
4.

5.

REFERENCES

Janik JS et al: Spectrum of anorectal anomalies in
pygopagus twins. J Pediatr Surg. 38(4):608-12, 2003
Gilbert-Barness E et al: Conjoined twins: morphogenesis of
the heart and a review. Am J Med Genet. 120A(4):568-82,
2003
Mackenzie TC et al: The natural history of prenatally
diagnosed conjoined twins. J Pediatr Surg. 37:303-9, 2002
Spielman AL et al: MRI of conjoined twins illustrating
advances in fetal imaging. J Com put Assist Tomogr.
25:88-90, 2001
Kingston CA et ai: Imaging in the preoperative assessment
of conjoined twins. Radiographies. 21(5):1187-208, 2001

CONJOINED TWINS

I IMAGE

GALLERY
(Left) Coronal T7 WI MR
shows omphalopagus
conjoined twins with a
shared liver (arrows). The
fetus on the maternal right
has the larger share of the
liver. These twins also had
complex pelvic fusion.
(Right) Axial ultrasound in
different omphalopagus
twins shows a fused liver
(open arrows) in the midline.
There are separate stomachs
(arrows). Note contiguous
skin cover between the
fetuses.

(Left) Axial ultrasound in
thoracopagus conjoined
twins shows a common heart
with three ventricular
chambers(V) and a common
atrium (A). There are two
spines (arrows). Infants died
within minutes of delivery.
(Right) Axial T2WI MR
autopsy study in the same
case shows the single
common atrium (arrow) and
two of the three ventricles
(the third was seen in a
different scan plane). Note
four arms (curved arrows)
and two spines (open
arrows).

(Left) Ultrasound shows the
first trimester appearance of
conjoined twins. Two
embryos are delineated by
cursors, note a single yolk
sac (arrow). The embryos
were inseparable. Conjoined
twins confirmed at
follow-up. (Right) Gross
pathology of dicephalus
conjoined twins shows two
heads. One cranium is
anencephalic (arrow) and
the other has a cleft lip.
Multiple anomalies are
common with conjoined
twins.

TRIPLETS AND BEYOND

Ultrasound shows a trichorionic, triamnioUc triplet
gestation at 73 weeks gestational age. Thick intervening
membranes are evident (arrows) with fetuses in all 3
sacs.

ITERMINOlOGY
Abbreviations

and Synonyms

• Triplets, quadruplets, quintuplets,
• Higher order multiple gestation
• Multifetal pregnancy

sextuplets, etc.

Definitions
• Three or more fetuses
o Separate or shared chorionic sacs
o Separate or shared amniotic sacs

Ultrasound shows a thick intervening membrane in a
trichorionic triplet gestation. Two disUnct echogenic
chorions are seen (arrows). It is imperative to establish
chorionicityon the initialstudy.

• Maternal serum screening not accurate in multiple
gestations
• Ultrasound assumes key role in screening for
aneuploidy
• Second trimester
o Thin vs. thick intervening membranes
o "Twin peak" or "lambda sign"
• Chorionic tissue extends into inter-twin
membrane at placenta
• Indicates dichorionic membrane
o Anomaly screen

Imaging Recommendations

IIMAGING FINDINGS
Ultrasonographic

Findings

• First trimester
o Count total number of yolk sacs per chorionic sac
o Document presence or absence of intervening
amniotic membrane in monochorionic
pair
o Measure crown rump length (CRL)
• CRL discordance poor prognostic sign
o Cardiac activity normal range> 120 beats per
minute at 6 wk
• Low heart rate is poor prognostic signs
o Short interval follow-up indicated for viability
o Measure nuchal translucency

DDx: Multiple

Twins

Intrauterine

• Best imaging tool: Endovaginal ultrasound in 1st
trimester
• Protocol advice
o First trimester is a critical time in higher order
multiple
• Establish chorionicity
• Number of embryos
• Normal cardiac activity
o Second trimester
• Intervening membranes
• Anomaly screen
• Growth and amniotic fluid
• Cervical length (baseline)
o Third trimester
• Growth and amniotic fluid

Sacs

Embryonic Demises

Large I iemorrhage

TRIPLETS AND BEYOND
Key Facts
Terminology
• Higher order multiple ge tation
• Multi fetal pregnancy

Imaging Findings
• ount total number of yolk sac per chorioni sac
• Document pre n e or ab ence of intervening
amniotic membrane in monochorionic
pair
• Measure crown rump I ngth ( RL)
• RL discordanc
poor progno tic sign
• hort interval follow-up indicated for viability
• B st imaging tool: Endovaginalultra
ound in 1
trime ter

Pathology
• Majority of higher order multiples r ul t of assi ted
reproduction

• Cervical length

I DIFFERENTIAL

DIAGNOSIS

Twins
• Two fetuses

Multifetal gestation with 1 or more demises
or empty sacs
• Absent heartbeat
• Sac shrinks over time

Multifetal gestation with perigestational
hemorrhage
• No yolk sac or embryo
• Resolves over time

I PATHOLOGY
General Features
• Genetics
o Maternal serum screening for aneuploidy limited in
multifetal gestations
o 1st trimester nuchal translucency has important role
in screening for aneuploidy
o Invasive prenatal diagnosis by amniocentesis
o Chorionic villus sampling (CVS) available in some
centers
• Epidemiology
o Incidence of triplets or greater approximately 185
per 100,000 live births
o Majority of higher order multiples result of assisted
reproduction
• 42% assisted reproductive technology (ART)
including in vitro fertilization (IVF)
• 38% ovulation induction medications such as
Pergonal
• Only about 20% of triplets are spontaneously
conceived

• Only about 20% of
conceived
• Increa ed incidence
maternal age
• Increased incidence
age when compared

Clinical

triplet

are pontan

ou Iy

of all multiples with increasing
of aneuploidy at lower maternal
with singleton

Issues

• A ociated with significantly increased maternal and
fetal complication
• Risk increases with increasing number of fetu es
• Pret rm delivery risk is significant
• Infant death rate in triplets and above is 12 times
higher than ingleton (94 vs. 8 per 1,000 live births)

Diagnostic Checklist
• Determination

of chorionicity

asiest in 1 t trimester

• Recommendations
to limit number of embryos
transferred to limit multifetal gestations
o Maternal age
• Increased incidence of all multiples with
increasing maternal age
• 1/3 chance of multiple gestation over age 45
o Other risk factors for spontaneous multiple gestation
• Increased parity
• Geographic location (Northeastern U.S., Nebraska)
• Associated abnormalities
o Increased incidence of aneuploidy at lower maternal
age when compared with singletons
o Increased incidence of sex chromosome
abnormalities in ART pregnancies
o Discordance for structural birth defects common

Gross Pathologic & Surgical Features
• Vascular communications
common in monochorionic
placenta
o Evidence of twin-twin transfusion (TITS) in
monochorionic
pair
• Risk of unequal placental sharing increases with
increased number of fetuses
• Abnormal cord insertions including velamentous cord
• Increased risk of vasa previa
o Fetal vessels cross internal as
o Evaluate cervix with color Doppler
o May lead to catastrophic fetal bleed and demise if
unrecognized

IClINICAllSSUES
Presentation
• Most common signs/symptoms: Multiple gestational
sacs on endovaginal imaging in 1st trimester
• Other signs/symptoms: Vaginal spotting common,
often with no ultrasound evidence of bleed

Natural History & Prognosis
• Associated with significantly increased maternal and
fetal complications
o Risk increases with increasing number of fetuses

TRIPLETS AND BEYOND
• Maternal complications
o 1st trimester bleeding
o Hyperemesis gravidarum
o Ovarian hyperstimulation
syndrome
• Dehydration, electrolyte abnormalities, effusions,
need for hospitalization
• Hyperstimulated ovaries may remain enlarged
until mid-gestation
o Preeclampsia risk increased at least 2 fold in ART
pregnancies
o Gestational diabetes
o Anemia and malnutrition
o Premature labor
o Cesarean delivery required in most higher order
multiples
• Vaginal birth possible in concordantly grown
triplets with cephalic presentations
• Fetal complications
o Spontaneous reduction (embryonic demise) occurs
in up to 10% in 1st trimester
o Discordant growth
o Risk of TTTS in monochorionic
pairs
o Preterm delivery risk is significant
• Increased rates of preterm birth and low birth
weight in U.S. largely due to increasing rate of
multiple gestations
• Perinatal complication rate increases with
increasing plurality
• Approximately 90% of triplets deliver preterm
• Average gestational age at delivery of triplets is
33.5 weeks
• 13% of triplets deliver prior to 28 weeks
• Average birth weight of triplets is 1/2 that of
singletons
• Virtually 100% of quadruplets and above deliver
prematurely
• Average gestational age for delivery of quadruplets
is 30 weeks
• Increased need for newborn intensive care unit
(NBICU) admission
• Infant death rate in triplets and above is 12 times
higher than singletons (94 vs. 8 per 1,000 live
births)
• Risk of lifelong disability including cerebral palsy
common in very low birth weight survivors

Treatment
• Role of prophylactic cerclage in higher order multiples
controversial
o Likely of limited or no benefit
• Multifetal pregnancy reduction
o Reduction to twins may offer survival advantage
o Reduction to singleton controversial
o Timing of procedure 10-13 weeks gestational age
o Should be done only by someone highly skilled in
technique
o Risk of procedure involves potential loss of entire
pregnancy
o Selective reduction
• Fetuses discordant for anomaly or aneuploidy
• Following CVS in cases of advanced maternal age requires precise mapping of gestational sacs
• Delayed interval delivery

o Rare cases of previable delivery of 1 fetus of a
multifetal gestation
o Conservative management with antibiotics, cerclage,
tocolytics in attempt to prolong pregnancy
• Monthly scans for growth and fluid
o More frequent follow-up with cervical shortening,
monochorionicity
o Assessment for complications
• Discordant growth or fluid
• Anomalies
• Clinical monitoring for evidence of preterm labor,
preeclampsia, diabetes

I DIAGNOSTIC

CHECKLIST

Consider
• Document chorionicity, amnionicity and number of
fetuses in every multiple gestation
• Determination of chorionicity easiest in 1st trimester
• Baseline cervical length in 2nd trimester

Image Interpretation

Pearls

• Careful documentation
of fetal positions beginning in
the 2nd trimester to facilitate tracking of individual
fetal growth rates
• 4 quadrant amniotic fluid index not possible in
multiple gestation - use single deepest vertical pocket
per fetus
• Increased surveillance of monochorionic
pairs in a
higher order multiple gestation

I SELECTED
1.

REFERENCES

Blickstein I: Growth aberration in multiple pregnancy.
Obstet Gynecol Clin North Am. 32(1):39-54, 2005
2.
Dickey RP: Embryonic Loss in Iatrogenic Multiples. Obstet
Gynecol Clin North Am. 32(1):17-27, 2005
3.
Bhide A et al: What prenatal diagnosis should be offered in
multiple pregnancy? Best Pract Res Clin Obstet Gynaecol.
18(4):531-42,2004
4.
Brambati Bet al: First-trimester fetal reduction to a
singleton infant or twins: outcome in relation to the final
number and karyotyping before reduction by
transabdominal chorionic villus sampling. Am J Obstet
Gynecol. 191(6):2035-40, 2004
5.
Evans MI et al: Fetal reduction from twins to a singleton: a
reasonable consideration? Obstet Gynecol. 104(1):102-9,
2004
6. Magee BD: Role of multiple births in very low birth weight
and infant mortality. J Reprod Med. 49(10):812-6, 2004
7.
Topp M et al: Multiple birth and cerebral palsy in Europe: a
multicenter study. Acta Obstet Gynecol Scand.
83(6):548-53, 2004
8. Wright VC et al: Assisted reproductive technology
surveillance--United States, 2001. MMWR Surveill Summ.
53(1):1-20, 2004
9. Odibo AO et al: Screening for aneuploidy in twins and
higher-order multiples: is first-trimester nuchal
translucency the solution? Obstet Gynecol Surv.
58(9):609-14,2003
10. Salihu HM et al: Potentially preventable excess mortality
among higher-order multiples. Obstet Gynecol.
102(4):679-84,2003
11. Farkouh LJ et al: Delayed-interval delivery: extended series
from a single maternal-fetal medicine practice. Am J Obstet
Gynecol. 183(6):1499-503,2000

TRIPLETS AND BEYOND
I IMAGE GALLERY
Typical
(Left) Ultrasound shows a
trichorionic, triamniotic
triplet gestation at 17 weeks
gestation. The "twin peak"
sign (arrows) represents
placental tissue interposed
between the membranes.
(Right) Ultrasound shows
trichorionic, triamniotic
triplets at 14 weeks gestation
with thick intervening
membranes (arrows).

Variant
(Left) Ultrasound shows a
quadruplet gestation at 13
weeks. Fetuses Band C are a
monochorionic pair
separated by a thin amniotic
membrane (arrow). Thicker
dichorionic membranes are
shown by curved arrows.
(Right) Endovaginal
ultrasound shows a 6 week
triplet gestation. The upper
gestational sac contains 2
yolk sacs (arrows) indicating
this pair is monochorionic.
They are separated from the
lower yolk sac by a thick
dichorionic membrane
(curved arrow).

Variant
(Left) Ultrasound shows the
same triplet gestation at 14
weeks. A thin membrane is
seen (arrow) between
triplets A and B. A thick
dichorionic membrane is
seen between A and C
(curved arrow). (Right)
Ultrasound shows the same
triplet gestation at 19 weeks
gestation with a thin
intervening membrane
(amnion) between the
monochorionic pair
(arrows).

SECTION 14: Chromosomes

Trisomy 21
Trisomy 18
Trisomy 13
Turner Syndrome (XO)
Triploidy
Monosomy 21

14-2
14-6
14-10
14-14
14-18
14-22

TRISOMY 21

Sagittal ultrasound of the fetal head and neck shows
increased nuchal translucency (cursors) in a 73 wk fetus
with trisomy 27. The arrow points to the amnion, which
can be confused with fetal skin.

• Duodenal atresia
• Esophageal atresia
• Omphalocele: More common with trisomy 18
o Central nervous system anomalies (4%)
• Mild ventriculomegaly
• First trimester markers
o Increased nuchal translucency (NT)
• > 3 mm always abnormal
• Performed at 11-14 wks
• Crown rump length of 45-84 mm
• Biparietal diameter < 27 mm
• Detection rates near 90% when used in
conjunction with biochemical screening
o Absent nasal bone (NB)
• Midsagittal view
• Must see fetal skin separate from NB
• 60-70% T21 fetuses have absent NB
• Likelihood ratio (LR) = 35 (35 times more likely
that fetus has T21 than a priori risk)
• Second trimester minor markers (15-21 wks): ~ 1
marker seen in 50-70% of T21 fetuses
o Nuchal thickening
• Second trimester nuchal skin measures> 5 mm
• Performed on routine posterior fossa image
• Overly coronal image may cause false positive
result
• Measurement from skull outer table to
skin/amniotic fluid interface

ITERMINOLOGY
Abbreviations

and Synonyms

• Down syndrome
• Trisomy 21 (T21)

Definitions
• Autosomal trisomy of chromosome

IIMAGING

21

FINDINGS

General Features
• Best diagnostic clue
o First trimester
• Increased nuchal translucency (NT)
o Second trimester
• Multiple minor markers
• Major anomaly associated with T21

Ultrasonographic

Findings

• Major anomalies
o Cardiac defects (25%)
• Atrioventricular septal defect
• Ventricular septal defect (VSD)
• Tetralogy of Fallot
• Color Doppler helps detect small VSD
o Gastrointestinal anomalies (8%)

DDx: Other Chromosome

Turner Syndrome

Axial ultrasound through the second trimester fetal heart
shows a large atrioventricular septal defect (arrow)
Note the lack of any central valvular structures on this
four-chamber heart view.

Abnormalities

Trisomy 78

T18 - /lands

T13-VSD

TRISOMY 21
Key Facts
Terminology

Top Differential Diagnoses

• Down syndrome

• Isolated minor markers

Imaging Findings

Pathology

•
•
•
•

• First trimester ultrascreen test
• Second trimester genetic ultrasound + biochemistry
results

•
•
•
•
•
•
•

Atrioventricular septal defect
Duodenal atresia
Increased nuchal translucency (NT)
Second trimester minor markers (15-21 wks): ~ 1
marker seen in 50-70% of T21 fetuses
Nuchal thickening
Short femur and humerus
Echogenic bowel
Intracardiac echogenic focus (IEF)
Renal pelviectasis
Absent or hypoplastic nasal bone
Isolated choroid plexus cysts (CPC) are not a marker
for trisomy 21
• Most sensitive and specific single marker
• LR = 11 if isolated finding
• LR = 55 if seen with other markers
o Short femur and humerus
• Short humerus length (HL) more sensitive than
short femur length (FL)
• FL or HL compared to BPD
• Expected FL = -9.3 + 0.90 (BPD)
• Expected HL = -7.9 + 0.84 (BPD)
• Abnormal ratio = measured:expected FL ~ 0.91
and HL ~ 0.90
• LR = 5.1 for short HL, 1.5 for short FL
o Echogenic bowel
• Usually focal
• Echogenic bowel as bright as bone (grade 2)
• LR = 6.7
o Intracardiac echogenic focus (IEF)
• Bright dot in left or right ventricle of heart
• Echogenicity usually as bright as bone
• Multiple or bilateral IEF increases risk
• 3-4% of normal fetuses have IEF
• More common in Asian population (normal)
• LR = 1.8

o Renal pelviectasis
• Fluid-filled renal pelvis
• Anterior-posterior measurement on axial view
• > 3 mm considered positive
• No calyceal or ureteral distention
• 3% of normal fetuses
• LR

=

1.6

• May need follow up to rule out progressive
hydronephrosis
o Absent or hypoplastic nasal bone
• Sagittal view of fetal face
• Easier to see than in first trimester
• LR = 9

o Fifth finger clinodactyly
• Hypoplastic mid-phalanx
• Distal finger curves inward
o Sandal gap foot
• Wide gap between 1st and 2nd toes

Clinical Issues
•
•
•
•

Abnormal first trimester screen
Abnormal maternal serum quadruple test screen
Advanced maternal age (AMA) at higher risk
35% T21 born to AMA women

Diagnostic Checklist
• Correlate ultrasound findings with clinical
information when isolated minor markers are seen

o Isolated choroid plexus cysts (CPC) are not a marker
for trisomy 21
• More suggestive of trisomy 18
• Higher risk for T21 when CPC seen with other
markers for T21

Imaging Recommendations
• Best imaging tool
o First trimester NT screening
o Second trimester genetic sonogram
• Protocol advice
o First trimester NT measurements performed only by
trained sonologists
o Look for additional minor markers when one marker
is seen during second trimester screening
o Routine nuchal fold measurements in all fetuses
between 15-21 wks
o Correlate ultrasound findings with maternal serum
biochemical tests

I DIFFERENTIAL DIAGNOSIS
Isolated minor markers
• All minor markers, in isolation, are more common in
normal fetuses
• Presence of multiple minor markers raises more
suspicion
• By definition, minor markers are not pathologic

Turner syndrome
• Cystic hygroma more likely than skin thickening
o Large and with septations
• First trimester large NT
• Hydrops at presentation more common

Trisomy 18
• Choroid plexus cysts
• Major cardiac anomalies
• Major extremity anomalies
o Clenched fist with overlapping fingers
• Severe intrauterine growth restriction
• Maternal serum screen results differ from T21

TRISOMY 21
• Often seen in late 2nd or 3rd trimester
• Duodenal atresia
• Esophageal atresia
o Hydrops fetalis
• Cardiac failure
• Lymphatic drainage abnormality

Trisomy 13
•
•
•
•

Holoprosencephaly
Facial anomalies
IEF associated with severe cardiac anomalies
Polydactyly

Demographics

I PATHOLOGY
General Features
• Genetics
o Autosomal trisomy of all or part of chromosome 21
• Critical zone on chromosome 21 is 21q22.3
• Etiology
o 95% from triplicate copy of chromosome 21
o 5% caused by translocation
• Chromosome 14 or 21
• Epidemiology
o 1:700 births
o 1:500 2nd trimester fetuses
o 1:300 1st trimester fetuses

Staging, Grading or Classification Criteria
• First trimester ultrascreen test
o NT + maternal age + biochemical assay
• Data used to assign risk for T21
o 90% T21 detection rates
o Chorionic villus sampling or amniocentesis when
positive result
• Second trimester genetic ultrasound + maternal age
o Age adjusted ultrasound risk (AAUR)
o Minor marker LRnumbers used to adjust risk
• Example: Age related risk = 1:1,000, IEF seen (LR =
2), new risk = 1:500
• Second trimester genetic ultrasound + biochemistry
results
o Biochemistry results compared with minor marker

LR

• Example: Biochemistry result = 1:1,100 risk,
increased nuchal fold seen (LR = II), new risk
1:100
o 80% T21 detection rates reported

=

• Age
o Advanced maternal age (AMA)at higher risk
• AMA : ;:: 35 yrs at time of delivery
• 35% T21 born to AMA women
• 1:1,176 at 20 yrs
• 1:274 at 35 yrs
• 1:42 at 42 yrs
• Gender: M = F

Natural History & Prognosis
• Mean survival to age 20
o Prognosis related to associated anomalies, i.e.
severity of cardiac anomalies
• Mental retardation
o Mean IQ of 50-60
• 20-fold increased risk for acute leukemia
• Hearing loss in 90%

I DIAGNOSTIC

CHECKLIST

Consider
• Correlate ultrasound findings with clinical
information when isolated minor markers are seen
o Maternal age
o Biochemistry results
• Absence of second trimester findings decreases risk for
T21
o LR = 0.5

• Example: Maternal risk 1:200, no markers seen,
new risk 1:400
• Prenatal ultrasound and biochemistry testing used to
decrease number of invasive tests performed

I SELECTED REFERENCES
I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Abnormal first trimester screen
o Abnormal genetic sonogram
o Abnormal maternal serum quadruple test screen
•
.J, Alpha-fetoprotein
(AFP)
• t Human chorionic gonadotropin protein (hCG)
•
.J, Estriol
• t Inhibin A protein
o Abnormal first trimester serum biochemistry result
•
.J, Pregnancy associated plasma protein-A (PAPP-A)
• t Beta subunit human chorionic gonadotropin
hormone (l3-hCG)
o Major anomaly detected on routine study
o Incidental minor markers in low risk patient
• Other signs/symptoms
o Polyhydramnios

1.

2.

3.
4.
5.

6.

7.

Nicolaides KH: Nuchal translucency
and other
first-trimester
sonographic
markers of chromosomal
abnormalities.
Am J Obstet Gynecol. 191(1):45-67, 2004
Souter VL et al: Correlation
of second-trimester
sonographic
and biochemical
markers. J Ultrasound
Med.
23(4):505-11,2004
Bromley B et al: The Genetic Sonogram Scoring Index.
Semin Perinatol. 27(2):124-9, 2003
Graupe MH et al: Trisomy 21. Second-trimester
ultrasound.
Clin Perinatol. 28(2):303-19,
2001
Smith-Bindman
R et al: Second-trimester
ultrasound
to
detect fetuses with Down syndrome:
a meta-analysis.
JAMA. 285(8):1044-55,
2001
Winter TC et al: The "genetic sonogram": comparison
of
the index scoring system with the age-adjusted
US risk
assessment.
Radiology. 215(3):775-82,
2000
Benacerraf BR et al: Sonographic
scoring index for prenatal
detection of chromosomal
abnormalities.
J Ultrasound
Med 11:449-58, 1992

TRISOMY 21
I IMAGE

GALLERY

Typical
(Left) Axial ultrasound of the
posterior fossa shows mild
nuchal fold thickening
(cursors measured 5.5 mm).
The measurement is taken
from the outer table of the
skull to the skin/fluid
interface. (Right) Sagillal
ultrasound of the fetal face
shows a hypoplastic nasal
bone (curved arrow) often
seen with Down syndrome.
This fetus also had a
thickened nuchal fold and a
cardiac defect.

Typical
(Left) Axial ultrasound
through the heart shows an
isolated intracardiac
echogenic focus in the left
ventricle (arrow) in this fetus
with T21. The patient's
abnormal biochemistry
results also placed her at
high risk for T21. (Right)
Axial ultrasound shows
bilateral renal pelvis
distention (arrows point to
urine within the renal
pelvises). There was no
calyceal or ureteral
distention.

(Left) Sagittal ultrasound
shows diffuse body wall
edema (curved arrows). The
fetus also had a pleural
effusion. Trisomy 21 can
present with hydrops fetalis
and the prognosis is grim.
(Right) Coronal ultrasound
shows fifth finger
clinodactyly (curved arrow
points to tip of fifth finger
and arrows point to other
four). Medial curvature is
from a shortened middle
phalanx.

TRISOMY 18

Coronal ultrasound of the fetal hand shows classic
appearance of a trisomy 18 hand. The hand is
consistently clenched and there is an overlapping index
finger (arrow).

ITERMINOLOGY
Abbreviations

and Synonyms

• Edwards syndrome
• Trisomy 18 (TI8)
• Trisomy E

Definitions
• Autosomal trisomy of chromosome

IIMAGING

18

FINDINGS

General Features
• Best diagnostic clue
o Second trimester
• Multiple major anomalies
• Single major anomaly + T18 minor marker
• Choroid plexus cyst + other anomalies
• Early intrauterine growth restriction (IUGR)
o First trimester
• Increased nuchal translucency (NT)

Ultrasonographic

Findings

• Multiple major anomalies
o IUGR (51%)
• Early onset (14-24 wk)
• Symmetric IUGR

DDx: Pena-Shokeir

Coronal gross pathology correlation confirms the finding
of a clenched hand with overlapping fingers. In
particular, the index finger overlaps other flexed fingers.

• 20% with early IUGR have aneuploidy
o Cardiac defects
• Autopsy series: 90%
• Prenatal detection: 50%
• Ventricular septal defect
• Atrial septal defect
• Double outlet right ventricle
• Dextrocardia
o Musculoskeletal findings (75%)
• Findings may be unilateral or bilateral
• Clenched hands + overlapping index finger (50%)
• Arthrogryposis
• Rockerbottom foot
• Clubfoot
• Radial ray malformation
o Cystic hygroma (CH)/nuchal thickening (20%)
• CH not as large as with Turner syndrome
• May present with hydrops
o Brain anomalies (30%)
• Ventriculomegaly
• Dandy-Walker malformation
• Dandy-Walker variant (T18 common)
• Cerebellar hypoplasia
• Agenesis of the corpus callosum
o Meningomyelocele/open
spina bifida (OSB) (12%)
• Karyotype recommended when OSB seen
• T18 most common karyotype abnormality
o Gastrointestinal anomalies

Phenotype Similarities With T18
r

.

',~- ;12
• #'~

Rockerbotlom Foot

·~')·I
.~
I.... .

Clenched Hand

Wrist Contracture

Club Foot

TRISOMY 18
Key Facts
Terminology
• Edwards syndrome

Imaging Findings
•
•
•
•
•
•
•
•
•
•
•
•

Multiple major anomalies
Choroid plexus cy t + other anomalies
Early intrauterine growth restriction (IUGR)
Increa ed nuchal translucency ( T)
Cardiac defects
Clenched hands + overlapping index finger (50%)
Arthrogrypo is
Rockerbottom foot
Dandy-Walker variant (T18 common)
Omphalocele: Often bowel-containing (20%)
Strawberry shaped calvarium (45%)
Single umbilical artery (SUA)

• Omphalocele: Often bowel-containing (20%)
• Diaphragmatic hernia (T18 most common)
• Esophageal atresia (trisomy 21(T21) more
common)
o Urinary tract anomalies (35%)
• Bladder outlet obstruction
• Hydronephrosis
o Facial anomalies
• Cleft lip and palate (15%)
• Micrognathia
• Low set ears
• Hypertelorism
• Microphthalmia or anophthalmia
o Abnormal placenta
• Small placenta
• Rarely cystic (more likely triploidy)
• Second trimester markers
o Choroid plexus cysts (CPC)
• 50% of T18 have CPC
• 1% of normal fetuses have CPC
• Large CPC more worrisome
• Bilateral not associated with higher risk
• Almost always resolve by 32 wks
o Strawberry shaped calvarium (45%)
• Brachycephaly
• Lateral calvarial bulge
o Mega cisterna magna
• Cisterna magna measures> 10 mm
• From cerebellar hypoplasia in T18
• Measure cerebellar diameter to identify normals
o Single umbilical artery (SUA)
• 50% of TI8 have SUA
• 1% of normal fetuses have SUA
o Umbilical cord cyst
• Pseudocyst
• Not associated with aneuploidy when isolated
o Polyhydramnios
• IUGR + polyhydramnios most worrisome
• First trimester marker
o Increased nuchal translucency (NT)
• Subcutaneous fluid behind fetal neck measured
• 11-14 wks

• Do not change pregnancy dating when IUGR is the
correct diagnosis

Top Differential

Diagnoses

• Isolated choroid plexus cy t
• Pena-Shokeir yndrome (pseudo-trisomy
• Triploidy

18)

Clinical Issues
• Abnormal maternal serum quadruple test screen
• 2/3 of fetuses alive at 16 wks die before term
• 90% of live-born die in first year of life

Diagnostic Checklist
• Correlate ultra ound finding with clinical
information when an isolated T18 marker is seen
• Obtain open hand views and cardiac views when
isolated choroid lexus c sts are seen
• Crown rump length of 45-84 mm
• > 3 mm always abnormal
• t NT larger with TI8 than T21
• Detection rate = 90%

Imaging Recommendations
• Best imaging tool
o Second trimester genetic sonogram
o First trimester NT screening
• Protocol advice
o When CPC seen, look carefully at extremities and
heart
• Consider echocardiography
o Do not change pregnancy dating when IUGR is the
correct diagnosis
• Example: Fetus with CPC measures 2 wks small

I DIFFERENTIAL DIAGNOSIS
Isolated choroid plexus cysts
• Seen in 1% of all fetuses
• No other anomalies
o Normal hands, feet, heart
• Risk assessment for T18 advised
o Compare with maternal serum biochemistry results
o Compare with maternal age
o Risk is < 1:400 in low risk group
• Amniocentesis not done in low risk patients

Pena-Shokeir

syndrome (pseudo-trisomy

• Neurogenic arthrogryposis
o Clenched hands
o Joint contractures
• IUGR
• 92% die within first month of life

Smith-Lemli-Opitz
•
•
•
•
•

syndrome

IUGR
Clenched hands
Microcephaly
Abnormal genitalia
Autosomal recessive inheritance

18)

TRISOMY 18
o Fluid abnormalities
• Polyhydramnios with esophageal atresia
• Oligohydramnios with urinary tract anomalies
o Hydrops fetalis
• Cardiac failure
• Cystic hygroma
o Elevated AFP if OSB present

• Type II is lethal

Triploidy
• Complete extra set of chromosomes
• Severe early IUGR
o More likely asymmetric than symmetric
• Abnormal thickened cystic placenta
o Resembles molar placenta
• Multiple anomalies
• Fatal

Trisomy 13
• Holoprosencephaly
• Facial anomalies
o Cyclopia
o Proboscis
• Cardiac anomalies
• IUGR
• Polydactyly

Demographics
• Age
o Advanced maternal age (AMA) at higher risk
• AMA ~ 35 yrs at time of delivery
• Risk not as high as for T21

Natural History & Prognosis

I PATHOLOGY

• Intrauterine fetal demise
o 2/3 of fetuses alive at 16 wks die before term
• 90% of live-born die in first year of life
o Median survival 8 wks
• Survivors are severely retarded and handicapped
o Feeding difficulties
o Hypotonia

General Features

Treatment

• Genetics: Autosomal trisomy of all or most of
chromosome 18
• Etiology
o. 80% triplicate copy of chromosome 18
o 10% mosaic
o 10% translocation
• Epidemiology: Incidence: 1:3,000-6,000 births

• Termination offered
• Tocolysis and cesarean section avoided

Staging, Grading or Classification Criteria
• First trimester ultrascreen test
o NT + maternal age + biochemical assay
• Data used to assign risk for T18
o 90% detection rates
o Invasive testing offered for positive result
• Second trimester genetic ultrasound + biochemistry
o Helpful when minor markers present
o Most fetuses with T18 have major anomalies

I DIAGNOSTIC

CHECKLIST

Consider
• Correlate ultrasound findings with clinical
information when an isolated T18 marker is seen
o Maternal age
o Biochemistry results
• Amniocentesis in cases with early symmetric IUGR

Image Interpretation

Pearls

• Obtain open hand views and cardiac views when
isolated choroid plexus cysts are seen

ISElECTED REFERENCES
IClINICAllSSUES

1.

Presentation
• Most common signs/symptoms
o Multiple anomalies
o Single severe anomaly + T18 markers
• Example: Cardiac defect + CPC
o Multiple minor or subtle markers
• Example: CPC + clenched hands
o Increased first trimester NT
o Abnormal maternal serum quadruple test screen
• .j, Alpha-fetoprotein
(AFP)
• .j, Human chorionic gonadotropin
protein (hCG)
• .j, Estriol
• .j, Inhibin A protein
• 67% T18 detection rate
o Abnormal first trimester serum biochemistry result
• .j, Pregnancy associated plasma protein-A (PAPP-A)
• .j, Beta subunit HCG (~-HCG)
• 89% T18 detection rate
• Other signs/symptoms

2.
3.

4.

5.
6.

7.

8.

Bronsteen R et al: Second-trimester sonography and
trisomy 18: the significance of isolated choroid plexus cysts
after an examination that includes the fetal hands. J
Ultrasound Med. 23(2):241-5, 2004
Bronsteen R et al: Second-trimester sonography and
trisomy 18. J Ultrasound Med. 23(2):233-40, 2004
Nicolaides KH: Nuchal translucency and other
first-trimester sonographic markers of chromosomal
abnormalities. AmJ Obstet Gynecol. 191(1):45-67,2004
Stewart TL: Screening for aneuploidy: the genetic
sonogram. Obstet Gynecol Clin North Am. 31(1):21-33,
2004
Wapner R et al: First-trimester screening for trisomies 21
and 18. N EnglJ Med. 349(15):1405-13, 2003
Yeo Let al: Prenatal detection of fetal trisomy 18 through
abnormal sonographic features. J Ultrasound Med.
22(6):581-90; quiz 591-2, 2003
Gupta JK et al: Clinical significance of fetal choroid plexus
cysts. Lancet. 346(8977):724-9, 1995
Nyberg DA et al: Prenatal sonographic findings of trisomy
18: review of 47 cases. J Ultrasound Med. 12(2):103-13,
1993

TRISOMY 18
IIMAGE

GALLERY
(Left) Axial ultrasound
through the fetal calvarium
shows bilateral multiple
choroid plexus cysts (CPCJ
which vary in size (arrows).
Also, the head has a mild
strawberry shape. (Right)
Axial ultrasound through the
fetal heart of the same fetus
shows a hypoplastic left
ventricle (curved arrow) and
a small membranous
ventricular septal defect
(arrow).

(Left) Axial ultrasound shows
a bowel containing
omphalocele
(arrows).
Notice how the cord (curved
arrow) inserts on
omphalocele
(versus
gastroschisis where bowel
floats freely and cord inserts
normally). (Right) Axial
ultrasound through the
cerebellum in the same fetus
shows an inferior vermian
defect (open arrows). The
distended 4th ventricle
(curved arrow) has a
"key-hole" appearance.

(Left) Sagittal ultrasound of
rockerbottom
foot in T7 8
shows the convex curvature
of the foot (curved arrows).
The toes (open arrow) lie
parallel to the shin (arrows).
(Right) Coronal ultrasound of
another fetus with T7 8
shows radial ray
malformation.
Only the ulna
is seen (arrow) and the hand
(curved arrow) is
malpositioned
since the
radius and thumb are
missing.

TRISOMY 13

Axial ultrasound of the brain shows holoprosencephaly
in lrisomy 13. The thalamus (arrow) is fused. Minimal
brain tissue (curved arrows) is seen in lhe fluid-filled
calvarium (monoventricle).

ITERMINOlOGY
Abbreviations

and Synonyms

• Patau syndrome
• Trisomy 13 (Tl3)

Definitions
• Autosomal trisomy of chromosome

13

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Second trimester
• Multiple major anomalies in > 90%
• Holoprosencephaly
• Midline facial anomalies
• Cardiac defects
• Polydactyly
• Early intrauterine growth restriction (IUGR)
o First trimester
• Increased nuchal translucency (NT)

Ultrasonographic

Findings

• Central nervous system anomalies (70%)
o Holoprosencephaly
sequence (40%)
• Alobar, semilobar, lobar

Axial ultrasound of the heart in lrisomy 13 shows an
echogenic cardiac focus (open arrow), venlricular
septal defect (curved arrow) and a large atrial septal
defecl (arrow).

• Alobar most severe
• Fused thalami
• Monoventricle/dorsal
sac
• Variable amount of brain mantle
• Absent cavum septi pellucidi
• Variable presence of falx
• 90% with associated facial anomaly
o Microcephaly
• Head circumference < 3 standard deviations
o Cerebellar anomalies
• Dandy-Walker malformation/variant
• Cerebellar hypoplasia + mega cisterna magna
o Agenesis of corpus callosum
o Ventriculomegaly
• May be mild
• Facial anomalies (50%)
o "The face predicts the brain"
o Orbit anomalies
• Cyclopia
• Hypotelorism
• Microphthalmos
• Anophthalmia
o Proboscis
• Tube-like nose
• Located superior to orbits
• Seen best on profile view
o Midline or bilateral cleft lip
• Palate always involved

DDx: Anomalies Similar To TB Seen With Meckel Gruber Syndrome

MG Cystic KidneY5

MC Polydactyly

MC Encephalocele

MC Encephalocele

TRISOMY 13
Key Facts
Terminology

Top Differential

• Patau syndrome

• Meckel-Gruber yndrome
• Hydranencephaly
• Trisomy 18

Imaging Findings
•
•
•
•
•
•
•
•
•
•
•
•

•

•

•

•

•
•

•

Holoprosen ephaly sequence (40%)
"The face predicts the brain"
yclopia
Proboscis
Midline or bilateral cleft lip
Post axial polydactyly (75%)
ardiac defect (800AI)
Echogenic kidneys
Omphalocel : Often bowel containing
lUGR (501}())
Echogenic ardiac focus (30(}())
lncrea ed T

• Premaxillary protrusion on profile view
o Low set ears
Musculoskeletal findings (50%)
o Post axial polydactyly (75%)
• Extra finger on ulna side
o Club feet
o Rockerbottom feet
• More common with trisomy 18 (TI8)
o Clenched hand/overlapping
digits
• More common with T18
Cardiac defects (80%)
o Ventricular septal defect
o Atrial septal defect
o Hypoplastic left heart (HLH)
• + Intracardiac echogenic focus (IEF) highly
associated with T13
o Aortic atresia
o Mitral atresia
o Pulmonary stenosis
o Anomalous pulmonary venous return
Renal anomalies (50%)
o Echogenic kidneys
• Cystic dysplasia
• Often enlarged
o Hydronephrosis
o Duplication anomalies
Gastrointestinal anomalies
o Omphalocele: Often bowel containing
o Umbilical hernia
o Echogenic bowel
IUGR (50%)
o Early onset
o lUGR + polyhydramnios worrisome for T13 and T18
Second trimester markers
o Almost never isolated
o Echogenic cardiac focus (30%)
o Single umbilical artery (25%)
o Increased nuchal thickening/cystic
hygroma (20%)
o Echogenic bowel (5%)
First trimester marker
o Increased NT
• Subcutaneous fluid behind fetal neck

Diagnoses
(MG)

Clinical Issues
• Holoprosencephaly
i hallmark anomaly
• Most survive to delivery
• 750;()live-born die in first 6 month of life

Diagnostic Checklist
• Suspect TI3 when midline
anomalie
een
• Early IU R rai e suspicion
• onsider MRI when ubtle
• Routinely vi ualize cavum

brain, heart or facial
for aneuploidy
brain anomalies suspected
epti pellucidi

• Measured 11-14 wks
• Crown rump length of 45-84 mm
• > 3 mm always abnormal
• Detection rate = 80%
o May see proboscis in first trimester

Other Modality

Findings

• Fetal MR
o Can detect subtle brain anomalies
• Lobar holoprosencephaly
• Absence of cavum septi pellucidi
• Agenesis of corpus callosum

Imaging Recommendations
• Best imaging tool
o Second trimester genetic sonogram
o First trimester NT screening
• Protocol advice
o Suspect brain anomaly when midline facial anomaly
seen
o Consider fetal MR when CNS findings are minimal

I DIFFERENTIAL
Meckel-Gruber

DIAGNOSIS
syndrome (MG)

• Brain anomalies
o Encephalocele
o Dandy-Walker
o Holoprosencephaly
(rare)
• Polydactyly
• Echogenic kidneys
• Autosomal recessive with 25% recurrence risk

Holoprosencephaly

without

T13

• Alobar
• Semilobar
• Lobar
o May be missed with ultrasound
• Less severe cases are compatible with life

Hydranencephaly
• In utero brain infarction
• Fluid filled calvarium mimics monoventricle

TRISOMY 13
• + Beta subunit HCG (~-HCG)
• + Pregnancy associated plasma protein-A (PAPP-A)

• No associated anomalies

Trisomy 18
• Choroid plexus cyst + other anomalies common
• Multiple severe anomalies
o Cardiac anomalies
o Musculoskeletal
• Clenched hand with overlapping fingers
o Holoprosencephaly not typical
• Early IUGR
• Increased NT in first trimester

I PATHOLOGY
General Features
• General path comments
o Holoprosencephaly
• Failure of prosencephalon cleavage
• Cleavage defects in brain, ventricles and face
• Genetics: Autosomal trisomy of chromosome 13
• Etiology
o 75% triplicate copy of chromosome 13
o 20% translocation
o 5% mosaic
• Epidemiology
o 1:6,000 births
• Less common than trisomy 21 (T21) and T18
o 1% spontaneous abortions are T13
o Associated with advanced maternal age

Staging, Grading or Classification Criteria
• First trimester ultras ere en test
o NT + maternal age + biochemistry assay
• Data used to assign risk for aneuploidy
o 90% detection rates
o Invasive testing offered for positive result
• Holoprosencephaly brain mantle classification
o Pancake
• Brain flattened at base of skull
• Large dorsal monoventricle
o Cup
• Brain mantle anterior and base of skull
• Does not cover monoventricle
o Ball
• Brain mantle surrounds monoventricle

I CLINICAL

• Results identical for trisomy 18
• 90% T13 detection rate

Demographics
• Age
o Advanced maternal age (AMA) at higher risk
• AMA: ~ 35 yrs at time of delivery

Natural History & Prognosis
• Most survive to delivery
• 75% live-born die in first 6 months of life
o Mean survival of 180 days
o < 5% survive beyond three years
o T13 mosaics with better survival
• Survivors are severely retarded and handicapped
o Hypotonia and hypertonia
o Seizures
o Feeding difficulties

Treatment
• Termination offered
• Tocolysis and cesarean section avoided

I DIAGNOSTIC
Consider

• Suspect T13 when midline brain, heart or facial
anomalies seen
• Early IUGR raises suspicion for aneuploidy
• Consider MRI when subtle brain anomalies suspected

Image Interpretation

I SELECTED
1.

2.

• Most common signs/symptoms
o Multiple second trimester anomalies
• Holoprosencephaly is hallmark anomaly
o Increased first trimester nuchal translucency
• Most common aneuploidy is T21
o Abnormal maternal serum quadruple test screen
• Mildly t alpha-fetoprotein (AFP)
• t Inhibin A protein
• Normal human chorionic gonadotropin (HCG)
protein
• Normal estriol
• 71% T13 detection rate
o Abnormal first trimester serum biochemistry result

Pearls

• Routinely visualize cavum septi pellucidi
o Biparietal diameter view
• Look carefully at fetal brain when midline or bilateral
cleft lip/palate diagnosed
• Count finger and toes when holoprosencephaly
diagnosed

ISSUES

Presentation

CHECKLIST

3.

4.

5.
6.
7.
8.

REFERENCES

Chen M et al: Trisomy 13 mosaicism: study of serial
cytogenetic changes in a case from early pregnancy to
infancy. Prenat Diagn. 24(2):137-43, 2004
Nicolaides KH: Nuchal translucency and other
first-trimester sonographic markers of chromosomal
abnormalities. Am J Obstet Gynecol. 191(1):45-67, 2004
Stewart TL: Screening for aneuploidy: the genetic
sonogram. Obstet Gynecol Clin North Am. 31(1):21-33,
2004
Chen M et al: Trisomy 13 manifested as hypoplastic left
heart and other structural abnormalities. Prenat Diagn.
23(13):1102-3, 2003
Tongsong T et al: Sonographic features of trisomy 13 at
midpregnancy. Int J Gynaecol Obstet. 76(2):143-8, 2002
Nyberg DA et al: Sonographic markers of fetal trisomies:
second trimester. J Ultrasound Med. 20(6):655-74, 2001
Tongsong T et al: Prenatal sonographic diagnosis of
holoprosencephaly. J Med Assoc Thai. 81(3):208-13, 1998
Lehman CD et al: Trisomy 13 syndrome: prenatal US
findings in a review of 33 cases. Radiology. 194(1):217-22,
1995

TRISOMY 13
IIMAGE

GALLERY

Typical
(Left) Coronal ultrasound of
the face shows cyclopia
(curved arrow) and a
proboscis (arrow) superiorly.
This fetus also had alobar
holoprosencephaly and
single umbilical artery (open
arrow). (Right) Coronal gross
pathology of another fetus
with T73 shows dysplastic
tissue overlying a single orbit
(curved arrow), a tube like
proboscis (arrow), and low
set ears.

Typical
(Left) Sagittal ultrasound of
the fetal face shows
premaxillary protrusion
(arrow). The mass-like region
under the nose is central
palate dysplasia associated
with bilateral cleft lip and
palate. (Right) Coronal
ultrasound of the hand in the
same fetus shows
polydactyly (arrows point to
six fingers). While brain
findings were minimal in this
case, T73 was suspected
given these two findings and
a cardiac defect.

(Left) Axial ultrasound of the
cord insertion site shows a
small bowel containing
omphalocele (arrows). This
fetus with T73 also had
holoprosencephaly.
Omphalocele with bowel is
highly associated with
aneuploidy. (Right) Sagittal
ultrasound shows enlarged
echogenic kidney (calipers,
arrows). Occasional
macrocysts are seen (curved
arrow) though mostly, the
increased echogenicity is
from microcysts.

TURNER SYNDROME

Sagittal ultrasound shows markedly increased nuchal
translucency (arrow) as well as diffuse body wall edema
(curved arrows). Notice presence of thin septations in
cystic hygroma.

ITERMINOlOGY
Abbreviations
•
•
•
•

and Synonyms

Ullrich-Turner syndrome
XO syndrome (XO)
Monosomy X
45X syndrome

Definitions
• Deficiency or absence of one sex chromosome

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Second trimester
• Female fetus with large, septated cystic hygroma
(CH)

• Hydrops fetalis
o First trimester
• Markedly increased nuchal translucency

Ultrasonographic

Findings

• Nuchal cystic hygroma
o Hallmark anomaly
• 60% of all fetuses with CH have XO
o Fluid collection of posterior and lateral neck

(XO)

Clinical photograph
shows a large cystic hygroma
(arrows) and body wall edema (curved arrows) in
another fetus with Turner syndrome.
Upper body
edema is usually worse than lower.

• Large CH most common
• May be confused with amniotic fluid
o Internal septations
• Midline thick septum is nuchal ligament
• Multiple thin septations common
o Small CH
• Mimics edematous thickened nuchal fold
• More common with trisomy 21 than XO
• Non-immune hydrops
o Excess fetal fluid accumulation
• Fluid in two separate areas
• Example: Skin edema + pleural effusion
• Example: Pleural effusion + ascites
o Skin edema
• Lymphangiectasia
• Usually diffuse
o Chest
• Bilateral pleural effusions
• Pericardial effusion
o Abdomen
• Ascites
• Cardiovascular anomalies (60%)
o Coarctation of aorta (45%)
• Narrow aortic arch
• Difficult diagnosis
o Hypoplastic left heart (15%)
• Genitourinary findings
o Horseshoe kidneys

DDx: Anomalies Similar To Turner Syndrome Seen With Trisomy 21

Increased

NT In T27

Small CH In T27

AV Canal In T27

Pelviectasis

In T27

TURNER SYNDROME (XO)
o 15% mosaic
o 5% partial defect of one X
• Long arm duplication [46, X, i(Xq)]
• Etiology
o CH
• Failed or delayed connection between internal
jugular veins and nuchal lymph sacs
• Hypoplastic dermal lymph vessels
o Hydrops
• Fluid overload from lymphatic failure
• Epidemiology
o Not associated with advanced maternal age
o Live birth rate is 1:3,000 females
o 25% spontaneous loss from aneuploidy are XO
o 9% of all first trimester spontaneous abortions are

o Infertile
• Ovarian dysgenesis
o Cardiac defects
• Bicuspid aortic valve most common
• Aorta coarctation
o Cubitus valgus
o Short 4th metacarpal/metatarsal
o Normal verbal IQ
o Delayed motor skills
o Hearing impairment

Treatment
• Termination offered
o Prognosis with hydrops is dismal
• Respiratory resuscitation often necessary at delivery

XO

I CLINICAL

I DIAGNOSTIC
ISSUES

Presentation
• Most common signs/symptoms
o Second trimester anomalies
• Cystic hygroma
• Hydrops fetalis
• Horseshoe kidney
o Increased first trimester NT
• Largest NT seen with XO
• Septations common
• Associated hydrops
o Abnormal maternal serum quadruple test screen
• + Alpha-fetoprotein (AFP)
• + Estriol
• + Human chorionic gonadotropin protein (HCG)
• + Inhibin
• t HCG if hydrops
• t Inhibin if hydrops
• Detection rate of XO 53%
o Abnormal first trimester serum biochemistry result
• Used in conjunction with NT
• Mildly t beta subunit HCG
• + Pregnancy associated plasma protein-A (PAPP-A)
• 96% first trimester detection rate
• Other signs/symptoms
o Oligohydramnios
• Intrauterine growth restriction
• Renal dysfunction
• Hydrops and heart failure
o Polyhydramnios
• Less common
• Hydrops

Demographics
• Age
o Advanced maternal age (AMA) not at higher risk
• AMA ~ 35 yrs at time of delivery
• Gender: Female fetus

Natural History & Prognosis
• Majority spontaneously abort in first trimester
• Better prognosis for mosaic 45X
• Survivors
o Webbed neck
o Short stature

CHECKLIST

Consider
• Suspect Turner syndrome with cystic hygroma

Image Interpretation

Pearls

• Obtain routine aorta arch views
o Compare caliber with ductal arch
• Look for horseshoe kidney

ISELECTED REFERENCES
Hamamy HA et al: Parental decisions following the
prenatal diagnosis of sex chromosome abnormalities. Eur J
Obstet Gynecol Reprod BioI. 116(1):58-62, 2004
2. Bronshtein M et al: A characteristic cluster of fetal
sonographic markers that are predictive of fetal Turner
syndrome in early pregnancy. Am J Obstet Gynecol.
188(4):1016-20,2003
3.
Surerus E et al: Turner's syndrome in fetal life. Ultrasound
Obstet Gynecol. 22(3):264-7, 2003
4.
Haak MC et al: Cardiac malformations in first-trimester
fetuses with increased nuchal translucency: ultrasound
diagnosis and postmortem morphology. Ultrasound Obstet
Gynecol. 20(1):14-21, 2002
5.
Huang B et al: Prenatal diagnosis of 45,X and 45,X
mosaicism: the need for thorough cytogenetic and clinical
evaluations. Prenat Diagn. 22(2):105-10, 2002
6. Spencer K et al: Maternal serum free beta-hCG and PAPP-A
in fetal sex chromosome defects in the first trimester.
Prenat Diagn. 20(5):390-4, 2000
7.
von Kaisenberg CS et al: Lymphatic vessel hypoplasia in
fetuses with Turner syndrome. Hum Reprod. 14(3):823-6,
1999
8.
Martinez JM et al: Fetal heart rate and nuchal translucency
in detecting chromosomal abnormalities other than Down
syndrome. Obstet Gynecol. 92(1):68-71, 1998
9.
Gravholr CH et al: Prenatal and postnatal prevalence of
Turner's syndrome: A registry study. BM]. 312:16-21, 1996
10. Saller DN et at: Multiple-marker screening in pregnancies
with hydrops and non-hydropic Turner syndrome. Am J
Obstet Gynecol. 167:1021-4, 1992
11. Phillips HE et al: Intrauterine fetal cystic hygroma:
Sonographic detection. AJR. 136:799-802, 1981
1.

TURNER SYNDROME
o 15% mosaic
o 5% partial defect of one X
• Long arm duplication [46, X, i(Xq)]
• Etiology
o CH
• Failed or delayed connection between internal
jugular veins and nuchal lymph sacs
• Hypoplastic dermal lymph vessels
o Hydrops
• Fluid overload from lymphatic failure
• Epidemiology
o Not associated with advanced maternal age
o Live birth rate is 1:3,000 females
o 25% spontaneous loss from aneuploidy are XO
o 9% of all first trimester spontaneous abortions are

(XO)

o Infertile
• Ovarian dysgenesis
o Cardiac defects
• Bicuspid aortic valve most common
• Aorta coarctation
o Cubitus valgus
o Short 4th metacarpal/metatarsal
o Normal verbal IQ
o Delayed motor skills
o Hearing impairment

Treatment
• Termination offered
o Prognosis with hydrops is dismal
• Respiratory resuscitation often necessary at delivery

XO

I DIAGNOSTIC

CHECKLIST

ICLINICALISSUES

Consider

Presentation

• Suspect Turner syndrome with cystic hygroma

• Most common signs/symptoms
o Second trimester anomalies
• Cystic hygroma
• Hydrops fetalis
• Horseshoe kidney
o Increased first trimester NT
• Largest NT seen with XO
• Septations common
• Associated hydrops
o Abnormal maternal serum quadruple test screen
• ~ Alpha-fetoprotein
(AFP)
• ~ Estriol
• ~ Human chorionic gonadotropin protein (HCG)
• ~ Inhibin
• t HCG if hydrops
• t Inhibin if hydrops
• Detection rate of XO 53%
o Abnormal first trimester serum biochemistry result
• Used in conjunction with NT
• Mildly t beta subunit HCG
• ~ Pregnancy associated plasma protein-A (PAPP-A)
• 96% first trimester detection rate
• Other signs/symptoms
o Oligohydramnios
• Intrauterine growth restriction
• Renal dysfunction
• Hydrops and heart failure
o Polyhydramnios
• Less common
• Hydrops

Demographics
• Age
o Advanced maternal age (AMA) not at higher risk
• AMA ~ 35 yrs at time of delivery
• Gender: Female fetus

Natural History & Prognosis
• Majority spontaneously abort in first trimester
• Better prognosis for mosaic 45X
• Survivors
o Webbed neck
o Short stature

Image Interpretation

Pearls

• Obtain routine aorta arch views
o Compare caliber with ductal arch
• Look for horseshoe kidney

ISELECTED REFERENCES
Hamamy HA et al: Parental decisions following the
prenatal diagnosis of sex chromosome abnormalities. Em J
Obstet Gynecol Reprod BioI. 116(1):58-62, 2004
2.
Bronshtein M et al: A characteristic cluster of fetal
sonographic markers that are predictive of fetal Turner
syndrome in early pregnancy. Am J Obstet Gynecol.
188(4):1016-20, 2003
3.
Surerus E et al: Turner's syndrome in fetal life. Ultrasound
Obstet Gynecol. 22(3):264-7, 2003
4.
Haak MC et al: Cardiac malformations in first-trimester
fetuses with increased nuchal translucency: ultrasound
diagnosis and postmortem morphology. Ultrasound Obstet
Gynecol. 20(1):14-21, 2002
5. Huang B et al: Prenatal diagnosis of 45,X and 45,X
mosaicism: the need for thorough cytogenetic and clinical
evaluations. Prenat Diagn. 22(2):105-10, 2002
6. Spencer K et al: Maternal serum free beta-hCG and PAPP-A
in fetal sex chromosome defects in the first trimester.
Prenat Diagn. 20(5):390-4, 2000
7.
von Kaisenberg CS et al: Lymphatic vessel hypoplasia in
fetuses with Turner syndrome. Hum Reprod. 14(3):823-6,
1999
8.
Martinez JM et al: Fetal heart rate and nuchal translucency
in detecting chromosomal abnormalities other than Down
syndrome. Obstet Gynecol. 92(1):68-71, 1998
9. Gravholr CH et al: Prenatal and postnatal prevalence of
Turner's syndrome: A registry study. BM]. 312:16-21, 1996
10. Saller DN et al: Multiple-marker screening in pregnancies
with hydrops and non-hydropic Turner syndrome. Am J
Obstet Gynecol. 167:1021-4, 1992
11. Phillips HE et al: Intrauterine fetal cystic hygroma:
Sonographic detection. AJR. 136:799-802, 1981
1.

TURNER SYNDROME

I IMAGE

(XO)

GAllERY
(Left) Axial ultrasound shows
a large nuchal cystic
hygroma in fetus with XO
and oligohydramnios.
The
fluid from the cystic hygroma
(curved arrows) mimics
amniotic fluid. The central
septation is the nuchal
ligament (arrow). Mild scalp
edema is also seen (open
arrows). (Right) Cross
pathology of a large CH in
another fetus shows multiple
thin and thick septations
(arrows) inside the hygroma.
Multiple septations in CH is
a common finding.

(Left) Axial ultrasound shows
bilateral pleural effusion
(curved arrows) and
hypoplastic left ventricle
(open arrow). The normal
lung is surrounded by
anechoic fluid and the left
(LT) ventricle is smaller than
the right (RT). This XO fetus
also had cystic hygroma and
body wall edema. (Right)
Sagittal ultrasound shows
ascites (curved arrow) and
skin edema (arrows) in
another XO fetus with a
cystic hygroma.

(Left) Coronal ultrasound
shows a horseshoe kidney. A
central isthmus of renal
tissue connects the kidneys
(arrows). Mild renal pelvis
distention is also seen (open
arrows). (Right) Coronal
gross pathology shows a
horseshoe kidney (arrows) in
another fetus. Ureters (open
arrows) are seen joining the
bladder (curved arrows).
Photo is taken from the back
and the bowel is anterior.

TRIPLOIDY

Sagittal ultrasound of a 74 week pregnancy shows a
markedly
enlarged,
cystic placenta.
There is
oligohydramnios with a small fetus crowded posteriorly
(arrow). This is typical of triploidy of paternal origin.

o Maternal
• Placenta normal or small
• Profound asymmetric IVGR

ITERMINOLOGY
Abbreviations

and Synonyms

• Partial mole
o Occurs when extra set of chromosomes

is paternal

Definitions
• 69 chromosomes
o One entire extra haploid set

IIMAGING

FINDINGS

General Features
• Best diagnostic clue
o First trimester
• Increased nuchal translucency
o Second trimester
• Early, severe asymmetric intrauterine growth
restriction (lVGR)
• Ventriculomegaly + syndactyly (3rd and 4th
digits) most common combination of findings
• Findings vary according to source of extra
chromosome
o Paternal (diandry)
• Hydropic, cystic placenta (partial mole)
• More commonly abort in 1st trimester
• Symmetric IVGR if pregnancy continues

DDx: Cystic Appearing

Cross pathology of a placenta from a triploid
pregnancy Hydropic villi give the placental surface an
irregular, cystic appearance and results in the classic
ultrasound findings.

Ultrasonographic

Findings

• Often multiple malformations
• Placenta variable appearance based on origin of extra
chromosomes
o Large, cystic placenta
• Extra haploid chromosome set paternal
• Partial mole
o Small or normal
• Extra haploid chromosome set maternal
• Severe IVGR
o Early onset
• Can be diagnosed by 11 weeks
o Asymmetric IUGR if maternal origin
• Abdomen and skeleton more profoundly affected
than head
o Symmetric IVGR more common if paternal origin
• Central nervous system
o Ventriculomegaly
o Dandy-Walker spectrum
o Agenesis of corpus callosum
o Holoprosencephaly
spectrum
o Neural tube defects
• Face/neck
o Micrognathia

Placenta With Fetus

Placental

Lakes

TRIPLOIDY
Key Facts
Terminology

Top Differential

• Partial mole
• 69 chromosome

• Twin pregnancy: Hydatidiform mole with coexistent
fetu
• D mise with hydropic degen ration of placenta
• Infection
• Trisomie 18, 13

Imaging Findings
• L:arly,severe asymm tric intrauterine growth
re triction (IUGR)
• Ventriculomegaly + yndactyly (3rd and 4th digit)
most common
ombination of finding
• Often multipl malformations
• Placenta variable appearance ba ed on origin of extra
chromosome
• ardiac defect
• Oligohydramnios common
• Ovarian theca lutein cy t

•

•
•

•

•

•

o Hypertelorism
o Microphthalmia
o Cleft lip/palate
o Cystic hygroma
Musculoskeletal
o Syndactyly 3rd and 4th digit
o Clubbed feet
Cardiac defects
Gastrointestinal
o Omphalocele
• Usually small bowel containing
o Umbilical hernia
Genitourinary
o Hydronephrosis
o Renal dysplasia
o Hypospadias
o Cryptorchidism
o Ambiguous genitalia
Amniotic fluid
o Oligohydramnios common
• May be profound
• Makes evaluation of anomalies difficult
o Polyhydramnios reported rarely
Other anomalies
o Single umbilical artery
o Ovarian theca lutein cysts
• Seen with partial mole

Imaging Recommendations
• When to have high index of suspicion
o Abnormal cystic placenta
o Severe asymmetric IUGR regardless of placental
appearance
• Short follow-up interval in 1st trimester (7-10 days)
o IUGR and anomalies seen early
• Perform endovaginal for fetal anatomy if poor
visualization
o Ventriculomegaly + syndactyly most common
combination of findings

Diagnoses

Pathology
• 1-2% of conceptions
• 25-301)i1 of 1st trime ter abortuses

Diagnostic Checklist
• Be suspicious of triploidy in 2 different circumstances
• Anytime there i an enlarged, cystic placenta
• In the etting of s vere asymmetric lU R even if the
placenta i normal

I DIFFERENTIAL

DIAGNOSIS

Twin pregnancy: Hydatidiform
coexistent fetus

mole with

• Living fetus has a separate, normal appearing placenta
• Fetus should have normal anatomy and growth

Demise with hydropic degeneration
placenta

of

• Represents hydropic change without trophoblastic
proliferation
• Can look identical to triploidy and pathologist must
make diagnosis

Placental lakes
•
•
•
•

Commonly seen after 20 weeks
May see slow blood flow
Often change size and shape during examination
Fetus is normal

Placental pseudomoles
• Mesenchymal dysplasia of placenta results in villus
hydrops
• Often seen with preeclampsia and normal fetus
• May be seen with placentomegaly and
Beckwith- Wiedemann syndrome

Infection
•
•
•
•
•

Varies according to infectious agent
Intracranial and intrahepatic calcifications
IUGR does not manifest as early
Ventriculomegaly
Positive maternal serology

Trisomies 18, 13
• Many fetal findings overlap
• Placenta is usually normal
• IUGR does not manifest as early

Neu-Laxova

syndrome

• Early IUGR
• Ichthyosis
• Severe microcephaly

common

TRIPLOIDY

I PATHOLOGY
General Features
• Genetics
o Sporadic occurrence
o Rare recurrent cases reported
060% 69,XXY
037% 69,XXX
03% 69,XYY
• Etiology
o Diandry
• Extra chromosome set paternal
• Fertilization with 2 sperm most common
(dispermy)
• Fertilization with diploid sperm
• More common in 1st trimester abortuses
o Digyny
• Extra chromosome set maternal
• Diploid egg
o Tetraploidy may also occur
• Four sets of chromosomes
• Ratio of tetraploidy:triploidy is 1:3
• Abort in 1st trimester
• Epidemiology
o 1-2% of conceptions
o 25-30% of 1st trimester abortuses
o Rare at birth

Microscopic

Features

• Partial molar placental changes usually present with
diandry
o Two populations of villi
o Enlarged villi (~ 3 mm)
o Irregular villi with scalloped borders and
trophoblastic inclusions
o Trophoblastic hyperplasia

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Vaginal bleeding most common maternal
presentation
o Ventriculomegaly + syndactyly most common
combination of findings
• Anomalies and IUGR seen in 1st trimester
• Laboratory abnormalities vary according to source of
extra chromosomes
o Paternal
• t Human chorionic gonadotropin protein (HCG)
• t Alpha-fetoprotein (AFP)
• t Inhibin A
• t Pregnancy associated plasma protein A (PAPP-A)
o Maternal
• t HCG
• t AFP
• t Estriol
• t PAPP-A
o Preeclampsia
• Occurs with partial mole
• Often presents < 20 weeks
• May be severe

Demographics
• Age
o Advanced maternal age not at higher risk
• Incidence may actually decrease

Natural History & Prognosis
• Most spontaneously abort before 20 weeks
o Paternal (diandry) early demise
• Lethal in neonatal period if live birth

Treatment
• Chorionic villus sampling or amniocentesis for
karyotype
• Termination offered
• Monitor mother for preeclampsia
• Avoid fetal monitoring and cesarian section

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Be suspicious of triploidy in 2 different circumstances
o Anytime there is an enlarged, cystic placenta
o In the setting of severe asymmetric IUGR even if the
placenta is normal

I SELECTED

REFERENCES

Blaicher W et al: Dandy-Walker malformation as
sonographic marker for fetal triploidy. Ultraschall Med.
23(2):129-33, 2002
2.
Giannattasio M et al: Preeclampsia and fetal triploidy: a
rarely reported association in nephrologic literature. ]
Nephrol. 15(1):74-8,2002
3. Daniel A et al: Karyotype, phenotype and parental origin in
19 cases of triploidy. Prenat Diagn. 21(12):1034-48, 2001
4.
Genest DR: Partial hydatidiform mole: clinicopathological
features, differential diagnosis, ploidy and molecular
studies, and gold standards for diagnosis. lnt] Gynecol
Pathol. 20(4):315-22, 2001
5.
Spencer K et al: Screening for triploidy by fetal nuchal
translucency and maternal serum free beta-hCG and
PAPP-Aat 10-14 weeks of gestation. Prenat Diagn.
20(6):495-9, 2000
6.
Mittal TK et al: Triploidy: antenatal sonographic features
with post-mortem correlation. Prenat Diagn.
18(12):1253-62, 1998
7.
]auniaux E et al: Prenatal diagnosis of triploidy during the
second trimester of pregnancy. Obstet Gynecol.
88(6):983-9, 1996
8. ]auniaux E et al: Partial mole and triploidy: screening
patients with first-trimester spontaneous abortion. Obstet
Gynecol. 88(4 Pt 1):616-9, 1996
9. Lockwood C et al: Sonographic features of the triploid
fetus. Am] Obstet Gynecol. 157(2):285-7, 1987
10. Crane]P et al: Antenatal ultrasound findings in fetal
triploidy syndrome.] Ultrasound Med. 4(10):519-24, 1985
1.

TRIPLOIDY
I IMAGE GALLERY
(Left) Axial ultrasound of the
brain shows
ventriculomegaly (cursors) in
this fetus with triploidy.
(Right) Fetal biometry is
significant for asymmetric
IUCR with the abdomen
being the most severely
affected. Early asymmetric
IUCR is very concerning for
triploidy especially when
other anomalies such as
ventriculomegaly are
present.

(Left) Ultrasound of the
placenta in the same case
shows that it is small but
otherwise normal in
appearance. This case is
typical for a maternal origin
of the triploidy (digyny).
(Right) Clinical photograph
of a fetus showing the typical
features of triploidy. Note
the relative small size of the
body to the head. There is
also bilateral syndactyly of
the third and fourth digits
(arrows), another common
feature seen in triploidy.

(Left) Sagittal ultrasound of
the right ovary in a triploid
pregnancy shows an
enlarged cystic ovary
(cursors). This was bilateral
and is a typical finding of
theca lutein ovarian cysts,
which sometimes can be
seen in triploid pregnancies.
(Right) Intra-Operative
photograph of the uterus and
ovaries in another case of
triploidy shows bilateral
theca lutein cysts with the
ovaries (arrows).

MONOSOMY21

Coronal T2WI MR of a fetus with monosomy 21 and
semilobar holoprosencephaly. There is a monoventricle
with fused frontal lobes (open arrow) and separate
thalami (curved arrow).

ITERMINOlOGY
Abbreviations

and Synonyms

• 21 deletion syndrome, chromosome
syndrome, del(21) syndrome

G1 deletion

Definitions
• Partial or complete deletion of chromosome

IIMAGING

21

growth restriction

I DIFFERENTIAL

Findings

DIAGNOSIS

Trisomy 21 (T21)

• Thickened nuchal fold
• Central nervous system (CNS)
o Holoprosencephaly
spectrum
o Microcephaly
o Dysgenesis of the corpus callosum
o Cleft lip/palate
• Extremity abnormalities
o Syndactyly/camplodactyly
o Clinodactyly
o Reduction/malposition
defects

• Many overlapping features
• CNS findings much less common

Trisomy 13 (T13)
•
•
•
•
•

DDx: Conditions Mimicking

Trisomy 21

Findings

• Fetal MR: Clarify subtle central nervous system
anomalies
• Fetal echocardiogram: Evaluate cardiac defects

General Features

Ultrasonographic

• Genitourinary anomalies
o Pyelectasis/megacystis
• Cardiac defects
o Atrial or ventricular septal defect
o Pulmonic or subaortic stenosis
o Tricuspid atresia
o Tetralogy of Fallot
• Other minor markers
o Single umbilical artery

Other Modality

FINDINGS

• Best diagnostic clue
o Early or severe intrauterine
o Multiple anomalies

Sagittal ultrasound shows thickening of the nuchal fold
(arrow). Although this finding is more typical of trisomy
21, it may be seen with other chromosomal
abnormalities, as in this case of monosomy 21.

Monosomy

Trisomy 21

Holoprosencephaly
Craniofacial anomalies
Omphalocele
Cystic kidneys
Polydactyly

21

Holopros

T13

Polydactyly

T 13

MONOSOMY21
Key Facts
Terminology

Top Differential

• Partial or complete deletion of chromo

• Trisomy 21 ('1'21)
• Trisomy 13 (1'13)

orne 21

Imaging Findings
•
•
•
•
•

Early or severe intrauterine growth re triction
Multiple anomalie
Thi k ned nuchal fold
Ilolopro encephaly pectrum
ardiac defects

Clinical

Diagnoses

Issues

• Grave prognosis
• Partial mono omy greater urvival than complete
• Chorionic villus sampling or amniocentesis required
for diagnosis

I PATHOLOGY

I DIAGNOSTIC

General Features

Consider

• Genetics
o Chromosome region 21q22 key area
o Altered chromosome may have paternal, maternal,
or de novo origin
• Epidemiology
o Extremely rare and rarely diagnosed in utero
o Partial monosomy 21 appears more frequently than
complete deletion (more lethal)
• Wide range of phenotypic manifestations
• More severe anomalies due to larger deletions

• When features of both T21 and T13 are present

!ClINICALISSUES
Natural History & Prognosis
• Grave prognosis
o Neurologic anomalies
• Severe mental retardation and delayed
development
• Microcephaly
• Hypertonia
• Seizures
o Cardiac anomalies
• Structural defects
• Electrical anomalies
• Cardiac failure most common cause of death
o Ophthalmologic defects
• Microphthalmia
• Absent anterior or posterior eye chamber
o Musculoskeletal anomalies
• Arthrogryposis-like symptoms: Restricted joint
mobility
• Flat or clubbed feet
• Hand malformations
a Genitourinary anomalies
o Failure to thrive
• Partial monosomy greater survival than complete
o 50% infant mortality if survive until birth

Treatment
• Chorionic villus sampling or amniocentesis required
for diagnosis
o Determine if deletion is partial or complete

CHECKLIST

Image Interpretation

Pearls

• No imaging findings are diagnostic
• Karyotyping needed for diagnosis

I SELECTED
1.

2.

3.

4.

REFERENCES

Mari MA et al: A prenatally

diagnosed patient with full
monosomy 21: ultrasound, cytogenetic, clinical, molecular,
and necropsy findings. Am J Med Genet. 127 A(1):69-73,
2004
Lee C et al: Prenatal diagnosis and molecular cytogenetics
in a case of partial trisomy 14 and monosomy 21. Am J
Med Genet. 100(3):246-50, 2001
Joosten AM et al: Full monosomy 21, prenatally diagnosed
by fluorescent in situ hybridization. Prenat Diagn.
17(3):271-5,1997
Huret JL et al: Monosomy 21q: two cases of del(21q) and
review of the literature. Clin Genet. 48(3):140-7, 1995

IIMAGE

GALLERY

(Left) Axial ultrasound shows bilateral pelviectasis (arrows) in a fetus
with monosomy 27. (Right) Coronal ultrasound shows fusion of the
frontal lobes with a single choroid plexus crossing the midline
(arrow). There is no falx anteriorly and the thalami are not fused
(semilobar holoprosencephaly) .

SECTION 15: Syndromes & Multisystem

Aicardi Syndrome
Amniotic Band Syndrome
Apert Syndrome
Beckwith-Wiedemann
Syndrome
Carpenter Syndrome
Cornelia de Lange Syndrome
Cystic Fibrosis
Fryns Syndrome
Joubert Syndrome
Meckel-Gruber Syndrome
Pierre Robin Syndrome
Sirenomelia
Smith-Lemli-Opitz Syndrome
Tuberous Sclerosis
VACTERL Association

15-2
15-4
15-8
15-10
15-12
15-14
15-16
15-18
15-20
15-22
15-26
15-28
15-32
15-36
15-40

Disorders

AICARDI SYNDROME

Coronal T2WI MR shows agenesis of the corpus
callosum (arrow) and an interhemispheric cyst in a 28
week fetus with Aicardi syndrome. Cortical dysplasia is
also present (curved arrow).

Coronal T2WI MR more posteriorly shows a coexistent
OWC anomaly with a cyst in the posterior fossa
(arrow). Axial views confirmed absence of the vermis.

!TERMINOlOGY

MR Findings

Definitions

• Broad spectrum of cerebral malformations
o Most consistent feature is ACC
• May be partially formed (dysgenesis)
o Absence of cavum septi pellucidi
o Colpocephaly
o Pachygyria
o Cortical heterotopias
o OWC with hypoplasia/aplasia
of cerebellar vermis
o Optic nerve and chiasmal hypoplasia
• May only be recognized on postnatal scans

• Rare, severe developmental disorder characterized by
clinical triad of infantile spasms, agenesis of corpus
callosum (ACC) and chorioretinallacunae

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: ACC in a female fetus

Ultrasonographic

Imaging Recommendations

Findings

• Callosal agenesis/dysgenesis
o Inability to visualize corpus callosum in entirety on
mid-sagittal and coronal imaging
o Elevation of 3rd ventricle
o Absent cavum septi pellucidi
o Colpocephaly ("teardrop-shaped" ventricles)
o Interhemispheric cyst/lipoma
• Other central nervous system (CNS) findings
o Dandy-Walker continuum (OWe)
• Inferior vermian dysgenesis, posterior fossa cyst
o Ventriculomegaly
o Choroid plexus cysts/papillomas

• Protocol advice: Fetal MRI may be helpful in a
suspected prenatal diagnosis

I DIFFERENTIAL DIAGNOSIS
Corpus callosal agenesis/dysgenesis
• Isolated or other syndrome

Dandy Walker continuum
• Isolated or syndromic

DDx: Aicardi Syndrome

owe,

Isolated

owe, Syndromic

AICARDI SYNDROME
Key Facts
Terminology

Pathology

• Rare, evere developmental disorder characterized by
clinical triad of infantile pa ms, agenesis of corpus
callo urn (A ) and chorioretinallacunae

• Probable X-linked dominant with early embryonic
lethality in hemizygou male

Imaging Findings

• Consider Aicardi in a female fetu with
,
uch a
especially when 0 xi tent abnormalities
DW are present
• Aicardi yndrome remains a clinical diagnosis

• Mo t consi tent feature i A

Top Differential
•

orpu

Diagnoses

callosal agenesis/dy

Diagnostic Checklist

g nesi

I PATHOLOGY

I DIAGNOSTIC

CHECKLIST

General Features

Image Interpretation

• Genetics
o Probable X-linked dominant with early embryonic
lethality in hemizygous males
o Rare reports of males with 47,XXY karyotype
o Report of recurrence in 2 siblings attributed to
possible germinal mosaicism
o Discordance in monozygotic twins reported
• Epidemiology
o Early lethality in males resulting in spontaneous
abortion
o Second trimester and beyond almost exclusively
female

• Always check sex in fetus with ACC
• Consider Aicardi in a female fetus with ACC, especially
when coexistent abnormalities such as DWC are
present
• Aicardi syndrome remains a clinical diagnosis
o No characteristic facial phenotype or genetic testing
for confirmation of diagnosis
o Chorioretinallacunae
are pathognomonic
for the
disorder

I CLINICAL

I SELECTED
1.
2.

ISSUES
3.

Presentation
• Most common signs/symptoms: In utero ACC is most
consistent finding
• Postnatal findings
o Infantile spasms
• Usual clinical presentation, average onset 9 weeks
o Chorioretinallacunae
(pathognomonic)
o Agenesis of the corpus callosum
• Total 72%
• Partial 28%
o Mental retardation
• Most with no meaningful language skills
o Costovertebral defects (39%)
• Hemivertebrae, scoliosis, absent/malformed
ribs
o Orofacial clefts, colobomata, microphthalmia
o Phenotypic overlap with MLS syndrome
(microphthalmia
with linear skin defects) and Goltz
syndrome (focal dermal hypoplasia)

4.

Pearls

REFERENCES

Aicardi J: Aicardi syndrome.
Brain Dev. 27(3):164-71,
2005
Rosser T: Aicardi syndrome.
Arch Neurol. 60(10):1471-3,
2003
Rosser TL et al: Aicardi syndrome:
spectrum
of disease and
long-term
prognosis
in 77 females. Pediatr Neurol.
27(5):343-6,
2002
Van den Veyver IB: Microphthalmia
with linear skin
defects (MLS), Aicardi, and Goltz syndromes:
are they
related X-linked dominant
male-lethal
disorders?
Cytogenet
Genome
Res. 99(1-4):289-96,
2002

IIMAGE

GALLERY

Natural History & Prognosis
• High early childhood mortality
o Rare reports of milder phenotype with less severe
clinical course
• Severe mental retardation and seizures, often
non-ambulatory
• Sparing of macula and smaller lacunar size correlated
with better vision

(Left) Axial ultrasound of a female fetus at 24 weeks gestation shows
a high-riding 3rd ventricle (arrow), which communicated with an
interhemispheric
cyst. (Right) Axial oblique
ultrasound shows
absence of the cavum septi pellucidi (curved arrow) and inferior
vermian agenesis (arrow) in this case of Aicardi syndrome.

AMNIOTIC BAND SYNDROME

Graphic shows various manifestations of amniotic band
syndrome, including constrictions (white arrow),
amputations (black open arrow), facial clefls (black
arrow), and a cephalocele (white open arrow).

• Defects may be isolated or multiple, but not in specific
pattern

ITERMINOlOGY
Abbreviations
•
•
•
•
•

and Synonyms

ADAM (amniotic deformity, adhesion,
Amniotic band sequence (ABS)
Amniotic disruption complex
Streeter dysplasia/bands
Congenital constriction bands

mutilation)

Definitions
• Entrapment of fetal parts by disrupted amnion
• Formation of fibrous amniotic bands
• Resulting anomalies (usually multiple)
o Clefts
o Constrictions
o Amputations
o Malformation
o Deformation

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Asymmetric distribution of defects is hallmark of
syndrome
o Amniotic band in contact with deformity
o Asymmetric craniofacial deformities

DDx: Amniotic

Stuck Tlvin

Coronal ultrasound shows a typical case of amniotic
band syndrome with multiple defecls. Imaging of the
face shows a cleft lip (arrow) with the extrathoracic
heart (open arrows) adjacent to the face.

Ultrasonographic

Band Mimics

Body Stal" Anomaly

Findings

• Bands in amniotic fluid appear as multiple thin
membranes
o Bands may be difficult to discern, especially in
setting of oligohydramnios
o May restrict fetal motion
• Face and head
o Craniofacial deformities often severe
o Facial clefts
• Do not conform to pattern of developmental
clefts
• Often oblique
• Cleft lip is usually bilateral
• Nasal deformity
• Single orbital involvement typical
o Cephaloceles
• Occur in area other than along sutures
o Anencephaly-like defect
• Absent/defective cranial vault
• Little or no remaining brain parenchyma
• Often asymmetric or absent orbit (vs. true
anencephaly ~ "frog eye" appearance)
o Acrania/acalvaria-like defect
• Some cerebral tissue remains

Encephalocele

AMNIOTIC BAND SYNDROME
Key Facts
Top Differential

Terminology
• Entrapment

of fetal parts by disrupted amnion

Imaging Findings
• Amniotic band in contact with deformity
• Defects may be isolated or multiple, but not in
specific pattern
• Bands in amnioti fluid appear a multiple thin
membranes
• Bands may be difficult to discern, e p ially in etting
of oligohydramnio
• raniofacial deformitie often evere
• onstriction with edema of di tal extremity
• Limb amputations
• Abdominal wall defects
• If unusual distribution of defects, look carefully for
bands

•

•

•

•
•
•
•

• Remaining parenchymal abnormal and
disorganized
a Microcephaly
a Hydrocephalus
a Meningocele
Extremities
a Constriction with edema of distal extremity
• May lead to eventual amputation
• Most common deformity
• Usually involves fingers and toes
a Limb amputations
• Often fingers and toes
• Easily missed if isolated
a Clubbed feet and hands
a Multiple joint contractures
a Pseudosyndactyly
• Fusion of distal digits
Chest wall defects
a Ectopia cordis
a Rib clefts
Abdominal wall defects
a Gastroschisis-like bowel extrusion
a Omphalocele-Iike liver herniation
a Bladder exstrophy
Scoliosis
Ambiguous genitalia
Imperforate anus
Oligohydramnios in some cases
a Fluid leaks between amnion and chorion and is
reabsorbed

Imaging Recommendations
• If unusual distribution of defects, look carefully for
bands
a May be tightly adherent and difficult to see
a Consider scanning patient in decubitus position
• Fetus stays in fixed position
• Bands restrict movement of involved area
• Color Doppler to assess flow to affected extremity

Diagnoses

• Body stalk anomaly
• Developmental defects
• Amniotic sheets
• horioamniotic
eparation

Pathology
• enerally no recurrence risk
• ot as ociated with aneuploidy
• Ruptured amnion do not always lead to amniotic
band syndrome
•
0 two fetuses affected identically

Clinical Issues
• Defects range from minor to I thai
• lIccessful in utero lysis of bands for at-ri k extremity
reported

I DIFFERENTIAL

DIAGNOSIS

Body stalk anomaly
•
•
•
•
•
•

Fetal abdominal wall adherent to placenta
Amnion in continuity with peritoneum
Absent or short umbilical cord
Scoliosis major finding
Absence of limb defects
Cranial defects uncommon

Developmental

defects

• All have defined anatomic distributions from
embryologic development
• Cephalocele
a Occipital and frontal
• Neural tube defects
a Most commonly lumbar
a Associated Chiari II brain findings
• Obliteration of cisterna magna
• Compression of cerebellum ("banana" sign)
• Flattening of frontal bones ("lemon" sign)
• Acrania/acalvaria
a Difficult to distinguish from amniotic bands in
absence of associated malformations
• Anencephaly
a Both orbits remain
• Very proptotic ("frog eye" appearance)
• Cleft lip
o Unilateral, bilateral or midline
a Not oblique
• Gastroschisis
a Abdominal wall defect
a Free-floating bowel loops
a Right of midline adjacent to cord insertion
• Omphalocele
a Midline abdominal wall defect covered by
peritoneum
a Contains bowel and/or liver
a Umbilical cord inserts on mass

Amniotic sheets
• Amnion wrapping around synechiae

AMNIOTIC BAND SYNDROME
• Thick at base with free edge
• Fetus freely mobile

Chorioamniotic

separation

• Normal in early pregnancy
• No entrapment of fetal parts
• May occur post-procedural
o Serial amniotic reductions
• May be associated with aneuploidy
o Malformations not associated with bands

I PATHOLOGY
General Features
• Genetics
o Sporadic
o Generally no recurrence risk
• Rare recurrence risk in association with
Ehlers-Danlos and epidermolysis bullosa
o Not associated with aneuploidy
• Etiology
o Incompletely understood
o Proposed theories do not completely explain some
cases
o Exogenous theory: Rupture of amnion
• Amnion ruptures, chorion intact
• Fetus passes through defect
• Chorionic side of amnion is "sticky"
• Entrapment of fetal part
• Vascular constriction ~ edema ~ deformity or
amputation
• 6-18 weeks: Estimated gestational age at time of
insult
• Severity of defect correlates with age at occurrence
(early = more severe)
• Loss of fluid through chorion ~ oligohydramnios
• Theory does not explain cases of amniotic band
syndrome with normal membranes
o Endogenous theory: Focal developmental error of
limb connective tissue
o Described risk factors
• Amniocentesis
• Drugs: Methadone, lysergic acid diethylamide
(LSD)
• Maternal trauma
• Intrauterine contraceptive device
• Ehlers-Danlos syndrome
• Osteogenesis imperfecta
• Epidermolysis bullosa
o Ruptured amnion does not always lead to amniotic
band syndrome
o No two fetuses affected identically
• Epidemiology
o 1:1,200-15,000 live births
o No gender predilection

I CLINICAL

ISSUES

Presentation
• Evaluation of major malformation
o May be detected in 1st trimester
• Incidental finding of minor extremity deformity

Natural History & Prognosis
• Depends on degree of malformation
o Defects range from minor to lethal
o Variable prognosis
o Constriction alone = good prognosis and normal life
expectancy
• Postnatal physical exam may demonstrate additional
defects
o Ocular defects often present
• Microphthalmos,
hypertelorism
• Eyelid colobomas, ectropion
• Ptosis, lacrimal outflow obstruction, corneal
opacities
o Defective cranial ossification
o Dermal ridges, simian crease

Treatment
• Termination offered for major defects
• Successful in utero lysis of bands for at-risk extremity
reported

I DIAGNOSTIC

CHECKLIST

Consider
• Amniotic band syndrome when body defects do not
follow a developmental anatomic distribution

Image Interpretation

Pearls

• Extremities most commonly involved
o Both constrictions and amputations
o Easily missed when only digits are involved

I SELECTED REFERENCES
1.

Chen CP et al: Prenatal sonographic diagnosis of acrania
associated with amniotic bands. J Clin Ultrasound.
32(5):256-60, 2004
2. Marino T: Ultrasound abnormalities of the amniotic fluid,
membranes, umbilical cord, and placenta. Obstet Gynecol
Clin North Am. 31(1):177-200, 2004
3. Paladini D et al: Congenital constriction band of the upper
arm: the role of three-dimensional
ultrasound in diagnosis,
counseling and multidisciplinary consultation. Ultrasound
Obstet Gynecol. 23(5):520-2, 2004
4.
Chen CP et al: Prenatal diagnosis of acrania associated with
facial defects, amniotic bands and limb-body wall complex.
Ultrasound Obstet Gynecol. 20(1):94-5, 2002
5. Chen CP: Prenatal diagnosis of limb-body wall complex
with craniofacial defects, amniotic bands, adhesions and
upper limb deficiency. Prenat Diagn. 21(5):418-9, 2001
6.
Strauss A et al: Intra-uterine fetal demise caused by
amniotic band syndrome after standard amniocentesis.
Fetal Diagn Ther. 15(1):4-7, 2000
7.
Bronshtein M et al: Do amniotic bands amputate fetal
organs? Ultrasound Obstet Gynecol. 10(5):309-11, 1997
8.
Quintero RA et al: In utero lysis of amniotic bands.
Ultrasound Obstet Gynecol. 10:316-20, 1997
9. Tadmor OP et al: Limb amputation in amniotic band
syndrome: Serial ultrasonographic
and Doppler
observations. Ultrasound Obstet Gynecol. 10:312-5, 1997
10. Mahony BS et al: The amniotic band syndrome: antenatal
sonographic diagnosis and potential pitfalls. Am J Obstet
Gynecol. 152:63-8, 1985

AMNIOTIC BAND SYNDROME
IIMAGE GALLERY
(Left) Ultrasound shows
several free-floating,
fluid-filled loops of bowel
(open arrows). An amniotic
band (arrow) can be seen
extending from the bowel
loops to the placenta edge.
(Right) Ultrasound shows an
extremity (arrow) lassoed by
an apparent amniotic band
(open arrows). The fetus was
one of twins affected by
twin-twin transfusion
syndrome. Repeated
amnioreductions resulted in
chorioamnionic separation.
There was no resulting
extremity constriction.

(Left) Coronal ultrasound
shows absence of the cranial
vault, with externalized brain
tissue (arrow) superior to the
skull base. Note the amniotic
band (open arrow)
extending from the base of
the cranium toward the
placenta. (Right) 30
ultrasound from the same
case confirms lack of a
cranial vault, with
externalized brain tissue
(arrow) above the face.
(Courtesy B. Oshiro, Mo).

(Left) Radiograph shows
amputation of the right
hemipelvis and lower
extremity due to amniotic
bands. Scoliosis (arrow) is
also present. (Right) Gross
pathology from the same
case shows the extent of the
amputation of the right
hemipelvis with extrusion of
abdominal contents (arrow).

APERT SYNDROME

Sagittal ultrasound shows midface hypoplasia (curved
arrow), prognathism (open arrow), flat occiput (arrow)
and abnormal calvarial shape in this 29 week fetus with
Apert syndrome.

ITERMINOLOGY
Abbreviations

and Synonyms

• Acrocephalosyndactyly

type I

Clinical photograph shows the abnormal, conical skull
shape caused by multiple suture synostosis. Other
typical features include midface hypoplasia, high
forehead and downslanting palpebral fissures (arrows).

o Pulmonic stenosis, overriding aorta, ventricular
septal defect, endocardial fibroelastosis
• Genitourinary (10%)
o Cystic kidneys, hydronephrosis,
mullerian
anomalies, cryptorchidism

Definitions
• Craniofacial dysostosis characterized by
craniosynostosis, midface hypoplasia and syndactyly
of hands and feet

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Abnormal calvarial shape with
severe syndactyly on mid-trimester ultrasound

Ultrasonographic

Findings

• Craniosynostosis with brachyturricephaly
o Fusion of coronal sutures +/- other sutures resulting
in conical skull shape
• "Mitten" syndactyly
o Extensive, often boney, fusion of fingers/toes
• Central nervous system (CNS) abnormalities in 60%
o Ventriculomegaly,
megalencephaly, arachnoid cyst,
agenesis of corpus callosum, absent cavum septi
pellucidi
• Cardiac defects (10%)

I DIFFERENTIAL

DIAGNOSIS

Pfeiffer syndrome
• Acrocephalosyndactyly,
Pfeiffer type
• Severe craniosynostosis; kleeblattschadel (cloverleaf
skull) common
• Broad distal thumbs, toes with syndactyly of central
digits

Carpenter
•
•
•
•

syndrome

Acrocephalopolysyndactyly
type II
Craniosynostosis of multiple sutures
Preaxial polydactyly, soft tissue syndactyly
Cardiac defects, ventral wall abnormalities

Saethre-Chotzen

syndrome

• Coronal suture synostosis
• Shallow orbits, dysplastic ears
• Partial cutaneous syndactyly of fingers, toes

Crouzon syndrome
• Craniosynostosis

involving multiple sutures

DDx: Syndromic Craniosynostosis

Carpenter

Pfeiffer Syndrome

APERT SYNDROME
Key Facts
Terminology

Top Differential

• Acrocephalo ynda tyly type [
• raniofacial dysosto i characterized by
raniosyno to is, midfac hypopla ia and syndactyly
of hands and f et

• Pfeiffer syndrome
• Carpenter syndrome
• Saethre-Chotzen
yndrome
• rouzon yndrome

Pathology

Imaging Findings
• Pu ion of coronal utures +/- other suture
in conical kull hape
• "Mitten" yndact I

re ulting

• Severe proptosis with hypertelorism
• Syndactyly uncommon

Thanatophoric

dysplasia

• Lethal skeletal dysplasia with micromelia, small chest
• Craniosynostosis with kleeblattschadel in type II
• Trident hand without syndactyly

I PATHOLOGY
General Features
• Genetics: Autosomal dominant
• Etiology
o Due to mutations in fibroblast growth factor
receptor 2 gene (FGFR2)
• Most due to point mutations S252W or P253R
which cause activation of FGFR2
• Epidemiology: Associated with increased paternal age

I CLINICAL

Diagnoses

ISSUES

Presentation
• Postnatal findings
o Craniofacial
• Bilateral coronal suture synostosis, variable other
sutures
• Midface hypoplasia, maxillary hypoplasia
• Exophthalmos, hypertelorism, down slanting
palpebral fissures, supraorbital horizontal groove
• High forehead and flat occiput
• Narrow palate with median groove, +/- cleft
• Malocclusion, dental abnormalities
o Complex syndactyly of hands and feet: "Mitten"
syndactyly
• Short broad thumb in valgus position
• Bony fusion involving digits 2-4, symphalangism
(synostosis of joints)
• Involves the muscles, tendon insertions and
neurovascular bundles of hand
• Simple syndactyly of soft tissue between digits 4-5
o Mental retardation common (I.Q. 44-90)
o Fusion of cervical vertebrae (C5-C6)

• Genetics: Autosomal dominant
• Due to mutation
in fibroblast growth factor r
2 gene (FGFR2)

eptor

• Sever pustular acne at puberty is characteristic
• Upper and lower airway compromise may be
responsible for early death

Treatment
• Surgical correction of craniosynostosis, craniofacial
reconstruction
• Extensive/complex surgical management of syndactyly
with goal of increasing functionality

I DIAGNOSTIC

CHECKLIST

Consider
• 3D ultrasound to evaluate extremities,
calvarial abnormality identified

Image Interpretation

face when

Pearls

• Prenatal diagnosis possible by 19-20 weeks on basis of
abnormal calvarial shape, syndactyly

ISELECTED REFERENCES
1.

2.
3.

Da Costa AC et al: Neuropsychological
Diversity in Apert
Syndrome: A Comparison of Cognitive Profiles. Ann Plast
Surg. 54(4):450-455, 2005
Ibrahimi OA et al: Understanding the molecular basis of
apert syndrome. Plast Reconstr Surg. 115(1):264-70, 2005
Skidmore DL et al: Prenatal diagnosis of Apert syndrome:
report of two cases. Prenat Diagn. 23(12):1009-13, 2003

IIMAGE

GALLERY

Natural History & Prognosis
• Early repair of craniosynostosis does not prevent
mental retardation
• Intracranial hypertension common
• Hearing loss due to chronic otitis, fixation of stapes

(Left) Ultrasound shows complex syndactyly (arrow) of
and valgus deviation of the thumb (open arrow) in a fetus
syndrome. (Right) Radiograph shows complex bony and
syndactyly (arrow) in this infant with Apert syndrome.
phalanx of the thumb is broad (curved arrow).

the fingers
with Apert
soft tissue
The distal

BECKWITH-WIEDEMANN

Ultrasound shows a moderately enlarged (6.5 em)
kidney (calipers) in a third trimester fetus with
Beckwith-Wiedemann syndrome.

SYNDROME

Ultrasound shows macroglossia, typical of that seen in
fetal Beckwith-Wiedemann syndrome. The mouth is
open and there is a protuberant, large tongue (arrow).

ITERMINOLOGY

Mesoblastic nephroma

Abbreviations

• Massive unilateral renal enlargement

and Synonyms

• Beckwith-Wiedemann
• Wiedemann-Beckwith

Simpson-Golabi-Behmel

syndrome (BWS)
syndrome

syndrome

Definitions

• Prenatal overgrowth
• Macroglossia, postaxial polydactyly

• Characterized by macrosomia, hemihyperplasia,
macroglossia, ventral wall defects, predisposition to
embryonal tumors, and neonatal hypoglycemia

• Diagnosis of exclusion
• Predisposition to embryonal tumors

IIMAGING

I PATHOLOGY

FINDINGS

Hemihyperplasia,

isolated

General Features

General Features

• Best diagnostic clue: Large for dates fetus with
enlarged kidneys, omphalocele and protruding tongue
on mid-trimester ultrasound

• Genetics
o Genetically heterogeneous: 85% are sporadic with
normal karyotype
o 10-15% are inherited in autosomal dominant
fashion
o 10-20% with paternal uniparental disomy
• Both copies of llp15 derived from father
o Less than 1% cases with chromosome translocation,
inversion or duplication involving llp15 region
• As high as 50% recurrence risk if translocation is
maternal in origin
• Etiology

I DIFFERENTIAL DIAGNOSIS
Omphalocele,

isolated vs. syndromic

• Increased aneuploidy risk

Macrosomia

from maternal diabetes (100M)

• Heart, central nervous system, extremity
malformations
• Omphalocele uncommon

DOx: Enlarged Abdominal

100M

Circumference

Mesoblastic Nephroma

Omphalocele

BECKWITH-WIEDEMANN
Key

SYNDROME

Facts

Terminology

Top Differential

• Characterized by macrosomia, hemihyperplasia,
macroglossia, ventral wall defects, predisposition to
embryonal tumors, and neonatal hypoglycemia

• Omphalocele, isolated vs. syndromic
• Macrosomia from maternal diabete (100M)
• Mesoblastic nephroma

Diagnoses

Imaging Findings

Pathology

• Best diagnostic clue: Large for dates fetus with
enlarged kidneys, omphalocele and protruding
tongue on mid-trimester ultrasound

• Increased risk of imprinting-related disorders
(including BWS) in assisted reproductive technology
pregnancies

o Multigenic disorder due to epigenetic alterations
(alteration in gene activity without changing actual
structure) in growth regulatory genes at Up15
• Many imprinted genes (genes which are expressed
differently depending on which parent they are
inherited from) in this region
o Increased risk of imprinting-related disorders
(including BWS) in assisted reproductive technology
pregnancies
• Epidemiology: 1/13,000 births

Microscopic

Features

Treatment
• Delivery in a tertiary care center with availability of
pediatric surgery, neonatal intensive care
o Preparation for potential airway obstruction due to
macroglossia, glossectomy infrequently required
• Tumor surveillance protocol involving
alpha-fetoprotein and abdominal ultrasound every 3
months until age 8 years

I DIAGNOSTIC

CHECKLIST

• Adrenal cytomegaly characteristic feature
o Hyperplastic adrenal gland with unusual, large,
polyhedral cells
• Renal medullary dysplasia

• Accelerated fetal growth in presence of characteristic
anomalies is suggestive of BWS

ICLINICALISSUES

I SELECTED

Presentation
• Most common signs/symptoms
o Overgrowth
• Macrosomia, advanced skeletal maturation
o Characteristic facies
• Macroglossia: Neonatal airway obstruction if
severe
• Nevus flammeus over forehead, eyelids
• Mid-face hypoplasia, prognathism, malocclusion,
infraorbital creases
o Enlarged kidneys, pancreas, adrenals, liver
o Hemihypertrophy
o Abdominal wall defects
• Omphalocele, diastasis recti, umbilical hernia
o Variable developmental delay

Natural History & Prognosis
• Pregnancy with fetal BWS
o Polyhydramnios, maternal risk of preeclampsia,
increased premature delivery
• Neonatal period
o Hypoglycemia, apnea, airway difficulties
o High infant mortality rate (20%)
• Childhood
o Increased risk of Wilms tumor, hepatoblastoma,
neuroblastoma, rhabdomyosarcoma, adrenocortical
carcinoma
• Overall tumor risk 7.5-10%; Wilms tumor = 60%
of all tumors

Image Interpretation

1.

2.

3.

Pearls

REFERENCES

Bliek J et al: Epigenotyping as a tool for the prediction of
tumor risk and tumor type in patients with
Beckwith-Wiedemann syndrome (BWS). J Pediatr.
145(6):796-9,2004
Murrell A et al: An association between variants in the
IGF2 gene and Beckwith-Wiedemann syndrome:
interaction between genotype and epigenotype. Hum Mol
Genet. 13(2):247-55, 2004
Weksberg R et al: Beckwith-Wiedemann syndrome
demonstrates a role for epigenetic control of normal
development. Hum Mol Genet. 12 Spec No I:R61-8, 2003

I IMAGE

GALLERY

'~
r

-.~

r"

1;

1.J:~1'
"'.'

.....
' ," ....

,

-

,

..

,~

---~

"

.~
b

-"-'~

...
--..,r'

~

(Left) Transverse ultrasound shows a small omphalocele (arrows) in a
mid-trimester
fetus with
BW5.
(Right)
Photomicrograph
of
adrenocortical cytomegaly, a characteristic finding in BW5. There are
large polyhedral cells with hyperchromatic nuclei (arrows). (Courtesy
E. Klatt, MO).

CARPENTER SYNDROME

Clinical photograph shows the typical facial appearance
in Carpenter syndrome.
Note the severe proptosis
(arrows), small mouth (curved arrow) and abnormal
calvarial shape (open arrows).

Axial oblique ultrasound shows severe exophthalmos
(arrows) in a mid-trimester
fetus with Carpenter
syndrome.

o Omphalocele,

ITERMINOlOGY
Abbreviations

Radiographic

and Synonyms

• Acrocephalopolysyndactyly

type II

Definitions
• Characterized by craniosynostosis of multiple sutures,
preaxial polydactyly, soft tissue syndactyly, cardiac
defects and ventral wall abnormalities

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Abnormal calvarial shape with
proptosis and polysyndactyly of hands and feet on
mid-trimester ultrasound

Ultrasonographic

Findings

• Craniosynostosis results in shallow orbits, causing
prominent proptosis
• Cardiac defects in 30-50%
o Septal defects, pulmonic stenosis, tetralogy of Pallot
• Preaxial polydactyly with partial syndactyly
o Hands may appear clenched
o Polysyndactyly not an absolute requirement for
syndrome
• Abdominal wall defects

DDx: Abnormal

ApC'rt Syndrome

hernia

Findings

• Prenatal fluoroscopy of limited value
• Postnatal radiographs important for diagnosis
o Craniosynostosis of sagittal, lambdoid, occasionally
coronal sutures
o Variable calvarial shape including kleeblattschadel
(cloverleaf)
o Genu valga, lateral patellar displacement, flared ilia,
flat acetabula
o Shortened/hypoplastic
middle phalanges, duplicated
2nd phalanx of thumb

Imaging Recommendations
• Protocol advice
o Evaluation of extremities to exclude skeletal
dysplasia
o Careful search for evidence of cardiac and
abdominal wall defects

I DIFFERENTIAL DIAGNOSIS
Apert syndrome
• Acrocephalosyndactyly,
type I
• Partial or complete syndactyly of fingers and toes
("mitten syndactyly")
• Craniosynostosis with brachyturricephaly

Calvarial Shape

Pfeiffer Syndrome

TO Type /I

CARPENTER SYNDROME
Key Facts
Terminology

Top Differential

•
•

•
•
•
•
•
•

crocephalopoly yndactyly type II
haracterized by craniosynostosis of multipl
utur s,
preaxial polydactyly, soft tissue syndactyly, cardiac
def ct and ventral wall abnormalities

Imaging Findings
• Be t diagnostic clue: Abnormal calvarial shape with
proptosis and p Iysyndactyly of hand and feet on
mid-trime ter ultrasound
• Broad thumbs held in valgus position
• Mental retardation

Pfeiffer syndrome

Crouzon syndrome
• Severe proptosis, hypertelorism
• Craniosynostosis of multiple sutures
• Syndactyly not a prominent feature

syndrome

• Craniosynostosis of coronal, lambdoid
• High flat forehead, dysplastic ears
• Partial syndactyly of fingers, toes

Pathology
• Genetics: Auto omal recessive

Natural History & Prognosis

• Acrocephalosyndactyly,
Pfeiffer type
• Severe craniosynostosis, kleeblattschadel common
• Broad distal thumbs, toes with syndactyly of central
digits

Saethre-Chotzen

sutures

• Truncal obesity common
• Intellectual function variable (I.Q. range 52-104)
• Articulation problems and fine motor impairment

Treatment
• No prenatal treatment
• Referral for genetic counseling
• Neurosurgical repair of craniosynostosis
o Impact on intellectual functioning variable
• Surgical correction of cardiac, abdominal wall defects
• Surgical management of polysyndactyly centers on
improving functionality of hands

I SELECTED
1.

Bardet-Biedl syndrome
•
•
•
•

Diagnoses

Apert syndrome
Pfeiffer yndrome
rouzon yndrome
aethre- hotzen yndrome
Bardet-Biedl syndrome
Thanatophoric dysplasia (TO)

Post-axial polydactyly, syndactyly, brachydactyly
Renal cysts
Retinal dystrophy
Mental retardation, obesity, hypogonadism

2.

3.

REFERENCES

Balci S et al: A case of Carpenter syndrome diagnosed in a
20-week-old fetus with postmortem examination. Clin
Genet. 51(6):412-6, 1997
Jamil MN et al: Carpenter's syndrome
(acrocephalopolysyndactyly
type II) with normal
intelligence. Br J Neurosurg. 6(3):243-7, 1992
Cohen OM et al: Acrocephalopolysyndactyly
type
II Carpenter
syndrome: clinical spectrum and an attempt
at unification with Goodman and Summit syndromes. Am
J Med Genet. 28(2):311-24, 1987
Robinson LK et al: Carpenter syndrome: natural history
and clinical spectrum. Am J Med Genet. 20(3):461-9, 1985
n

Thanatophoric

dysplasia (TO)

• Lethal skeletal dysplasia with micromelia
• Craniosynostosis with kleeblattschadel skull in type II
• Small chest

4.

I PATHOLOGY

IIMAGE

GALLERY

General Features
• Genetics: Autosomal recessive

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms: Abnormal skull shape
• Postnatal
o Brachydactyly with broad thumbs, soft tissue
syndactyly of fingers
o Dystopia canthorum (lateral displacement of inner
canthi), downslanting palpebral fissures
o Dental abnormalities with delayed eruption,
prolonged retention of primary teeth, hypodontia
o Hypogonadism

(Leh)
Ultrasound shows persistently clenched hands in a
mid-trimester fetus (arrows). Polysyndactyly was found at birth. Also
note the shallow orbits with proptosis (curved arrow). (Right) Clinical
photograph shows complex polysyndactyly in Carpenter syndrome.
Note the broad thumb (arrow), which was duplicated on X-ray, and
syndactyly of the remaining fingers (open arrow).

CORNELIA DE LANGE SYNDROME

Clinical photograph shows fine arched brows (arrow),
thin lips, crescent shaped mouth (curved arrow), and
severe limb reduction defects (open arrows) in CdLS.
(Courtesy A. Lowichik, MO).

Sagittal ultrasound shows an abnormal profile in CdLS.
Note
the
hypoplastic
mid-face
(arrow),
the
characteristic prominent upper lip (curved arrow) and
micrognathia (open arrow).

ITERMINOLOGY

Imaging Recommendations

Abbreviations

• Protocol advice: Consider 3D ultrasound to evaluate
craniofacial, limb anatomy when CdLS suspected

and Synonyms

• Cornelia de Lange Syndrome (CdLS)
• Brachmann-de Lange syndrome

Definitions

I DIFFERENTIAL DIAGNOSIS

• Syndrome characterized by characteristic facial
features, growth and mental retardation, limb defects,
gastrointestinal abnormalities, cardiac defects and
hypertrichosis

• CDH (89%), distal limb hypoplasia (75%), coarse facies
• Polyhydramnios, normal fetal growth

Fryns syndrome

Chromosome

IIMAGING

FINDINGS

Ultrasonographic

Findings

• Intrauterine growth restriction (lUGR)
• Upper limb reduction defects
• Micrognathia with protruding upper lip
o Best evaluated in profile view
• Diaphragmatic hernia (CDH), occasionally

bilateral

Radiographic Findings
• Most characteristic feature: Short 1st metacarpal
relatively long 3rd-4th metacarpals
• Subluxation of radial head

with

aneuploidy

• Pallister-Killian syndrome
o Tissue mosaicism with supernumerary
isochromosome 12p (mosaic tetrasomy 12p)
o CDH, polyhydramnios
o Rhizomelic limb shortening, rare acral hypoplasia
o Mental retardation
• Partial duplication of 3q
o Craniosynostosis, cardiac, renal anomalies
o Mental retardation
o Normal fetal growth/postnatal
growth failure
o Low anterior hairline, bushy eyebrows, long lashes
o Depressed nasal bridge, anteverted nares, long
prominent philtrum
• Trisomy 18
o IUGR, radial ray defects, overlapping digits
o CDH occasional finding

DDx: CDH With Limb Anomalies

T7 8, Radial Ray

T7 8, Radial Ray

Fryns Syndrome,

COIl

(ryns, Oigilall1ypoplas

CORNELIA DE LANGE SYNDROME
Key

Facts

Terminology

Clinical Issues

•

• Wide spectrum of everity
• Perinatal lethality -+ milder case of adults capable of
living independently
• Behavioral phenotype: Self-injury, aggression, sleep
disturbance, autistic behaviors

yndrome characterized by characteristi
facial
features, growth and mental retardation, limb defects,
ga trointestinal abnormalities, cardiac defect and
hypertricho i

Top Differential

Diagnoses

Diagnostic Checklist

• Fryns syndrome
• hromosome aneuploidy
• Fetal alcohol s ndrome

•

on ider dL when
limb anomali s

DI I found in association with

Fetal alcohol syndrome

Natural History & Prognosis

• Pre- and postnatal growth restriction
• Microcephaly, cardiac defects, developmental delay
• Short palpebral fissures, smooth philtrum, thin upper
lip

• Wide spectrum of severity
o Perinatal lethality -+ milder cases of adults capable
of living independently
• Mental retardation (moderate to profound)
• Significant speech and language delay (some
non-verbal), hearing loss, seizures (11-23%)
• Behavioral phenotype: Self-injury, aggression, sleep
disturbance, autistic behaviors

Congenital diaphragmatic

hernia, isolated

• Look carefully for other malformations

Limb reduction defects
• Isolated vs. syndromic

I DIAGNOSTIC

CHECKLIST

!PATHOLOGY

Image Interpretation

General Features

• Consider CdLS when CDH found in association with
limb anomalies

• Genetics
o Autosomal dominant
o Most sporadic (99%); rare familial cases
• Etiology
o Caused by mutations in NIPBL
• Human homolog of the Drosophila Nipped -B
gene
• Epidemiology: Prevalence estimated to be as high as
1/10,000

ISELECTED REFERENCES
1.

2.

3.

ICLINICAL

ISSUES

Pearls

Gillis LA et al: NIPBL mutational analysis in 120
individuals with Cornelia de Lange syndrome and
evaluation of genotype-phenotype
correlations. Am J Hum
Genet. 75(4):610-23,2004
Krantz ID et at: Cornelia de Lange syndrome is caused by
mutations in NIPBL, the human homolog of Drosophila
melanogaster Nipped-B. Nat Genet. 36(6):631-5, 2004
Berney TP et at: Behaviourat phenotype of Cornelia de
Lange syndrome. Arch Dis Child. 81(4):333-6, 1999

Presentation
• Distinctive facial phenotype
o Fine arched eyebrows ("penciled in"), long smooth
philtrum, thin lips, "crescent" shaped mouth,
synophrys (fused eyebrows), long lashes, ptosis,
down slanting eyes, depressed nasal bridge,
anteverted nares, small jaw
• Limb defects
o Short arms/small hands to severe limb reduction
defects, monodactyly
• Microbrachycephaly,
short neck, low posterior
hairline, anterior hairline extends over forehead
• IUGR, postnatal short stature
• Cardiac defects (25%): Pulmonary stenosis, ventricular
septal defect most common
• Diaphragmatic hernia (CDH)
• Other gastrointestinal anomalies: Malrotation, colonic
duplication, cecal volvulus, pyloric stenosis, reflux
• Genitourinary: Horseshoe kidney, hypospadias,
cryptorchidism

IIMAGE

GALLERY

(Left) Transverse ultrasound shows a CDH in a 26 wk fetus with
CdLS. The heart is pushed to the chest wall (curved arrow) and the
stomach is seen in the chest (arrow). Skin edema is also seen. (Right)
Ultrasound shows a severe limb reduction defect (arrow). A single
hypoplastic bone is noted in the lower arm (curved arrow).

CYSTIC FIBROSIS

Axial oblique ultrasound of a mid-trimester fetus shows
a focal area of echogenic bowel (arrows). Prenatal
testing was positive for cystic fibrosis.

Axial ultrasound of the same fetus in the 3rd trimester
now shows dilated, echogenic, bowel loops (arrows).
This is the in utero appearance of meconium ileus.

Definitions

• Atresias may also be present
• Perforation with meconium peritonitis
o 8% of fetuses with meconium peritonitis have CF

• Cystic fibrosis (CF) is an autosomal recessive
multisystem disorder caused by dysfunctional chloride
ion transport across epithelial surfaces

I DIFFERENTIALDIAGNOSIS

ITERMINOlOGY

Other causes of echogenic bowel

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Echogenic bowel in 2nd trimester
progressing to bowel dilatation in 3rd trimester

Ultrasonographic

Findings

• Echogenic bowel in second trimester
o Echogenicity ~ bone to be considered abnormal
o Increased echogenicity likely secondary to
inspissated, mucus secretions in bowel lumen
o Risk of fetus with echogenic bowel having cystic
fibrosis varies dramatically between studies (0-33%)
• Must take into consideration population base
• In a large study where CF was common, 9.9% with
echogenic bowel had CF
o 11% of fetuses with CF have echogenic bowel
• Meconium ileus
o Dilated, echogenic small bowel
o Appearance often indistinguishable from ileal atresia

• Trisomy 21
o Look for associated findings
• Infection
o Cytomegalovirus (CMV) most common
o Look for calcification in brain and liver
• Intrauterine growth restriction
• Bowel ischemia

Ileal atresia
• May be indistinguishable

from CF

!PATHOlOGY
General Features
• Genetics: Autosomal recessive (25% recurrence risk)
• Etiology
o Caused by mutations in gene which encodes cystic
fibrosis transmembrane conductance regulator
(CFTR)
• Chromosome 7q32

DDx: Echogenic Bowel

CMV

Trisomy 27

Trisomy 27

Ischemic Bowel

CYSTIC FIBROSIS
Key Facts
Imaging Findings

Pathology

• Best diagnostic clue: Echogenic bowel in 2nd
trimester progressing to bowel dilatation in 3rd
trimester
• In a large study where F was common, 9.9% with
echogenic bowel had F
• 11% of fetu es with F have echogenic bowel
• 8% of fetuses with meconium peritoniti have CF

• Genetics: Autosomal recessive (2591)recurrence risk)
• Highe t prevalence in Caucasian of orthern
European origin

• > 1,000 mutations possible
o CFTR gene mutation => lack of chloride ion
secretion => increased sodium retention and fluid
absorption => increased viscosity of luminal
secretions => obstructed ducts of solid organs and
hollow viscera
• Epidemiology
o 1:2,000 to 5,000 births
o Carrier rate 1/25 to 1/35
o Highest prevalence in Caucasians of Northern
European origin

ICLINICAL

ISSUES

Presentation
• Most common signs/symptoms: Echogenic or dilated
bowel in fetus
• 60% diagnosed in first year of life
• 85% diagnosis by age 5
• May present in neonatal period with failure to pass
meconium
• Gastrointestinal symptoms
o Constipation, obstruction
o Malabsorption from pancreatic insufficiency,
diabetes
o Neonatal hepatitis, cholelithiasis, biliary cirrhosis
• Respiratory
o Recurrent infections, mucus plugging
o Bronchiectasis, hyperinflation, cystic disease,
spontaneous pneumothorax
o Nasal polyps, sinusitis
• Male infertility

Diagnostic Checklist
• ormal ultrasound exam doe not rule out F
• Meconium ileus may be indistinguishable
from ileal
atresia

I DIAGNOSTIC

CHECKLIST

Consider
• Normal ultrasound exam does not rule out CF
o Echogenic bowel/meconium
ileus only seen in 11%
of cases

Image Interpretation

Pearls

• Meconium ileus may be indistinguishable
from ileal
atresia
o Work-up for cystic fibrosis should be done in all
cases of fetal bowel obstruction

I SELECTED
1.

2.

3.

4.

5.

REFERENCES

Scotet V et al: Prenatal detection of cystic fibrosis by
ultrasonography: a retrospective study of more than 346
000 pregnancies. J Med Genet. 39(6):443-8, 2002
Al-Kouatly HB et al: The clinical significance of fetal
echogenic bowel. Am J Obstet Gynecol. 185(5): 1035-8,
2001
Ghose I et al: Hyperechogenic fetal bowel: a prospective
analysis of sixty consecutive cases. BJOG. 107(3):426-9,
2000
Corteville JE et al: Bowel abnormalities in the
fetus--correlation of prenatal ultrasonographic findings
with outcome. Am J Obstet Gynecol. 175(3 Pt 1):724-9,
1996
Estroff JA et al: Prevalence of cystic fibrosis in fetuses with
dilated bowel. Radiology. 183(3):677-80, 1992

I IMAGE

GALLERY

Natural History & Prognosis
• Median survival currently 32 years
• Death usually caused by lung disease

Treatment
• Test parents for carrier status
• Amniocentesis for direct detection of mutation in
fetus
o Testing for 3 most common mutations 87%
detection rate
o Extended analysis 98.5% detection rate
o Fetuses with echogenic bowel tend to have more
severe mutations
• Genetic counseling
o Chorionic villus sampling may be offered in first
trimester on future pregnancies

(Left) Axial oblique ultrasound of a fetus with cystic fibrosis shows
echogenic, dilated, fluid-filled loops of bowel (arrows). (Right)
Water-soluble contrast enema in a newborn failing to pass meconium
shows a microcolon (open arrow) with reflux of contrast into the
terminal ileum, which has multiple filling defects (arrows). This
appearance is diagnostic of meconium ileus.

FRYNS SYNDROME

Clinical photograph shows a preterm stillborn infant
with Fryns syndrome. Note the coarse face, broad
depressed nasal bridge (curved arrow), anteverted
nares, thin lips and small jaw.

Transverse ultrasound shows a large COH in a fetus
with Fryns syndrome. The stomach (curved arrow) and
loops of dilated bowel (open arrows) are in the chest.
The heart (arrow) was also abnormal.

ITERMINOlOGY

I DIFFERENTIAL DIAGNOSIS

Definitions

Chromosome

• Perinatal lethal disorder characterized by congenital
diaphragmatic hernia (CDH) with pulmonary
hypoplasia, coarse facies, distal digital hypoplasia and
internal malformations

• Pallister-Killian syndrome
o Tissue specific mosaic tetrasomy 12p due to
supernumerary isochromosome 12p
o CDH, polyhydramnios, rhizomelia, cardiac
malformations, polydactyly
o Coarse facies, severe mental retardation, pigmentary
abnormalities
o Diagnosis generally made in older infant with
developmental delay and coarse facies in contrast to
perinatal lethality in Fryns
• Trisomy 18
o Intrauterine growth restriction (IUGR), radial ray
defects, cardiac defects, choroid plexus cysts
o CDH occasional finding

IIMAGING

FINDINGS

Ultrasonographic

Findings

• CDH most obvious finding and should prompt search
for other features
• Micrognathia
• Orofacial cleft
• Cardiac defects
• Polyhydramnios
• Digital hypoplasia may not be apparent on ultrasound

Imaging Recommendations
• Protocol advice: Careful search for other anomalies,
including craniofacial and extremities when CDH
identified

aneuploidy

Cornelia de Lange syndrome
• Characteristic facies: Fine arched eyebrows, long
smooth philtrum, thin lips, crescent shaped mouth
• Limb defects variable from small hands to severe limb
reduction abnormalities
• CDH
• Cardiac defects, mental retardation, IUGR,
gastrointestinal abnormalities, hypertrichosis

DDx: CDH Associated Conditions

Trisomy 78

Isolated CDH

Cornelia de Lange

FRYNS SYNDROME
Key Facts
Terminology

• Diaphragmatic

• Perinatal lethal disorder characterized by congenital
diaphragmatic hernia ( DH) with pulmonary
hypoplasia, coarse facies, distal digital hypoplasia and
internal malformations

• Genetics: Autosomal recessive

Top Differential

Diagnoses

Diagnostic Checklist

o Survivors less likely to have CDH or cardiac defect

hernia, isolated

• Must carefully exclude other anomalies
• Most are sporadic but reports of dominant, recessive
and X-linked familial cases
• Familial cases more likely to be isolated; higher
incidence of bilateral defects

Thoracoabdominal

syndrome

• CDH, ventral hernias, hypoplastic
anomalies

lungs, cardiac

!PATHOLOGY
General Features
• Genetics: Autosomal recessive
• Epidemiology: Estimated 1/15,000 births

I CLINICAL

Pathology

• 3D ultrasound for evaluation of face and distal
extremities when Fryns syndrome suspected
• Diagnosis can be made in 2nd trimester, especially in
cases with positive family history

• Pallister-Killian syndrome
• Trisomy 18
• Cornelia de Lange syndrome

Diaphragmatic

hernia, isolated

ISSUES

Presentation
• CDH most obvious in utero finding (89%)
• Polyhydramnios
• Other pre- or postnatal findings
o Craniofacial
• Coarse facies (100%), broad nasal bridge,
macrostomia, micrognathia, anteverted nares,
poorly formed ears, orofacial cleft
o Extremities
• Distal digital hypoplasia (100%):
Hypoplastic/absent
nails and hypoplastic distal
phalanges (brachytelephalangy)
o Genitourinary (86%)
• Mullerian anomalies in females, hypospadias,
cryptorchidism in males, cystic dysplasia of
kidneys (54%)
o Central nervous system (50%)
• Dandy-Walker continuum, agenesis of corpus
callosum, hypoplasia of optic/olfactory tracts,
microphthalmos,
cloudy corneae
o Cardiac abnormalities, gut malrotation, pulmonary
hypoplasia/agenesis,
anorectal anomalies,
camptodactyly

Natural History & Prognosis
• Most are stillborn or die in the neonatal period
• Rare reports of survival into late infancy, early
childhood with severe mental retardation

Treatment
• No prenatal treatment
• Pregnancy termination

I DIAGNOSTIC

should be offered

CHECKLIST

Consider
• 3D ultrasound for evaluation of face and distal
extremities when Fryns syndrome suspected

Image Interpretation

Pearls

• Diagnosis can be made in 2nd trimester, especially in
cases with positive family history

I SELECTED
1.

2.
3.

REFERENCES

Slavotinek AM: Fryns syndrome: a review of the phenotype
and diagnostic guidelines. Am J Med Genet A.
124(4):427 -33, 2004
Pellissier MC et al: Prenatal diagnosis of Fryns' syndrome.
Prenat Diagn. 12(4):299-303, 1992
Cunniff C et al: Fryns syndrome: an autosomal recessive
disorder associated with craniofacial anomalies,
diaphragmatic hernia, and distal digital hypoplasia.
Pediatrics. 85(4):499-504, 1990

I IMAGE GALLERY

(Left) Clinical photograph of an infant with Fryns syndrome shows
nail hypoplasia (arrow) and distal digital hypoplasia (curved arrow).
Skin slippage is due to intrauterine demise. (Right) Sagittal ultrasound
shows an abnormal profile in a fetus with Fryns syndrome. Note the
hypoplastic mid-face (arrow) and subcutaneous edema (curved
arrow).

JOUBERT SYNDROME

Axial oblique ultrasound shows an unusual cleft
between the cerebellar hemispheres. This could be
confused with a Dandy-Walker variant. MRI was
performed for further evaluation.

ITERMINOLOGY
Definitions
• Initial description in 1969: Consanguineous
family
with 4 affected children
o Hyperpnea, ataxia, mental retardation, abnormal
eye movements
• Subsequent descriptions of "Joubert-plus": Additional
findings may include
o Encephalocele
o Dandy-Walker continuum
o Tectocerebellar dysraphia
o Polydactyly

IIMAGING

Findings

• Abnormal nuchal translucency: Nonspecific
concerning in at-risk family
• Abnormal posterior fossa: Cerebellar cleft
• Additional findings with ''joubert-plus''
o Ventriculomegaly/encephalocele
o Polydactyly/micropenis

but

MR Findings
• "Molar tooth" sign
o Deepening of interpeduncular

DDx: Abnormal

owe

o Thick, straight superior cerebellar peduncles
o Hypoplastic vermis
o Abnormal midbrain with decreased anteroposterior
diameter

Imaging Recommendations
• Best imaging tool: Fetal MRI
• Careful posterior fossa evaluation
• Look at fetal breathing pattern
o Episodic fetal hyperpnea (140-160 breaths/min)
reported

I DIFFERENTIAL
Dandy-Walker

FINDINGS

Ultrasonographic

Axial T2WI MR shows the cleft is a deep
interpeduncular fossa (arrow) with elongated superior
cerebellar peduncles (curved arrow) forming the "molar
tooth" sign, seen in 85% of casesof loubert syndrome.

DIAGNOSIS

continuum

(DWC)

• 4th ventricle communicates with cisterna magna
• "Molar tooth" sign not a feature
• Midbrain is normal in DWC, thinned in Joubert

Arnold Chiari malformation
• Obliteration of cisterna magna
• Herniation of cerebellar tonsils with "banana"
appearance to cerebellum

Mega cisterna magna
• Cisterna magna> 10 mm in depth
• No associated structural malformation

fossa

Posterior Fossa

Encephalocele

JOUBERT SYNDROME
Key

Clinical Issues

Imaging Findings
• "Molar tooth" sign
• Abnormal nuchal translucency:
concerning in at-risk family

Top Differential

onspecific but

• Recurrence risk 25%
• Outcome independent of everity imaging findings
• Affected siblings vary widely in presentation

Diagnostic Checklist

Diagnoses

• Fetal MR to characterize central nervous system
anomalies particularly of posterior fossa

• Dandy-Walker continuum (DW
• Arnold Chiari malformation
• Occipital encephalocele

I DIAGNOSTIC

Occipital encephalocele
• Defect in occipital cortical bone
• Herniation of meninges/brain
parenchyma
defect

through

General Features
• Genetics: Autosomal recessive
• Epidemiology
o True incidence unknown: Many cases likely
misdiagnosed
• Generic clinical diagnosis of "cerebral palsy"
• Most common diagnostic imaging error is to label
as DWC
• Embryology
o Defect thought to occur at 6-8 weeks gestation

Gross Pathologic & Surgical Features
Abnormal deep cerebral nuclei and midbrain
Abnormal fibers in cerebellar peduncles
~ Volume of occulomotor nucleus
Vermian hypoplasia/aplasia

Consider
• Fetal MR to characterize central nervous system
anomalies particularly of posterior fossa

ISSUES

Pearls

• Major pitfall is Dandy-Walker continuum
o "Molar tooth" sign not seen in DWC
o Present in 85% Joubert cases
• Accurate diagnosis important as prognosis/recurrence
risk are different
• "Molar tooth" sign is not pathognomonic
o Infants need complete neurological evaluation
including ophthalmologic
assessment of
occulomotor apraxia

I SELECTED
1.

2.
3.

ICLINICAL

CHECKLIST

Image Interpretation

I PATHOLOGY

•
•
•
•

Facts

REFERENCES

Gleeson JG et al: Molar tooth sign of the
midbrain-hindbrain junction: occurrence in multiple
distinct syndromes. Am J Med Genet A. 125(2): 125-34;
discussion 117, 2004
Hodgkins PR et al: Joubert syndrome: long-term follow-up.
Dev Med Child Neurol. 46(10):694-9, 2004
Maria BL et al: Clinical features and revised diagnostic
criteria in Joubert syndrome. J Child Neurol. 14(9):583-90;
discussion 590-1, 1999

Natural History & Prognosis
• Affected children have spectrum of abnormalities
o Developmental delay/mental retardation
o Occulomotor apraxia: Characteristic for Joubert
syndrome
o Hypotonia
o Variable respiratory difficulties
• Hyperpnea/apnea
o Typical facies
• High rounded eyebrows, upturned nostrils,
triangular-shaped
mouth, low-set ears
• Recurrence risk 25%
o Outcome independent of severity imaging findings
o Affected siblings vary widely in presentation

Treatment
• No specific treatment
• Decreased life expectancy
o Sudden infant death attributed

to apneic attacks

IIMAGE

GALLERY

(Leh) Sagittal T2WI MR shows an abnormal, horizontal appearance
of the superior cerebellar peduncles
(curved arrow) and thin
midbrain (arrow). (Right) Axial T2WI MR shows a very small,
associated occipital bone defect (arrow) with protrusion of the
meninges beyond the skull vault.

MECKEL-GRUBER

Radiograph shows typical features of Meckel-Gruber
syndrome, including an encephalocele
(open arrow),
post-axial polydactyly
(arrows), and a markedly
protuberant abdomen from enlarged, cystic kidneys.

!TERMINOlOGY
Abbreviations
•
•
•
•

and Synonyms

Meckel-Gruber syndrome
Meckel syndrome
Gruber syndrome
Dysencephalia splanchnocystica

Definitions
• First described in 1822 by Johann Meckel
• Triad of findings
o Renal cystic dysplasia in 95-100%
o Encephalocele in 60-80%
o Postaxial polydactyly in 55-75%

IIMAGING FINDINGS
General Features
• Best diagnostic clue: At least 2 of 3 classic features in
fetus with normal karyotype

Ultrasonographic

Findings

• Genitourinary
o Renal cystic dysplasia most consistent finding
o Variable sonographic appearance of kidneys
• Grossly enlarged, echogenic kidneys most
common

DDx: Meckel-Gruber

T13, Kidney

SYNDROME

Ultrasound shows a calvarial defect (arrows) with a
large encephalocele
(curved arrow) in a fetus with
Meckel-Gruber
syndrome.
There
is
also
oligohydramnios secondary to renal dysplasia.

• 10-20x normal size
• Large, macroscopic cysts may be present
o Abdominal circumference may be significantly
increased
o Rarely renal agenesis
o Bladder may be small or absent
o 2nd trimester oligohydramnios
• Often anhydramnios
• Fluid normal in 1st trimester, before kidneys
become major contributor to amniotic fluid
production
• Central nervous system
o Encephalocele
• Variable size
• Occipital location
o Microcephaly common
o Dandy-Walker continuum
o Agenesis of corpus callosum
o Ventriculomegaly
o Holoprosencephaly
• Extremities
o Postaxial polydactyly
• Extra digit may be small or angulated
• Usually affects all 4 extremities similarly, although
this is most variable finding in classic triad
• May be difficult to see with oligohydramnios
o Uncommonly preaxial
o Clubbed feet common

Syndrome

T13, Polydactyly

ARPKD

Bilateral MCDK

MECKE~GRUBERSYNDROME
Key Facts
• Auto omal re e sive polycystic kidney disease
(ARPKD)
• Encephalocel

Terminology
•
•
•
•

Triad of findings
Renal cystic dyspla ia in 95-1000,1>
Encephalocele in 60-80%
Po taxial polydactyly in 55-75(J1)

Pathology

Imaging Findings
• Best diagno tic clue: t least 2 of 3 cIa ic features in
f tu with normal karyotype
• Renal cystic dysplasia mo t consistent finding
• Abdominal circumference may be significantly
increased
• 2nd trimester oligohydramnios

Top Differential

feature in all cases

Clinical Issues
• Genetic counseling for future pr gnancies
• Thorough 1 t trimester endovaginal scans on all
future pregnancie

Diagnostic

Diagnoses

Checklist

• Renal appearance is variable, from large, e hogenic
kidney to kidneys completely replaced by
macrosco Jic c t

• Tri omy 13 (T13)

o Short limbs
o Bowing of long bones
• Facial malformation
o Cleft lip/palate
o Micrognathia
o Microphthalmia
o Ear malformations
o Sloping forehead
• Cardiac
o Septal defects
o Coarctation of aorta
• Other anomalies
o Small, bell-shaped chest
o Hepatic fibrosis
• Universally seen at autopsy
• Difficult to appreciate in utero
• Look for hepatomegaly and poor intrahepatic
o Cryptorchidism
o Ambiguous genitalia

• Auto omal recessive
• 25% r urrence risk
• Hepatic fibro i consistent

flow

Imaging Recommendations
• When one finding seen, careful search for others
• MRI helpful if oligohydramnios
limits visualization
• Endovaginal ultrasound in 1st trimester, if there is a
positive family history
o Early normal scan does not completely exclude
Meckel-Gruber syndrome
• Follow-up scan at 18-20 weeks

I DIFFERENTIAL DIAGNOSIS
Trisomy 13 (Tn)
• Significant overlap in findings
• Renal anomalies in 50%
o Cystic dysplasia
• Echogenic kidneys with scattered cysts
• Kidneys may be large but typically smaller than in
Meckel-Gruber syndrome
o Hydronephrosis
• Central nervous system
o Holoprosencephaly
sequence in 40%
o Encephalocele reported, but less common

• Extremities
o Postaxial polydactyly in 75%
o Rockerbottom foot
• Cardiac defect in 80%
o Septal defects
o Hypoplastic left heart
o Aortic/mitral atresia
• Other anomalies
o Facial anomalies
• Cyclopia
• Hypotelorism
• Microphthalmus
• Midline or bilateral cleft lip
o Intrauterine growth restriction
o Omphalocele
o Oligohydramnios less common
• May have polyhydramnios

Autosomal recessive polycystic
disease (ARPKD)

kidney

• Enlarged echogenic kidneys
• Does not have encephalocele or polydactyly
• Variable degrees of oligohydramnios

Multicystic

dysplastic kidneys (MCDK)

• Consider in differential if it is bilateral
o MCDK bilateral in '" 20% of cases
• Anhydramnios
• Lethal anomaly

Encephalocele
• Isolated or with other syndromes
• Kidneys and extremities normal

I PATHOLOGY
General Features
• Genetics
o Autosomal recessive
• 25% recurrence risk
o Several loci have been mapped
• MKSI on 17q21-q24

MECKEL-GRUBER
• MKS2 on 11g13
• MKS3 on 8g24
• Multiple different chromosomes explains
phenotypic variability
o Increased incidence in consanguineous
families
• Etiology
o Postulated
• Failure of mesodermal induction
• Epidemiology
00.1-0.7 in 10,000 births
o Finnish population 1:9,000
oM

=F

o 5% of encephaloceles

Microscopic

have Meckel-Gruber

syndrome

Features

• Kidneys
o Cystic dysplasia
o Nephrons severely deficient
o Poor/absent corticomedullary differentiation
o May be 10-20x normal size
• Myofibroblastic cells in liver and kidney
• Hepatic fibrosis consistent feature in all cases
o Arrested development of intrahepatic biliary system
• Reactive bile duct proliferation
• Bile duct dilation
o Periportal fibrosis
• Leads to portal vascular obliteration

ICLINICALISSUES

SYNDROME
I DIAGNOSTIC
Consider
• MRI when anatomic visualization compromised by
oligohydramnios
• Look carefully for other findings when one of the
major abnormalities is seen

Image Interpretation

ISELECTED REFERENCES
1.

2.

3.

4.
5.
6.

7.

8.

9.

Natural History & Prognosis
• Lethal

o Oligohydramnios leads to pulmonary hypoplasia
o Most stillborn or die within a few hours

Treatment
• Karyotype to exclude trisomy 13
• Termination offered
• Fetal monitoring and cesarean section to be avoided if
pregnancy continued
• Enlarged abdominal circumference may cause
abdominal dystocia
• External examination and autopsy by experienced
pathologist/geneticist
to confirm diagnosis
• Genetic counseling for future pregnancies
o 25% recurrence risk
• Thorough 1st trimester endovaginal scans on all future
pregnancies

Pearls

• Significant overlap in imaging features with trisomy
13
o Amniocentesis should be done for karyotype to
appropriately counsel for future pregnancies
• 1% recurrence risk for trisomy 13 vs. 25% for
Meckel-Gruber syndrome
• Renal appearance is variable, from large, echogenic
kidneys to kidneys completely replaced by
macroscopic cysts
o Renal size is often massive, causing an enlarged
abdominal circumference

Presentation
• Most common signs/symptoms
o Oligohydramnios
• May measure small for dates on clinical exam
• Other signs/symptoms
o May have history of prior affected child
o Elevated maternal serum alpha-fetoprotein
from
encephalocele
• May be normal if covered by membrane
o Diagnosis possible in first trimester
o Wide phenotypic variability
• Associated findings vary significantly between
cases

CHECKLIST

10.

11.
12.
13.
14.

Mittermayer C et al: Prenatal diagnosis of the
Meckel-Gruber syndrome from 11th to 20th gestational
week. Ultraschall Med. 25(4):275-9, 2004
Johnson CA et al: Molecular pathology and genetics of
congenital hepatorenal fibrocystic syndromes. ] Med
Genet. 40(5):311-9, 2003
Tanriverdi HA et al: Meckel Gruber syndrome: a first
trimester diagnosis of a recurrent case. Eur] Ultrasound.
15(1-2):69-72, 2002
Salonen R et al: Meckel syndrome. ] Med Genet.
35(6):497-501, 1998
Paavola Pet al: Clinical and genetic heterogeneity in
Meckel syndrome. Hum Genet. 101(1):88-92, 1997
Sepulveda W et al: Diagnosis of the Meckel-Gruber
syndrome at eleven to fourteen weeks gestation. Am]
Obstet Gynecol. 176:316-9, 1997
Yapar EG et al: Meckel-Gruber syndrome concomitant with
Dandy-Walker malformation: prenatal sonographic
diagnosis in two cases. Clin Dysmorphol. 5(4):357-62, 1996
Paavola P et al: The locus for Meckel syndrome with
multiple congenital anomalies maps to chromosome
17q21-q24. Nat Genet. 11(2):213-5, 1995
Dumez Y et al: Meckel-Gruber syndrome: prenatal
diagnosis at 10 menstrual weeks using embryoscopy.
Prenat Diagn. 14(2):141-4, 1994
Gallimore AP et al: Meckel syndrome: prenatal
ultrasonographic diagnosis in two cases showing marked
differences in phenotypic expression. Australas Radiol.
36(1):62-4, 1992
Ramadani HM et al: Prenatal diagnosis of recurrent Meckel
syndrome. lnt] Gynaecol Obstet. 39(4):327-32,1992
Farag TI et al: Phenotypic variability in Meckel-Gruber
syndrome. Clin Genet. 38(3):176-9, 1990
Nyberg DA et al: Meckel-Gruber syndrome. Importance of
prenatal diagnosis.] Ultrasound Med. 9:691-6, 1990
Salonen R The Meckel syndrome: Clinicopathological
findings in 67 patients. Am] Med Genet. 18:671-89, 1984

MECKEL-GRUBER

SYNDROME

IIMAGE GAllERY
Typical
(Left) Sagittal ultrasound
shows a massively enlarged,
echogenic kidney (cursors)
with a few scattered
macroscopic
cysts.
Additional findings include
oligohydramnios,
small chest
(open arrow), and
protuberant abdomen
(arrow). (Right) Sagittal left
renal sonogram and gross
specimen in a newborn with
Meckel-Gruber
syndrome
shows a very similar
appearance, with grossly
enlarged, echogenic kidneys.
Histology confirmed diffuse
cystic dysplasia.

(Left) Axial ultrasound of the
kidneys in a case of
Meckel-Gruber
syndrome
shows bilateral enlargement
with the renal parenchyma
replaced by multiple,
macroscopic
cysts (arrows).
(Right) Gross pathology from
this case confirms bilaterally
enlarged kidneys with
multiple, large cysts. Renal
cystic dysplasia is the most
commonly seen feature of
Meckel-Gruber
syndrome.
Appearance
may vary from
diffusely echogenic kidneys
to well-defined cysts.

Typical
(Left) Ultrasound shows a
calvarial defect (arrows) with
an occipital encephalocele
(curved arrow). There is
oligohydramnios
secondary
to renal dysplasia, which
compromises
visualization of
intracranial structures.
(Right) Ultrasound of the
foot in the same case shows
polydactyly
(arrows).

PIERRE ROBIN SYNDROME

Graphic shows the typical "U" shaped palatal defect
seen in Pierre Robin syndrome (arrows). Micrognathia
(curved arrow) is also a prominent feature.

o Consider 3D ultrasound to enhance craniofacial
evaluation
o MRI may be helpful in evaluating profile/palate
• Tongue may protrude through "U" shaped palatal
defect

ITERMINOLOGY
Abbreviations

Sagittal T2WI MR shows a fetus with Pierre Robin
sequence. Note severe micrognathia (open arrow) and
glossoptosis (arrow). The tongue protrudes through the
palatal defect (curved arrow).

and Synonyms

• Pierre Robin sequence
• Robin sequence
• Pierre Robin malformation sequence

Definitions

I DIFFERENTIAL DIAGNOSIS

• Association of micrognathia (often severe),
glossoptosis and cleft palate or high arched palate
o Glossoptosis: Posterior displacement of tongue

Cleft palate, isolated

IIMAGING

• "V"shaped defect as opposed to characteristic "U"
shape seen in Pierre Robin

Micrognathia,

FINDINGS

isolated

• Palate intact

General Features

Chromosome

• Best diagnostic clue
o Detection of micrognathia on mid-sagittal view in
mid-trimester
• 1st trimester diagnosis has been reported
o Cleft palate often not detectible sonographically
• Primarily affects posterior palate

• Trisomy 18, triploidy
o Multiple anomalies, growth restriction (IUGR)

Imaging Recommendations
• Protocol advice
o Careful evaluation of fetal anatomy given significant
association of other anomalies with micrognathia
o Fetal karyotype when other anomalies present

aneuploidy

Genetic syndromes
• Stickler syndrome
o Pierre Robin sequence + additional findings
• Severe myopia with retinal detachment, cataracts
• Spondyloepiphyseal dysplasia, progressive
arthropathy
o Autosomal dominant: Mutations in type II collagen
gene (COL2Al)
• Treacher Collins syndrome

DDx: Orofacial Anomalies

71
Triploidy

Micrognathia

Cleft Palate

Cleft Lip/Palate

PIERRE ROBIN SYNDROME
Key Facts
Terminology

Top Differential

• Pierre Robin sequence
• Association of micrognathia (oft n severe),
glossoptosi and cleft palate or high arched palate
• Glossoptosi : Po terior displacem nt of tongue

• Micrognathia, i olat d
• hromo om aneuploidy
• Stickler yndrome

Imaging Findings

•
•
•
•

• left palate often not detectible onographically
• Primarily affects po terior palate
• MRI may be helpful in evaluatin
o Malar hypoplasia, microtia
• Goldenhar syndrome
o Microtia, macrostomia, cardiac anomalies,
hemivertebrae
• Hemifacial microsomia
o Asymmetrical, clefts unusual, microtia
• Seckel syndrome
o Microcephaly (severe), abnormal profile with
prominent nose
• Pena-Shokeir
o Multiple joint contractures
• DiGeorge syndrome
o Cardiac anomalies, characteristic dysmorphic facies
• Diastrophic dysplasia
o Short limbs, club feet, cleft palate, "hitchhiker"
thumbs

Deformation:

Mechanical

forces

• Intrauterine constraint
• Oligohydramnios sequence

I PATHOLOGY
General Features
• Genetics
o Usually sporadic, but cannot exclude mendelian
inheritance in some cases
o Approximately 80% of cases are syndromic
• In syndromic cases, inheritance dependent upon
underlying diagnosis
• Etiology
o Unknown, but likely causally heterogeneous
o Hypoplasia of mandible prior to 9 wk gestation with
posterior displacement of tongue
• Prevents tongue from moving out of plane of
palatine shelf closure, thus resulting in palatal
defect

I CLINICAL

Diagnoses

Clinical Issues
Mo t common ign / ymptoms: Micrognathia
Airway ob truction due to glossopto is
"U" shaped cleft palate
Up to 30% mortality with severe defects

Natural History & Prognosis
• Mandibular growth often improves over time
• Airway obstruction may lessen with development of
the mandible
• Chronic hypoxia in some children may lead to cor
pulmonale
• Up to 30% mortality with severe defects
• Feeding difficulties, hearing loss, sleep apnea

Treatment
• Airway protection critical in infant
o Delivery in a tertiary care center
o Lip, tongue adhesion as temporizing procedure to
protect the airway
o Intubation, tracheostomy for severe airway
obstruction
• Surgical repair of cleft palate
• Distraction procedures to lengthen mandible

I SELECTED REFERENCES
1.
2.

3.

Singh DJ et al: Congenital mandibular hypoplasia: analysis
and classification. J Craniofac Surg. 16(2):291-300, 2005
Hermann NV et al: Early craniofacial morphology and
growth in children with nonsyndromic Robin Sequence.
Cleft Palate CraniofacJ. 40(2):131-43, 2003
Soulier M et al: Prenatal diagnosis of Pierre-Robin sequence
as part of Stickler syndrome. Prenat Diagn. 22(7):567-8,
2002

IIMAGE

GALLERY

ISSUES

Presentation
• Most common signs/symptoms: Micrognathia
• Polyhydramnios common in 3rd trimester
o Predicts increased potential for neonatal airway
obstruction
• Postnatal
o Airway obstruction due to glossoptosis
o "U" shaped cleft palate

(Left) Clinical photograph shows a newborn with severe micrognathia
(open arrow) and a cleft palate typical of Pierre Robin. Note the foam
pad (arrow) under the neck for airway stabilization. (Right) Sagittal
ultrasound shows an abnormal profile, with severe micrognathia
(arrow).
This fetus had Pierre Robin sequence as part of
Smith-Lemli-Opitz syndrome.

SIRENOMELIA

Clinical photograph shows a stillborn with sirenomelia.
The single fused lower extremity is evident (arrow) as
well as a radial ray defect (open arrow).

Radiograph of the same infant shows a single femur
(arrow) and shortened single bone in the distal lower
extremity (open arrow).

• "Mermaid" syndrome
• Symelia dipus, apus
• Sirenomelia sequence

• Absence of a normally tapered lumbosacral spine
• Third trimester and late 2nd trimester diagnoses
usually hampered by lack of amniotic fluid required
for adequate visualization
o At least 50% of diagnoses missed prenatally
o Diagnosis often made at autopsy

Definitions

MR Findings

• Rare, lethal malformation characterized by varying
degrees of lower extremity fusion, as well as other
skeletal, gastrointestinal and genitourinary
abnormalities

• Very useful for confirming renal agenesis
• Better anatomic evaluation in setting of
oligohydramnios

ITERMINOlOGY
Abbreviations

and Synonyms

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Renal agenesis with lower
extremity fusion

Ultrasonographic

Findings

• Mid-trimester anhydramnios, due to bilateral renal
agenesis
• Single or fused lower extremities
o Elucidation of extremity abnormality often very
difficult due to lack of amniotic fluid
o Single femur or single bone in distal lower
extremities suggests diagnosis

Imaging Recommendations
• Protocol advice
o Endovaginal ultrasound particularly useful in 1st
trimester
o Color Doppler
• Look for renal arteries
• Look for branching of aorta
• Frequently lacks normal bifurcation of aorta into
iliac arteries
o Amnioinfusion, although invasive, has been utilized
in enhancing visualization
o 3D ultrasound has been used in early 2nd trimester
diagnosis
• Dependent on adequate amniotic fluid for
visualization
o Consider fetal MRI to confirm renal agenesis,
evaluate lower extremities

DDx: Renal And Limb Anomalies

Sacral Agenesis

Renal Agenesis

Arthrogryposis

Fibular Hemimelia

SIRENOMELIA
Key Facts
Terminology

Top Differential

• Rare, lethal malformation characterized by varying
degrees of lower extremity fu ion, a well as other
kel tal, gastrointe tinal and genitourinary
abnormalities

• Renal anomalies, bilateral
• audal regression sequence
• Lower extremity malformation
• Arthrogrypo i

Imaging Findings

Pathology

• Mid-trimester anhydramnio
, due to bilateral renal
agen sis
• ingle or fu ed lower xtremities
• Elucidation of extremity abnormality often very
difficult due to lack of amniotic fluid
• ingle femur or single bone in di tal lower extremities
ugge ts diagnosis
• Ab ence of a normally tapered lumbosacral spine
• Frequently lacks normal bifurcation of aorta into iliac
arteries

• Several theorie of pathogenesis
• Vascular teal theory
• Abnormality of blastogenesi

I DIFFERENTIAL DIAGNOSIS
Renal anomalies, bilateral
• Renal agenesis
• Multicystic dysplastic kidneys
• Extremities are normal, but evaluation
to oligohydramnios

is difficult due

Caudal regression sequence
• Lower extremities in crossed-legged
• Fluid usually normal
• More common in diabetic mothers

"Buddha" pose

Lower extremity malformations
•
•
•
•
•
•

Diagnoses

Femoral hypoplasia
Tibial hemimelia
Fibular hemimelia
Proximal femoral focal deficiency
Limb reduction defects
Split hand/foot malformation

Arth rogryposis
• Limb malposition may mimic limb fusion
• Polyhydramnios more common than decreased fluid

VACTERL association
• Vertebral anomalies, cardiac malformation,
tracheo-esophageal
fistula, esophageal atresia, renal
anomalies, limb defects (radial ray)
• Several overlapping features
• Limb defects are typically upper, not lower, extremities

I PATHOLOGY
General Features
• Genetics
o Sporadic
• No increased recurrence risk
• Etiology
o Several theories of pathogenesis
o Vascular steal theory
• Originally proposed by Stevenson, et al in 1986

Diagnostic Checklist
• Fetal MRI to ev~luate lower extremitie and renal
agenesis
• 3D ultrasound may be helpful, if ufficient amniotic
fluid
• Color Doppler ultra ound for abdominal vessels

• Alteration in early vascular development, with
abnormal persistence of a vitelline artery
• Vessel arises from aorta below diaphragm; no
tributaries off aorta below this vessel
• Resulting blood flow is diverted via this "vitelline
artery steal" to placenta, with subsequent
hypoplasia of caudal embryonic structures
• Presence or absence of kidneys predicted by
whether the vessel is above or below location of
renal arteries
• Limitations: Theory does not adequately explain
other midline, non-caudal anomalies (e.g. radial
ray defects, neural tube defect)
• Not all sirenomelics have a pathologically
demonstrable "steal" vessel
• Similar vessel has been described in a case of a
normal fetus
o Abnormality of blastogenesis
• Predominant theory
• Very early defect, due to disruption of caudal
mesoderm occurring during gastrulation (3rd
gestational week)
• Interference with formation of notochord may
disrupt further development of caudal structures
o Sirenomelia as a severe form of caudal dysplasia
• Recent evidence suggests that these entities are
likely pathogenetically distinct
• Fusion of extremities, single umbilical artery
uncommon in caudal dysplasia
• Association of diabetes much less common in
sirenomelia
o Teratogen
• Diabetes is a risk factor
• However, rare even in diabetics
• Epidemiology
o 1/60,000 to 1/100,000 births
o Found in higher frequency in monozygotic twins,
reflecting early timing of malformation
• Majority are discordant
• Associated abnormalities
a Bilateral renal abnormalities
• Renal agenesis

SIRENOMELIA
o
o
o
o
o
o
o
o
o

o

• Multicystic dysplastic kidneys less common than
agenesis
Other defects of midline development
• Neural tube defects
Radial ray abnormalities
Genital ambiguity/absence
of external genitalia
Mullerian anomalies
Anorectal atresia
Cloacal abnormalities
Single umbilical artery
Vestigial tail
Skeletal
• Hypoplasia/aplasia of pelvic girdle
• Varying degrees of limb reduction, soft tissue
fusion of lower extremities
• Complex fusion of feet (sympodia)
• Absent feet
• Lumbosacral agenesis
• Phocomelia
• Rotational abnormalities of lower limbs
• Hip dislocation
Less common: Cardiac, central nervous system
anomalies

I DIAGNOSTIC
Consider

• Fetal MRI to evaluate lower extremities and renal
agenesis
• 3D ultrasound may be helpful, if sufficient amniotic
fluid

Image Interpretation

I SELECTED REFERENCES
1.

2.

3.

4.

5.
6.
7.

8.

I CLINICAL

ISSUES

9.

Presentation
• Most common signs/symptoms
o Severe oligohydramnios
o Renal agenesis
o Fused lower extremities
• Gender: Preponderance

10.
11.

12.

Demographics
of males 2.7:1 ratio (M:F)

Natural History & Prognosis
• Majority lethal, prenatal or perinatal
• If liveborn, death from pulmonary hypoplasia within
few hours
• In rare survivors, obstruction of genitourinary and
gastrointestinal systems may be life-limiting

Treatment
• No prenatal treatment available
• Termination of pregnancy should be offered
• No monitoring or intervention in labor in continuing
pregnancies

Pearls

• Color Doppler ultrasound for abdominal vessels
o Demonstration of absence of renal arteries
o Confirmation of lack of branching of iliac arteries,
frequently seen in sirenomeli a (normal in renal
agenesis without sirenomelia)

Gross Pathologic & Surgical Features
• In some cases, single large vessel arising from distal
aorta can be demonstrated
o No aortic bifurcation seen in these cases
• Varied renal anomalies, from complete absence of
kidneys to multicystic dysplastic kidneys, secondary to
obstruction
• Absence of bladder, ureters
• Cloacal malformations

CHECKLIST

13.
14.
15.

16.

17.
18.

Parikh TB et al: Sirenomeli a apus with vestigial tail. Indian
J Pediatr. 72(4):367,2005
Assimakopoulos E et al: Caudal regression syndrome and
sirenomelia in only one twin in two diabetic pregnancies.
Clin Exp Obstet Gynecol. 31(2):151-3, 2004
Drossou-Agakidou V et al: Rare manifestations of
sirenomelia syndrome: a report of five cases. Am J
Perinatol. 21(7):395-401, 2004
Kulkarni ML et al: Sirenomeli a with radial dysplasia. Indian
J Pediatr. 71(5):447-9,2004
Lutz N et al: Mermaid syndrome: virtually no hope for
survival. Pediatr Surg Int. 20(7):559-61, 2004
Banerjee A et al: Sirenomelia. Indian J Pediatr.
70(7):589-91, 2003
Kjaer KW et al: Sirenomeli a sequence according to the
distance between the first sacral vertebra and the ilia. Am J
Med Genet A. 120(4):503-8,2003
Schiesser M et al: Sirenomelia, the mermaid
syndrome--detection in the first trimester. Prenat Diagn.
23(6):493-5, 2003
Stanton MP et al: A surviving infant with sirenomeli a
(Mermaid syndrome) associated with absent bladder. J
Pediatr Surg. 38(8):1266-8, 2003
Das BBet al: Caudal regression syndrome versus
sirenomelia: a case report. J Perinatol. 22(2):168-70, 2002
Dasgupta S et al: An interesting rare case of sirenomelia. J
Indian Med Assoc. 100(12):715-6, 2002
Gamzu R et al: Type II single umbilical artery (persistent
vitelline artery) in an otherwise normal fetus. Prenat
Diagn. 22(11):1040-3, 2002
Monteagudo A et al: Sirenomelia sequence: first-trimester
diagnosis with both two- and three-dimensional
sonography. J Ultrasound Med. 21(8):915-20, 2002
Opitz JM et al: Defects of blastogenesis. Am J Med Genet.
115(4):269-86,2002
Valenzano M et al: Sirenomelia. Pathological features,
antenatal ultrasonographic clues, and a review of current
embryogenic theories. Hum Reprod Update. 5(1):82-6,
1999
Sepulveda Wet al: Sirenomeli a sequence versus renal
agenesis: prenatal differentiation with power Doppler
ultrasound. Ultrasound Obstet Gynecol. 11(6):445-9, 1998
Twickler D et al: Caudal regression versus sirenomelia:
sonographic clues. J Ultrasound Med. 12(6):323-30, 1993
Stevenson RE et al: Vascular steal: the pathogenetic
mechanism producing sirenomelia and associated defects
of the viscera and soft tissues. Pediatrics. 78(3):451-7, 1986

SIRENOMELIA
I IMAGE GALLERY
(Left) Cross pathology shows
a vitelline artery "steal"
vessel (curved arrow) arising
from the distal aorta (arrow)
in a stillborn fetus with
sirenomelia. No renal or iliac
arteries are identified. (Right)
Anteroposterior radiograph
shows soft tissue fusion of
the lower extremities
(arrow), bilateral absence of
the fibulae (open arrows)
and sacral agenesis (curved
arrow) in sirenomelia.

(Left) Ultrasound shows
sacral agenesis (arrow),
absent pelvic bones (open
arrow), abnormal lower
extremities (curved arrow)
and oligohydramnios in this
mid-trimester fetus with
sirenomelia. (Right)
Ultrasound shows a single
fused lower extremity in
another mid-trimester fetus
with sirenomelia (arrows).

(Left) Ultrasound of the legs
shows 2 tibiae (arrows) and
only I fibula (curved arrow).
The legs and feet (open
arrow) could not be
separated. Visualization
limited secondary to renal
dysplasia and anhydramnios.
Findings of sirenomelia
confirmed by X-ray. (Right)
Clinical photograph shows
sympodia (complex fusion of
the feet) in a stillborn with
siren omelia. Note the deep
cleft between the 1st and
2nd toes on one foot
(arrow).

SMITH-LEMLI-OPITZ

Clinical photograph
shows
postaxial
polydactyly
(arrow) of the hand in an older child with SLOS/RSH
syndrome.
Clinodactyly
of the 3rd finger is also
apparent (open arrow).

ITERMINOlOGY
Abbreviations

and Synonyms

• Smith-Lemli-Opitz syndrome (SLOS)
• RSH syndrome (initials of first 3 patients)
• SLOS/RSH syndrome

Definitions
• Disorder of cholesterol biosynthesis characterized by
intrauterine growth restriction (IUGR), multiple
congenital anomalies and developmental delay
o SLOS I and II in older literature: Part of phenotypic
spectrum of same disorder

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: Combination of IUGR, cardiac
defects, polydactyly, genital ambiguity on
mid-trimester ultrasound

Ultrasonographic

Findings

• Increased nuchal translucency common on 1st
trimester ultrasound
• Central nervous system (CNS)
o Microcephaly, holoprosencephaly,
hydrocephalus,
agenesis of corpus callosum

DDx: Chromosomal

Trisomy 78

SYNDROME

Ultrasound shows postaxial polydactyly (arrow) in a 3rd
trimester fetus with Smith-Lemli-Opitz syndrome.

• Cardiac
o Atrioventricular (AV) canal, ventricular septal defect,
hypoplastic left heart
• Genitourinary
o Ambiguous genitalia, cystic renal disease
• Postaxial polydactyly
• Facial malformations
o Hypertelorism, short up-turned nose, low-set ears,
micrognathia

I DIFFERENTIAL
Chromosomal

DIAGNOSIS

aneuploidy

• Trisomy 13
o Holoprosencephaly
o Cardiac anomalies
o Omphalocele
o Cleft lip/palate
o Postaxial polydactyly
o Cryptorchidism
• Trisomy 18
o IUGR
o Cardiac anomalies
o Overlapping digits, "rocker bottom" feet
o Radial ray defects
o Cleft palate
• Triploidy

Aneuploidy

T13, Holopros

Triploid, Ambig Genit

SMITH-LEMLI-OPITZ

SYNDROME

Key Facts
Terminology

Pathology

• Di order of chole terol bio ynthesis characterized
intrauterine growth restriction (IUGR), multiple
congenital anomalie and developmental delay

by

Imaging Findings

Clinical Issues
• Severe perinatal pre entation u ually lethal
• Postnatal clinical everity inver ely correlated with
level of plasma cholesterol or ratio of cholesterol to
total terols

Top Differential

• Low to undet ctable I vels of unconjugated e triol
(MSuE3) on maternal erum creen should prompt
careful onographic evaluation for characteristic
anomalies
• Diagnosis can be confirmed by amniocentesi
or

Diagnoses

olUGR
o 2-3 toe/3-4 finger syndactyly
o Genitourinary tract anomalies
o Variable CNS anomalies
• Deletion lOq
o Severe hypogenitalism

Hydrolethalus
Hydrocephalus
Cardiac anomalies
Cleft lip/palate
Polydactyly
Cryptorchidism
Short limbs

Meckel Gruber syndrome
• Cystic renal dysplasia
• Postaxial polydactyly
• Encephalocele

Holoprosencephaly
• Isolated or in association
anomalies

with other structural

Pseudotrisomy 13
•
•
•
•

with carrier

• Be t diagno tic clue: ombination of IUGR, cardiac
defects, polydactyly, genital ambiguity on
mid-trimester ultrasound
• Increased nuchal translucency common on 1st
trimester ultrasound
• hromosomal aneuploidy
• Hydrolethalus
• Meckel Gruber syndrome
• Holopro encephaly

•
•
•
•
•
•

• Genetics: Autosomal recessive
• More frequent in European
aucasian
frequency a high a 1/30

Holoprosencephaly
Postaxial polydactyly
Ambiguous genitalia
Normal karyotype

I PATHOLOGY
General Features
• Genetics: Autosomal recessive
• Etiology
o Disorder of cholesterol biosynthesis
• Mutations in the 3 beta-hydroxysterol
Delta (7)reductase gene (DHCR7) which catalyzes the
reduction of 7-dehydrocholesterol
(7DHC) to
cholesterol
• Results in elevated serum and tissue levels of
7DHC, low levels of circulating cholesterol

Diagnostic Checklist

• Sterols are critical components in myelin, other
central nervous system proteins, membranes:
Altered sterol profile associated with abnormal
intellectual, motor function
• Sonic hedgehog and Patched (embryonic signaling
proteins) both rely on cholesterol for proper
function; abnormalities associated with
holoprosencephaly
• Decrease in testosterone and estrogen production
result in hypogenitalism in males, low MSuE3 in
affected pregnancies
o Carrier status may be determined by mutation
analysis
• Prediction of carrier status not possible by analysis
of cholesterol, 7DHC due to wide range of normal
• Epidemiology
o 1/20,000 births in North American Caucasians
o Rare in individuals of African/Asian descent
o More frequent in European Caucasians with carrier
frequency as high as 1/30
o Up to 7% of stillbirths may be due to SLOS/RSH
o Common mutation found in about 60% of
Caucasian cases (IVS8-1G -+ C)

Microscopic

Features

• Giant cells in pancreatic
• Thymic hypoplasia

I CLINICAL

islets

ISSUES

Presentation
• Most common signs/symptoms
o Craniofacial: Microcephaly (90%), narrow bifrontal
diameter, ptosis (60%), downslanting palpebral
fissures, anteverted nares, cleft palate (37-52%),
tongue cysts, low set ears
o Genitourinary (90%): Sex reversal in males or genital
ambiguity, micropenis, hypospadias, renal agenesis,
cystic renal dysplasia, hydronephrosis
o Growth: Pre- and postnatal growth restriction

SMITH-LEMLI-OPITZ
o Extremities: Postaxial polydactyly (50%), 2-3 "Y"
syndactyly of toes (95%), high frequency of whorl
dermal ridge pattern
o Cardiac (38%): Atrioventricular (AV)canal defect,
anomalous pulmonary venous return
o Cognitive: Moderate to profound mental retardation
• Other signs/symptoms
o Characteristic behavioral phenotype with autism,
self injury, food aversions, extreme tactile
sensitivity, abnormal sleep patterns, unusual upper
body arching, irritability
o Adrenal dysfunction, Hirschsprung disease,
anorectal atresia
o Holoprosencephaly

o Diagnosis can be confirmed by amniocentesis or
CVS

I SELECTED
1.

2.

3.

4.

Demographics
• Gender: Excess of males

Natural History & Prognosis
• Severe perinatal presentation usually lethal
• Survivors with moderate to profound mental
retardation, multiple medical problems
• Rare mild phenotype with delayed diagnosis, milder
course
• Prenatal level of 7DHC correlates with clinical severity
• Postnatal clinical severity inversely correlated with
level of plasma cholesterol or ratio of cholesterol to
total sterols

5.

6.

7.

8.

Treatment
• Dietary supplementation with cholesterol and bile
acids
o Variable results in developmental improvement
o Improvement or elimination of behavioral, feeding
and growth problems
o Baseline cholesterol prior to treatment better
predictor of developmental potential
• Case reports of prenatal treatment
o Intravascular and intraperitoneal infusions of fresh
frozen plasma
o Resulted in improvement in fetal plasma cholesterol
levels
o Long term outcome unchanged but demonstrated
feasibility of intrauterine treatment
o Other case of maternal dietary cholesterol
supplementation less effective
• Prenatal diagnosis possible
o Sterol analysis of amniotic fluid in mid-trimester
(7DHC/total sterol ratio)
o 7DHC content of tissue from chorionic villus
sampling (CVS)
o Molecular analysis by CVS, amniocentesis when
specific mutation known
o Experimental analysis of sterols in maternal urine

9.

10.

11.

12.
13.

14.

15.

16.

17.

I DIAGNOSTIC

CHECKLIST

Image Interpretation

Pearls

• Low to undetectable levels of unconjugated estriol
(MSuE3) on maternal serum screen should prompt
careful sonographic evaluation for characteristic
anomalies

SYNDROME

18.

19.

REFERENCES

Goldenberg A et al: Antenatal manifestations of
Smith-Lemli-Opitz (RSH) syndrome: a retrospective survey
of 30 cases. Am] Med Genet A. 124(4):423-6,2004
Sikora DM et al: Cholesterol supplementation does not
improve developmental progress in Smith-Lemli-Opitz
syndrome.] Pediatr. 144(6):783-91, 2004
Witsch-Baumgartner M et al: Maternal apo E genotype is a
modifier of the Smith-Lemli-Opitz syndrome. ] Med Genet.
41(8):577-84,2004
Digilio MC et al: Specific congenital heart defects in
RSH/Smith-Lemli-Opitz syndrome: postulated involvement
of the sonic hedgehog pathway in syndromes with
postaxial polydactyly or heterotaxia. Birth Defects Res A
Clin Mol Teratol. 67(3):149-53, 2003
Gofflot F et al: Molecular mechanisms underlying limb
anomalies associated with cholesterol deficiency during
gestation: implications of Hedgehog signaling. Hum Mol
Genet. 12(10):1187-98,2003
Mueller C et al: Normal cognition and behavior in a
Smith-Lemli-Opitz syndrome patient who presented with
Hirschsprung disease. Am] Med Genet A. 123(1):100-6,
2003
Schoen E et al: Maternal serum unconjugated estriol as a
predictor for Smith-Lemli-Opitz syndrome and other fetal
conditions. Obstet Gynecol. 102(1):167-72,2003
Loeffler] et al: Molecular prenatal diagnosis of
Smith-Lemli-Opitz syndrome is reliable and efficient.
Prenat Diagn. 22(9):827-30, 2002
Palomaki GE et al: Assigning risk for Smith-Lemli-Opitz
syndrome as part of 2nd trimester screening for Down's
syndrome.] Med Screen. 9(1):43-4, 2002
Fitzky BU et al: 7-Dehydrocholesterol-dependent
proteolysis of HMG-CoA reductase suppresses sterol
biosynthesis in a mouse model of Smith-Lemli-Opitz/RSH
syndrome.] Clin Invest. 108(6):905-15,2001
Tierney E et al: Behavior phenotype in the
RSH/Smith-Lemli-Opitz syndrome. Am] Med Genet.
98(2):191-200,2001
Kelley RI et al: The Smith-Lemli-Opitz syndrome. ] Med
Genet. 37(5):321-35, 2000
Yu H et al: Spectrum of Delta(7)-dehydrocholesterol
reductase mutations in patients with the
Smith-Lemli-Opitz (RSH) syndrome. Hum Mol Genet.
9(9):1385-91, 2000
Yu H et al: Detection of a common mutation in the RSH or
Smith-Lemli-Opitz syndrome by a PCR-RFLPassay:
IVS8-G-->C is found in over sixty percent of US propositi.
Am] Med Genet. 90(4):347-50, 2000
Irons M et al: Treatment of Smith-Lemli-Opitz syndrome:
results of a multicenter trial. Am] Med Genet. 68(3):311-4,
1997
Nwokoro NA et al: Cholesterol and bile acid replacement
therapy in children and adults with Smith-Lemli-Opitz
(SLO/RSH) syndrome. Am] Med Genet. 68(3):315-21, 1997
Kelley RL et al: Holoprosencephaly in
RSH/Smith-Lemli-Opitz syndrome: does abnormal
cholesterol metabolism affect the function of Sonic
Hedgehog? Am] Med Genet. 66(4):478-84, 1996
Opitz]M et al: Cholesterol metabolism in the
RSH/Smith-Lemli-Opitz syndrome: summary of an NICHD
conference. Am] Med Genet. 50(4):326-38, 1994
Tint GS et al: Defective cholesterol biosynthesis associated
with the Smith-Lemli-Opitz syndrome. N Engl] Med.
330(2):107-13, 1994

SMITH-LEMLI-OPITZ

SYNDROME

IIMAGE GALLERY
Typical
(Left) Axial ullrasound of a
3rd trimester fetus with
severe SLOS/RSH syndrome.
There is an AV canal with the
alrial portion of the defect
(arrow) best seen on this
view. There is also skin
edema (curved arrow) and
pleural effusions (open
arrow). (RighI) Clinical
photograph shows typical
2-3 "Y" syndactyly of the
toes in an older child with
SLOS/RSH syndrome
(arrows). The foot posture is
a withdrawal response to
tactile stimulation.

Typical
(Left) Clinical photograph
shows an infant with severe
SLOS/RSH. Note the short
upturned nose with
anteverted nares (arrow),
short neck, low-set ears
(open arrow) and small
mouth (curved arrow).
(Right) Sagittal ullrasound
shows an abnormal profile
with short upturned nose
(arrow) and severe
micrognathia (open arrow)
in a different case of
SLOS/RSH syndrome.

Typical
(Left) Ultrasound shows
hypoplastic alar nasi (curved
arrow) and anteverted nares
(arrow) in a fetus with
SLOS/RSH syndrome at 30
weeks. (Right) Clinical
photograph shows
ambiguous genitalia (arrow)
in a male infant with severe
SLOS/RSH syndrome.
(Courtesy A. Putnam, MO
and /. Szakacs, MO).

TUBEROUS SCLEROSIS

Axial graphic shows the typical locations of
subependymal hamartomas (arrow), subcortical tubers
(curved arrows), and giant cell astrocytoma (open
arrow).

ITERMINOlOGY
Abbreviations

and Synonyms

• Tuberous sclerosis (TS), tuberous sclerosis complex
• Bourneville disease

Definitions
• Inherited tumor disorder with multiorgan hamartomas
• Included in spectrum of phakomatoses
• Clinical triad: Facial angiofibromas, mental
retardation, seizures

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Cardiac rhabdomyomas
common prenatal finding

Ultrasonographic

most

Findings

~

• Monitor for growth
• Size increases with advancing gestational age
o Monitor cardiac function for potential
complications
• Arrhythmia
• Atrioventricular valve dysfunction
• Outflow tract obstruction
o Associated dysrhythmias may result in hydrops
• Central nervous system (CNS) findings may be subtle
in utero
o Subependymal hamartomas
• Subependymal, echogenic nodules
• Irregularity of ventricular wall may be initial clue
o Subcortical tubers often not discernible
o Subependymal giant cell astrocytoma
• Located near foramen of Monro
• Larger mass, which grows on subsequent scans
• May present with hydrocephalus
• Usually do not present in utero

MR Findings

• Cardiac rhabdomyoma
o Well-defined, hyperechoic, intracardiac mass
• Tumor typically involves ventricles or
interventricular septum
• Most often affects left ventricle
o Often multiple
o May detect as early as 22 weeks gestation
o Requires close follow-up

DDx: Periventricular

Axial T2WI MR of the brain shows two, small,
hypointense, subependymal nodules (arrow) in this
fetus with tuberous sclerosis. These findings are subtle
and often missed by ultrasound.

• Primarily for evaluation of intracranial abnormalities
o MR more sensitive than ultrasound for detection of
CNS lesions
• Subependymal nodules
o Typically iso-hyperintense on Tl WI
o Low signal intensity on T2WI
• Can be mistaken for hemorrhage

Masses

\~'.·
."
....
U

~''.-.

~

I

'.

'If")o

'J'~

Cortical Dy~pla~ia

Ilemorrhagc

TUBEROUS

SCLEROSIS

Key Facts
Terminology

Pathology

• Inherited tumor disorder with multiorgan
hamartoma

• Autosomal dominant
• > 50% new mutation

Imaging Findings

Clinical Issues

• Best diagnostic clue: ardiac rhabdomyomas most
common prenatal finding
• Central nervous y tern (
S) findings may be subtle
in utero
• Subependymal, echogenic nodules
• Irregularity of ventricular wall may be initial clue

• Po tnatal eizure, may be intractable
• umber of C S lesion may predict everityof
cerebral dysfunction
• Watch for development of ubependymal giant cell
tumor

Top Differential

• Fetal MR more sensitive than ultrasound for detection
of C S lesions
• Even if prenatal scan is normal, postnatal MRI should
be con ide red for ubtle ca e
• Multiple rhabdomyoma
highly ugge tive of T

Diagnoses

• Bilateral periventricular
• ortical dy plasia

nodular heterotopia

o Located commonly along lateral ventricle margins,
near caudate/thalamus
• Cortical/subcortical
tubers
o Most often supratentorial
o High signal on T1 WI
o Low signal on T2WI
• Cortical/subcortical
white matter lesions
o High signal on T2WI
o Not routinely identified on prenatal scans
• If fetal MR negative in at-risk patient, consider
postnatal MRI
o May detect more subtle findings
o Gadolinium may be given
o Postnatal cardiac MRI may also be useful for
characterization of cardiac tumors

I DIFFERENTIAL DIAGNOSIS
Subependymal
•
•
•
•

gray matter heterotopia

Isointense to normal cortical gray matter on MRI
Unlike hamartomas, do not calcify
Associated with seizures
Variable intellectual deficits

Bilateral periventricular

nodular heterotopia

• Recently identified as X-linked hereditary disease
o Mutation within long arm of X chromosome, Xq28
• Sporadic or familial epilepsy with normal intelligence
• Primarily in females
• Associated with mega cisterna magna

Cortical dysplasias
• Subcortical heterotopia
• Polymicrogyria
• Focal cortical dysplasia
o Localized abnormality of lamination in cerebral
cortex
• Most present postnatally with seizures and/or
developmental delay

Diagnostic Checklist

Periventricular

germinal matrix

• Germinal matrix prominent in early brain
development up to 26 weeks gestation
• Can be confused with nodular heterotopia or
subependymal nodules because of location
o Signal characteristics similar to gray matter on MRI

Germinal matrix hemorrhage
• Because of location may be confused with
subependymal giant cell astrocytoma
• Look for other signs of evolving hemorrhage
o Intraventricular hemorrhage
o Decreasing echogenicity with time
o Porencephaly, hydrocephalus

I PATHOLOGY
General Features
• Genetics
o Autosomal dominant
• > 50% new mutation
• Variable expressivity
o Two separate genes localized
• TSCI on chromosome 9q34
• TSC2 on chromosome 16p13.3
o No difference in clinical phenotype between TSCI
and TSC2 mutations
• Etiology: Abnormal differentiation of germinal matrix
cells
• Epidemiology: 1:10,000-20,000
• Cardiac
o Rhabdomyomas
• Benign tumors
• 50-85% are associated with TS
• Multiple in 50% of cases
• > 80-90% risk of TS if multiple
• Intracranial
o Subependymal nodules
• Nonprogressing hamartomas
• Usually < 15 mm diameter

TUBEROUS SCLEROSIS
• May calcify postnatally beginning in second
decade
o Cortical tubers
• Lack central myelination
• Unorganized neurons and glial cells
o Subependymal giant cell astrocytoma
• Occur in 15% of TS patients
• Covered by ependymal layer
• Do not invade or disseminate in cerebral spinal
fluid
• May calcify
• Enhance with contrast administration in postnatal
imaging
o Cortical/subcortical
white matter lesions
• Bands of unmyelinated radial glial cells

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Usually incidental finding of cardiac mass
• Most commonly identified in second trimester
o Family history of TS
• Other signs/symptoms
o Arrhythmias
o Nonimmune hydrops secondary to cardiac
involvement
• Postnatal work-up for TS warranted in at-risk
pregnancies, even if prenatal work-up negative
• Check for other signs of TS after delivery
o Retinal nodular hamartomas
o Skin findings
• Facial angiofibromas (adenoma sebaceum),
shagreen patch, cafe-au-Iait spots, subungual
fibroma
o Renal lesions
• Cysts, angiomyolipoma
o Lymphangiomyomatosis
• Look carefully at parents for TS
o Family history and multifocality of lesions are
strongest predictors of TS
• Size of rhabdomyoma not directly linked to
likelihood of TS
o Affects counseling for future pregnancies

•
•
•
•

and is often

Treatment
• Cardiac rhabdomyomas
o May require prenatal therapy with antiarrhythmics
o Consider pre term cesarean section if hemodynamic
obstruction becomes apparent
o Resection may be warranted postnatally if affects
cardiac function
• CNS abnormalities
o Therapy directed at seizure control
• May require tuber resection if refractory to
medication
o Close imaging follow-up for developing
subependymal giant cell tumor
• Surgical resection usually curative
• Genetic counseling for parents

I DIAGNOSTIC

CHECKLIST

Consider
• Fetal echocardiography
to monitor cardiac function
• Fetal MR more sensitive than ultrasound for detection
of CNS lesions
o Even if prenatal scan is normal, postnatal MRI
should be considered for subtle cases
o Recommended for screening at-risk patients (family
history of TS)

Image Interpretation

Pearls

• Multiple rhabdomy'omas

highly suggestive of TS

I SELECTED REFERENCES
1.

2.

3.

Natural History & Prognosis
• Cardiac rhabdomyomas
o Often have benign clinical course prenatally
o May grow in conjunction with gestational age or
remain stable
o Usually spontaneously regress postnatally
o Poor prognostic indicator if associated with cardiac
dysfunction
• CNS findings
o Postnatal seizures, may be intractable
o Number of CNS lesions may predict severity of
cerebral dysfunction
• Risk of cognitive impairment associated with
number of tubers
• May have normal intelligence
o Watch for development of subependymal giant cell
tumor

Slow-growing tumor
Usually presents later in childhood
Favorable outcome if removed
Can rarely present in a fetus/neonate,
highly aggressive in such cases

4.

5.

6.

7.

8.

King]A et al: Maternal and fetal tuberous sclerosis
complicating pregnancy: a case report and overview of the
literature. Am] Perinatol. 22(2):103-8, 2005
Fesslova V et al: Natural history and long-term outcome of
cardiac rhabdomyomas detected prenatally. Prenat Diagn.
24(4):241-8,2004
Smirniotopoulos ]G: Neuroimaging of phakomatoses:
Sturge-Weber syndrome, tuberous sclerosis, von
Hippel-Lindau syndrome. Neuroimaging Clin
Am.
14(2):171-83, vii, 2004
Bader RS et al: Fetal rhabdomyoma: prenatal diagnosis,
clinical outcome, and incidence of associated tuberous
sclerosis complex.] Pediatr. 143(5):620-4, 2003
Bargallo N et al: Hereditary subependymal heterotopia
associated with mega cisterna magna: antenatal diagnosis
with magnetic resonance imaging. Ultrasound Obstet
Gynecol. 20(1):86-9, 2002
Gamzu R et al: Evaluating the risk of tuberous sclerosis in
cases with prenatal diagnosis of cardiac rhabdomyoma.
Prenat Diagn. 22(11):1044-7, 2002
Mitchell LA et al: Antenatal diagnosis of subependymal
heterotopia. A]NR Am] Neuroradiol. 21(2):296-300, 2000
Sgro M et al: Prenatal detection of cerebral lesions in a
fetus with tuberous sclerosis. Ultrasound Obstet Gynecol.
14(5):356-9, 1999

TUBEROUS SCLEROSIS
I IMAGE

GALLERY

(Left) Axial ultrasound shows
a subtle echogenic nodule
(arrow) along the posterior
lateral ventricle in this fetus
whose mother had tuberous
sclerosis. Subependymal
nodules may be very difficult
to diagnose prenatally and
fetal MRI is recommended
in
at-risk patients. (Right) Axial
TlWI MR after delivery
shows multiple, high signal,
subependymal
nodules
(arrows), which were not
appreciated prenatally.

(Left) Axial ultrasound shows
multiple, echogenic,
intracardiac masses involving
both ventricles and the
interventricular septum in a
second trimester fetus
(arrows). The multiplicity is
highly suggestive of tuberous
sclerosis. (Right) Four
chamber view shows a large
rhabdomyoma
(arrow)
within the left ventricle, and
multiple smaller ones in both
ventricles. The brain was
normal by ultrasound but
postnatal MR showed
subependymal
nodules.

(Left) Coronal ultrasound in
a neonate shows a large
subependymal
giant cell
tumor (arrow) in the region
of the foramen of Monro.
There is ipsilateral lateral
ventricular enlargement.
MR
showed multiple small
subependymal
nodules.
(Right) Clinical photograph
of a child shows the typical
appearance of facial
angiofibromas
(arrows) seen
in tuberous sclerosis. These
often appear before puberty
and start in the nasolabial
fold.

VACTERL ASSOCIATION

Radiograph shows an orogastric tube curled at the site
of esophageal atresia (curved arrow). A distal TE fistula
accounts for gas in bowel. There are vertebral anomalies
(arrow) and dilated bowel loops from anal atresia.

ITERMINOLOGY
Abbreviations

and Synonyms

• VATER/VACTER/VACTERLassociation

Definitions
• Non-random association of 7 core abnormalities
o Vertebral defects
o Anal atresia
o Cardiac anomalies
o Tracheoesophageal fistula (TE fistula)
o Esophageal atresia
o Renal anomalies
o Limb defects (radial)
• VATERincludes vertebral, anal atresia, TE fistula,
esophageal atresia, renal/radial defects

IIMAGING

FINDINGS

• Best diagnostic clue
o Multiple anomalies on mid-trimester ultrasound
o Renal, limb and vertebral anomalies most easily
identified

Findings

• Vertebral anomalies

DDx: Conditions With Overlapping

Trisomy 78: Hand

o Hemivertebrae
• Best demonstrated in coronal plane
• Kyphosis
• Scoliosis: Originates at area of hemivertebra(e)
o Butterfly vertebrae
o Fusion of vertebral bodies or posterior elements
(block vertebrae)
o Caudal dysplasia
• Anal atresia/imperforate
anus
o Normal anus is echogenic ring ("anal dimple")
o Absent in atresia
o Colon can occasionally be dilated
o Often not recognized prenatally
o Imperforate anus associated with increased
incidence of genital, urinary, lumbosacral spine
abnormalities
• Cardiac malformations
o Cardiac anomalies most common defect, seen in ""
80%

General Features

Ultrasonographic

Sagittal ultrasound shows a hemivertebra in the lumbar
spine (arrow) causing a mild lumbar kyphosis (open
arrow). Vertebral anomalies are one of the most obvious
findings in the VACTERLassociation.

I fait-Gram

o No specific type of cardiovascular malformation is
typical
• Esophageal atresia +/- TE fistula
o Present in 50-60% of individuals with VACTERL
o Often difficult to diagnose
o Stomach absent or small
o Look for an esophageal "pouch" sign
• Transient filling of proximal esophagus with
swallowing

Features Of VACTERL Association

Anorectal Atresia

VACTERL ASSOCIATION
Key Facts
Terminology
•

on-random association of 7 core abnormalities

Imaging Findings
• Multiple anomalies on mid-trimester ultrasound
• Renal, limb and vertebral anomalies most easily
identified
• Cardiac anomalies most common defect, seen in ""
80%

• Systematic search for associated anomalies when one
defect identified
• Karyotype to exclude chromosome abnormalities
• Polyhydramnios often a late finding, developing after
28 weeks

Top Differential

Diagnoses

•
•
•
•

Anorectal atresia
Radial ray anomalies
Holt-Oram syndrome
Diabetic embryopathy

Pathology
• Recurrence risk < 1%
• ot associated with chromosomal abnormality but
shares many common features
• Defective differentiation of mesoderm prior to 35
days of development (mechanism unknown)
• Diagnosis of exclusion
• All features found in VACTERLare commonly found
in other syndromes, as well as in isolation
• Few patients have all features
• Average findings per patient is 3-4

• Trisomy 18

o Polyhydramnios may be a late finding
• Rarely present < 20 wks
o Persistent absent gastric fundus associated with
increased amniotic fluid best sign
• Renal anomalies
o Agenesis, may be unilateral or bilateral (lethal)
o Multicystic dysplastic kidney
o Hydronephrosis
o Ectopic kidney
• Limb malformation
o Restricted to upper limbs
o Usually bilateral, may be asymmetric
o Radial ray malformation common
• Hypoplasia/aplasia of thumbs
• Hypoplasia/aplasia of radius with radial club hand
• Other associated malformations/abnormalities
o Polyhydramnios
• Most often associated with esophageal atresia
o Rib anomalies (bifid, fused, absent)
• Commonly associated with vertebral
segmentation abnormalities
o Single umbilical artery often associated with renal
anomalies
o Genital
• Hypospadias, bifid scrotum, hypoplastic labia
• More common in those with anorectal
malformation
o Intrauterine growth restriction (IUGR)
o Cleft lip/palate, high arched palate
o Oligohydramnios with bilateral renal anomalies

Imaging Recommendations
• Protocol advice
o Systematic search for associated anomalies when
one defect identified
o Dedicated fetal echo
o Karyotype to exclude chromosome abnormalities
o Polyhydramnios often a late finding, developing
after 28 weeks
• Repeat ultrasound in 3rd trimester to evaluate
fluid and growth

I DIFFERENTIAL

DIAGNOSIS

Trisomy 18
• Central nervous system (CNS) malformations
• Gastrointestinal anomalies
• Significant overlap with VACTERLassociation with
other anomalies
o Cardiac anomalies
o Radial ray abnormalities
o TE fistula
o Renal abnormalities
o IUGR

Anorectal atresia
• Isolated vs. syndromic
• High associated rate of genitourinary, lumbar spine
abnormalities

Radial ray anomalies
• Isolated vs. syndromic
• Wide range of thumb abnormalities

Syndromes with overlapping features
• Holt-Oram syndrome
o Radial ray anomalies, upper limb phocomelia
o Cardiac defects (atrial septal and ventricular septal
defects, hypoplastic left heart)
o Vertebral anomalies
o Thoracic scoliosis
• Diabetic embryopathy
o Cardiac anomalies
o Renal anomalies
o CNS anomalies
o Limb anomalies
• Thrombocytopenia absent radius (TAR)
o Bilateral radial ray abnormalities with normal
thumbs
o Cardiac, renal, other skeletal defects
o High infant mortality due to hemorrhage, cardiac
disease
• MURCS association
o Mullerian abnormalities, renal anomalies and
cervicothoracic vertebral dysplasia

VACTERL ASSOCIATION
• CHARGE association
o Colobomata, heart defects, choanal atresia, genital
anomalies, growth abnormalities, ear anomalies
o TE fistula +/- esophageal atresia, anal atresia
• Townes-Brock syndrome
o Dysplastic ears, triphalangeal thumbs, anal and
renal anomalies
• Roberts syndrome/Roberts SC/Pseudothalidomide
syndrome
o Tetraphocomelia (90%), oro facial clefts, IUGR
o Wide phenotypic overlap with TAR
• ]archo-Levin syndrome
o Multiple rib and vertebral anomalies associated with
characteristic "crab claw" appearance of ribs
o Higher incidence in individuals of Puerto Rican
descent
• VACTERL with hydrocephalus
o Separate entity
o X-linked and autosomal recessive types
o Often poor prognosis with severe retardation
• Arthrogryposis
o Limb contractures may simulate radial/ulnar ray
abnormalities
o Extremities remain in fixed position during scan
o Scoliosis

I PATHOLOGY
• Genetics
o Sporadic
• Rare report of parent to child transmission
• Occasional cases of single features of VACTERL in
siblings or parents of affected individuals
o Recurrence risk < 1%
o Not associated with chromosomal abnormality but
shares many common features
• Etiology
o Defective differentiation of mesoderm prior to 35
days of development (mechanism unknown)
o Risk factors: Maternal diabetes
• Epidemiology: 1.6/10,000 incidence

Staging, Grading or Classification Criteria
•
•
•
•

Diagnosis of exclusion
No specific tests for confirmation of diagnosis
No facial phenotype to aid in pattern recognition
All features found in VACTERL are commonly found
in other syndromes, as well as in isolation
• Few patients have all features
o Average findings per patient is 3-4
o No consensus on minimum diagnostic criteria,
although at least one anomaly in each of limb,
thorax and abdomen/pelvis probably needed to
secure a diagnosis

ISSUES

Presentation
• Most common signs/symptoms:
on mid-trimester scan

Treatment
• Karyotype to rule out trisomy
• Pregnancy termination an option, given multiple
severe anomalies
o Autopsy encouraged to establish diagnosis
• Delivery at tertiary care facility, if pregnancy
continued
• Complete work-up with cardiac echo, renal
ultrasound, spine and extremity X-rays
• All of the core features require surgical intervention
treatment
• Examination of parents and siblings for common
features may help elucidate diagnosis

I DIAGNOSTIC

Multiple anomalies

for

CHECKLIST

Image Interpretation

General Features

ICLINICAL

Natural History & Prognosis
• Variable based on type and number of anomalies
o 28% neonatal mortality
• Potentially life-threatening anomalies include TE
fistula, anal atresia and cardiac abnormalities
• Survivors have good prognosis for normal intellect
• Severe scoliosis may be progressive, difficult to treat
• Life-long need for treatment, therapy in severely
affected individual

Pearls

• One or more features should prompt thorough
evaluation for other associated anomalies
o Often anomalies which are not as obvious (e.g.
esophageal atresia and cardiac defects) have
potentially most serious complications

I SELECTED

REFERENCES

Bergmann C et al: Overlap between VACTERL and
hemifacial microsomia illustrating a spectrum of
malformations seen in axial mesodermal dysplasia
complex (AMOC). Am] Med Genet A. 121(2):151-5,2003
2.
Chen CP et al: Prenatal diagnosis of right pulmonary
agenesis associated with VACTERL sequence. Prenat Oiagn.
23(6):515-8,2003
3.
Spilde T et al: A role for sonic hedgehog signaling in the
pathogenesis of human tracheoesophageal
fistula. ] Pediatr
Surg. 38(3):465-8, 2003
Kim] et al: The VACTERL association: lessons from the
4.
Sonic hedgehog pathway. Clin Genet. 59(5):306-15, 2001
5.
Kim PC et al: Murine models of VACTERL syndrome: Role
of sonic hedgehog signaling pathway. ] Pediatr Surg.
36(2):381-4, 2001
6.
Miller OF et al: Prenatal diagnosis of VACTERL association.
] Urol. 166:2389-91, 2001
7.
Kolon TF et al: Upper urinary tract manifestations of the
VACTERLassociation.] Urol. 163(6):1949-51,2000
8.
Nezarati MM et al: VACTERL manifestations in two
generations of a family. Am] Med Genet. 82(1):40-2, 1999
9.
Tongsong T et al: Prenatal sonographic diagnosis of VATER
association.] Clin Ultrasound. 27:378-84, 1999
10. Lomas FE et al: VACTERL with hydrocephalus: family with
X-linked VACTERL-H. Am] Med Genet. 76(1):74-8, 1998
1.

VACTERL ASSOCIATION
IIMAGE

GALLERY
(Left) Coronal ultrasound of
the spine shows scoliosis
secondary to fused vertebrae
(arrow). There is also a
multicystic dysplastic kidney
(curved arrow). This finding
was bilateral, resulting in
severe oligohydramnios.
Lack of amniotic fluid
impairs anatomic
visualization. (Right) Four
chamber view of the heart
also shows a ventricular
septal defect (arrow). 80%
of VACTERL cases have a
cardiac defect.

Typical
(Left) Transverse ultrasound
shows an absent stomach
bubble (arrow), which was
persistent on all exams in this
fetus with esophageal atresia.
Polyhydramnios
is also
evident. (Right) Transverse
ultrasound shows unilateral
renal agenesis in this
mid-trimester fetus. The
adrenal gland is seen in the
renal fossa (open arrow) and
there is mild pelviectasis in
the contralateral kidney
(arrows). Finding one
anomaly in the VACTERL
association should prompt a
careful search for others.

(Left) Radiograph shows a
radial ray defect in a
newborn with multiple
anomalies, consistent with
VACTERL. There is a single
forearm bone (open arrow),
with radial clubbed hand
(arrow) and absent thumb
and 2nd digit (curved
arrow). (Right) Clinical
photograph shows a radial
club hand in a newborn.
Note the malpositioned
thumb (arrow) with absent
flexion creases (curved
arrow), a subtle but
important clinical finding.

SECTION 16: Infedion

Cytomegalovirus
Parvovirus
Toxoplasmosis
Varicella

16-2
16-6
16-8
16-10

CYTOMEGALOVIRUS

Four chamber
view ultrasound
shows dilated
cardiomyopathy in a 3rd trimester fetus with intrauterine
cytomegalovirus infection. A pericardia I effusion is also
noted (arrows).

Clinical photograph shows macular lesions (arrows),
consistent with extramedullary hematopoiesis, in the
skin of this premature infant with congenital CMV
infection.

ITERMINOLOGY

Imaging Recommendations

Abbreviations

• Presumptive fetal infection in documented
infection, when following are present
o Progressive IUGR
o Microcephaly
o Hepatomegaly
o Calcifications
o Hydrops

and Synonyms

• Cytomegalovirus

jlMAGING

(CMV)

FINDINGS

General Features
• Best diagnostic
calcifications

clue: Intracranial

Ultrasonographic

maternal

and intrahepatic

I DIFFERENTIAL DIAGNOSIS
Findings

• Calcifications may be widespread
o Brain (peri ventricular, cortical), diaphragm,
pericardium
o Calcifications are often non-shadowing
• Brain most commonly affected area
o Ventriculomegaly, microcephaly
o Cataract formation, chorioretinitis
• Hepatosplenomegaly
• Cardiomyopathy
• Intrauterine growth restriction (IUGR)
• Hydrops with severe disease
• Both polyhydramnios
and oligohydramnios
seen

Parvovirus 8-19 (Fifth disease)
•
•
•
•
•

Maculopapular rash in adults
Migratory, transient rash in children
> 50% of women are immune
20-30% fetal transmission in infected women
Infection may be fatal in sickle cell anemia (apiastic
crisis)
• Parvovirus attacks red blood cell precursors ~ anemia
• Ascites common presenting finding in fetus
• Fetal hydrops secondary to anemia
o 10-20% risk of fetal or neonatal death
o Treated with transfusions
o Spontaneous recovery has been reported

Toxoplasmosis (Toxoplasma gondii)
• Cats are definitive hosts: Oocyst shed in feces

DDx: Intrauterine

Varicella, Arm

Infections

CYTOMEGALOVIRUS
Key Facts
Imaging Findings
• Best diagno tic clue: Intra ranial and intrahepatic
calcification
• alcifications are often non-shadowing

Top Differential
•
•
•
•
•
•

• Mo t common congenital infection worldwide
• ongenital
MV is most common infectiou cau e of
mental retardation,
ensorineural deafne
and visual
impairment

Clinical Issues

Diagnoses

Parvovirus B-19 (Fifth disea e)
Toxoplasmo i (Toxoplasma gondii)
Varicella
Herpes simplex (type 2 IISV)
on-immun
hydrops
Echog nic bowel

Pathology
• Genetics: usceptibility, everity of in utero infection
likely influenced by host genetics
• Early expo ure increa es ri k to fetus

• 10% of congenitally infected infant symptomatic
• eurologic sequelae in up to 90% (sensorineural
hearing loss, visual impairment, mental retardation)
• 90% of congenitally infected infant a ymptomatic at
birth
• Even in absence of onographic finding in
documented fetal infection, neurologic sequelae
found in at least 20<}fl
• 10-1591)will sub equently have abnormal neurologic
development
• 10% will develop hearing loss in early childhood

• Human infection from contaminated soil, water,
undercooked meats
• 15-30% fetal infection rate
o Higher infection rate in 3rd trimester but not as
serious
• Intracranial calcifications
o Random distribution, echogenic non-shadowing
• Liver calcifications and hepatosplenomegaly

• IUGR, intrauterine death in severe cases
• Progressive cognitive, motor delay common in
infected infants
• Postnatal growth restriction
• Amniocentesis and other interventional procedures
contraindicated
o Increases exposure risk to fetus

Varicella

• Rare in developed countries
• 1st trimester most critical time for fetal infection
• Cardiac defects, microcephaly, microphthalmia,
mental retardation, IUGR

• Primary infection, chickenpox
• Latent virus in dorsal root ganglia
• > 90% of women are immune
• Low incidence of transmission to
• Neurotropic virus '* contractures,
• Calcifications (liver, heart, renal),

'* shingles
fetus
limb hypoplasia
skin lesions

Herpes simplex (type 2 HSV)
• Most infections from vaginal delivery with active viral
shedding
o Active lesions or prodromal symptoms of impending
outbreak
o Cervical shedding without evidence of lesions
• Transplacental infection rare
o Primary outbreak during pregnancy increases risk of
fetal infection
• Echogenic bowel, ventriculomegaly
• Cross-reactivity with HSV-1 may cause confusion in
making diagnosis

Syphilis (Treponema

pallidum)

• Risk of infection related to spirochete load
• Hepatosplenomegaly,
dilated bowel, bowing of long
bones, abnormal epiphyses
• Hydrops with severe cases
• 50% spontaneous abortion or perinatal death
• Jarisch-Herxheimer
reaction (severe response to
endotoxin release from killed organisms) with
treatment during pregnancy
o Associated with fetal death

HIV (AIDS embryopathy)
• 20% transplacental

infection

Rubella (German measles)

Non-immune

hydrops

• Many underlying causes, including
infection, dysrhythmia

fetal aneuploidy,

Echogenic bowel
• Underlying causes including aneuploidy,
gastrointestinal anomalies including bowel
obstructions, cystic fibrosis

I PATHOLOGY
General Features
• Genetics: Susceptibility, severity of in utero infection
likely influenced by host genetics
• Etiology
o Early exposure increases risk to fetus
o Control of passage of CMV across placenta involves
multiple regulatory events including local cytokines,
maternal CMV-specific neutralizing antibodies,
presence of other pathogens
o Herpes virus family
• Ubiquitous in humans, other mammals
o General population infection by direct contact,
exposure to secretions
• Infection also occurs via blood transfusion, organ
transplantation
from infected donor
• Usually restricted to immunocompromised
or
immunologically immature individuals

CYTOMEGALOVIRUS
o Fetal infection via placenta (vertical transmission)
• Epidemiology
o Most common congenital infection worldwide
• Incidence of congenital infection with CMV
approximately 1% of livebirths (0.3-2.4%
worldwide)
o Congenital CMV is most common infectious cause
of mental retardation, sensorineural deafness and
visual impairment
o Main reservoir is children under 2 years of age
o Viral load in maternal blood, amniotic fluid and
fetal blood important prognostic factors
o Prevalence of CMV antibodies in healthy adults ""
50% in most industrialized countries
• 100% in developing countries
o Incidence of primary infection in pregnancy = 1%
• 30-40% vertical transmission rate to fetus
o Non-primary infection rate in pregnancy
(reactivation of previous infection) = 5%
• Vertical transmission rate of 0.2-8%
o 90% of congenitally infected infants asymptomatic
at birth

Microscopic

Features

• Immunohistochemical
staining with CMV specific
antibodies reveals large multinucleated cells with
intracytoplasmic and intranuclear inclusion bodies

I CLINICAL

ISSUES

Presentation
• Fetal
o Microcephaly, growth retardation
o Intracerebral calcifications
o Spontaneous abortion, pre term birth, stillbirth
especially in primary infection during pregnancy
o Hydrops
• Neonate
o Up to 10% are symptomatic
o Most common clinical triad = jaundice, petechiae,
hepatosplenomegaly
o Purpuric rash, extramedullary hematopoiesis
(macular lesions)
o Ophthalmologic (optic nerve hypoplasia, coloboma,
microphthalmia, chorioretinitis)
o Sensorineural hearing loss in early childhood
• Adult infection asymptomatic (99%) or
mononucleosis-like

Demographics
• Gender: Female fetal gender may be a risk factor for
severe congenital infection, although males also
subject to infection

Natural History & Prognosis
• Primary infection during pregnancy
o 10% of congenitally infected infants symptomatic
• Mortality 30-60% within 2 years in symptomatic
infants
• Neurologic sequelae in up to 90% (sensorineural
hearing loss, visual impairment, mental

retardation)

o 90% of congenitally infected infants asymptomatic
at birth
• Even in absence of sonographic findings in
documented fetal infection, neurologic sequelae
found in at least 20%
• 10-15% will subsequently have abnormal
neurologic development
• 10% will develop hearing loss in early childhood

Treatment
• No approved prenatal treatment
• Termination of pregnancy an option when confirmed
fetal infection
• Maternal serology
o Acute and convalescent titers may suggest infection
with rising IgM titers
• Amniocentesis for diagnosis of fetal infection
o Amniotic fluid culture
o Polymerase chain reaction (PCR) for viral sequence
o Fetal cells from maternal circulation (research)
• Systemic antivirals approved for CMV treatment
(postnatal)
o Ganciclovir, (prodrug valganciclovir), foscarnet,
cidofovir
o Target viral DNA polymerase
• Ganciclovir therapy in symptomatic neonate may
prevent or ameliorate specific neurodevelopmental
injury (sensorineural hearing loss)
• Vaccine development research
• Routine screening of asymptomatic pregnant patients
not currently recommended

I SELECTED REFERENCES
1.

2.

3.

4.

5.

6.

7.

8.

9.

Chen HP et al: Diagnosis of human cytomegalovirus
intrauterine infection using fetal cells from maternal
blood. Int] Gynaecol Obstet. 89(1):14-8, 2005
Peters son K et al: Detection of parvovirus b19,
cytomegalovirus, and enterovirus infections in cases of
intrauterine fetal death. Obstet Gynecol Surv. 60(5):284-6,
2005
Arvin AM et al: Vaccine development to prevent
cytomegalovirus disease: report from the National Vaccine
Advisory Committee. Clin Infect Dis. 39(2):233-9, 2004
Fujikawa T et al: Frequency of human
cytomegalovirus-specific T cells during pregnancy
determined by intracellular cytokine staining. ] Med Virol.
71(4):527-31,2003
Lazzarotto T et al: Congenital cytomegalovirus infection in
twin pregnancies: viral load in the amniotic fluid and
pregnancy outcome. Pediatrics. 112(2):e153-7, 2003
Moinuddin A et al: Intracranial hemorrhage progressing to
porencephaly as a result of congenitally acquired
cytomegalovirus infection--an illustrative report. Prenat
Diagn. 23(10):797-800, 2003
Bale]F et al: Congenital Cytomegalovirus Infection. Curr
Treat Options Neurol. 4(3):225-230, 2002
Enders G et al: Prenatal diagnosis of congenital
cytomegalovirus infection in 189 pregnancies with known
outcome. Prenat Diagn. 21(5):362-77, 2001
Bale]F ]r et al: Intrauterine cytomegalovirus infection and
glycoprotein B genotypes. ] Infect Dis. 182(3):933-6, 2000

CYTOMEGALOVIRUS
IIMAGE GALLERY
(Left) Coronal ultrasound
shows calcifications over the
dome of the diaphragm
(open arrows) and
intrahepatic calcificalions
(arrows) in this fetus with
CMV infection. (Right)
Ultrasound shows very
subtle periventricular
(curved arrow) and
pericardia I (arrow)
calcifications in a different
fetus with CMV infection.
There may be minimal or no
prenatal findings in cases of
documented fetal infeclion.
Neurologic sequelae will still
occur in at least 20%.

(Left) Sagittal ultrasound of a
premature infant with
congenital CMV infection
shows periventricular
(arrows) and intrathalamic
(curved arrow)
calcifications. (Right) Axial
NECT shows profound
periventricular calcification
(arrows) in this newborn
with congenital CMV
infection. A very wide
spectrum of severity of
imaging findings may be
seen.

(Left) Coronal ultrasound in
a 25 week fetus with CMV
infection shows echogenic
bowel (arrow) and ascites
(curved arrows). (Right)
Image of the abdomen of the
same fetus in the 3rd
trimester shows a thin rim of
ascites (arrows), mildly
echogenic bowel (curved
arrow) and calcification
(open arrow).

PARVOVIRUS

Ultrasound shows a very thickened placenta (arrows) in
a mid-trimester fetus with known parvovirus infection.
Hydrops and polyhydramnios were present as well.
Check with Doppler for fetal anemia with these findings.

I DIFFERENTIAL

ITERMINOlOGY
Abbreviations

and Synonyms

• Erythema infectiosum
• HPV B19

Definitions

FINDINGS

Ultrasonographic

DIAGNOSIS

Other congenital infections

(Fifth disease)

• Erythema infectiosum (Fifth disease) is major clinical
manifestation of infection with human parvovirus B19
(HPV B19)

IIMAGING

Histology shows intranuclear inclusions (arrows) within
erythroid cells in the liver, typical of parvovirus infection
in the fetus. A normal erythroid cell is shown by the
curved arrow. (Courtesy j. Szakacs, MD).

Findings

• Ascites most common presenting finding
• Progression to hydrops in severe cases
o Secondary to fetal anemia
• Placentomegaly
• Polyhydramnios

Imaging Recommendations
• Non-invasive assessment for fetal anemia using pulsed
Doppler
o Middle cerebral artery (MCA) peak systolic velocity
elevated in fetal anemia
• Governs need for intrauterine transfusion

• Significant overlap in imaging findings
o Intrahepatic and intracranial calcifications most
common findings
• Requires maternal/fetal serology to make definitive
diagnosis
• Cytomegalovirus
o Most common intrauterine infection
o Calcifications, microcephaly, echogenic bowel
• Toxoplasmosis (Toxoplasma gondii)
o Human infection from undercooked meats,
contaminated soil, water
o Calcifications, hepatosplenomegaly
• Varicella
o Primary infection, chickenpox
o Calcification, skin lesions, limb anomalies
• Herpes Simplex (type 2 HSV)
o Most infections occur during vaginal delivery
o Echogenic bowel, ventriculomegaly
• Syphilis (Treponema pallid urn)
o Hepatosplenomegaly,
dilated bowel, bowing of long
bones, hydrops
• Rubella
o Cardiac defects, microcephaly, IUGR,
microphthalmia

DDx: Conditions With Hydrops

Rh Incompatibility

Bradycardia

Turner Syndrome

Trisomy 21

PARVOVIRUS
Key Facts
Clinical Issues

Imaging Findings
• Ascite most common

Top Differential
• Other congenital
• Ilydrops

presenting

finding

Diagnoses
infections

Pathology
• Parvoviru attack red blood cell precursor => anemia
• 2/3 of adult women are immune to parvoviru

o Increased spontaneous abortion with early infection
o High mortality rate with severe hydrops without
fetal transfusion
o Reports of spontaneous recovery without
transfusion in less severe hydrops
• Normal developmental outcome in children who
survive intrauterine infection with parvovirus

Hydrops
• Nonimmune (aneuploidy, lymphatic,
• Immune (alloimmunization)

arrhythmia)

Ascites
• Isolated, without other signs of hydrops

Treatment

I PATHOLOGY
General Features
• Etiology
o Parvovirus attacks red blood cell precursors =>
anemia
o Involvement of cardiac myocytes may contribute
hydrops
o Infection route: Transplacental, transfusion
• Epidemiology
o 2/3 of adult women are immune to parvovirus
o Infection more common January-June
o Main reservoir, school aged children

• 20-30°/6 of women who become infected during
pregnancy transmit infection to fetus
• Risk of hydrop with fetal infection 4%
• Risk of fetal death highe t (11-20%) when infection
acquired < 20 wks ge tation
• ormal developmental outcome in children who
survive intrauterine infection with parvovirus
• Intrauterine transfu ion for fetal anemia

to

• Maternal infection in pregnancy should prompt
referral to high-risk specialist
• Maternal serology for HPV B19 specific IgG and IgM
• Amniocentesis for viral polymerase chain reaction
• Weekly ultrasound to exclude hydrops for 10-12 weeks
following seroconversion
• Monitor fetal anemia with MCA Doppler
• Cordocentesis for fetal serology and hematocrit
• Intrauterine transfusion for fetal anemia
o Delivery if gestational age sufficiently advanced

I SELECTED
1.

I CLINICAL

ISSUES

Presentation
• Ascites progressing to hydrops in symptomatic fetus
• Adults
o Transient, migratory maculopapular rash
o May be asymptomatic
o Polyarthritis, polyarthralgia occurs in 60% of
symptomatic adults
o Aplastic crisis in immunocompromised,
chronic
hemolytic anemia
• Children
o "Slapped cheek" rash in children
o Mild febrile illness, upper respiratory symptoms in
children

2.

3.

REFERENCES

Enders M et al: Fetal morbidity and mortality after acute
human parvovirus B19 infection in pregnancy: prospective
evaluation of 1018 cases. Prenat Diagn. 24(7):513-8, 2004
Cosmi E et al: Noninvasive diagnosis by Doppler
ultrasonography of fetal anemia resulting from parvovirus
infection. Am J Obstet Gynecol. 187(5):1290-3,2002
von Kaisenberg CS et al: Fetal Parvovirus B19 infection.
Ultrasound Obstet Gynecol. 18:280-8, 2001

IIMAGE

GALLERY

Natural History & Prognosis
• Infection usually self-limited in mothers
o Immunocompromised
individuals may become
severely ill or die
• 20-30% of women who become infected during
pregnancy transmit infection to fetus
o Risk of hydrops with fetal infection 4%
o Risk of fetal death highest (11-20%) when infection
acquired < 20 wks gestation
o Stillbirth rate, with or without hydrops 0.6%

(Left) Pulsed Doppler ultrasound shows the peak systolic velocity
(curved arrow) in the MCA (arrow) of a fetus with severe anemia.
MCA velocity monitoring is used to screen for anemia in Parvovirus.
(Right) Clinical photograph shows ascites (arrow) typically seen in
fetuses severely affected with Parvovirus. The bowel is noted by the
curved arrow.

TOXOPLASMOSIS

Transverse ultrasound shows multiple, punctate,
non-shadowing calcificauons (arrows) in the liver of a
mid-trimester fetus with confirmed
toxoplasmosis
infection.

o All positive screening tests in pregnancy should be
confirmed in a toxoplasmosis reference lab
o Confirm fetal infection by amniocentesis or cord
blood sampling for viral polymerase chain reaction

ITERMINOlOGY
Abbreviations
• Toxoplasmosis

and Synonyms
is the "T" in T.O.R.C.H. infections

Definitions

I DIFFERENTIAL DIAGNOSIS

• Transplacental infection with the protozoan
Toxoplasma gondii

IIMAGING

Other congenital infections

FINDINGS

Ultrasonographic

Findings

• Non-shadowing intracranial and intrahepatic
calcifications
o Intracranial calcifications may be periventricular
random in distribution
• May be subtle and easily missed
o Intrauterine growth restriction (IUGR)
o Ventriculomegaly, echogenic bowel

Imaging Recommendations
• Protocol advice
o Monthly ultrasound
infection to look for
calcifications, follow
o Fetal MRI to evaluate
counseling

when suspected or confirmed
brain abnormalities,
growth
brain, assist in prognostic

Axial NECT shows punctate calcifications in a newborn
with congenital toxoplasmosis. Calcifications may either
be periventricular
(curved arrow)
or scattered
throughout the parenchyma (arrows).

or

• Significant overlap in imaging findings
o Intrahepatic and intracranial calcifications most
common finding
• Requires maternal/fetal serology to make definitive
diagnosis
• Cytomegalovirus (CMV)
o Most common in utero infection
o Calcifications, microcephaly, echogenic bowel
• Varicella (chicken pox)
o Calcifications, skin lesions, limb anomalies
• Parvovirus
o Attacks red blood cell precursors ~ anemia
o Ascites, hydrops
• Herpes simplex (type 2 HSV)
o Most infections occur during vaginal delivery
o Echogenic bowel, ventriculomegaly

Echogenic bowel, abdominal

calcifications

• Multiple etiologies including aneuploidy,
obstruction, meconium ileus

DDx: Toxoplasmosis

CMV

Herpes

Varicella

Echogenic Bowel

bowel

TOXOPLASMOSIS
Key Facts
Imaging Findings

Clinical Issues

•

• Congenital infection cause classic triad of
hydrocephalus, intracranial calcifications,
chorioreti n itis
• 1st trimester infection less likely to result in
congenital infection (2-10%), but more likely to be
severe or result in abortion
• Infection> 20 wks has much higher congenital
infection rate (20-30%), but generally less severe

on-shadowing intracranial and intrahepatic
calcifications
• Intracranial calcifications may be periventricular
random in distribution
• May be subtle and easily missed

Top Differential

or

Diagnoses

• Other congenital infections

I PATHOLOGY
General Features
• Etiology
o Toxoplasma gondii is a unicellular protozoan
• Cats are the definitive hosts: Oocysts shed in feces
=> soil contamination
• Ingestion => parasitemia => latent
infection/formation
of cysts in muscle, central
nervous system
o Both humoral and cellular immunity involved in
resistance to parasite
o Detection of IgM not sufficient to prove recent
infection; IgM often detectible for months
o 3 principal routes of infection in humans
• Ingestion of inadequately cooked (infected) meat
• Ingestion of oocytes from contaminated soil or
water
• Transplacental
• Epidemiology
o Estimated 400-4,000 cases per year of congenital
toxoplasmosis in United States with 750 deaths
o Seroprevalence 10-30% in developed countries
o Seroprevalence in developing countries may exceed
60-75%
o Prevention of infection centers on education
regarding risk factors

• Sequelae of congenital infection include blindness,
epilepsy, mental retardation
o Prognosis for normal neurologic outcome is good in
absence of brain abnormalities
o Effect of prenatal therapy uncertain
• May decrease fetal infection rate or ameliorate
severity

Treatment
• Therapy with folate synthesis inhibitors
(pyrimethamine/sulfadiazine
or sulfadoxine) with or
without spiramycin in confirmed prenatal and
congenital infections
o Severe side effects including pancytopenia
• Termination of pregnancy is an option in confirmed
prenatal infection
• Serologic screening of all pregnant women in United
States not currently recommended due to low disease
prevalence

I SELECTED
1.

2.
3.

ICLINICAL

REFERENCES

Boyer KM et al: Risk factors for Toxoplasma gondii
infection in mothers of infants with congenital
toxoplasmosis: Implications for prenatal management and
screening. Am] Obstet Gynecol. 192(2):564-71,2005
Montoya]G et al: Toxoplasmosis. Lancet.
363(9425):1965-76,2004
Lopez A et al: Preventing congenital toxoplasmosis.
MMWR Recomm Rep. 49(RR-2):59-68, 2000

ISSUES

Presentation
• Maternal infection most often asymptomatic
o Mild symptoms include malaise, lethargy,
lymphadenopathy
o More severe if immunocompromised
• Splenomegaly, chorioretinitis, pneumonitis,
encephalitis, multisystem organ failure
• Congenital infection causes classic triad of
hydrocephalus, intracranial calcifications,
chorioretinitis

I IMAGE

GALLERY

Natural History & Prognosis
• 1st trimester infection less likely to result in congenital
infection (2-10%), but more likely to be severe or
result in abortion
• Infection> 20 wks has much higher congenital
infection rate (20-30%), but generally less severe

(Leh) Axial oblique
ultrasound shows periventricular and
intraparenchymal
calcifications typically seen in congenital
toxoplasmosis (arrows). (Right) Coronal ultrasound shows echogenic
bowel (arrows) typical of that seen in many congenital infections,
including toxoplasmosis. Note the echolucent "pseudoascites"
(curved arrow).

VARICELLA

Clinical photograph shows a zoster lesion (arrow) in an
infant with
fetal varicella syndrome.
Ipsilateral
diaphragmatic paralysis was noted. The mother had
chickenpox at 15 weeks gestation.

Transverse ultrasound shows multiple non-shadowing
hepatic calcifications (arrows) in the same fetus at 32
weeks
gestation.
There
was
also
massive
polyhydramnios.

ITERMINOLOGY

I DIFFERENTIAL

Abbreviations

Other congenital infections

and Synonyms

• Varicella-zoster (VZV)
• Fetal varicella syndrome/embryopathy

Definitions
• Transplacental infection of fetus following maternal
chickenpox infection
o Usually 8-20 weeks of gestation

IIMAGING

FINDINGS

Ultrasonographic

Findings

• Intrahepatic and intracranial calcifications
o May also see liver, heart, renal calcifications
• Polyhydramnios due to neurologic impairment of
swallowing
• Limb hypoplasia, contractures
• Paradoxical diaphragmatic motion on real time
sonography due to unilateral paralysis

DIAGNOSIS

• Significant overlap in imaging findings
o Intrahepatic and intracranial calcifications most
common findings
• Requires maternal/fetal serology to make definitive
diagnosis
• Cytomegalovirus (CMV)
o Most common in utero infection
o Calcifications, microcephaly, echogenic bowel
• Parvovirus B19 (Fifth disease)
o Attacks red blood cell precursors '* anemia
o Ascites, hydrops
• Toxoplasmosis (Toxoplasma gondii)
o Human infection from undercooked, infected meats,
contaminated soil or water
o Calcifications, hepatosplenomegaly
• Herpes simplex (type 2 HSV)
o Most infections occur during vaginal delivery
o Echogenic bowel, ventriculomegaly

limb reduction defects

Imaging Recommendations
• Monthly ultrasound for assessment of late findings of
fetal varicella syndrome
• Fetal MRI to further evaluate fetus, including central
nervous system (CNS)

• Terminal transverse defects, oligodactyly
• Amniotic bands

DDx: Congenital Infection

Herpes

Toxoplasmosis

CMV

CMV

VARICELLA
Key Facts
Imaging Findings
•
•
•
•

Intrahepatic and intracranial calcifications
May also see liver, heart, renal calcifications
Limb hypoplasia, contractu res
Paradoxical diaphragmatic motion on real time
sonography due to unilateral paralysis

Pathology

• Maternal varicella infection before 20 week gestation
:::::6% fetal transmis ion
• 1/3 of infected fetuses have clinical manifestations,
usually cutaneous
• 1-2% of infected fetuses will have severe clinical
stigmata of fetal varicella syndrome
• Peripartum maternal chickenpox associated with 25%
risk of life threatening neonatal infection

• Maternal zo ter outbreak in pregnancy
OT
associated with risk of fetal infection or malformation

I PATHOLOGY
General Features
• Etiology
o Neurotropic virus
• Sequelae due to neurologic damage in utero
• Remains dormant in the dorsal root ganglia;
reactivated as shingles (herpes zoster)
o Maternal zoster outbreak in pregnancy NOT
associated with risk of fetal infection or
malformation
• Epidemiology
o Majority of reproductive aged women (> 90%)
immune
o Maternal varicella infection before 20 weeks
gestation :::::6% fetal transmission
• 1/3 of infected fetuses have clinical
manifestations, usually cutaneous
• 1-2% of infected fetuses will have severe clinical
stigmata of fetal varicella syndrome
o Peripartum maternal chickenpox associated with
25% risk of life threatening neonatal infection

• Exposure of seronegative pregnant woman to
chickenpox
o Passive immunization with varicella-zoster
immunoglobulin
(VZIG)
• Reduces maternal complications; may prevent
fetal varicella syndrome
o Serious complications at any gestational age ~
hospitalization, intravenous Acyclovir
o Delivery should be delayed at least 5 days after the
onset of maternal rash to decrease risk of neonatal
varicella
• Treatment of infant with VZIG, if delivered less
than 5-7 days after onset of maternal rash

I SELECTED REFERENCES
1.

2.

3.

ICLINICALISSUES
Presentation
• Maternal pruritic pustular rash
• Elevated maternal serum and amniotic fluid
alpha-fetoprotein
and amniotic fluid
acetylcholinesterase
o May correlate with fetal skin, muscle and nerve
damage from VZV
• Neonate with fetal varicella syndrome with multiple
abnormalities
o Cutaneous lesions in dermatomal distribution, limb
hypoplasia, chorioretinitis, segmental intestinal
atresia, varying degrees of neurologic dysfunction

Mattson SN et al: Neurodevelopmental follow-up of
children of women infected with varicella during
pregnancy: a prospective study. Pediatr Infect Dis J.
22(9):819-23, 2003
Verstraelen H et al: Prenatal ultrasound and magnetic
resonance imaging in fetal varicella syndrome: correlation
with pathology findings. Prenat Diagn. 23(9):705-9, 2003
Heuchan AM et al: The management of varicella-zoster
virus exposure and infection in pregnancy and the
newborn period. Australasian Subgroup in Paediatric
Infectious Diseases of the Australasian Society for
Infectious Diseases. MedJ Aust. 174(6):288-92,2001

I IMAGE GALLERY

Natural History & Prognosis
• Increased incidence of fetal/neonatal death
• Asymptomatic, structurally normal children usually
neurodevelopmentally
normal
• Neurologic impairment dependent upon location,
extent of lesions

Treatment
• Documentation
of fetal infection
o Amniocentesis/cordocentesis
for viral polymerase
chain reaction

(Left) Anteroposterior radiograph shows the elevated hemidiaphragm
(arrows) in a neonate with diaphragmatic paralysis secondary to fetal
varicella syndrome. (Right) Radiograph shows a terminal transverse
limb defect in a growth restricted newborn with fetal varicella
syndrome. Note radioulnar hypoplasia (arrows) and the missing
hand.

SEe 10

17: F uid, Growth a d We I-Being

Polyhydramnios
Oligohydramnios
Symmetric IUGR
Asymmetric IUGR
Macrosomia
Biophysical Profile
MeA Doppler
Uterine Artery Doppler
Hydrops

17-2
17-6
17-10
17-14
17-18
17-20
17-24
17-28
17-32

1,711

P_O_L_Y_"_Y_D_RA_M_N_I_O_S

Graphic shows a distended
uterus secondary
to
polyhydramnios.
The uterus is divided into quadrants
and the sum of the largest pocket of fluid in each
quadrant determines the amniotic fluid index (AFI).

ITERMINOLOGY
Abbreviations

and Synonyms

• Hydramnios

Definitions
• Excessive amniotic fluid (AF)
o Idiopathic polyhydramnios (2/3)
o Fetal, placental or maternal disorder (1/3)

IIMAGING

FINDINGS

General Features
• Best diagnostic clue
o Larger than expected pockets of fluid
o t AFbetween anterior uterine wall and fetus

Ultrasonographic

Findings

• Subjective diagnosis of polyhydramnios
o 2nd trimester
• Fluid:fetus ratio> 1:1
o 3rd trimester
• Excessively large pockets of fluid
o Fetus displaced away from anterior uterine wall
• Gravity dependent fetus
• Semiquantitative measurements
o Maximum vertical pocket (MVP)

_

The four quadrant AFI calculation method is shown.
Fetal parts and umbilical cord are carefully avoided in
the measurement of AF depth. The AFI here is 38.9 cm
(> 24 cm is abnormal).

• Identify largest fluid pocket in uterus
• Measure depth of fluid
• Avoid fetal parts and cord
• Use color Doppler to avoid cord
• Polyhydramnios if > 8 cm
o Amniotic fluid index (API)
• Divide uterus into 4 equal quadrants
• Identify and measure MVP in each quadrant
• API = sum of 4 quadrant MVPs
• Polyhydramnios if AFI > 24 cm
• lcm API = 30 mL fluid (approximately)
• Can use normogram for API percentiles
o Two diameter pocket (TDP)
• Identify MVP
• Also measure width of same pocket
• TDP = MVP x width
• Polyhydramnios if TDP > SO cm2
• Idiopathic polyhydramnios (2/3)
o Normal fetus + polyhydramnios
o Associated with macrosomia (28%)
• Non-diabetic mom
o Often mild stable polyhydramnios
o Genetic amniocentesis not indicated
• Associated with diabetes mellitus
o Gestational diabetes most common
o t AF associated with poor control
o Fetus at risk for macrosomia
• Gastrointestinal (GI) anomalies

DDx: Large Fluid Pockets

Normal AF

Cystic Hygroma

Cystic Hygroma

Uterine Duplication

_______

I

PO_LY_"_Y_D_RA_M_N_I_O_S
Key Facts

Terminology

Top Differential Diagnoses

• Idiopathic polyhydramnios
(2/3)
• Fetal, placental or maternal di order (1/3)

• ormal fluid
• Cystic hygroma
• Uterine duplication

Imaging Findings
•
•
•
•
•
•
•
•
•
•
•

•

•

•

•

•

•

Polyhydramnios if AFI > 24 cm
lcm AFI = 30 mL fluid (approximately)
A sociated with diabetes mellitus
Gastrointe tinal (GI) anomalies
entral n rvou ystem/facial anomalie
Hydrop
Mu culoskeletal anomaly
ardiac defects
Twin-twin transfusion syndrome
Idiopathic polyhydramnios
i diagnosis of exclusion
Frequent follow up AFis

o Atresias
• Esophageal
• Duodenal
• ]ejunal/ilealless
common
o Obstruction
• Diaphragmatic hernia
• Gastroschisis/omphalocele
• Midgut volvulus
o t AF often seen in late 2nd or 3rd trimester
Central nervous system/facial anomalies
o Impaired swallowing from any cause
• Hydrocephalus, microcephaly
• Facial defects (micrognathia)
o Neural tube defects
o Polyhydramnios is a late finding
Hydrops
o Immune and nonimmune causes
• More prominent feature of immune hydrops
o Polyhydramnios may be early sign of hydrops
Musculoskeletal anomaly
o Skeletal dysplasia
o Any movement impairment
• Myotonic dystrophy
Cardiac defects
o Arrhythmia
o Anomalies
o Associated with heart failure
Fetal respiratory system anomaly
o Chest mass
• Mass may produce fluid
o Tracheal atresia
Polyhydramnios + intrauterine growth restriction
(IUGR)

o Combination is associated with poor outcome
• 92% with anomalies
• 38% with aneuploidy
• Trisomy 18 most common
o Amniocentesis warranted even if anomalies not seen
o Differentiate from idiopathic polyhydramnios
• Normal-sized or large fetus
• Ureteropelvic junction obstruction + paradoxical
polyhydramnios

anomaly

Pathology
• Polyhydramnios = AF volume>
• 0.4-3.3% of pr gnancie

1,500-2,000 mL

Clinical Issues
• Idiopathic polyhydramnio
has excellent progno i
• In diabetics, polyhydramnios improves as blood sugar
is better controlled
• Therapeutic amniocentesis

Diagnostic Checklist
• Polyhydramnios

+ IV R very poor progno tic sign

o Kidney loses ability to concentrate urine
o t Urine output
• Twin-twin transfusion syndrome
o Recipient twin with polyhydramnios
o Donor twin with oligohydramnios

Imaging Recommendations
• Best imaging tool
o AF evaluated at every 2nd/3rd trimester exam
o Semiquantitative measurement of AF
• AFI method most commonly used
• Protocol advice
o Idiopathic polyhydramnios
is diagnosis of exclusion
• Look carefully for fetal anomalies
• Rule out maternal diabetes
• Look for macrosomia
o Anatomy may be difficult to assess in severe cases
• Fetus too far displaced from transducer
o Assess for twin-twin transfusion syndrome
• Look for "stuck" twin
o Frequent follow up AFis
• Progressive polyhydramnios
more worrisome

I DIFFERENTIAL

DIAGNOSIS

Normal fluid
• Umbilical cord included in AF measurement
o Use color Doppler to avoid cord
• False positive polyhydramnios
o Quantitative methods not highly accurate

Cystic hygroma
• Nuchal cystic fluid collection
• Large cystic hygroma can mimic AF
o Look for septations
• Associated with aneuploidy
o Turner syndrome most common
o Trisomy 21
• Associated with hydrops
o Pleural effusion, ascites, anasarca

1137

?7j
4

I

P_O_L_Y_"_Y_D_R_A_M_N_IO_S

Uterine duplication

anomaly

_

Natural History & Prognosis

• Septate uterus
• Bicornuate uterus
• Fetus in one horn and fluid in another
o Can mimic polyhydramnios
• Difficult to quantitate fluid

• Idiopathic polyhydramnios has excellent prognosis
0 Often mild and stable
0 t Cesarean section rate secondary to macrosomia
• Severe/acute polyhydramnios
0 Preterm labor
o Premature rupture of membranes

I PATHOLOGY

Treatment

General Features
• General path comments
o Polyhydramnios = AF volume> 1,500-2,000 mL
• Normal: 800-1,000 mL at peak (36-37 wks)
• Genetics
o IUGR and anomalies associated with aneuploidy
• Trisomy 18 > trisomy 13
• Etiology
o t Production or ,j. removal of AF
o Normal AF removal
• Fetus swallows 25% body weight/day
• GI absorption: 200-1,200 cc/day near term
• Fetal lungs: 170 cc/day near term
o Normal AF production
• Fetus urinates 30% of body weight/day
• Kidneys: 800-1,200 cc/day near term
• Lungs: 170 cc/day near term
o Other important AF pathways
• Placenta, membranes, umbilical cord
• Transcutaneous diffusion
• Fetal movement affects absorption; contributes to
polyhydramnios in skeletal disorders affecting
movement
• Epidemiology
o 0.4-3.3% of pregnancies
• Idiopathic (65.4%)
• Diabetes mellitus (27.7 %)
• Congenital anomalies (4.3%)
• Multiple gestation (2.6%)
o May be seen with maternal use of lithium
• Fetal diabetes insipidus

Staging, Grading or Classification Criteria
• Mild polyhydramnios
o API > 24 cm, < 30 cm

ICLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Large for dates (t fundal height)
o 2/3 idiopathic
• Incidentally noted during ultrasound study
• Normal fetus
• Normal mom
o 1/3 polyhydramnios as a feature of other diagnosis
• Maternal diabetes
• Fetal anomaly
• Twin-twin transfusion syndrome
o Monochorionic diamniotic twins
o One twin with polyhydramnios and other with
oligohydramnios

• In diabetics, polyhydramnios improves as blood sugar
is better controlled
o Polyhydramnios ,j. from 12.7% to 2.1 % with early
glucose control
• Therapeutic amniocentesis
o Patient comfort
o ,j. Preterm labor risk
o Aid with anatomic visualization
• Indomethacin
o Rapid placental passage
o ,j. Fetal urine production
o ,j. Fetal lung AF production
o Reduction of fluid within 1 week
o Effective in > 90%
o Risk of treatment
• Constriction of ductus arteriosus

I DIAGNOSTIC

CHECKLIST

Consider
• Frequent follow-up AFI
o Is polyhydramnios stable or progressing?
• Genetic amniocentesis in minority of cases
o IUGR
o Fetal anomalies
o Severe or progressing polyhydramnios

Image Interpretation

Pearls

• Careful fetal survey to rule out anomalies associated
with polyhydramnios
• Polyhydramnios + IUGR very poor prognostic sign
• Idiopathic polyhydramnios is common but always a
diagnosis of exclusion

I SELECTED
1.

2.

3.

4.

5.

6.

REFERENCES

Leung WC et al: Procedure-related complications of rapid
amniodrainage in the treatment of polyhydramnios.
Ultrasound Obstet Gynecol. 23(2):154-8, 2004
Bartha]L et al: Early diagnosis of gestational diabetes
mellitus and prevention of diabetes-related complications.
Eur J Obstet Gynecol Reprod BioI. 109(1):41-4, 2003
Mcgann EF et al: The amniotic fluid index, single deepest
pocket, and two diameter pocket in normal human
pregnancy. Am] Obstet Gynecol. 182:1581-8,2000
Panting-Kemp A et al: Idiopathic polyhydramnios and
perinatal outcome. Am] Obstet Gynecol. 181(5 Pt
1):1079-82, 1999
Moise KJ:Polyhydramnios. Clin Obstet Gynecol. 40:
266-79, 1997
Many A, et al: The association between polyhydramnios
and pre term delivery. Obstet Gynecol. 86:389-91, 1995

===========-=-=-P-=-O-=-L-=-Y-=-H-=-Y_D
IIMAGE

I

RA--=-_M N---=-I_O
__S__~~

GALLERY
(Left) Axial ultrasound shows
a maximum vertical pocket
measurement
of 70.4 cm in
this case of polyhydramnios
and macrosomia. MVP> 8
cm is diagnostic of
(Right)
polyhydramnios.
Axial ultrasound in another
case of polyhydramnios
and
macrosomia shows excessive
amniotic fluid (arrows) and
an abdominal circumference
measurement>
98th
percentile. Polyhydramnios
is
associated with macrosomia
in both diabetic and
nondiabetic patients.

(Left) Ultrasound shows
polyhydramnios
(calipers
measure an AF pocket of 72
cm) and a persistently small
stomach (arrow) in a fetus
with esophageal atresia and
tracheoesophageal
fistula.
Polyhydramnios
progressively worsened
throughout the pregnancy.
(Right) Frontal radiograph of
the newborn neck shows an
orogastric tube terminating
within the esophageal pouch
(arrow).

(Left) Axial ultrasound shows
a distended duodenum
(arrow) in this fetus with
duodenal atresia (curved
arrow points to stomach)
and progressive
polyhydramnios
(open
arrow). Karyotype was
normal. (Right) Coronal
ultrasound shows massive
polyhydramnios
surrounding
an immobile,
gravity-dependent
fetus
(arrows) with arthrogryposis.
Anatomic visualization is
limited when
polyhydramnios
is severe.

115

7

1;II

O_L_IG_O_H_Y_D_RA_M_N_IO_S

Coronal ultrasound shows anhydramnios from renal
agenesis. The fetus is compressed and the chest
(arrows) is "bell shaped". Color Doppler of the aorta
(open arrows) shows absent renal arteries.

ITERMINOlOGY
Definitions
• Oligohydramnios
o Deficiency of amniotic
• Anhydramnios
o No amniotic fluid

fluid from any cause

IIMAGING FINDINGS
General Features
• Best diagnostic clue
o Smaller than expected pockets of fluid
o Fetus seems confined

Ultrasonographic

Findings

• Amniotic (AF) assessment part of every 2nd/3rd
trimester exam
o 2nd trimester
• Fetus takes up 1/2 uterine volume
o 3rd trimester
• Pockets of fluid should be easily seen
o Experienced sonographer can judge amniotic fluid
volume subjectively
• Subjective diagnosis of oligohydramnios
o Second trimester
• Fetus> 1/2 uterine volume

~

Clinical photograph shows a fetus with renal agenesis.
Severe prolonged oligohydramnios leads to dysmorphic
features from confinement such as Potter facies, club
foot (arrow) and contractures.

o Third trimester
• Diminished pockets of fluid
o Fetal crowding
• Semiquantitative measurements
o Maximum vertical pocket (MVP)
• Identify largest fluid pocket in uterus
• Measure depth of fluid
• Avoid fetal parts and cord
• Use color Doppler to avoid cord
• Oligohydramnios
if MVP < 2 cm
o Amniotic fluid index (AFI)
• Divide uterus into 4 equal quadrants
• Identify and measure MVP in each quadrant
• AFI = sum of 4 quadrant MVPs
• Oligohydramnios
if AFI < 5 cm
• 1 cm AFl = 30 mL fluid (approximately)
• Can use normogram for AFI percentiles
o Two diameter pocket (TOP)
• Identify MVP
• Also measure width of same pocket
• TOP = MVP x width
• Oligohydramnios
if TOP < 15 cm2
• Biophysical profile score (BPP) and amniotic fluid
o BPP assesses fetal well-being
o Score for fluid is 2 or 0 ( "1" not allowed)
• 2 = AF pocket ~ 2 cm in 2 perpendicular planes
• 0 = no AF pocket measuring ~ 2 cm x 2 cm
o Fluid score of 0 is highly significant finding

DDx: Subjective Low Fluid

Normal Fluid

Normal Fluid

Uterine Duplication

_______

I

O_L_IG_O_"_Y_D_RA_M_N_IO_S
Key Facts
Top Differential

Terminology
• Deficiency of amniotic

fluid from any cause

Imaging Findings
• Amniotic (AF) as e ment parl of ev ry 2nd/3rd
lrime ler exam
• Experien ed sonographer
an judge amniotic fluid
volume subjectively
• Oligohydramnio
if AFI < 5 cm
• onlraclures, club foot
• ligohydramnios may be early ign of IUGR
• Look for U anomalies
• A ses felal growth
• Asse pia ental function with Doppl r
• Frequ nl follow-up AFI often indicated
• Fetal MRI if kidneys can not be do umented with
ultrasound
• Genitourinary tract (GU) anomalies
o Bilateral renal agenesis
• Color Doppler of aorta shows no renal arteries
• Adrenal glands are present
o Bladder outlet obstruction
• Distended bladder + oligohydramnios
• +/- Renal/ureter distention
• +/- Post-obstructive renal cystic dysplasia
• Most often from posterior urethral valves
o Bilateral renal cystic dysplasia
• Multicystic dysplastic kidneys
• Autosomal recessive polycystic kidney disease
• Post obstructive cystic dysplasia
o Bilateral ureteropelvic junction obstruction
o AFI may be normal early in pregnancy
• t AF diffusion via fetal skin until 22 wks
• Anomalies from fetal confinement
o Common with early and prolonged
oligohydramnios
o Pulmonary hypoplasia
• Oligohydramnios restricts chest expansion
• Small bell-shaped chest
• 1 cause of mortality from oligohydramnios
o Extremity anomalies
• Contractures, club foot
• Post-term pregnancy (> 42 wks)
progresses quickly
o t Morbidity if oligohydramnios
• Premature rupture of membranes (PROM)
o Clinical diagnosis
o Early and prolonged with worse prognosis
• Early: PROM < 25 wks
• Prolonged: Oligohydramnios>
14 days
• Oligohydramnios + intrauterine growth restriction
(IUGR)
o Estimated fetal weight < 10th percentile
o IUGR from placental insufficiency if fetus normal
o Can be associated with aneuploidy if fetus abnormal
• Trisomy 18, trisomy 13, triploidy
o Amniotic fluid reflects placental function
• Oligohydramnios
may be early sign of IUGR
• Doppler assessment of IUGR
o Abnormal umbilical artery (UA) waveform
0

• ormal fluid
• Fibroid uteru
• Uterine duplication

Diagnoses

anomaly

Pathology
• ! Production or t removal of amniotic
• Fetal anomalie in 201M)
• IUGR in 30-40%

fluid

Clinical Issues
• PROM is a c1ini al diagnosis
• Pulmonary hypopla ia usually fatal
• Early and prolonged oligohydramnios
ha a poor
progno is
• Dismal progno i if bilateral renal anomaly

• Absent or reversed diastolic flow
o Abnormal middle cerebral artery (MCA) waveform
• Higher diastolic flow than UA
• Suggests "brain sparing" physiology
o Abnormal uterine artery waveform
• Earliest sign of placental dysfunction
• High resistive flow after 18 wks
• Postsystolic notch
• Idiopathic oligohydramnios
o May be related to maternal dehydration
• Resolves with hydration
o Often mild, isolated and transient
• Diagnosis of exclusion

MR Findings
• Helpful if ultrasound imaging severely limited
o Diagnosis of renal agenesis
• MR preferable to diagnostic amnioinfusion

Imaging Recommendations
• Best imaging tool
o Subjective assessment of AF
o Semiquantitative measurements of AF
• API most commonly used method
• Protocol advice
o Comment about AF in every 2nd/3rd trimester case
o Look for GU anomalies
o Assess fetal growth
o Assess placental function with Doppler
o Frequent follow-up AFI often indicated
o Fetal MRI if kidneys can not be documented with
ultrasound

I DIFFERENTIAL

DIAGNOSIS

Normal fluid
• Pockets of fluid may be difficult to see
o Obese patient, near term patient
• Excessive transducer pressure while measuring fluid
o Minimizes pocket depth
• False positive oligohydramnios
o Quantitative methods not highly sensitive

11;

?fj
8

O_L_IG_O_"_Y_D_R_A_M_N_IO_S

I
Fibroid uterus

0

• Large fibroids shield beam
• Fluid pockets difficult to see

Uterine duplication

anomaly

• Septate, bicornuate uterus
• Fetus in one horn and fluid in another
• More difficult to quantitate fluid

I PATHOLOGY
General Features
• Etiology
o ~ Production or t removal of amniotic fluid
o Normal amniotic fluid production
• Fetus urinates 30% of body weight/day
• Kidneys: 800-1200 cc/day near term
• Lungs: 170 cc/day near term
o Normal amniotic removal
• Fetus swallows 25% body weight/day
• Gastrointestinal absorption: 200-1200 cc/day near
term
• Lungs: 170 cc/day
o Other important amniotic fluid pathways
• Placenta, membranes, umbilical cord
• Transcutaneous diffusion ("leaky" fetal skin) before
22 wks
• Epidemiology: 0.5-5.5% of pregnancies
• Associated abnormalities
o Fetal anomalies in 20%
• Mostly genitourinary
o IUGR in 30-40%
o Potter facies
• Wide-set eyes, flattened palpebral fissures,
prominent epicanthus, flattened nasal bridge,
micrognathia, low-set ears

I CLINICAL

ISSUES

Presentation
• Most common signs/symptoms
o Patient may present as "small for dates"
o Oligohydramnios often seen as major feature of
other diagnosis
• IUGR
• Severe GU anomalies
• PROM
• Post-dates pregnancy
o Maternal conditions associated with
oligohydramnios
• Hypertension
• Preeclampsia
• Diabetes
• Autoimmune disorders
o PROM is a clinical diagnosis
• Sterile vaginal speculum exam
• Amniotic fluid has alkaline pH and "ferning"
o Incidentally noted during routine scan
• More likely benign course
• More common in 3rd trimester
• Other signs/symptoms

0

_

~w~:~~~~~~~~~~s~~anml1iotic twins
• One twin with oligohydramnios and other with
polyhydramnios
Maternal medication
• Prostaglandin synthetase inhibitors

Natural History & Prognosis
• Pulmonary hypoplasia usually fatal
o Difficult prenatal diagnosis
• Early and prolonged oligohydramnios has a poor
prognosis
o < 25 wks associated with 10% survival
• Progressive oligohydramnios with worse prognosis
• Dismal prognosis if bilateral renal anomaly

Treatment
• Depends on cause and severity of oligohydramnios
• Bladder outlet obstruction
o Bladder drainage procedures
• Determine renal function
o Bladder-amniotic shunt placement
• Can reduce incidence of pulmonary hypoplasia
• Consider early delivery for IUGR
• Post term
o Induction of labor if MVP < 2 cm or AFI < 5 cm
• Maternal hydration rarely helpful
• Amnioinfusion during active labor
o ~ Risk of cord compression

I DIAGNOSTIC

CHECKLIST

Consider
• Frequent follow-up AFI
o Twice/week AFI check if fetus is viable

Image Interpretation

Pearls

• Amniotic fluid volume reflects fetal well-being
o Perform BPP and Doppler if fetus is otherwise
normal
• Idiopathic oligohydramnios is rare
o Rule out growth and fetal abnormalities carefully
• MRI useful tool for anatomic evaluation when
sonographic visualization is inadequate

I SELECTED
1.

2.

3.
4.

5.

6.

REFERENCES

Ek S et al: Oligohydramnios
in uncomplicated pregnancies
beyond 40 completed weeks. A prospective, randomised,
pilot study on maternal and neonatal outcomes. Fetal
Oiagn Ther. 20(3):182-5, 2005
Baschat AA: Pathophysiology of fetal growth restriction:
implications for diagnosis and surveillance. Obstet Gynecol
Surv. 59(8):617-27, 2004
Schrimmer DB et al: Sonographic evaluation of amniotic
fluid volume. Clin Obstet Gynecol. 45(4):1026-38, 2002
Sherer OM: A review of amniotic fluid dynamics and the
enigma of isolated oligohydramnios.
Am J Perinatol.
19(5):253-66,2002
Mcgann EF et al: The amniotic fluid index, single deepest
pocket, and two diameter pocket in normal human
2000
pregnancy. Am J Obstet GynecoI182:1581-8,
Shipp TO et al: Outcome of singleton pregnancies with
severe oligohydramnios
in the second and third trimester.
Ultrasound Obstet Gynecol 7:108-13, 1996

========-=-=-=-=-_0

L-I_G-=-O-=-H-=-y---=--D---=--RA---=---=-M-=--N_-I_O--=-S--=--_-----I

I IMAGE GALLERY
Typical
(Left) Sagittal ultrasound
shows severe
oligohydramnios
in this case
of posterior urethral valves.
The bladder (arrows) fills the
abdomen (curved arrowfetal head). (Right)
Ultrasound performed after
placement of
bladder-amniotic
shunt
(arrow) shows a decrease in
bladder size (cursors). The
amniotic fluid volume has
normalized (curved arrow).
Renal function was assessed
prior to shunt placement.

(Left) Ultrasound in a case of
PROM shows only a tiny
pocket of amniotic fluid
(arrow) making anatomic
evaluation difficult. Normal
kidneys were identified
(open arrows - one kidney).
(Right) Sagittal T2WI MR of
another fetus with severe
oligohydramnios
in whom
kidneys could not be seen by
ultrasound. On MRI, a
kidney (arrows) and bladder
(curved arrow) are easily
seen. MRI can be very
helpful in evaluating
anatomy and ruling out renal
agenesis.

(Left) Ultrasound shows four
quadrant AFI determination
of oligohydramnios.
The sum
of the four maximum vertical
pockets is only 5.96 cm in
this late second trimester
pregnancy complicated
by
IUGR and preeclampsia.
(Right) Axial ultrasound with
and without color Doppler
shows what initially looks
like amniotic fluid (arrows) is
actually a collection of cord.
This "pocket" should not be
measured as amniotic fluid.

11;

17l

S_Y_M_M_E_T_R_IC_IU_G_R

1

----J

10

Chart shows biometry for a fetus with symmetric IUGR.
Because both the head growth (HC) and abdominal
growth (AC) are equally affected, the HC/AC ratio
remains in the normal range.

Clinical photograph of the donor twin in a case of
twin-twin transfusion syndrome. In utero scans showed
significant, symmetric growth restriction with abdominal
and head growth being equally affected.

o Multiple anomalies t suspicion for
aneuploidy/syndrome
• Second trimester finding of echogenic bowel
associated with IUGR in 10-20% of cases
• Pulsed Doppler is not as helpful as in asymmetric
IUGR
o Usually a primary fetal abnormality, not placental
insufficiency
o Does not exhibit "head sparing" flow pattern in
middle cerebral artery

ITERMINOlOGY
Abbreviations

and Synonyms

• Intrauterine growth restriction (IUGR)
• Intrauterine growth retardation
• Small for gestational age (SGA)

Definitions
• Estimated fetal weight (EFW) < 10th percentile for
gestational age (GA)
o Asymmetric IUGR: Abdomen < other biometric
parameters
o Symmetric IUGR: Fetus uniformly small for
gestational age (GA)
• IUGR implies fetus has not reached its full growth
potential
• SGA implies smaller than expected for GA but fetus
may be normally grown

Imaging Recommendations
• Accurate dating essential for evaluation of growth
disturbance
• Early ultrasound is more accurate than menstrual
dating (LMP) or clinical assessment of GA
• First trimester crown-rump length (CRL)
measurements accurate to within +/- 0.7 weeks
o CRL more accurate than mean sac diameter
o Biological variations do not manifest until after 13
weeks gestation
• Second trimester dating based on composite of several
measurements
o Biparietal diameter (BPD)
o Head circumference (HC)
o Abdominal circumference ( AC)
o Femur length (FL)

IIMAGING FINDINGS
Ultrasonographic

Findings

• Size less than expected for dates
o All biometric parameters equally affected
• Structural survey more likely to be abnormal than with
asymmetric IUGR

DDx: Symmetric

IUGR
LMP = 24w2d

MA

tSD

BPD 18wOdt12d
HC 20wSdtl0d
AC 20wldt14d
FL 18w3dt13d
MA

Asymmetric-Triploidy

Mean
3.97cm
18.29cm
14.91cm
2.74cm

= 19wOdtl0d

Wrong

Dates

Placental

Insufficiency

~=======~~~~~_S_Y~M~M~_E_T~R~I_C-=-_I_U-=-G-=-R-=--=---=---=---=--=--=--=--=--=--=--=I~~
Key Facts
Terminology

Top Differential

• Estimated fetal weight (EFW) < 10th percentile for
gestational age (GA)
• Symmetric IUGR: Fetus uniformly small for
gestational age (GA)

• Incorrect dates
• Small but normal
• Asymmetric IUGR

Imaging Findings

• By definition lUGR occurs in 10% of pregnancies
• Some of these will be normal, just constitutionally
small

• Multiple anomalie t suspicion for
aneuploidy/syndrome
• Look at os ification centers, helps verify dating when
patients present late in gestation
• Earliest ultrasound scan is most accurate for dating
• Triploidy may present with either symmetric or
asymmetric IUGR depending on source of extra
chromosomes
• Look for signs of intrauterine infection

•

•

•

•

•

•

•

o Second trimester dating accurate to within +/- 1.5
weeks
Third trimester: Same parameters measured but
accuracy decreased to +/- 3-4 weeks
o Patient presenting in third trimester at 34 weeks
may have a normal fetus measuring from 31-37
weeks
o Biological variation has maximum impact in third
trimester
Look at ossification centers, helps verify dating when
patients present late in gestation
o Distal femoral epiphysis ~ ~ 32 weeks gestation
o Proximal tibial epiphysis ~ ~ 3S weeks gestation
Earliest ultrasound scan is most accurate for dating
o Never change due date based of later scans
o Doing so will mask growth disturbance
Evaluate amniotic fluid volume
o Use of amniotic fluid index allows objective serial
assessment of fluid volume
o IUGR + polyhydramnios
ominous combination
• High risk for trisomy 18
o Low fluid correlates with poor outcome especially if
early onset/sustained
Look for anomalies
o Symmetric IUGR has strong association with
aneuploidy
o Multiple anomalies + early onset IUGR
• Triploidy, trisomy 18,13
o Triploidy may present with either symmetric or
asymmetric lUGR depending on source of extra
chromosomes
• Digynic triploidy (extra set of chromosomes
maternal) ~ severe early-onset asymmetric IUGR
• Diandric triploidy (extra set of chromosomes
paternal) ~ symmetric IUGR
Look at fetal hands
o Clenched fingers ~ trisomy 18
o Postaxial polydactyly ~ trisomy 13
o Syndactyly ~ triploidy
Look for signs of intrauterine infection
o Ventriculomegaly
o Hydrops

Diagnoses

Pathology

Diagnostic Checklist
• Accurate dating is essential for diagnosis of lUGR
• ever change due date based on later exams, doing so
masks a growth disturbance
• IUGR + polyhydramnios
~ high risk of aneuploidy,
especially trisomy 18

o Calcifications
• Intracranial: Cytomegalovirus, toxoplasmosis
• Liver: Cytomegalovirus, toxoplasmosis, herpes
simplex
• Evaluate placenta
o Diandric triploidy particularly associated with thick,
cystic placenta
• Also seen with trisomy 13, 18 and confined
placental mosaicism
• Evaluate maternal ovaries
o May see theca lutein cysts in diandric triploidy
• Secondary to t levels ~ human chorionic
gonadotrophin

I DIFFERENTIAL

DIAGNOSIS

Incorrect dates
• Menstrual history inaccurate
o Nursing
o Birth control pill
o Irregular cycles
• Normal anatomic survey
• Normal interval growth on follow-up exam

Small but normal
•
•
•
•

By definition 10% of pregnancies will be "too small"
Constitutional: Look at the parents
Ask about birthweight of other children
Interval growth normal
o Fetus remains SGA but exhibits normal growth rate

Asymmetric

IUGR

• Head measurements normal for GA
• Abdominal circumference small with poor interval
growth
• Often associated with abnormal Doppler studies
• Usually a primary problem of placental insufficiency
• Often presents later in pregnancy

17l IL-

~

SY_M_M_E_T_R_IC_I_U_G_R

I-p-j\-r-H-O-L-O-G-y-------------

0 Full monitoring
in labor
o Intervention/resuscitation
and prognosis established

General Features
• Genetics
o Trisomy 18, 13, 10
• Early onset IUGR seen in 43% trisomy 13 cases
• Early onset IUGR seen in 59% trisomy 18 cases
o IUGR not a dominant feature in trisomy 21
o Triploidy (diandric)
• Etiology
o Aneuploidy
o Intrauterine infection
• Cytomegalovirus
• Parvovirus
• Rubella
o Syndromes
o AIDS embryopathy
• Vertical transmission
• Characteristic craniofacial abnormalities: Lateral
bossing, hypertelorism, short nose, flat nasal
bridge
• Epidemiology
o By definition IUGR occurs in 10% of pregnancies
• Some of these will be normal, just constitutionally
small
• IUGR fetuses represent a larger percentage in
autopsy series of stillbirth

I DIAGNOSTIC

Image Interpretation

I SELECTED
1.
2.
3.

5.

6.

Natural History & Prognosis

Treatment
• Offer karyotype
o 5-27% incidence chromosomal abnormalities
associated with IUGR
• Infection screen
• If multiple anomalies/aneuploidy
o Offer termination
o Encourage autopsy for specific diagnosis
• If pregnancy progresses with known poor prognosis
(e.g. trisomy 18)
o No monitoring in labor
o Intervention for maternal indications only
o Full clinical evaluation of infant to confirm
diagnosis
o Encourage autopsy for fetal demise/perinatal death
• Accurate diagnosis important for recurrence risk
• If pregnancy progresses without clear diagnosis
o Follow as for asymmetric IUGR

Pearls

• IUGR + polyhydramnios '* high risk of aneuploidy,
especially trisomy 18
• Triploidy associated with both symmetric and
asymmetric IUGR patterns

Presentation

• Aneuploidy '* extremely poor prognosis
• Triploidy associated with severe early onset
pre-eclampsia
o May require pregnancy termination for maternal
indications
• SGA fetus with normal survey, normal chromosomes
and normal interval growth has good prognosis

CHECKLIST

• EFW percentiles are based on GA
o Accurate dating is essential for diagnosis of IUGR
o "Symmetric IUGR" fetus may be completely normal
if dates are incorrect
• Never change due date based on later exams, doing so
masks a growth disturbance

ISSUES

• Fundamental problem with fetus
o Presents earlier than asymmetric IUGR
o Often early 2nd trimester

appropriate until cause

Consider

4.

ICLINICAL

_

7.

8.
9.

10.

11.

12.

13.

14.

15.

16.

REFERENCES

Holemans K et al: Lifetime consequences of abnormal fetal
pancreatic development. J Physiol. 547(Pt 1):11-20, 2003
Rasmussen S et al: Fetal growth and body proportion in
preeclampsia. Obstet Gynecol. 101(3):575-83,2003
Resnick R: Intrauterine growth restriction. Obstet Gynecol.
99:490-6, 2002
Blackwell SC et al: Relationship between the sonographic
pattern of intrauterine growth restriction and acid-base
status at the time of cordocentensis. Arch Gynecol Obstet.
264(4):191-3,2001
May R et al: Early postnatal growth of low birthweight
infants in the WIC program. Am J Hum BioI. 13(2):261-7,
2001
Dashe JS et al: Effects of symmetric and asymmetric fetal
growth on pregnancy outcomes. Obstet Gynecol.
96(3):321-7, 2000
Langhoff-Roos J et al: Obstetric interventions and perinatal
asphyxia in growth retarded term infants. Acta Obstet
Gynecol Scand Suppl. 165:39-43, 1997
Sherwood RJ et al: Pattern and process of growth of the
abnormal human fetus. Hum BioI. 69(6):849-71, 1997
Sickler GK et al: Polyhydramnios and fetal intrauterine
growth restriction: ominous combination. J Ultrasound
Med. 16(9):609-14, 1997
Williams MC et al: A comparison of birth weight and
weight/length ratio for gestation as correlates of perinatal
morbidity. J Perinatol. 17(5):346-50, 1997
Vik T et al: Body proportions and early neonatal morbidity
in small-for-gestational-age infants of successive births.
Acta Obstet Gynecol Scand Suppl. 165:76-81, 1997
Vik T et al: Prenatal growth in symmetric and asymmetric
small-for-gestational-age infants. Early Hum Dev.
48(1-2):167-76, 1997
Todros T et al: Body proportionality of the small-for-date
fetus: is it related to aetiological factors? Early Hum Dev.
45(1-2):1-9, 1996
Salafia CM et al: Intrauterine growth restriction in infants
of less than thirty-two weeks' gestation: associated
placental pathologic features. Am J Obstet Gynecol.
173(4):1049-57,1995
Bromley B et al: Is fetal hyperechoic bowel on
second-trimester sonogram an indication for
amniocentesis? Obstet Gynecol. 83:647-51, 1994
Barkin SZ et al: Sever polyhydramnios: incidence 01"
anomalies. AJR 148:155-9, 1987

_______
_I

S_Y_M_M_E_T_R_IC_IU_G_R

I

~7
13

-----------------

IMAGE GAllERY
(Left)

Ultrasound in a patient
with no prenatal care who
should be 37.5 wks by LMP
but measured 33. 7 wks,
raising the question of
incorrect dates vs. symmetric
IUCR. Ossification of the
proximal tibial epiphysis
(arrow) implies the CA is at
least 35 weeks making IUCR
more likely. Ossification
centers can be helpful in
patients presenting late in
gestation. (Right) Axial
ultrasound shows multiple
liver calcifications (arrows)
in a fetus with symmetric
IUCR from toxoplasmosis.

Typical
(Left) Transabdominal
ultrasound shows different
cord sizes in discordant
twins with twin-twin
transfusion syndrome. Twin
A was smaller than twin B
with all growth parameters
equally affected. (Right)
Sagittal ultrasound shows a
very thick placenta with
multiple cysts. The fetus
(arrow) had severe,
symmetric IUCR typical for
triploidy of paternal origin
(diandry).

(Left) Transabdominal
ultrasound shows syndactyly
of the 3rd and 4th fingers
(arrow) as seen in triploidy.
Careful evaluation of the
hands can help narrow the
differential diagnosis in
symmetric IUCR. (Right)
T2WI MR shows post axial
polydactyly
(arrow) in a
fetus with trisomy 73. Early
onset IUCR prompted
amniocentesis.
The parents
wanted more information on
the brain anomalies before
deciding on termination.

~:

A_S_Y_M_M_E_T_R_IC_IU_G_R

II

Chart of biometric measurements shows EFW < 70th
percentile with most marked growth delay in the
abdominal circumference (AC). The head growth (HC)
is normal, resulting in an increased HC/AC ratio.

ITERMINOlOGY
Abbreviations

and Synonyms

• Intrauterine growth restriction (IUGR)
• Small for gestational age (SGA)
• Intrauterine growth retardation

Definitions
• Estimated fetal weight (EFW) < 10th percentile for
gestational age
o Asymmetric IUGR: Abdomen < other biometric
parameters
o Symmetric: Fetus uniformly small for gestational age
(GA)

• IUGR implies fetus has not reached full growth
potential
• SGA smaller than expected for GA but may be
normally grown

IIMAGING FINDINGS
General Features
• Best diagnostic clue: Fetus with abnormal
oligohydramnios

Ultrasonographic

growth and

Findings

• Grayscale Ultrasound

Pulsed Doppler shows no diastolic flow in the UA (50
ratio cannot be measured). There is increased diastolic
flow in the MCA in a "head sparing" pattern. The MCA
50 ratio should always be > UA 50 ratio.

o Abnormal biometry
• Head circumference (HC) and biparietal diameter
are preserved
• Abdominal circumference (AC) is small and
exhibits poor interval growth
o EFW calculations heavily weighted to AC
• Poor AC growth ~ EFW less than expected for GA
o Oligohydramnios
common
• Indicates chronic fetal stress
• Blood shunted to cerebral and coronary
circulations
• ~ Renal perfusion ~ ~ urine production ~
oligohydramnios
o Second trimester finding of echogenic bowel
associated with IUGR in 10-20% of cases
o In multiple gestations look at placental cord
insertion sites
• Significant increased risk of IUGR with
marginal/velamentous
insertion of cord
• Color Doppler
o Consider use of color Doppler when measuring
amniotic fluid index (AFI)
• AFI is four quadrant measurement
• Transducer perpendicular to table
• Measured pockets must contain neither cord nor
fetal parts
• Pulsed Doppler
o Umbilical artery (UA) Doppler

DDx: Growth Restriction

Diandric Triploidy

_

Toxoplasmosis

_______

I 117

A_S_Y_M_M_E_T_R_IC_IU_G_R

~

Key Facts
Terminology
• Estimated fetal weight (EFW) < 10th percentile for
ge tational age
• A ymmetric IVGR: bdomen < other biometric
parameter

Imaging Findings
• Head circumference (H ) and biparietal diameter are
pr served
• Abdominal circumference (A ) is small and exhibits
poor interval growth
• Oligohydramnios
common
• Second trime ter finding of echogenic bowel
associated with IVGR in 10-20lMl of cases
• VA 0 ralio hould be < 3 in third trime ter
• As placental resistance t, VA dia tolic flow ~

o

o

o

o

o

• VA blood flow quantified by systolic-diastolic (SO)
velocity
ratio = peak-systolic velocity/end-diastolic
• VA SO ratio should be < 3 in third trimester
As placental resistance t, VA diastolic flow ~
• Absent end diastolic flow (AEDF) ~ no flow into
placental vascular bed during diastole
• Reversed end diastolic flow (REDF) ~ vascular
resistance so high blood flows away from placenta
in diastole
• Studies suggest> 70% placental vascular bed
obliterated before REDF is seen
t Cardiac work required to perfuse abnormally
resistive placenta
• Eventual cardiac decompensation
• t Right atrial pressure
• Reversal of flow in inferior vena cava
• Reversal of "a" wave in ductus venosus
• Pulsatile flow in umbilical vein
Middle cerebral artery (MCA) flow also quantified by
SO ratio
• MCA SO ratio should be > UA SO ratio at all
gestational ages
• Reversal of this pattern = "head sparing" effect
Pulsatile flow in UV reflects breakdown of fetal
circulatory compensation to high placental
resistance
Maternal uterine artery (Ut A) Doppler may predict
patients at risk for IUGR
• Series of SGA fetuses with normal survey and UA
Doppler
• Ut A and MCA Doppler performed at time of
diagnosis as SGA
• Abnormal Ut A and MCA Doppler correlated
strongly and independently with need for
emergency cesarean section
• Consider delivery at lung maturity in this group

Imaging Recommendations
• Monitor amniotic fluid volume
o Use of API allows objective serial assessment
• Monitor growth
o Ideal minimum interval 3 weeks

ardiac work required to perfuse abnormally
re i tive placenta
• MAD
ratio should be > V 0 ratio at all
gestational age
• Rever al of this pattern = "head paring" eff ct

• t

Top Differential

Diagnoses

• Symmetric IUGR

Pathology
• Risk of IUGR up to 25% if pa t history IV R fetus +/maternal risk factor

Clinical Issues
• Fourfold increase in adverse perinatal outcome for
IVGR fetu es
• Long-term tudie show neurodevelopmental
morbidit in survivor
• Serial measurements taken at shorter intervals are
subject to error
• Monitor fetal response to hostile environment with
biophysical profile (BPP)
o Four parameters are "scored"
• Petal breathing
• Petal movement
• Petal tone
• Amniotic fluid volume
o Acute hypoxia ~ abnormalities of movement and
tone
o Chronic hypoxia ~ ~ amniotic fluid volume
• Nonstress test (NST): 5th parameter to assess fetal
reaction to environment

I DIFFERENTIAL

DIAGNOSIS

Symmetric IUGR
• Head no longer "spared"
o All growth parameters equally effected
• Generally due to problem with fetus rather than
placental insufficiency
• More likely with syndromes and aneuploidy
o Look for multiple anomalies
• More likely with infection
o Look for intracranial/abdominal
calcifications
o Look for signs hydrops

I PATHOLOGY
General Features
• Genetics
o Triploidy may present with either symmetric or
asymmetric IUGR, depending on source of extra
chromosomes
• Digynic triploidy (extra set of chromosomes
maternal) ~ severe, early-onset asymmetric IUGR
• Diandric triploidy (extra set of chromosomes
paternal) ~ abnormal thick/cystic placenta with
symmetric IUGR
• Etiology

~:

II-O-M-a-te-r-n-al-f-a-ct-o-rS-O-f-p-l-ac-e-n-ta-l-in-SU-f-f~-ci-~-c-:_M
__ M
__ E_T_R_IO_C-N-o-~-~-g-~-e
-pR-ar-a-m-e-t-er-d-e-t-er-m-i-n-e-s
-de-c-is-io-n-to-d-el-iv-e-r~
• Hypertension
• Collagen vascular disease
• Diabetes mellitus
• Drugs/alcohol/cigarette smoking
• Malnutrition
o Abnormalities in a number of placental hormonal
factors
• Vascular endothelial growth factor, leptin, resistin
o Failure of spiral artery changes in first trimester
• Normal low vascular tone in placenta fails to
develop
o Reduced placental transfer of amino acids/other
metabolic substrates
• In severe cases, even glucose transport is impaired
• Epidemiology
o IUGR occurs in 10% of pregnancies by definition
• Some of these infants will be normal, just
constitutionally small
o Risk of IUGR up to 25% if past history IUGR fetus
+/- maternal risk factors

Gross Pathologic & Surgical Features
• Primary placental abnormality

I CLINICAL

ISSUES

Presentation
• Asymmetric IUGR presents late second to early third
trimester
o Earlier presentation concerning for triploidy
• Increased risk in twins and higher order multiples

Natural History & Prognosis
• Fourfold increase in adverse perinatal outcome for
IUGR fetuses
o Additional 4-8 fold increase if IUGR + abnormal
Doppler
• Long-term studies show neurodevelopmental
morbidity in survivors
• "Fetal origins" hypothesis
o IUGR babies have t risk hypertension, diabetes,
stroke as adults

Treatment
• Offer karyotype, especially if early onset IUGR
• Infection screen
• Consider maternal testing for thrombophilic disorders,
especially if prior IUGR fetus or preeclampsia
o Antiphospholipid syndrome
o Protein C deficiency
• Aggressive treatment of any contributing maternal
condition
o Treat hypertension
o Control diabetes
• Increased surveillance
o Serial growth measurement
o Serial fluid check
o Frequent NST/BPP
o Frequent Doppler assessment of UA/MCA +/- Ut A
• 2nd trimester management difficult
o Significant risks of pre term delivery balanced with
significant risk of intrauterine demise

• Abnormal Doppler, fluid, BPP in 3rd trimester '*
deliver

I DIAGNOSTIC

CHECKLIST

Consider
• EFW percentiles are based on GA
o Accurate dating is essential to diagnosis of IUGR
o Early US is more accurate than menstrual history or
clinical findings
• Management decisions are based on multiple factors
o Gestational age
o Interval growth and API
o Non-stress testing and BPP
o Maternal factors

Image Interpretation

Pearls

• UA Doppler is "tip of the iceberg" with respect to fetal
hemodynamic status
o 70% of placental vascular bed obliterated before
REDFis seen
• Addition of venous Doppler '* more information of
fetal response to adverse conditions

I SELECTED

REFERENCES

Zuk L et al: Neonatal general movements: an early
predictor for neurodevelopmental outcome in infants with
intrauterine growth retardation. J Child Neurol. 19(1):14-8,
2004
2. Rasmussen S et al: Fetal growth and body proportion in
preeclampsia. Obstet Gynecol. 101(3):575-83,2003
3.
Galan HL et al: Intrauterine growth restriction (lUGR):
Biometric and Doppler assessment. Prenat Diagn. 22:331-7,
2002
4.
Hofstaetter C et al: Venous Doppler velocimetry in the
surveillance of severely compromised fetuses. Ultrasound
Obstet Gynecol. 20:233-9, 2002
5. Severi FM et al: Uterine and fetal cerebral Doppler predict
the outcome of third trimester small for gestational age
fetuses with normal umbilical artery Doppler. Ultrasound
Obstet Gynecol. 19:225-8,2002
6. Vergani P et al: Prognostic value of uterine artery Doppler
velocimetry in growth-restricted fetuses delivered near
term. AmJ Obstet Gynecol. 187(4):932-6,2002
7.
May R et al: Early postnatal growth of low birthweight
infants in the WIC program. Am J Hum BioI. 13(2):261-7,
2001
8.
Dashe JS et al: Effects of symmetric and asymmetric fetal
growth on pregnancy outcomes. Obstet Gynecol.
96(3):321-7, 2000
9.
Markestad T et al: Small-for-gestational-age (SGA) infants
born at term: growth and development during the first
year of life. Acta Obstet Gynecol Scand Suppl. 165:93-101,
1997
10. Sherwood RJ et al: Pattern and process of growth of the
abnormal human fetus. Hum BioI. 69(6):849-71, 1997
11. Vik T et al: Prenatal growth in symmetric and asymmetric
small-for-gestational-age infants. Early Hum Dev.
48(1-2):167-76, 1997
12. Vik T et al: Body proportions and early neonatal morbidity
in small-for-gestational-age infants of successive births.
Acta Obstet Gynecol Scand SuppI. 165:76-81, 1997
1.

'---

A_S_Y_M_M_ET_R_I_C_IU_G_R

I

~----------------_

~7
17

I IMAGE GALLERY
(Left) Pulsed Doppler
ultrasound shows absent
end-diastolic flow (arrows)
with normal venous flow.
Note paucity of amniotic
fluid. BPP score was zero.
This fetus was delivered by
emergency cesarean section
at 35 weeks. (Right) Pulsed
Doppler ultrasound shows
difference in UA waveforms
in twins with discordant
growth. Twin A has severe
IUCR with reversed
end-diastolic flow (arrows)
in the UA. Twin B has
normal low resistance flow.

(Left) Pulsed Doppler
ultrasound shows absent
end-diastolic flow (arrow)
associated with pulsation in
the umbilical vein (curved
arrow). This indicates
advanced cardiac
decompensation.
(Right)
Color Doppler ultrasound
shows low resistance flow in
the cerebral circulation of
the same fetus, indicating
"head sparing".

(Left) Ultrasound of a
triploid fetus shows
ventriculomegaly
(calipers)
and early-onset of
asymmetric IUCR with the
AC (arrow) lagging behind
the other measurements.
Asymmetric IUCR is seen
when extra chromosomes
are maternal in origin
(digyny). (Right) Clinical
photograph of a fetus with
triploidy shows the body
affected to a greater degree
than the head. There is also
syndactyly of the 3rd and
4th digits (arrows), another
common finding in triploidy.

171

M_A_C_R_O_S_O_M_I_A

1

~

AC
MA
01
02

=

37.94 em

= 41'N6d
= 11.74 em
= 12.42 em

Axial ultrasound shows a greater than expected AC
measurement
in a 36 wk fetus. A large amount of
echogenic subcutaneous
fat is easily seen (arrows).
Truncal obesity is common with macrosomia.

ITERMINOlOGY
Abbreviations

and Synonyms

• Large for gestational

age (LGA)

Definitions
• Estimated fetal weight> 90th percentile
• Birth weight (BW) > 4,000-4,500 g

IIMAGING

FINDINGS

General Features
• Best diagnostic clue: LGA fetus + t abdominal
circumference (AC) + polyhydramnios

Ultrasonographic

_

Findings

• Estimated fetal weight (EFW) > 90th percentile
o Fetal biometry used to estimate weight
• Biparietal diameter (BPD)
• Head circumference (HC)
• Abdominal circumference (AC)
• Femur length (FL)
o EFW accuracy for macrosomia is 85%
• AC heavily weighted in calculation of EFW
o Macrosomia often manifests in 3rd trimester
• AC alone may be predictive of macrosomia
o Risk for macrosomia < 1% if AC < 35 cm

Clinical photograph shows the large baby of a diabetic
patient. Excessive adipose deposition in trunk, arms and
face are apparent. These babies are at risk for shoulder
dystocia, asphyxia and hypoglycemia.

o Risk for macrosomia = 37% if AC > 37 cm
o AC often first measurement to t
• t Subcutaneous adipose tissue
o Adipose tissue is diffusely echogenic
o Truncal obesity common
o Seen best on routine AC view
• Macrosomia and idiopathic polyhydramnios
o 1/3 of fetuses with idiopathic polyhydramnios
macrosomic
o Must rule out other causes for polyhydramnios

Imaging Recommendations
• Best imaging tool: Accurate AC measurement
• Protocol advice: Growth graphs are useful visual tools

I DIFFERENTIAL

DIAGNOSIS

Beckwith-Wiedemann

(BW) syndrome

• Early excessive growth
• Macrosomia + anomalies common
o Macroglossia
o Enlarged kidneys (often echogenic)
o Omphalocele

Hydrops
• Excessive fluid collection
o Skin edema more hypoechoic
o Pleural effusions

than fat

DDx: large Fetus

Ilydrops

are

SVY, Tongue

SVY, Kidney

'---

I

M_AC_R_O_S_O_M_IA
Key

Terminology
• Estimated fetal weight> 90th per en tile
• Birth weight (BW) > 4,000-4,500 g

Imaging Findings
• Best diagno tic lue: LGA felu + t abdominal
circumference (A ) + polyhydramnios
• Macrosomia often manife ts in 3rd trimester
• AC often first mea urement to t

o Ascites
• Immune vs. non-immune

causes

I PATHOLOGY

~

Facts
• 1/3 of fetuses with idiopathic
macrosomic

• Epidemiology
o 6-8% in non-diabetics
o 16-18% in diabetics
• Associated abnormalities:

Clinical Issues
• houlder dystocia in 1O(}(j
• Elective cesarean section delivery

Image Interpretation
• Look for macrosomia
polyhydramnios

Thick placenta
2.

ICLINICALISSUES
3.

• Most common signs/symptoms
o Larger than expected fundal height measurement
o Pregnancies at risk for macrosomia
• Diabetes
• Maternal obesity
• Post-term pregnancy (> 42 wks)
• Prior child with macrosomia
• Polyhydramnios
o Diabetes and macrosomia
• Less risk if diabetes well controlled

are

Pathology

1.

Presentation

polyhydramnios

• 6-8% in non-diabetic
• 16-18(}(jin diabetics

I SELECTED

General Features

4.

5.

6.

Pearls

in patients with unexplained

REFERENCES

Culligan PJ et al: Elective cesarean section to prevent anal
incontinence and brachial plexus injuries associated with
macrosomia--a decision analysis. Int Urogynecol J Pelvic
Floor Dysfunct. 16(1):19-28; discussion 28,2005
Schaefer-Graf UM et al: Determinants of fetal growth at
different periods of pregnancies complicated by gestational
diabetes mellitus or impaired glucose tolerance. Diabetes
Care. 26(1):193-8, 2003
Conway DL: Choosing route of delivery for the
macrosomic infant of a diabetic mother: Cesarean section
versus vaginal delivery. J Matern Fetal Neonatal Med.
12(6):442-8, 2002
Gilby JR et al: Fetal abdominal circumference
measurements of 35 and 38 cm as predictors of
macrosomia. A risk factor for shoulder dystocia. J Reprod
Med. 45:936-8, 2000
Sokol RJ et al: Correctly identifying the macrosomic fetus:
improving ultrasonography-based
prediction. Am J Obstet
Gynecol. 182(6):1489-95, 2000
Sohaey R et al: Idiopathic polyhydramnios:
Association
with fetal macrosomia. Radiology. 190:393-6, 1994

Natural History & Prognosis
• Fetal complications related to delivery
o Shoulder dystocia in 10%
• Brachial plexus injury
o Asphyxia
o Hypoglycemia (t risk with diabetes)
o Low plasma calcium levels (t risk with diabetes)
• Maternal complications from delivery
o Anal and urinary incontinence

IIMAGE

GALLERY

Treatment
• Early delivery
• Elective cesarean section delivery

I DIAGNOSTIC

CHECKLIST

Consider
• t Risk for macrosomia

if AC > 90th percentile
o EFW may initially be within normal limits
• Follow fetal growth carefully in diabetics

117

(Left) Growth chart of a fetus with gestational diabetes shows
excessive AC growth. HC growth remains normal and there is a
decreased HC/AC ratio. Estimated fetal weight (EFW) is > 95th
percentile in the 3rd trimester. (Right) AFI of 38.9 cm is measured in
a pregnancy with macrosomia. Polyhydramnios is often seen in
association with macrosomia, regardless of cause.

17l

I

B_IO_P_H_YS_I_C_A_L_P_R_O_F_IL_E

_

20

Graphic shows the correct method for measuring
amniotic fluid for the BPP The uterus is completely
examined and the largest pocket of amniotic fluid,
devoid of cord and fetus, is measured.

Axial ultrasound shows correct caliper placement for
BPP fluid assessment. The depth (#7 calipers) and the
transverse diameter (#2 calipers) of the largest pocket of
fluid should be at least 2 em.

ITERMINOlOGY

IIMAGING FINDINGS

Abbreviations

General Features

and Synonyms

• Biophysical profile (BPP)
• Nonstress test (NST)

• Best diagnostic clue: BPP + NST score of < 6/10
associated with fetal acidemia

Definitions

Ultrasonographic

• BPP score
o Ultrasound-based method to test for fetal hypoxia
o Total of 8 points possible
• 4 variables tested
• 2 points maximum/variable
o Performed on viable fetuses only
• Test used to decide fetal delivery
• NST score
o Electronic fetal monitoring
o Does not use ultrasound
o NST complimentary to BPP
o Total of 2 points possible
• BPP + NST score
o Used together for management decisions
o Total of 10 possible points
• 8 points from BPP
• 2 points from NST

• Biophysical profile score
o 4 ultrasound variables observed
• Fetal breathing
• Gross body movement
• Fetal tone
• Amniotic fluid
o Observation time = 30 minutes
• Fetal sleep state'" 20 min
• Abnormal score cannot be given in < 30 min
• Normal BPP possible in < 30 min
o Scoring
• Each variable scored 0 or 2 points
• 2 points awarded if fetus meets criteria
• No "1"s allowed
• Total of 8 points possible
o Normal result is BPP score of 8/8
• BPP + NST score ~ 8/10
• NST score less important than BPP
o Abnormal result is BPP score ~ 4/8
• If NST is 2 then 6/10 score is equivocal
• If NST is 0 then ~ 4/10 score is abnormal

DDx: Oligohydramnios

Renal Agenesis

Findings

From Fetal Anomalies

Renal Agenesis

Renal Cystic Dysplasia

Bladder Obstruction

______

I

B_I_O_P_"_Y_S_IC_A_L_P_R_O_F_I_LE

~

Key Facts
Terminology
• Ultrasound-based method
• Total of 8 points possible

•

•

•

•

Top Differential

Diagnoses

• Oligohydramnios
• Arthrogryposi

2° to fetal anomaly

Imaging Findings

Pathology

• Best diagno tic clue: BPP + ST score of < 6/10
a ociated with fetal acidemia
• Fetal breathing
• Gross body movement
• Fetal tone
• Amniotic fluid
• Ob ervation time = 30 minutes
• Ea h variable cor dOor 2 points
• ormal result is EPP score of 8/8
• Abnormal result i BPP score ~ 4/8
• Equivocal result is BPP core 6/8

•
•
•
•
•

o Equivocal result is BPP score 6/8
• If NST is 2 then 8/10 is normal
• If NST is 0 then 6/10 is equivocal
Fetal breathing
o Sustained thoracic movement
• Diaphragm excursion
• Chest expansion
• M-mode of diaphragm can show movement
o Scoring
• ~ 1 episode of "breathing " ~ 30 sec = 2 points
• No episode of "breathing" ~ 30 sec = 0 points
Gross body movement
o Trunk roll
o Spine flexion or extension
o Gross limb movement
o Scoring
• ~ 3 trunk or limb movements = 2 points
• < 3 trunk or limb movements = 0 points
Fetal tone
o Active limb movement
• Flexion -+ extension -+ flexion
• Hand opens and closes
o Scoring
• ~ 1 episode = 2 points
• 0 episodes = 0 points
Amniotic fluid (AF) volume
o Largest AF pocket is found
• Vertical and transverse measurements
• Different than 4 quadrant amniotic fluid index
o Scoring
• ~ 1 pocket of fluid ~ 2 cm x 2 cm = 2 points
• No pocket of fluid ~ 2 cm x 2 cm = 0 points

Other Modality
•

to test for fetal hypoxia

ST

Findings

o Non-ultrasound
based testing
• Cardiac reactivity
• Fetal movement
• Uterine contractility
• Observation time = 20 minutes
o Heart rate acceleration criteria
• ~ 15 beats per minute for 15 sec
o Scoring

Tissue hypoxia ~ loss of function
Oligohydramnio
reflects chronic hypoxia
Fetal breathing lost first
Fetal tone lost second
Gross body movement lost last

Clinical Issues
• ormal EPP almost never associated with acidemia
• Early delivery of fetus if abnormal BPP/ ST

Diagnostic Checklist
• Obtain cord Doppler if BPP i abnormal

• ~ 2 accelerations in 20 min = 2 points
• ~ 1 acceleration in 20 min = 0 points
• Umbilical artery (UA) Doppler
o Complimentary to BPP
• Not part of BPP or NST score
o Normal UA Doppler
• Antegrade flow throughout diastole
• Low resistive waveform pattern
o Abnormal UA Doppler
• Absent or reversed diastolic flow
• Associated with hypoxia

Imaging Recommendations
• Best imaging tool
o Experienced sonographer
• Careful fetal observation
o Accurate amniotic fluid assessment
o Assess for intrauterine growth restriction (IUGR)
• Associated with abnormal BPP
• Protocol advice
o BPP < 8/8
• Observe at least 30 minutes
• Send patient for NST
• Perform UA Doppler
o Use color Doppler for AF assessment
• Helps avoid measurement of cord in AF pockets

I DIFFERENTIAL
Oligohydramnios

117

DIAGNOSIS
2° to fetal anomaly

• Renal agenesis
o Anhydramnios
o Pulmonary hypoplasia
o Fatal
• Bilateral renal anomalies
o Bilateral cystic dysplasia
o Sever autosomal recessive polycystic kidney disease
• Genitourinary tract obstruction
o Bilateral renal obstruction
o Bladder outlet obstruction
• Posterior urethral valves

17l

~

I~

B_I_O_P_H_Y_S_IC_A_L_P_R_O_F_I_L_E

_

Arthrogryposis

Natural History & Prognosis

• Fetal hypokinesia/akinesia sequence
• Abnormal fetal movement
o Fetus may show no movement
• Contractures
• Polyhydramnios

• BPP/NST used to avoid stillbirth
0 70% stillbirth fetuses with IUGR
0 90% show evidence for chronic hypoxia
0 Use of BPP/NST will ~ perinatal mortality from 8%
to 2%
• BPP/NST ~ 8/10 accurately predicts normal tissue
oxygenation
o Normal BPP almost never associated with acidemia
o False negative rate < 1%
• BPP/NST ~ 6/10 relatively accurate predictor of
acidemia
o 6/10 is an equivocal score
• 75% false positive rate for acidemia
• May reflect fetal ability to compensate for hypoxia
o 0/10 near 100% predictive for acidemia
• Specific test results
o Normal acute variables + normal fluid
• Normal blood gas + normal pH
o Normal acute variables + abnormal fluid
• Normal blood gas + normal pH + hypoxemia with
compensation
o Abnormal acute variables + normal fluid
• Abnormal blood gas + abnormal pH in acute
setting
o Abnormal acute variables + abnormal fluid
• Abnormal blood gas + abnormal pH in chronic
setting

Aneuploidy
• BPP not designed for abnormal fetuses
• False positive results more likely
o Central nervous system anomalies
o Cardiac defects
• IUGR common

!PATHOLOGY
General Features
• General path comments
o Tissue hypoxia ~ loss of function
• Neuronal tissue most sensitive
o Hypoxia ~ cardiac output redistribution
• Chemoreceptors in aorta and carotids
o Hypoxia ~ IUGR
• Placental insufficiency
• Etiology
o Variables affected by acute hypoxia
• Fetal breathing
• Gross body movement
• Fetal tone
• Fetal heart rate accelerations
o Oligohydramnios reflects chronic hypoxia
• Blood shunted away from kidneys
• Blood shunted away from lungs
• Fetal swallowing t with hypoxia
• ~ 3 wks for significant oligohydramnios to
develop
o Predictable order of function loss
• Fetal breathing lost first
• Fetal tone lost second
• Gross body movement lost last
• Epidemiology
o Low death rate following normal BPP
• 0.4-0.6:1,000 high risk pregnancies
• Associated abnormalities: IUGR

Staging, Grading or Classification Criteria

Treatment
• Early delivery of fetus if abnormal BPP/NST
o Avoid stillbirth
• Repeat noninvasive testing for equivocal results

I DIAGNOSTIC
Consider

• Correlate BPP score with NST score
• BPP exam in viable fetuses with IUGR
• BPP in viable fetuses with oligohydramnios

Image Interpretation

I SELECTED

I CLINICAL

2.

Presentation
• Most common signs/symptoms
o BPP/NST to assess fetal health in high-risk cases
• Intrauterine growth restriction (IUGR)
• ~ Fetal movement
• Maternal hypertension
• Maternal diabetes
• Post dates
• Premature ruptured membranes

Pearls

• Obtain cord Doppler if BPP is abnormal
• Must observe fetus for 30 minutes before giving 0
score for any acute variable

• Normal BPP = 8/8 or ~ 8/10 with NST
• Equivocal BPP = 6/8 or 6/10 with NST
• Abnormal BPP = < 6/8 or < 6/10 with NST

ISSUES

CHECKLIST

1.

3.

4.
5.

REFERENCES

Gojnic M et al: The importance of Doppler ultrasound in
delivery planning. Clin Exp Obstet Gynecol. 31(4):282-4,
2004
Magann EFet al: Biophysical profile with amniotic fluid
volume assessments. Obstet Gynecol. 104(1):5-10, 2004
Odibo AO et al: What antepartum fetal test should guide
the timing of delivery of the preterm growth-restricted
fetus? A decision-analysis. Am J Obstet Gynecol.
191(4):1477-82,2004
Manning FA:Fetal biophysical profile: a critical appraisal.
Clin Obstet Gynecol. 45(4):975-85, 2002
Manning FA:Fetal biophysical profile. Obstet Gynecol Clin
North Am. 26(4):557-77, v, 1999

============B=I=O=P="=Y=S=IC=A=L=P=R=O=F=I=LE==

I

I IMAGE GALLERY

(Left) Coronal M-mode
ultrasound shows caliper
placement in order to
document fetal thoracic
movement. The area to be
studied passes through the
diaphragm (arrows) and
"fetal breathing" can be
documented. (Right)
Coronal M-mode ultrasound
shows fetal breathing. The
undulating M-mode wave
(arrows) is from diaphragm
and lung motion.

Typical
(Left) Coronal ultrasound
shows normal fetal tone. The
fetal leg (arrows) was seen
extending from a flexed
position. (Right) Coronal
ultrasound in the same case
shows the leg (arrows)
returning to a flexed position
(curved arrow points to
knee). At least 7 episode of
flexion to extension and back
to flexion is required for a
score of 2 for tone. Opening
and closing of a hand counts
as well.

Typical
(Left) An abnormal NST strip
shows lack of cardiac
acceleration (arrows) and a
mild deceleration (curved
arrow) during 3 uterine
contractions (open arrows)
in a non-laboring patient.
The NST score here is O.
(Right) Pulsed Doppler
ultrasound of the umbilical
artery in a fetus with IUCR
and a BPP score of 4/8
shows reversed diastolic flow
(arrows). UA Doppler can
also help identify fetuses al
risk for hypoxia.

I

~:

171

I

M_C_A_D_O_P_P_LE_R

_

24

Color
middle
plane.
arrow)

Doppler ultrasound shows circle of Willis. The
cerebral arteries (arrows) are easiest to see in this
The anterior (curved arrow) and posterior (open
cerebral arteries are also visible.

ITERMINOlOGY
Abbreviations

Axial color Doppler ultrasound shows correct technique
for sampling the MCA. There must be no angle between
the long axis of the vessel (curved arrow) and the
ultrasound beam (open arrows).

IIMAGING FINDINGS

and Synonyms

Ultrasonographic

•
•
•
•

Middle cerebral artery (MCA)
Peak systolic velocity (PSV)
End diastolic velocity (EDV)
Systolic-diastolic (SD) ratio
o PSV-EDV/PSV
• Umbilical artery (UA)

Definitions
• MCA Doppler is a useful tool in assessing fetal
well-being in varying clinical conditions, including
intrauterine growth restriction and fetal anemia
o Intrauterine growth restriction (IUGR)
• Estimated fetal weight < 10th percentile for
gestational age
• Most useful for asymmetric IUGR
o Fetal anemia
• Fetal hematocrit varies with gestational age
• Characterized as severe when fetal hematocrit
<15%, hemoglobin 4-6 g/dL
• Color Doppler of circle of Willis and branches also aids
in evaluation of cerebral malformations

Findings

• Asymmetric IUGR
o SD ratio of MCA should be > SD ratio of UA
throughout gestation
• Reversal of this ratio in IUGR is called "head
sparing" pattern
o Abdominal circumference less than other biometric
parameters
o Estimated fetal weight less than < 10th percentile
o Oligohydramnios common
• Fetal anemia
o Anemia caused by red cell alloimmunization
syndromes and infection, particularly parvovirus
o May see signs of hydrops
• Color Doppler of circle of Willis and branches helpful
in evaluation brain malformations
o Hydranencephaly
• Cerebral destruction due to vascular catastrophe
• No flow seen in circle of Willis
o Holoprosencephaly
• Brian malformation associated with abnormal
cleavage of prosencephalon
• Lobar holoprosencephaly associated with azygos
anterior cerebral artery
• Single vessel runs just beneath skull vault
o Agenesis of corpus callosum

DDx: Errors In MeA PSV Measurement
.-..;....

-.

Sl.-;X .
.

~'~

"

v = O.180m/s

!Mean

=

O.060m/s

7:~.~}~~~,i;J~·'.:~,:,',~.)f'I,:;··'·\
..~;5'~··~
~ii:'.)·
\\ .• t.

,L ...• h' ,'.

'j.,_"

~ ..••...

Wrong Vessel

Wrong Angle

Fetal Breathing

~

I

M_C_A_D_O_P_P_LE_R

~

Key Facts
Terminology

Top Differential

• M A Doppler i a u eful tool in assessing fetal
well-being in varying clinical conditions, including
intrauterine growth restriction and fetal anemia
• olor Doppler of circle of Willi and branches al 0
aids in evaluation of cerebral malformations

•
•
•
•

Imaging Findings

• Most data support p rformance of intrauterine
transfu i n ba ed on velocity data

•
•
•
•

Diagnoses

Wrong ve el
Wrong ample site
Wrong angle
Fetal breathing

Clinical Issues
blood

U e color Doppler to identify ir Ie of Willis
"Zoom" image to ee entire length M A
Place cursor clo to origin of M A
Statistically ignificant differences
en in
mea ur ments from proximal and distal part of
ve sel
• Angle of in onation hould be zero
• Avoid ampling during period of fetal breathing and
increased activity

• U e of M A Doppler has changed management of
pregnancie complicated by alloimmunization
• If s rial measurements
how differing velocitie ,
repeat before making management deci ion
• Hydrop and massive ascites may cause t MCA P V in
the ab enc of anemia

• Corpus callosum induces formation of pericallosal
and callosomarginal branches of anterior cerebral
artery
• Sagittal view with color Doppler used to
demonstrate flow
• Presence of vessels implies presence of corpus
callosum
o Arteriovenous malformations
• Neck and cerebral vessels increased in size in
presence of shunt flow

o Hydrops may cause elevation of MCA PSV even if
not due to anemia
• May relate to fetal stress response/"head sparing"
o IUGR
• IUGR fetuses may also be anemic (23% in one
series)
• "Head sparing" effect in severe IUGR results in
shunting of blood to fetal brain
• MCA PSV measurements have less predictive value
in this clinical situation

Diagnostic Checklist

Imaging Recommendations
• Protocol advice
o Assessment of IUGR
• Measure MCA SO ratio and compare to that of UA
• Assessment of anemia
o Use color Doppler to identify circle of Willis
o "Zoom" image to see entire length MCA
o Place cursor close to origin of MCA
• Statistically significant differences seen in
measurements from proximal and distal parts of
vessel
• No significant difference in velocities of
near/far-field MCA if proximal sample site used
o Angle of insonation should be zero
o Do not use angle correction
o Take several measurements (at least three) with
15-30 waveforms
o Velocities should be similar
o Take best measurement
o Do not average several velocities
• Avoid sampling during periods of fetal breathing and
increased activity
o Fetal breathing causes highly variable waveform
with beat-to-beat PSV variations
o Fetal activity causes mean PSV to increase by
4cm/sec
• Potential pitfalls in assessment of anemia
o Massive fetal ascites
• Reported case with elevated MCA PSV but normal
hematocrit at birth
• MCA PSV correlates with volume of ascites

I DIFFERENTIAL DIAGNOSIS
Wrong vessel
• Management criteria based on MCA flow velocities
• Anterior/posterior
cerebral arteries have different
velocity profile
• Cannot use measurements from these vessels

Wrong sample site
• Best to sample within 2 mm of origin MCA from circle
of Willis
• Statistically significant differences seen in
measurements from proximal and distal parts of vessel
• Incorrect measurements =:> incorrect management
decisions

Wrong angle
• Flow calculations are affected by angle of insonation
• Frequency shift proportional to cosine of angle of
insonation
• Keeping angle at zero avoids need for angle correction
• Technically feasible in most cases
o Scan plane akin to that for head measurements
therefore easily reproduced

Fetal breathing
•
•
•
•

IV

Alters flow in all fetal vessels
Variable height of waveforms
Velocity measurements unreliable
Incorrect measurements => incorrect management
decisions

~: I

1'=P=f\=I=H=O==L=O==G=V===============M==C==A==D=-_O_P-p-.-~-~-s-~-a-ta-s-u-pp-o-rt-s
-pe-r-fo-rm-a-n-ce-o-f-in-t-ra-ut-e-rin-e·

General Features

blood transfusion based on velocity data
route preferred but intraperitoneal
injection can be performed if UV not accessible
• Repeat MCA Doppler after transfusion shows
decreased MCA PSV
Parvovirus may cause fetal anemia
• Transplacental transmission estimated to occur in
33% of cases
• Hydropic changes occurs within 4 wks of
symptomatic maternal infections, rare after 8 wks
• No reported fetal deaths> 12 weeks post exposure
• Optimal interval uncertain: Many centers use
weekly Doppler/check for signs hydrops
• Follow for 12 weeks then return to routine
obstetric care

• Intravenous

• Epidemiology
o IUGR
• By definition occurs in 10% of pregnancies
o Rhesus (Rh) alloimmunization
• 10.2:10,000 total births
o Other alloimmune syndromes (Kell, Duffy, C, c, E
and others)
• 35:10,000 live births
o Parvovirus
• Transplacental transmission in 33% of cases
• Physiology
o IUGR
• Intrauterine environment become hostile to fetus
• Most common cause is placental insufficiency
• Protective mechanism allows t proportion of
umbilical blood flow to go to brain
• Normally 20-30% of ductus venosus blood shunts
across foramen ovale to supply coronary arteries
and brain
• With IUGR/hypoxia up to 70% of flow is shunted
to brain/coronaries
• Diastolic flow t ~ SD ratio +
• UA SD ratio t as placental resistance t
• Eventually UA SD ratio> MCA SD ratio = "head
sparing" pattern
o Fetal anemia
• + Blood viscosity ~ t velocity of flow even if
vessel diameter stable
• Hypoxia ~ t cerebral blood flow as protective
mechanism
• Result is measurable difference in MCA PSV

I DIAGNOSTIC

ICLINICAL

I SELECTED

ISSUES

• Use of MCA Doppler has changed management of
pregnancies complicated by alloimmunization
o Serial amniocentesis no longer required
o Less risk of procedure-related pregnancy loss
o Less risk fetal-maternal hemorrhage

Image Interpretation

• Anemia
o Monitor velocities
o Plot measurements of MCA PSV in cm/sec against
gestational age in weeks
o Intervention based on relationship of velocity to GA
• Zone A: Intervene
• Zone B: Repeat measurements in 5-7 days
• Zone C: Repeat measurements in 7-10 days
• Zone D: Repeat measurements in 2-3 weeks
o Follow-up interval may be adjusted based on
• Maternal antibody titers
• Prior history of affected infants
o Moderate anemia detected with 100% sensitivity
and 12% false positive rate
• Using cut off of PSV values at 1.5 multiples of the
median (MoM) for GA
o Severe anemia detected with 100% sensitivity and
15% false positive rate with cut off of 1.55 MoM
o Number of false positives increase after 35 weeks
gestation but delivery is safe option at that GA
o Intervention

Pearls

• Check all waveforms and select best measurement
• If serial measurements show differing velocities, repeat
before making management decision
o Fetal breathing
o Poor technique
• Hydrops and massive ascites may cause t MCA PSV in
the absence of anemia

at-risk pregnancies

Treatment

CHECKLIST

Consider

1.

Presentation
• Performed electively to monitor

0

2.

3.

4.

5.

6.

7.

8.

9.

REFERENCES

Chiang G et al: Massive fetal ascites causing increased
middle cerebral artery systolic velocity. Obstet Gynecol.
104(5 Pt 2):1136-40,2004
Enders M et al: Fetal morbidity and mortality after acute
human parvovirus B19 infection in pregnancy: prospective
evaluation of 1018 cases. Prenat Diagn. 24(7):513-8, 2004
Sallout Bl et al: The effect of fetal behavioral states on
middle cerebral artery peak systolic velocity. AmJ Obstet
Gynecol. 191(4):1283-7, 2004
Segata M et al: Fetal anemia: new technologies. CUffOpin
Obstet Gynecol. 16(2):153-8,2004
Shah NK et al: Middle cerebral artery Doppler velocimetric
assessment in two cases of hydrops fetalis without fetal
anaemia. Prenat Diagn. 24(1):17-8, 2004
Abel DE et al: Ultrasound assessment of the fetal middle
cerebral artery peak systolic velocity: A comparison of the
near-field versus far-field vessel. Am J Obstet Gynecol.
189(4):986-9, 2003
Gagnon R et al: The use of fetal Doppler in obstetrics. J
Obstet Gynaecol Can. 25(7):601-14; quiz 615-6, 2003
Habek D et al: Fetal grasping of the umbilical cord and
perinatal outcome. Arch Gynecol Obstet. 268(4):274-7,
2003
Makh DS et al: Is Doppler prediction of anemia effective in
the growth-restricted fetus? Ultrasound Obstet Gynecol.
22(5):489-92, 2003

~

I ~7

M_CA_D_O_P_P_LE_R

-----------------

27

1

IMAGE GALLERY

Typical
(Left) Pulsed Doppler
ultrasound shows normal
high-resistance waveform in
the MCA. The SO ratio in
this second trimester fetus is
normal at 5.2. Note: Sharp
upstroke and little antegrade
diastolic flow (arrows).
(Right) Pulsed Doppler
ultrasound shows abnormal
low resistance flow in the
MCA in a fetus with growth
restriction. The SO ratio of
2.19 was less than that of the
UA. Note the prominent
antegrade diastolic flow
(arrows).

Typical
(Left) Graphic of MCA PSV
plots in a Rh-sensitized
patient. The length of
interval follow-up is based
on the zone in which the
PSV plots. Intrauterine
transfusion (fUT - arrow)
was performed when the
fetus was in zone A with a
subsequent drop in PSV
(Right) Pulsed Doppler
ultrasound shows a PSVof
40.6 cm/sec, which plotted
in zone C. The appropriate
follow-up interval in zone C
is 1-70 days.

(Left) Coronal ultrasound
shows features of hydrops. It
is important to be aware that
hydrops may cause
elevations in the PSV without
anemia. This fetus was
anemic and improved after
transfusion. (Right) Sagittal
color Doppler ultrasound
shows the anterior cerebral
artery (arrow) branching into
the pericallosal and
callosomarginal branches as
it runs over the corpus
callosum. Doppler of the
major cerebral vessels helps
evaluate for structural
anomalies.

17l

IL--

U_T_ER_I_N_E_A_R_T_E_R_Y_D_O_P_P_L_E_R

_

~

Color Doppler ultrasound shows the uterine artery
(arrow) extending toward the lateral myometrium
(curved arrow) as seen through a full bladder. Note the
close proximity of the internal iliac artery (open arrow).

Pulsed Doppler ultrasound shows a normal uterine
artery waveform with a gentle slope to the upstroke
(curved arrow) and no diastolic notch (arrows). Open
arrow indicates fetal lumbar spine.

ITERMINOLOGY

IIMAGING FINDINGS

Abbreviations

General Features

and Synonyms

• Uterine Artery (Ut A) Doppler
• Resistive index (RI)
o Peaks systolic velocity (PSV) - end diastolic velocity
(EDV)/PSV
• Pulsatility index (PI)
o PSV-EDV/time average velocity (average flow
velocity over a complete cardiac cycle)
• Systolic to diastolic (SD) ratio
o PSV/EDV

• Ut A spectrum changes early in normal pregnancy
o Switch from high to low resistance usually occurs in
first trimester
o May be delayed until second trimester
o Little change after 24 weeks
• Abnormal Ut A Doppler implies abnormal
placentation
• Umbilical artery (UA) Doppler reflects fetal response to
abnormal placentation
o As fetus grows, abnormal placenta becomes more of
a problem
o Eventually causes IUGR
o UA Doppler reflects fetal response to stress of hostile
intrauterine environment
• Changes more likely to develop and progress in
third trimester
• Normal values for uterine artery RI at 11-14 weeks
o 5th percentile = 0.53
o 50th percentile = 0.71
o 95th percentile = 0.85
• Abnormal findings
o Persistent diastolic notch beyond first trimester
o Conversion from high to low resistance delayed
until second trimester

Definitions
• Doppler interrogation of uterine artery flow
• Clinical applications of uterine artery Doppler
o In vitro fertilization
• Uterine receptiveness for implantation
o Risk assessment for maternal complications of
pregnancy
• Pregnancy-induced
hypertension
• Pre-eclamptic toxemia
o Risk assessment for poor fetal outcome
• Intrauterine growth restriction (IUGR)
• Small for gestational age (SGA) infant

DDx: Pitfalls In Measuring Uterine Artery Doppler

.. -

.~"~..__ ·"H'
··.. 1t.-.,.,.,
-~
-,~."
--.
\'"

~
External Iliac artery

-

-.

,-,-

~.

-

~-,

Internal Iliac Artery

Myometrial Branches

______

U_T_E_R_IN_E_A_R_T_E_R_Y_D_O_P_P_LE_R

~I IV

Key Facts
Imaging Findings

Pathology

• Switch from high to low resistance usually occur in
first trimester
• Abnormal Ut A Doppler implies abnormal
placentation
• Umbilical artery (UA) Doppler reflects fetal re ponse
to abnormal placentation
• ample just cephalad to where Ut A appear to cross
internal iliac artery
• Obtain 3 similar con ecutive waveforms
• Measure RI (PI and SD ratio also used in some studies)
• Evaluate both vessels and average measurements
• Document presence of "notch"

• Pathologic changes found in 79% of placental bed
biopsies in IUGR + abnormal Ut A Doppler (UA
Doppler normal)
• Control cases had 0% pathologic findings in
placental bed biopsies

Top Differential

Diagnoses

Diagnostic Checklist
• Use results in addition to other information
including umbilical artery Doppler and tests of fetal
well-being
• Data established for high-risk singleton pregnancies
• Low ensitivity for adverse outcome in multiple
pregnancies de pite use of twin-specific nomograms
• Diastolic notch beyond the first trimester i abnormal

• Wrong vessel

o Abnormal findings with 71.4% positive predictive
value for adverse outcome in selected high-risk
group
• Unilateral notch and mean RI ~ 0.6S at 20 weeks
• Bilateral notches and mean RI ~ .SS at 20 weeks
• High-risk women with normal values at 20 weeks
had similar outcome to controls
• Normal result in this study had a negative
predictive value of 93.4%

Imaging Recommendations
• Protocol advice
o Transabdominal or endovaginal (EV) approach
• EV may be necessary with obese maternal habitus
o Find cervical canal for mid-cervical plane
o Move transducer laterally to find para cervical plexus
o Sample just cephalad to where Ut A appears to cross
internal iliac artery
o Obtain 3 similar consecutive waveforms
o Measure RI (PI and SD ratio also used in some
studies)
o Evaluate both vessels and average measurements
• Avoids bias from lateral placental implantation
o Document presence of "notch"
• Defined as decreased velocity in early diastole (less
than peak diastolic velocity)
• Is notch unilateral or bilateral?

I DIFFERENTIAL

DIAGNOSIS

Wrong vessel
• Internal iliac artery
o Sharp systolic upstroke
o Very low diastolic velocity
o Early diastolic notch is normal
• External iliac artery
o Early diastolic flow reversal is normal
o Much higher velocity than uterine artery
• Spiral artery
o Very low velocity
o Very low resistance

I PATHOLOGY
General Features
• Etiology: Impaired trophoblastic invasion of spiral
arteries '* increased impedance to flow in uterine
arteries
• Epidemiology
o Incidence abnormal Ut A Doppler in general
population not known
• IUGR in S or 10% depending on definition
• Normal development of maternofetal circulation
o Placental trophoblast cells invade maternal spiral
arteries
o Vessel walls transformed from non-pregnant smooth
muscle to flaccid channels without contractile
properties
o Uterine artery blood flow in early pregnancy
SOml/min
o Uterine artery blood flow at term reaches 700
ml/min
• Spiral artery impedance decreases between Sth and 7th
week gestation
• Uterine and arcuate artery impedance decreases after
8th week
• Uterine artery Doppler reveals information about
maternal side
• Umbilical artery Doppler reveals information about
fetal side

Gross Pathologic & Surgical Features
• Series of pregnancies complicated by IUGR with
abnormal Ut A and UA Doppler
o 82% abnormal placental biopsy
• Villous infarcts
• Cytotrophoblast
proliferation
• Thick villous trophoblastic basal membrane
o 91% abnormal placental bed biopsy
• Inadequate endovascular trophoblast invasion
• Thrombosis or luminal obliteration of spiral
arteries
• Increased extra villous trophoblasts

~

1:I I~

-.-A-th-e-ro-Si-S-(f-ib-ri-n-o-id-n-e-cr-~-si-~-O~-v-~-SS-~]-~-a-~-s-~-it-~_T_E_~-A-~-n-~-rm-O-al-u-~-~-D-~-P-~-I~-r-c-or-re-la-t-eS-W-i-

subintimal accumulation of lipid laden cells)
• Pathologic changes found in 79% of placental bed
biopsies in IUGR + abnormal Ut A Doppler (UA
Doppler normal)
o Control cases had 0% pathologic findings in
placental bed biopsies

IClINICALISSUES
Presentation
• Infertility-especially in older women
o Ut A impedance increases in women> 35 yrs of age
o May partly explain increase in pregnancy
complications in this age group
o PI may predict uterine "receptivity" for implantation
• Prior history of complicated pregnancy
o Prior pre-eclamptic toxemia
o Prior IUGR/SGA fetus
• Risk assessment for preterm delivery
o Defective placentation thought to increase risk for
preterm delivery, however Ut A Doppler has not
been shown to reliably predict recurrence

Natural History & Prognosis
• In vitro fertilization patients
o Ut A PI > 3.26 ~ very low chance of achieving
pregnancy
o Measures to decrease vascular impedance might
enhance uterine receptivity in this group
• Abnormal uteroplacental vascular resistance (Ut A
Doppler) associated with
o Preterm delivery
o Operative delivery
o SGA infants
• Patients with abnormal Ut A and UA Doppler
o Deliver early
o Lower mean birth weight
o Lower placental weight
• Abnormal Ut A Doppler in patients with pre-eclamptic
toxemia (PET) predicts adverse outcome in future
pregnancies
o 3.4x likelihood of PET again in subsequent
pregnancy
o 9.7x likelihood of delivering SGA infant in
subsequent pregnancy
• Individualized risk assessment in inner city population
in London
o Mean PI > 1.45 at 23 weeks ~ 5x likelihood ratio of
severe adverse pregnancy outcome
o Maternal smoking doubled the risk for any given PI
• Pregnant women with chronic hypertension at risk for
PET
o Ut A and UA Doppler abnormal in all who
developed PET
• IUGR significant risk factor for adverse perinatal
outcome
o Abnormal Ut A Doppler implies worse prognosis
o Bilateral Ut A notching or mean RI > 0.58 ~ 4-fold
risk of admission to new born intensive care unit
• Series of IUGR fetuses delivered at ~ 24 weeks
gestation

even after correction for confounding
including maternal smoking

variables

Treatment
• Randomized controlled trials are currently in progress
0 Aim to see if abnormal uterine artery Doppler in
early pregnancy can be effectively treated before
onset of pregnancy complications
• Treatment options
o Aspirin
o Vitamins C/E
o Low molecular weight heparin

I DIAGNOSTIC

CHECKLIST

Consider
• Studies use different criteria for "adverse outcome" and
for normal/abnormal values of uterine artery Doppler
o If applying in practice establish consistent technique
• When to measure: First or second trimester
• Define normal for population: Absolute value,
percentile range, which Doppler parameters
o Use results in addition to other information
including umbilical artery Doppler and tests of fetal
well-being
• Data established for high-risk singleton pregnancies
o Low sensitivity for adverse outcome in multiple
pregnancies despite use of twin-specific nomograms
o Benefit not clearly proven in low-risk population

Image Interpretation

Pearls

• Diastolic notch beyond the first trimester is abnormal

I SELECTED
1.

2.

3.

4.

5.
6.

7.

8.

REFERENCES

Bats AS et al: Antiphospholipid syndrome and second- or
third-trimester fetal death: follow-up in the next
pregnancy. Eur J Obstet Gynecol Reprod BioI. 114(2):125-9,
2004
Harrington K et al: The value of uterine artery Doppler in
the prediction of uteroplacental complications in
multiparous women. Ultrasound Obstet Gynecol.
23(1):50-5, 2004
Papageorghiou AT et al: Second-trimester uterine artery
Doppler screening in un selected populations: a review. J
Matern Fetal Neonatal Med. 12(2):78-88, 2002
Vergani Pet al: Prognostic value of uterine artery Doppler
velocimetry in growth-restricted fetuses delivered near
term. Am J Obstet Gynecol. 187(4):932-6,2002
Lees C et al: Individualized risk assessment for adverse
pregnancy outcome by uterine artery Doppler at 23 weeks.
Obstet Gynecol. 98(3):369-73, 2001
Mires GJ et al: Assessment of uterine arterial notching as a
screening test for adverse pregnancy outcome. Am J Obstet
Gynecol. 179(5):1317-23, 1998
Kurdi W et al: The role of color Doppler imaging of the
uterine arteries at 20 weeks' gestation in stratifying
antenatal care. Ultrasound Obstet Gynecol. 12(5):339-45,
1998
Bower SJ et al: Prediction of pre-eclampsia by abnormal
uterine Doppler ultrasound and modification by aspirin. Br
J Obstet Gynaecol. 103(7):625-9, 1996

===========U=T_E_R=I=N=E=A=R=T=E=R=y=D=O=P=P=L=E=-R----_I
I IMAGE GALLERY
Typical
(Left) Pulsed Doppler
ultrasound shows
measurement of various
Doppler parameters
including RI, PI and S/D
ratio. Both vessels are
evaluated and the mean
measurement is used for risk
assessment. (Right) Pulsed
Doppler ultrasound shows
normal continuous diastolic
flow in the uterine artery at
20 weeks gestation. Uterine
artery flow increases from 50
to 700 ml/min by term.

(Left) Pulsed Doppler
ultrasound shows the typical
features of a normal uterine
artery waveform in early
pregnancy after converting
from high to low resistance.
This usually occurs in the
first trimester. (Right) Pulsed
Doppler ultrasound of the
uterine artery shows an early
diastolic notch (arrows). This
pattern is abnormal, as the
spiral arteries should have
converted to a low-resistance
vascular bed.

(Left) Pulsed Doppler
ultrasound of the umbilical
artery shows reversed end
diastolic flow in a fetus with
IUGR in the third trimester.
Abnormal placentation is a
significant risk factor for
IUGR. (Right) Pulsed
Doppler ultrasound of the
middle cerebral artery in
another fetus with IUGR and
abnormal UA Doppler shows
low resistance flow, which
implies "head sparing" and
significant fetal compromise.

I ~;

17l

"_y_D_R_O_P_S

1

_

32

Sagittal ultrasound shows immune hydrops from red cell
isoimmunization.
The presence
of anasarca (open
arrow), pleural effusion (arrow) and ascites (curved
arrow) are diagnostic of hydrops.

Clinical photograph shows a fetus with trisomy 2 7 and
hydrops. Diffuse facial and truncal anasarca is seen. The
abdomen
is distended
from ascites. Nonimmune
hydrops is associated with aneuploidy

I TERMI NOlOGY
Abbreviations

and Synonyms
•

• Hydrops fetalis
• Erythroblastosis fetalis

Definitions
• Excessive fetal body fluid
• Immune hydrops (10%)
o Hemolytic disease ~ fetal anemia
• Nonimmune hydrops (90%)
o Any other cause besides immune

IIMAGING

•

FINDINGS

•

General Features
• Best diagnostic clue
o Fluid accumulation in 2 or more body cavities
o Anasarca + body cavity fluid

Ultrasonographic

•

Findings

• Body cavity fluid collections
o Ascites
• Anechoic fluid
• Best seen between liver and abdominal wall
o Bilateral pleural effusions
• Hydrothorax

•

o Pericardial effusion
• Associated with cardiac defects
• < 2 mm considered physiologic
Anasarca
o Skin/subcutaneous edema
• Hypoechoic fluid
• Scalp edema often first sign
o Anasarca + cystic hygroma
• Turner syndrome
• Trisomy 21 (T21)
Placentomegaly
o From placental edema
o Placenta thickness> 40 mm
o More often with immune hydrops
Amniotic fluid abnormalities
o Polyhydramnios
• More common with immune hydrops
• May be early isolated finding
o Oligohydramnios
• More often seen with fetal anomalies
Fetal cardiac abnormalities
o 22% of nonimmune hydrops with cardiac defect
• Poor contractility ~ heart failure ~ hydrops
o Tachyarrhythmia
• > 180-200 bpm
Non-cardiac causes of high-output cardiac failure
o Vascular fetal mass
o Placental mass (chorioangioma)

DDx: Hydropic Fetus

Isolated Ascites

Chylothorax

Pericardial Effusion

Redundant Skin

~

H_Y_D_R_O_P_S
Key Facts

Terminology
• Excessive fetal body fluid
• Immune hydrops (l0(}6)
• onimmune hydrop (90%)

Imaging Findings
•
•
•
•
•
•
•

A cites
Bilateral pleural effu ions
Skin/subcutaneou
dema
Placentomegaly
Polyhydramnios
MCA Doppler screening for fetal anemia
M-mode to rule out tachyarrhythmia

Top Differential

Diagnoses

• I olated a cite
• hylothorax
o Twin-twin transfusion syndrome
• Aneuploidy and fetal syndromes
o 16% of nonimmune hydrops
o Turner syndrome
• Hydrops + cystic hygroma

• Isolated pericardia I effusion
• Redundant
kin

Pathology
•
•
•
•
•
•
•

Turner yndrome (45,XO)
Tri omies: 21 > 18, 13
Maternal Rh s nsitization
Atypical antibodies
Fetal anemia lead to hydrops
Variety of cause for nonimmune hydrops
0 underlying cause found in 50-80% of cas

Clinical Issues
• I Iydrops + fetal anomaly nearly 100(}()fatal

Diagnostic Checklist
• Look for treatable causes of hydrop

o Look for additional fluid collections when one
collection seen
o Search for cause of nonimmune hydrops
• M-mode to rule out tachyarrhythmia
• Fetal anomalies

0'1'21

• May present with hydrops
• Other markers often seen
o Trisomy 18 and trisomy 13
• Less likely to present with hydrops
• Severe intrauterine growth restriction (IUGR)
• Other typical anomalies often seen
o Noonan syndrome
• Normal chromosomes
• Phenotypic features of Turner syndrome
o Other hereditary and metabolic syndromes
• Family history helpful
• First trimester hydrops
o Increased nuchal translucency + anasarca
o Pleural effusion and ascites can be seen
o Highly associated with aneuploidy
• Turner, '1'21 most common
• Middle cerebral artery (MCA) Doppler
o t MCA peak systolic velocity (PSV)
• Non invasive way to screen for anemia
• Red cell alloimmunization
screening
o MCA Doppler technique
• MCA easily seen with color Doppler
• MCA sampled near origin
• 0° Doppler angle necessary
• Peak systolic velocity (PSV) compared with
gestational age
• > 1.5 multiples of median considered abnormal
o Abnormal MCA PSV
• Anemia confirmed with cordocentesis
• Treatment with in utero transfusion

Imaging Recommendations
• Best imaging tool
o MCA Doppler screening for fetal anemia
o Careful ultrasound to detect early hydrops
• Protocol advice

I DIFFERENTIAL DIAGNOSIS
Isolated ascites
• Urinary ascites
o Other signs of obstruction often seen
• Hydronephrosis
• Ureteral distention
• Distended bladder
• Gastrointestinal perforation
o Meconium peritonitis
o Ascitic fluid often complex
• Better prognosis than hydrops

Chylothorax
• Unilateral pleural effusion
o Thoracic duct anomaly
• Can progress to hydrops
• Associated with '1'21 and Turner syndrome

Isolated pericardial effusion
• Often a transient normal finding
o < 2 mm considered normal
• Associated with cardiac abnormality
o Often early sign of hydrops

Redundant skin
• Lethal skeletal dysplasia
o Extremely short bones
o Excess echogenic skin
• Macrosomia
o Excessive subcutaneous fat
o More echogenic than edema

I r17
~

171

I

~

'-p-A,-r-H-O-L-O-G-y-------------

"_YD_R_O_P_S

.

0

General Features

0

• Genetics
o Turner syndrome (45,XO)
o Trisomies: 21 > 18, 13
• Etiology
o Maternal Rh sensitization
• Maternal lack of D antigen
• Fetal D antigen causes antibody response
• Maternal antibodies attack fetal red blood cells
0
• Sensitization 2 to fetal-maternal hemorrhage
• < 1 cc fetal cells can lead to anti-D antibody
o Atypical antibodies
• Non-D antigen causes immunization
• Anti-Kell, anti-c, anti-e most often detected
• Becoming more common
o Fetal anemia leads to hydrops
• Anemia from any cause
• t Extramedullary erythropoiesis
• Hepatosplenomegaly
• t Cardiac output ~ cardiac failure
o Nonimmune hydrops and infection
• Infection ~ myocarditis, anemia
• Parvovirus most common
o Variety of causes for nonimmune hydrops
• Primary cardiac anomaly
• Large thoracic mass displaces heart
• High-output heart failure from extrathoracic mass
• Heart failure from tachyarrhythmia
• Lymphatic obstruction
• Maternal-fetal hemorrhage ~ anemia
o No underlying cause found in 50-80% of cases
• Epidemiology
o Rh negative
• 15% Caucasians
• 8% African-American
o Rh sensitization
• 6.7:1,000 births
• 20-25% develop fetal anemia if untreated
• 50% of anemic fetuses develop hydrops
o Non-D antibody sensitization
• Develop in 1% after blood transfusion
• 2% immune hydrops cases
o Nonimmune hydrops in 1:3,000 births
• 22% cardiac abnormality
• 16% aneuploidy
• 10% alpha thalassemia
• 6% twin-twin transfusion
• 5% congenital infection
• Associated abnormalities: Cystic hygroma

0

IClINICALISSUES

• Hydrops + fetal anomaly nearly 100% fatal
• Hydrops + tachyarrhythmia
0 Treatable with good prognosis
• Fetal anemia
0 75% survival if treated after onset of hydrops
0 95% survival if treated before onset of hydrops
• MCA PSV can identify anemic fetus

Treatment
• Rh immunoglobulin
(RhoGAM)
0 Blocks antigen sites on fetal blood cells
0 Given after every pregnancy/procedure
0 Only useful for D antibodies
• Atypical antibody isoimmunization
0 No prophylactic
immunoglobulins
yet
• Identify anemia prior to onset of hydrops
0 MCA Doppler
0 Treatment
with in utero transfusion
• Immune hydrops
0 Treat anemia with in utero transfusion
• Nonimmune hydrops
0 Treat cause if possible
• Tachyarrhythmia
treated pharmacologically
0 Anemia from any cause
• In utero transfusion

I DIAGNOSTIC

CHECKLIST

Consider
• Hydrops is a nonspecific ultrasound diagnosis
o Immune causes ruled out with history and serology
o Infectious causes often ruled out by serology

Image Interpretation

Pearls

• Look for treatable causes of hydrops
o Tachyarrhythmia,
anemia
• Look for causes of nonimmune hydrops
o Fetal anomalies, aneuploidy

I SELECTED
1.

2.

REFERENCES

MaTiG: Middle cerebral artery peak systolic velocity: is it
the standard of care for the diagnosis of fetal anemia? J
Ultrasound Med. 24(5):697-702, 2005
Ganapathy R et at: Natural history and outcome of
prenatally diagnosed cystic hygroma. Prenat Diagn.
24(12):965-8, 2004

3.

Has R:Non-immune hydrops fetalis in the first trimester: a
review of 30 cases. Clin Exp Obstet Gynecol. 28(3):187-90,

4.

Ismail KMet al: Etiology and outcome of hydrops fetalis. J
Matern Fetal Med. 10(3):175-81, 2001
Jenderny J et al: Increased nuchal translucency, hydrops
fetalis or hygroma colli. A new test strategy for early fetal
aneuploidy detection. Fetal Diagn Ther. 16(4):211-4,2001
IsakarosJ et al: Outcome of nonimmune hydrops fetalis
diagnosed during the first half of pregnancy. Obstet
Gynecol. 3:321-5, 1997

2001

5.

Presentation
• Most common signs/symptoms
o Large for dates
• Polyhydramnios

• Large fetus from hydrops
Exposure to parvovirus
Red cell alloimmunization
Cystic hygroma

Natural History & Prognosis

Staging, Grading or Classification Criteria
• Immune hydrops
• Nonimmune hydrops

_

6.

________

~---------------~

H_y_D_R_O_P_S

1

8E7
35

I IMAGE GALLERY
Typical
(Left) Axial ullrasound shows
bilateral small pleural
effusions (arrows) as an
isolated finding at 18 weeks.
(Right) Coronal oblique
ultrasound in the same fetus
6 weeks later shows full
blown hydrops. Skin edema
(open arrows), large pleural
effusions (curved arrows)
and ascites (arrow) have
developed. We were unable
to find a cause for hydrops in
this case. Many nonimmune
hydrops cases are
unexplained.

Typical
(Left) Coronal ultrasound
shows bilateral pleural
effusions (arrows) in a fetus
with late onset hydrops of
unknown etiology. The lungs
(open arrows) are
surrounded by anechoic
serous pleural fluid. (Right)
Frontal radiograph after
delivery shows bilateral
pleural effusions (arrows)
and skin edema (open
arrows). A small amount of
ascites was also present. This
neonate did fine after
thoracentesis.

Typical
(Left) Axial ultrasound shows
placentomegaly (arrows)
and polyhydramnios (curved
arrow) in a pregnancy with
immune hydrops. The
placenta measures 7 cm
thick. (Right) Axial and
sagittal ultrasound through
the fetal head and back
show extensive anasarca
(arrows) and cystic hygroma
(open arrows) in a fetus with
trisomy 21. Cystic hygroma
is highly associated with
both hydrops and
aneuploidy.

INDEX
A
Abdomen, 7-6 to 7-25
acute, in pregnancy, 18-48 to 18-50, 18-Sli
calcifications
meconium peritonitis/pseudocyst vs., 8-21
toxoplasmosis vs., 8-34i, 16-8i
intra-abdominal neoplasms, ovarian cysts vs.,
9-70
trauma to, acute abdomen vs., 18-49
Abdominal cysts
duodenal atresia vs., 8-10i, 8-11
jejunal/ileal atresia vs., 8-15
ovarian cysts vs., 9-68i, 9-69
umbilical cord aneurysm vs., 11-18i, 11-19
urachal anomalies vs., 9-S6i
Abdominal ectopic pregnancy, 1-26 to 1-27
Abnormal cord Doppler ultrasound, 11-6 to 11-8,
11-9i
Abortion, spontaneous, cervical ectopic pregnancy
vs., 1-22i, 1-23
Abscess, incidental ovarian mass vs., 18-35
Absent nasal bone, 4-10 to 4-12, 4-13i
Acalvaria
amniotic band syndrome vs., 15-5
atelencephaly/aprosencephaly vs., 2-87
Acampomelic campomelic dysplasia, campomelic
dysplasia vs., 10-16
Acetylcholine receptor (AChR) antibodies, in
arthrogryposis/akinesia sequence, 10-55
Achondrogenesis, 10-2 to 10-4, lO-Si
differential diagnosis, 10-2i, 10-3
micromelia vs., 10-11
osteogenesis imperfecta vs., IO-20i, 10-21
thanatophoric dysplasia vs., IO-26i, 10-27
type lA, hypophosphatasia vs., 1O-18i, 10-18-19
warfarin (coumadin) embryopathy vs., 18-46i
Achondroplasia, 10-6 to 10-8, 1O-9i
differential diagnosis, IO-6i, 10-7
homozygous
achondrogenesis vs., 10-3
achondroplasia vs., 10-7
thanatophoric dysplasia vs., 10-27
warfarin (coumadin) embryopathy vs., 18-46i
Acrania, 2-10 to 2-11
amniotic band syndrome vs., 15-5

anencephaly/exencephalyvs.,
2-6i, 2-7
atelencephaly/aprosencephaly vs., 2-86i, 2-87
differential diagnosis, 2-10i, 2-10 to 2-11
occipital encephalocele vs., 2-12i, 2-13
Acro-dermato-ungual-lacrimal- tooth syndrome,
ectrodactylyvs.,10-53
Acute abdomen, in pregnancy, 18-48 to 18-50,
18-Sli
Adenoma, hemorrhagic, HELLPsyndrome vs.,
18-60i,18-61
Adenomyoma, focal, leiomyoma vs., 18-11
Adenomyosis
cervical ectopic pregnancy vs., 1-28i, 1-28 to
1-29
focal, leiomyoma vs., 18-11
Adnexal mass
incidental, tubal ectopic pregnancy vs., 1-15 to
1-16
non-ovarian origin, incidental ovarian mass vs.,
18-35
solid, leiomyoma vs., 18-11
without torsion, adnexal/tuboovarian torsion
vs'! 18-38i, 18-39
Adnexal torsion. See Torsion, adnexal/tuboovarian.
Adrenal glands
hemorrhage, neuroblastoma vs., 9-42i, 9-43
lesions, mesoblastic nephroma vs., 9-39
masses, renal developmental variants vs., 9-6i,
9-7

normal, renal developmental variants vs., 9-6i,
9-7

Agenesis. See specific anatomic part.
Agnathia, micrognathia vs., 4-14i
Aicardi syndrome, 15-2 to 15-3
Akinesia sequence. See Arthrogryposis, akinesia
sequence.
Allantoic cyst
omphalocele vs., 7-6i, 7-7
umbilical cord aneurysm vs., 11-19
Alloimmune syndromes, minor antigen, Rh
incompatibility vs., 18-66
Alobar holoprosencephaly. See Holoprosencephaly,
alobar.
Ambiguous genitalia, 9-58 to 9-60, 9-6li
differential diagnosis, 9-S8i, 9-59 to 9-60
hypospadias vs., 9-62

INDEX

II

Amelia, 10-10 to 10-12, lO-13i
Amnion, increased nuchal translucency vs., 1-32i,
1-34
Amniotic band syndrome, 15-4 to 15-6, 15-7i
acrania vs., 2-10
amelia vs., 10-10i, 10-11
anencephaly/exencephaly vs., 2-7
body stalk anomaly vs., 7-14i, 7-15
chorioamniotic separation vs., 12-10i, 12-11
circumvallate placenta vs., 12-24i, 12-25
cleft lip, cleft palate vs., 4-6i, 4-7
cloacal exstrophy vs., 7-20
clubfoot vs., 1O-30i, 10-31
differential diagnosis, 15-4i, 15-5 to 15-6
ectrodactyly vs., 1O-52i, 10-53
epignathus vs., 4-23
frontal encephalocele vs., 2-16, 2-16i
gastroschisis vs., 7-lOi, 7-11
lymphangioma vs., 5-28i, 5-29
micrognathia vs., 4-15
occipital encephalocele vs., 2-13
OElS syndrome vs., 7-22i
omphalocele vs., 7-8
orbital tumors vs., 4-42
pentalogy of Cantrell vs., 7-24i, 7-25
radial ray malformation vs., 10-38i, 10-39
rockerbottom foot vs., 10-34i, 10-35
sandal gap foot vS., 1O-36i, 10-37
spina bifida vs., 3-6i, 3-7
syndactyly vs., 10-47
uterine synechia vs., 18-14i
Amniotic fluid, normal
oligohydramnios vs., 17-6i, 17-7
polyhydramnios vs., 17-2i, 17-3
Amniotic sheets, amniotic band syndrome vs., 15-5
to 15-6
Amputation defects. See Amniotic band syndrome.
Amyoplasia, arthrogryposis/akinesia sequence vs.,
10-54i, 10-55
Anal atresia, 8-18 to 8-19
ascites in, 8-27
differential diagnosis, 8-18i, 8-18 to 8-19
duodenal atresia vs., 8-10i, 8-11
enterolithiasis with, echogenic bowel vs., 8-2i,
8-4

jejunal/ileal atresia vs., 8-14i, 8-15
VACTERLassociation vs., 15-40i, 15-41
Anembryonic pregnancy, 1-6 to 1-8, 1-9i
Anemia, fetal, arteriovenous fistula vs., 2-99
Anencephaly, 2-6 to 2-8, 2-9i
acrania vS., 2-10, 2-10i
amniotic band syndrome vs., 15-5
atelencephaly/aprosencephaly
vs., 2-86i, 2-87
differential diagnosis of, 2-6i, 2-7
ear anomalies vs., 4-26i

microcephaly vs., 2-84i, 2-85
occipital encephalocele vs., 2-12i, 2-13
twin reversed arterial perfusion vs., 13-22i, 13-23
Aneuploidy
Cornelia de Lange syndrome vs., 15-14
differential diagnosis, 18-52i, 18-53
Fryns syndrome vs., 15-18
hydantoin syndrome vS., 18-42
oligohydramnios due to, biophysical profile of,
17-21
Pierre Robin syndrome vs., 15-26i
Smith-Lemli-Opitz syndrome vs., 15-32i
symmetric, fetal alcohol syndrome vs., 18-40
valproic acid syndrome vS., 18-42
Aneurysm
foramen ovale, 6-8 to 6-9
umbilical cord. See Umbilical cord aneurysm.
Anophthalmia
hypertelorism vs., 4-38i, 4-40
hypotelorism vs., 4-35
Anorectal atresia. See Anal atresia.
Antley-Bixler syndrome, craniosynostosis vs., 2-91
Antral web/atresia, duodenal atresia vs., 8-10i, 8-11
Aortic arch, interrupted, aortic stenosis vs., 6-35
Aortic atresia
hypertrophic cardiomyopathy vs., 6-63
rhabdomyoma vs., 6-81
truncus arteriosus vs., 6-58i, 6-59
Aortic coarctation, 6-30 to 32, 6-33i
aortic stenosis vs., 6-34i, 6-35
differential diagnosis, 6-30i, 6-31
hypoplastic left heart vs., 6-26i, 6-27
Aortic stenosis, 6-34 to 36, 6-37i
coarctation of aorta vs., 6-30i, 6-31
differential diagnosis, 6-34i, 6-35
dilated cardiomyopathyvs., 6-67
hypertrophic cardiomyopathy vs., 6-63
rhabdomyoma vs., 6-81
severe, hypoplastic left heart vs., 6-26i, 6-27
Apert syndrome, 15-8 to 15-9
Carpenter syndrome vS., 15-12i
craniosynostosis vs., 2-91
differential diagnosis, 15-8i, 15-8 to 15-9
syndactyly vs., 10-47
Appendicitis
acute abdomen vs., 18-48
adnexal/tuboovarian torsion vs., 18-38i, 18-39
ovarian vein thrombosis vs., 18-64i, 18-65
ruptured, incidental ovarian mass vs., 18-34i,
18-35
Aprosencephaly, 2-86 to 2-88, 2-89i
alobar holoprosencephaly vs., 2-43
anencephaly/exencephaly vs., 2-7
differential diagnosis, 2-86i, 2-87
hydranencephaly vs., 2-57

INDEX
microcephaly vs., 2-85
Aqueductal stenosis, 2-22 to 2-24, 2-25i
alobar holoprosencephaly vs., 2-43, 2-46i, 2-47
Chiari II malformation vs., 2-18i, 2-19
differential diagnosis, 2-22i, 2-23 to 2-24
hydranencephaly vs., 2-S6i, 2-57
mild ventriculomegaly vs., 2-40i
semilobar holoprosencephaly vs., 2-46i, 2-47
x-linked, radial ray malformation vs., 10-39
Arachnoid cyst, 2-72 to 2-74, 2-7Si
alobar holoprosencephaly vs., 2-42i, 2-43
arteriovenous fistula vs., 2-98i
central nervous system tumors vs., 2-102i, 2-103
classic Dandy-Walker continuum vs., 2-26i, 2-27
differential diagnosis, 2-72i, 2-73
encephalomalacia vs., 2-60i, 2-61
glioependymal cyst vs., 2-76i, 2-77
mega-cisterna magna vs., 2-32i, 2-33
schizencephaly vs., 2-81
variant Dandy-Walker continuum vs., 2-30i,
2-31
vein of Galen malformation vs., 2-94i, 2-95
Arnold-Chiari malformation. See Chiari II
malformation.
ARPKD.See Polycystic kidney disease, autosomal
recessive.
Arrhythmias. See Dysrythmias.
Arteriovenous fistula, 2-98 to 2-100, 2-10li
congenital dural, vein of Galen malformation
vs., 2-94i, 2-95
differential diagnosis, 2-98i, 2-99
Arthrogryposis, akinesia sequence, 10-54 to 10-57,
10-S8i
caudal regression syndrome vs., 3-14i, 3-15
differential diagnosis, 10-S4i, 10-55 to 10-56
distal arthrogryposis vs., 10-55
kyphosis/scoliosis vs., 3-19
multiple pterygium syndrome vs., 10-S8i, 10-59
oligohydramnios due to, biophysical profile of,
17-21
radial ray malformation vs., 10-38i, 10-39
sirenomeli a vs., lS-28i, 15-29
VACTERLassociation vs., lS-40i, 15-42
Ascites, 8-26 to 8-28, 8-29i
differential diagnosis, 8-26i, 8-27 to 8-28
genitourinary, 8-27
isolated, hydrops vs., 17 -32i, 17-33
meconium peritonitis/pseudocyst vs., 8-21
parvovirus B19 infection vs., 16-7
Asphyxiating thoracic dysplasia, 10-14 to 10-15
differential diagnosis, 1O-14i, 10-14 to 10-15
polydactyly vs., 10-43
short rib-polydactyly syndrome vs., 1O-24i,
10-25
Atelencephaly, 2-86 to 2-88, 2-89i

alobar holoprosencephaly vs., 2-43
anencephaly/exencephaly vs., 2-7
differential diagnosis, 2-86i, 2-87
hydranencephaly vs., 2-57
microcephaly vs., 2-84i, 2-85
Atelosteogenesis
micromelia vs., 10-11
type II, achondrogenesis vs., 10-3
Atresia. See specific anatomic location.
Atrial contractions, premature
blocked, bradyarrhythmia vs., 6-76i, 6-77
irregular rhythm vs., 6-70
Atrial fibrillation, tachyarrhythmia vs., 6-73
Atrial flap, reversed, foramen ovale aneurysm vs.,
6-8i
Atrial flutter
irregular rhythm vs., 6-70i, 6-71
tachyarrhythmia vs., 6-72i, 6-73
Atrial isomerism. See also Heterotaxy syndromes.
left, situs inversus vs., 6-14
right, situs inversus vs., 6-14
Atrial septal defect, large, atrioventricular septal
defect vs., 6-23
Atrioventricular block, partial, bradyarrhythmia
vs., 6-76i, 6-77
Atrioventricular septal defect, 6-22 to 24, 6-2Si
complete, ventricular septal defect vs., 6-20i,
6-20
differential diagnosis, 6-22i, 6-23
Ebstein anomaly, tricuspid dysplasia vs., 6-42i,
6-43
echogenic cardiac focus vs., 6-6i, 6-7
partial
atrioventricular septal defect vs., 6-23
ventricular septal defect vs., 6-20i, 6-20
primum, atrioventricular septal defect vs., 6-22i,
6-23
unbalanced, single ventricle vs., 6-48i
unbalanced left dominant, tricuspid atresia vs.,
6-44i,6-45
Autosomal dominant polycystic kidney disease. See
Polycystic kidney disease, autosomal
dominant.
Autosomal recessive polycystic kidney disease. See
Polycystic kidney disease, autosomal recessive.

B
Bardet-Biedl syndrome
Carpenter syndrome vs., 15-13
polydactyly vs., 10-44
Barnes syndrome, asphyxiating thoracic dysplasia
vs., 10-15
Battledore placenta, 12-26 to 12-27
differential diagnosis, 12-26i, 12-26 to 12-27

iii

INDEX

IV

velamentous cord vs., 12-16i, 12-16 to 12-17
Beckwith-Wiedemann syndrome, 15-10 to 15-15-11
autosomal recessive polycystic kidney disease vs.,
9-35
differential diagnosis, lS-lOi
hepatic tumors vs., 8-43
hepatomegaly/splenomegaly vs., 8-39
macrosomia vs., 17-18i
mesoblastic nephroma vs., 9-38i, 9-39
renal enlargement due to, 9-11
Bicornuate uterus. See Uterus, bicornuate.
Biliary disease, acute abdomen vs., 18-48 to 18-49
Binder syndrome, warfarin (coumadin)
embryopathy vs., 18-46
Biophysical profile, 17-20 to 17-22, 17-23i
Bladder
absent
bladder exstrophy vs., 7-18
renal agenesis vs., 9-26i, 9-27
exstrophy of. See Bladder exstrophy.
full, placenta previa vs., 12-12i, 12-13
"Hutch" diverticulum of, ureterocele vs., 9-54
mass of, ureterocele vs., 9-53
obstruction of. See Bladder outlet obstruction.
rupture of, renal agenesis vs., 9-28
Bladder exstrophy, 7-18 to 7-19
absent bladder vs., 7-18
cloacal exstrophy vs., 7-20i
differential diagnosis, 7-18i, 7-18 to 19
gastroschisis vs., 7-11
omphalocele vs., 7-7
renal agenesis vs., 9-28
Bladder outlet obstruction
mild pelviectasis vs., 9-15
oligohydramnios due to, biophysical profile of,
17-20i,17-21
urachal anomalies vs., 9-56
ureteropelvic junction obstruction vs., 9-19
Blake pouch cyst, persistent
classic Dandy-Walker continuum vs., 2-27
variant Dandy-Walker continuum vs., 2-31
Body stalk anomaly (limb-body-wall complex), 7-14
to 7-16, 7-17i
acrania vs., 2-10
amniotic band syndrome vs., lS-4i, 15-5
cloacal exstrophy vs., 7-20
differential diagnosis, 7-14i, 7-15
gastroschisis vs., 7-10i, 7-11
occipital encephalocele vs., 2-13
OEIS syndrome vs., 7-22
omphalocele vs., 7-8
pentalogy of Cantrell vs., 7-24i
Bone tumor, of skull vault, scalp masses vs., 4-45

Bowel
dilated
enteric duplication cyst vS., 8-31
ovarian cysts vS., 9-69
echogenic. See Echogenic bowel.
herniation. See Gut herniation, physiologic.
ischemia of, cystic fibrosis vS., lS-16i
obstruction, acute abdomen vS., 18-49
perforation, acute abdomen vs., 18-49
Bradyarrhythmia, 6-76 to 6-78, 6-79i
differential diagnosis, 6-76i, 6-77
parvovirus B19 infection vs., 16-6i
transient sinus, bradyarrhythmia vs., 6-76i, 6-77
Brain, hemorrhagic metastases, choriocarcinoma
vs.,12-45
Brain and skull anomalies, 2-6 to 2-105
Branchial cyst, goiter vs., 4-53
Bronchogenic cyst, congenital diaphragmatic
hernia vs., S-8i, 5-9
Bronchopulmonary sequestration, 5-16 to 5-18,
S-19i
with cystic adenomatoid malformation (hybrid
lesion)
congenital diaphragmatic hernia vs., 5-9
differential diagnosis, 5-13, 5-17
cystic adenomatoid malformation vs., S-12i,
5-13
differential diagnosis, S-16i, 5-17
teratoma of chest vs., 5-25
tracheal atresia vs., S-26i, 5-27

c
Caliectasis, physiologic, maternal hydronephrosis
vs.,18-57
Campomelic dysplasia, 10-16 to 10-17
differential diagnosis, 10-16i, 10-16 to 10-17
osteogenesis imperfecta vs., 1O-20i, 10-21
thanatophoric dysplasia vs., 10-27
Cantrell's pentalogy. See Pentalogy of Cantrell.
Cardiac dextroposition. See Dextrocardia.
Cardiac focus, echogenic, 6-6 to 6-7
differential diagnosis, 6-6i, 6-7
rhabdomyoma vs., 6-80i, 6-81
Cardiac malformations. See Heart defects,
congeni tal.
Cardiomyopathy
aortic stenosis vs., 6-34i, 6-35
dilated, 6-66 to 6-68, 6-69i
hypertrophic, 6-62 to 6-64, 6-6Si
differential diagnosis, 6-62i, 6-63
rhabdomyoma vs., 6-80i, 6-81
Cardiosplenic syndromes, 6-16 to 6-18, 6-19i
Cardiovascular anomalies/disorders, 6-6 to 6-83
Carpenter syndrome, 15-12 to 15-13

INDEX
Apert syndrome vs., lS-8i
craniosynostosis vs., 2-91
differential diagnosis, lS-12i, 15-12 to 15-13
polydactyly vs., 10-43
syndactyly vs., lO-46i, 10-47
thanatophoric dysplasia vs., 10-27
Cartilage oligomeric matrix protein (COMP)associated disorders, achondroplasia vs., 10-7
Caudal dysplasia sequence, diabetic embryopathy
vs., 18-53
Caudal regression sequence, 3-14 to 3-16, 3-17i
arthrogryposis/akinesia sequence vs., lO-S4i,
10-56
differential diagnosis, 3-14i, 3-15
kyphosis/scoliosis vs., 3-18i, 3-19
sirenomelia vs., 15-29
Cavum septi pellucidi, absent, 2-54 to 2-55
differential diagnosis, 2-S4i, 2-54 to 2-55
semilobar/lobar holoprosencephaly vs., 2-47
CCAM. See Cystic adenomatoid malformation.
Central nervous system tumors, 2-102 to 2-104,
2-lOSi
Cephalocele. See Encephalocele.
Cerebellar hypoplasia, rhombencephalosynapsis
vs., 2-34
Cerebellum, normal early development of, megacisterna magna vs., 2-33
Cervical canal, hyperechoic, incompetent cervix vs.,
18-2i,18-3
Cervical ectopic pregnancy, 1-22 to 1-24, 1-2Si
cesarean section scar ectopic vs., 1-28i
differential diagnosis, 1-22i, 1-23
Cervical hyperextension, iniencephaly vs., 3-10i,
3-11
Cervical masses
carcinoma, cervical ectopic pregnancy vs., 1-23
cervical ectopic pregnancy vs., 1-22i, 1-23
fibroid tumor, cervical ectopic pregnancy vs.,
1-23
prolapsed polyp, cervical ectopic pregnancy vs.,
1-22i,l-23
Cervical neuroblastoma, goiter vs., 4-53
Cervical teratoma, 4-56 to 4-58, 4-S9i
cystic hygroma vs., 4-48i, 4-49 to 4-50
differential diagnosis, 4-S6i, 4-57
epignathus vs., 4-23
goiter vs., 4-S2i, 4-53
iniencephaly vs., 3-lOi, 3-11
Cervix, incompetent, 18-2 to 18-4, 18-Si
Cesarean section scar, prominent, cervical ectopic
pregnancy vs., 1-28i
Cesarean section scar ectopic pregnancy, 1-28 to
1-29
cervical ectopic pregnancy vs., 1-22i, 1-23
differential diagnosis, 1-28i, 1-28 to 1-29

CHARGEassociation, VACTERLassociation vs.,
15-42
Chest. See also Thoracic anomalies.
abnormalities of, pulmonary hypoplasia vs., 5-6
masses
pleural effusion vs., S-20i, 5-21
pulmonary hypoplasia vs., 5-5
teratoma, 5-24 to 5-25
Chest wall, normal musculature of, pleural effusion
vs.,5-21
Chiari II malformation, 2-18 to 2-20, 2-2li
absent cavum septi pellucidi vs., 2-55
aqueductal stenosis vs., 2-23
craniosynostosis vs., 2-90i
differential diagnosis, 2-18i, 2-19
Joubert syndrome vs., lS-2Oi
sacrococcygeal teratoma vs., 3-22i, 3-23
Choledochal cyst, 8-40 to 8-41
differential diagnosis, 8-40i, 8-40 to 8-41
duodenal atresia vs., 8-10i, 8-11
enteric duplication cyst vs., 8-30i, 8-31
meconium peritonitis/pseudocyst vs., 8-21
mesenteric cyst vs., 8-33
ovarian cysts vs., 9-69
umbilical cord aneurysm vs., 11-18i, 11-19
Chondrodysplasia punctata, warfarin (coumadin)
embryopathy vs., 18-46i
Chondroectodermal dysplasia. See Ellis van Creveld
syndrome.
Chorioamniotic separation, 12-10 to 12-11
amniotic band syndrome vs., 15-6
differential diagnosis, 12-10i, 12-11
increased nuchal translucency vs., 1-32i, 1-34
peri gestational hemorrhage vs., 1-10i, 1-11
uterine synechia vs., 18-15
Chorioangioma, 12-34 to 12-36, 12-37i
differential diagnosis, 12-34i, 12-35 to 12-36
leiomyoma vs., 18-lOi, 18-11
placental abruption vs., 12-18i, 12-19
placental sonolucencies vs., 12-6i, 12-7
Choriocarcinoma, 12-44 to 12-46, 12-47i
Choroid plexus cyst, 2-68 to 2-70, 2-7li
central nervous system tumors vs., 2-103
differential diagnosis, 2-68i, 2-69 to 2-70
isolated, trisomy 18 vs., 14-7
vein of Galen malformation vs., 2-95
Choroid plexus papilloma
choroid plexus cyst vs., 2-68i, 2-69
intracranial hemorrhage vs., 2-64i, 2-65
Chromosome 3q duplication, Cornelia de Lange
syndrome vs., 15-14
Chromosome lOq deletion, Smith-Lemli-Opitz
syndrome vs., 15-33
Chromosome 13q deletion syndrome, radial ray
malformation vs., 10-39

v

INDEX

vi

Chromosome 22q 11 deletion, fetal alcohol
syndrome vs., 18-4Oi
Chromosome abnormalities, 14-2 to 14-23
Chromosome aneuploidy. See Aneuploidy.
Chylothorax, hydrops vs., 17-32i, 17-33
Chylous ascites, congenital, ascites vs., 8-28
Circumvallate placenta, 12-24 to 12-25
differential diagnosis, 12-24i, 12-24 to 12-25
uterine synechia vs., 18-14i
Cisterna magna. See Mega-cisterna magna.
Cleft lip, palate, 4-6 to 4-8, 4-9i
amniotic band syndrome vs., 15-5
differential diagnosis, 4-6i, 4-7
ear anomalies vs., 4-26i, 4-28
hydantoin syndrome vs., 18-42i
isolated cleft palate, Pierre Robin syndrome vs.,
15-26i
midface anomalies vs., 4-30i, 4-31
valproic acid syndrome vs., 18-42i
Cleft sternum, pentalogy of Cantrell vs., 7-24
Clinodactyly, 10-50 to 10-52, 1O-S3i
Clitoromegaly, hypospadias vs., 9-62i
Cloacal exstrophy, 7-20 to 7-21
bladder exstrophy vs., 7-18i
body stalk anomaly vs., 7-15
differential diagnosis, 7-20i
gastroschisis vs., 7-10i, 7-11
GElS syndrome vs., 7-22
omphalocele vs., 7-7
Cloacal malformation
with perforation, ascites vs., 8-27
posterior urethral valves vs., 9-46i, 9-47
Clubfoot, 10-30 to 10-32, 1O-33i
arthrogryposis/akinesia sequence vs., 10-S4i,
10-56
differential diagnosis, 10-30i, 10-31
rockerbottom foot vs., 10-34i, 10-35
Coagulopathy, HELLPsyndrome vs., 18-60i, 18-61
Coarctation of aorta, 6-30 to 32, 6-33i
aortic stenosis vs., 6-34i, 6-35
differential diagnosis, 6-30i, 6-31
hypoplastic left heart vs., 6-26i, 6-27
Collagen abnormalities, type I, achondroplasia vS.,
10-7
Colon
normal, jejunal/ileal atresia vs., 8-15
normal third trimester, anal atresia vs., 8-18i,
8-18
Colonic atresia
ascites in, 8-27
duodenal atresia vs., 8-10i, 8-11
jejunal/ileal atresia vs., 8-14i, 8-15
Complete hydatidiform mole. See Hydatidiform
mole, complete.
Complex congenital heart disease, situs inversus vs.,
6-14i

Conception, retained products of. See Retained
products of conception.
Congenital anomalies. See specific organ, e.g.,
Heart defects, congenital.
Conjoined twins, 13-26 to 13-28, 13-29i
differential diagnosis, 13-26i, 13-27
monochorionic monoamniotic twins vs., 13lOi,13-11
twin reversed arterial perfusion vs., 13-22i, 13-23
Cornelia de Lange syndrome, 15-14 to 15-15
differential diagnosis, IS-l4i, 15-14 to 15-15
fetal alcohol syndrome vs., 18-4Oi
Fryns syndrome vs., lS-18i
Cornual pregnancy, tubal ectopic pregnancy vs., 114i, 1-15
Corpus callosum
agenesis, 2-36 to 2-38, 2-39i
absent cavum septi pellucidi vs., 2-S4i, 2-55
Aicardi syndrome vS., lS-2i
with interhemispheric cyst, schizencephaly
vs., 2-81
mild ventriculomegaly vs., 2-40
semilobar/lobar holoprosencephaly vs., 2-47
septo-optic dysplasia vS., 2-S0i, 2-51
dysgenesis, 2-S0i
Corpus luteum cyst, 18-24 to 18-25
differential diagnosis, 18-24i, 18-24 to 18-25
hemorrhagic, adnexal/tuboovarian torsion vs.,
18-38i, 18-39
hyperstimulation syndrome vs., 18-26i
incidental ovarian mass vs., 18-34
theca lutein cysts vS., 18-30i, 18-31
tubal ectopic pregnancy vs., 1-14i, 1-15
Cortical dysplasias, tuberous sclerosis vs., IS-36i,
15-37
Coumadin embryopathy. See Warfarin (coumadin)
embryopathy.
Craniosynostosis, 2-90 to 2-92, 2-93i
differential diagnosis, 2-90i, 2-91 to 2-92
isolated, craniosynostosis vS., 2-91
microcephaly vS., 2-84
postnatal, 2-91
Crouzon syndrome
Carpenter syndrome vs., 15-13
craniosynostosis vs., 2-91
Cryptorchidism
hydrocele vs., 9-64i, 9-65
hypospadias vs., 9-62i
unilateral, testicular torsion vs., 9-66i
Cyst(s)
abdominal. See Abdominal cysts.
allantoic
omphalocele vs., 7-6i, 7-7
umbilical cord aneurysm vs., 11-19
arachnoid. See Arachnoid cyst.

INDEX
benign functional, incidental ovarian mass vs.,
18-34 to 18-35
bronchogenic, congenital diaphragmatic hernia
vs., S-8i, 5-9
choledochal. See Choledochal cyst.
choroid plexus. See Choroid plexus cyst.
corpus luteum. See Corpus luteum cyst.
dermoid
epignathus vs., 4-23
frontal encephalocele vs., 2-16
theca lutein cysts vs., 18-30i, 18-31
duplication. See Duplication cyst.
glioependymal. See Glioependymal cyst.
hepatic, choledochal cyst vs., 8-40
intracranial, arteriovenous fistula vs., 2-99
lingual, macroglossia vs., 4-19
meconium pseudocyst. See Meconium
pseudocyst.
mesenteric. See Mesenteric cyst.
Nabothian
cervical ectopic pregnancy vs., 1-22i, 1-23
incompetent cervix vs., 18-2i, 18-3
nuchal, goiter vs., 4-53
ovarian. See Ovarian cysts.
paraovarian, incidental ovarian mass vs., 1834i,18-35
para pelvic, maternal hydronephrosis vs., 18-S6i,
18-58
persistent Blake pouch
classic Dandy-Walker continuum vs., 2-27
variant Dandy- Walker continuum vs., 2-31
renal. See Renal cysts.
theca lutein, 18-30 to 18-32, 18-33i
differential diagnosis, 18-30i, 18-31
hyperstimulation syndrome vs., 18-26i
incidental ovarian mass vs., 18-34
umbilical cord, 11-14 to 11-16, 11-17i
differential diagnosis, 11-14i, 11-15 to 11-16
omphalocele vs., 7-6i, 7-7
umbilical cord aneurysm vs., 11-18i, 11-19
urachal. See Urachal cyst.
Wharton jelly, omphalocele vs., 7-7
Cystadenocarcinoma, theca lutein cysts vs., 18-31
Cystadenoma
incidental ovarian mass vs., 18-35
theca lutein cysts vs., 18-30i, 18-31
Cystic adenomatoid malformation, 5-12 to 5-14,
S-ISi
bilateral, tracheal atresia vs., S-26i, 5-27
with bronchopulmonary sequestration (hybrid
lesion)
congenital diaphragmatic hernia vs., 5-9
differential diagnosis, 5-13, 5-17
bronchopulmonary sequestration vs., S-16i, 5-17
congenital, heterotaxy vs" 6-16i, 6-17
congenital diaphragmatic hernia vs., S-8i, 5-9

differential diagnosis, S-12i, 5-13
pleural effusion vs., S-20i, 5-21
teratoma of chest vs., S-24i, 5-25
Cystic dysplasia, oligohydramnios due to,
biophysical profile of, 17-20i, 17-21
Cystic fibrosis, 15-16 to 15-17
Cystic hygroma, 4-48 to 4-50, 4-5 Ii
cervical teratoma vs., 4-S6i, 4-57
differential diagnosis, 4-48i, 4-49 to 4-50
goiter vs., 4-53
increased nuchal translucency vs., 1-32i, 1-34
nuchal, lymphangioma vs., S-28i, 5-29
nuchal umbilical cord vs., 11-26i
occipital encephalocele vs., 2-13
polyhydramnios vs., 17-2i, 17-3
Rh incompatibility vs., 18-66i
scalp masses vs., 4-44i
twin reversed arterial perfusion vs., 13-22i, 13-23
Cystic masses
congenital diaphragmatic hernia vs., S-8i, 5-9
cystic adenomatoid malformation vs., 5-13
nuchal, goiter vs., 4-S2i, 4-53
Cytomegalovirus infection, 16-2 to 16-4, 16-Si
abdominal calcifications due to
gallstones vs., 8-34
meconium peritonitis/pseudocyst vs., 8-21
echogenic bowel in, cystic fibrosis vs., IS-16i
hepatic tumors vs., 8-43
hepatomegaly/splenomegaly vs., 8-38
parvovirus B19 infection vs., 16-6
toxoplasmosis vs., 16-8i
varicella infection vs., 16-1Oi

o
Dacryocystocele
hypotelorism vs., 4-36
orbital tumors vs., 4-42i
Dandy-Walker continuum
Aicardi syndrome vs., IS-2i
aqueductal stenosis vs., 2-23
arachnoid cyst vs., 2-72i, 2-73
Chiari II malformation vs., 2-18i, 2-19
classic, 2-26 to 2-28, 2-29i
differential diagnosis, 2-26i, 2-27
variant Dandy-Walker continuum vs., 2-30,
2-3Oi
Joubert syndrome vs., IS-2Oi
mega-cisterna magna vs., 2-32, 2-32i
mild ventriculomegaly vs., 2-4Oi
rhombencephalosynapsis vs., 2-34, 2-34i
variant, 2-30 to 2-31
classic Dandy-Walker continuum vs., 2-26i,
2-27
differential diagnosis, 2-30i, 2-30 to 2-31
mega-cisterna magna vs., 2-33

vii

INDEX

viii

Date of last menstruation, symmetric intrauterine
growth restriction vs., 17-10i, 17-11
De Lange syndrome. See Cornelia de Lange
syndrome.
Demise
with clot, Rh incompatibility vs., 18-66i
with hydropic placental degeneration, triploidy
vs., 14-18i, 14-19
with overlapping sutures, atelencephaly/
aprosencephaly vs., 2-87
twin. See Twin demise.
Dermoid cyst
epignathus vs., 4-23
frontal encephalocele vs., 2-16
theca lutein cysts vs., 18-30i, 18-31
Dermopathy, restrictive, arthrogryposis/akinesia
sequence vs., 10-56
Dextrocardia
isolated, situs inversus vs., 6-14 to 6-15
situs inversus vs., 6-14
Diabetic embryopathy, 18-52 to 18-54, 18-SSi
differential diagnosis, 18-S2i, 18-53
VACTERLassociation vs., 15-41
Diamniotic twins
with "absent" inter-twin membrane,
monochorionic mono amniotic twins vs.,
13-11
dichorionic, 13-2 to 13-4, 13-Si
differential diagnosis, 13-2i, 13-3
monochorionic diamniotic twins vs., 13-6i,
13-7
monochorionic, 13-6 to 13-8, 13-9i
dichorionic diamniotic twins vs., 13-2i, 13-3
differential diagnosis, 13-6i, 13-7
perigestational hemorrhage vs., 1-lOi, 1-11
Diaphragmatic hernia, congenital, 5-8 to 5-10,
S-l1i
cystic adenomatoid malformation vs., S-12i,
5-13
differential diagnosis, 5-8i, 5-9
esophageal atresia vs., 8-6i, 8-7
heterotaxy vS., 6-16i, 6-17
isolated
Cornelia de Lange syndrome vs., 15-15
Fryns syndrome vs., lS-18i, 15-19
pleural effusion vs., S-20i, 5-21
teratoma of chest vS., S-24i, 5-25
Diastrophic dysplasia
micromelia vs., 10-12
Pierre Robin syndrome vs., 15-27
Dichorionic diamniotic twins, 13-2 to 13-4, 13-Si
differential diagnosis, 13-2i, 13-3
monochorionic diamniotic twins vs., 13-6i, 13-7
DiGeorge syndrome, Pierre Robin syndrome vs.,
15-27

Digit anomalies. See Clinodactyly; Ectrodactyly;
Polydactyly; Syndactyly.
Dilated cardiomyopathy, 6-66 to 6-68, 6-69i
Discordant twin growth, 13-14 to 13-16, 13-17i
Disomy 14, uniparental (paternal), asphyxiating
thoracic dysplasia vs., 10-15
Distal atresia, duodenal atresia vs., 8-10i, 8-11
DK-phocomelia, amelia vs., 10-11
Dolichocephaly, craniosynostosis vs., 2-92
Double inlet left ventricle
hypoplastic left heart vS., 6-26i, 6-27
tricuspid atresia vs., 6-44
Double outlet right ventricle, 6-46 to 6-47
differential diagnosis, 6-46i
tetralogy of Fallot vs., 6-S0i, 6-51
transposition of great arteries vs., 6-S4i, 6-55
Down syndrome. See Trisomy 21.
Ductus arteriosus, constriction of
dilated cardiomyopathy vs., 6-67
hypertrophic cardiomyopathy vs., 6-63
rhabdomyoma vs., 6-81
Ductus venosus, 1-36 to 1-38, 1-39i
absence of, 1-36i, 1-37
differential diagnosis, 1-36i, 1-37
Duodenal atresia, 8-10 to 8-12, 8-13i
choledochal cyst vS., 8-40i
differential diagnosis, 8-10i, 8-11
jejunal/ileal atresia vs., 8-14i, 8-15
volvulus vs., 8-24i
Duplicated collecting system. See Renal collecting
system, duplicated.
Duplication cyst
duodenal atresia vs., 8-11
enteric. See Enteric duplication cyst.
umbilical cord aneurysm vs., 11-19
urachal anomalies vs., 9-S6i
Dural arteriovenous fistula, congenital, vein of
Galen malformation vs., 2-94i, 2-95
Dysrythmias, 6-70 to 6-71
bradyarrhythmia, 6-76 to 6-78, 6-79i
differential diagnosis, 6-70i, 6-70 to 6-71
tachyarrhythmia, 6-72 to 74, 6-7Si
Dyssegmental dysplasia, micromelia vs., 10-11 to
10-12

E
Ear anomalies, 4-26 to 4-28, 4-29i
Ebstein anomaly, 6-42 to 6-43
differential diagnosis, 6-42i, 6-43
dilated cardiomyopathy vS., 6-66i, 6-67
Echogenic bowel, 8-2 to 8-4, 8-Si
ascites vS., 8-27
cystic fibrosis vs., lS-16i
cytomegalovirus infection vs., 16-3
differential diagnosis, 8-2i, 8-3 to 8-4

INDEX
hyperechoic, meconium peritonitis/pseudocyst
vs., 8-20i, 8-21 to 8-22
toxoplasmosis vs., 16-8i
Echogenic cardiac focus, 6-6 to 6-7
differential diagnosis, 6-6i, 6-7
rhabdomyoma vs., 6-80i, 6-81
Echogenic liver, gallstones vs., 8-34
Ectopia cordis, pentalogy of Cantrell vs., 7-24i
Ectopic pregnancy
abdominal, 1-26 to 1-27
adnexal/tuboovarian torsion vs., 18-38i, 18-39
cervical, 1-22 to 1-24, 1-2Si
cesarean section scar ectopic vs., 1-28i
differential diagnosis, 1-22i, 1-23
cesarean section scar ectopic, 1-28 to 1-29
cervical ectopic pregnancy vs., 1-22i, 1-23
differential diagnosis, 1-28i, 1-28 to 1-29
corpus luteum cyst vs., 18-24i
heterotopic pregnancy vs., 1-30i
hyperstimulation syndrome vs., 18-27
incidental ovarian mass vs., 18-34i, 18-35
interstitial, 1-18 to 1-20, 1-2li
abdominal ectopic pregnancy vs., 1-26
differential diagnosis, 1-18i, 1-19
uterine duplication vs., 18-6i, 18-7
pseudogestional sac of
anembryonic pregnancy vs., 1-6i, 1-7
perigestational hemorrhage vs., 1-lOi, 1-11
ruptured, abdominal ectopic pregnancy vs" 1-26
tubal, 1-14 to 1-16, 1-17i
abdominal ectopic pregnancy vs., 1-26i
differential diagnosis, 1-14i, 1-15 to 1-16
interstitial ectopic pregnancy vs., 1-19
Ectrodactyly, 10-52 to 10-53
clubfoot vs., 10-30i, 10-31
differential diagnosis, 10-52i, 10-52 to 10-53
rockerbottom foot vs., 10-34i, 10-35
sandal gap foot vs., 10-36i, 10-37
Ectrodactyly-ectodermal dysplasia clefting
syndrome
ectrodactylyvs., 10-52
syndactyly vs., 10-47 to 10-48
Edema. See also Ascites.
scalp, scalp masses vs., 4-44i
Effusion
pericardial. See Pericardia Ieffusion.
pleural. See Pleural effusion.
Ellis van Creveld syndrome
asphyxiating thoracic dysplasia vs., 10-14
polydactyly vs., 10-43
short rib-polydactyly syndrome vs., 10-25
Embryonic demise, higher order multiple gestation
vs., 13-30i, 13-31
Embryopathy, from anticonvulsants
hydantoin syndrome vs., 18-42
valproic acid syndrome vs., 18-42

Emphysema, congenital lobar
bronchopulmonary sequestration vs., 5-17
cystic adenomatoid malformation vs., 5-13
Encephalocele
acrania vs., 2-10, 2-10i
amniotic band syndrome vs., IS-4i, 15-5
anencephaly/exencephalyvs.,
2-6i, 2-7
frontal, 2-16 to 2-17
differential diagnosis, 2-16i, 2-16 to 2-17
epignathus vs., 4-23
midface anomalies vs., 4-30i, 4-32
orbital tumors vs., 4-42i
iniencephaly vs., 3-10i, 3-11
Meckel-Gruber syndrome vs., 15-23
occipital, 2-12 to 2-14, 2-ISi
cystic hygroma vs., 4-48i, 4-50
differential diagnosis, 2-12i, 2-13 to 2-14
Joubert syndrome vs., IS-20i, 15-21
scalp masses vs., 4-45
Encephalomalacia, 2-60 to 2-62, 2-63i
aqueductal stenosis vs., 2-24
differential diagnosis, 2-60i, 2-61
Endocardial fibroelastosis
coarctation of aorta vs., 6-30i, 6-31
constriction of
dilated cardiomyopathy vs., 6-67
rhabdomyoma vs., 6-81
Endometritis, 18-22 to 18-23
differential diagnosis, 18-22i, 18-22 to 18-23
ovarian vein thrombosis vs., 18-64i
retained products of conception vs., 18-20i,
18-21
uterine rupture vs., 18-17
Enteric duplication cyst, 8-30 to 8-31
choledochal cyst vs" 8-40i
differential diagnosis, 8-30i, 8-30 to 8-31
meconium peritonitis/pseudocyst vs., 8-21
mesenteric cyst vs., 8-32
ovarian cysts vs., 9-68i, 9-69
Enterolith(s), meconium peritonitis/pseudocyst vs.,
8-20i,8-21
Enterolithiasis, anal atresia, echogenic bowel vs.,
8-2i,8-4
Epignathus, 4-22 to 4-24, 4-2Si
cervical teratoma vs., 4-S6i, 4-57
differential diagnosis, 4-22i, 4-23
macroglossia vs., 4-19
midface anomalies vs., 4-30i, 4-32
Escobar syndrome. See Multiple pterygium
syndrome.
Esophageal atresia, 8-6 to 8-8, 8-9i
Exencephaly, 2-6 to 2-8, 2-9i
acrania vs., 2-10, 2-10i
differential diagnosis of, 2-6i, 2-7
Eyes. See also Anophthalmia.
hypertelorism, 4-38 to 4-40, 4-4li

ix

INDEX
hypotelorism, 4-34 to 4-36, 4-37i
normal, hypotelorism vs., 4-34i

F

x

Face, normal, midface anomalies vs., 4-31
Face and neck anomalies, 4-6 to 4-59
Facial anomalies
midface, 4-30 to 4-32, 4-33i
severe, ear anomalies vs., 4-28
Facial cleft. See also Cleft lip, palate.
ear anomalies vs., 4-26i, 4-28
macroglossia vs., 4-18i
Facial masses
cleft lip, cleft palate vs., 4-7
frontal encephalocele vs., 2-16i, 2-17
Fallot's tetralogy. See Tetralogy of Fallot.
Fatty liver of pregnancy, acute, HELLPsyndrome
vs., 18-61
Femoral focal deficiency, proximal, campomelic
dysplasia vs., 10-17
Femur-fibula-ulna complex, campomelic dysplasia
vs.,10-16
Fetal alcohol syndrome, 18-40 to 18-41
Cornelia de Lange syndrome vs., 15-15
differential diagnosis, 18-4Oi
Fetal breathing
abnormal cord Doppler ultrasound vs., 11-6i,
11-7
middle cerebral artery Doppler of, 17-24i, 17-25
Fetal demise. See Demise.
Fetal hair, scalp masses vs., 4-44i
Fever, postpartum, endometritis vs., 18-23
Fibroblast growth factor receptor(s)
craniosynostosis-related syndromes,
craniosynostosis vs., 2-91
mutation-associated disorders, achondroplasia
vs., 10-7
Fibrochondrogenesis
micromelia vs., 10-12
thanatophoric dysplasia vs., 10-27
Fibroelastosis, endocardial. See Endocardial
fibroelastosis.
Fibroid tumor. See Leiomyoma.
Fibroma, rhabdomyoma vs., 6-81
Fibromatosis
cervical teratoma vs., 4-57
epignathus vs., 4-23
Fibrosarcoma
cervical teratoma vs., 4-57
epignathus vs., 4-23
Fibular hemimelia
campomelic dysplasia vs., 10-16i, 10-17
sirenomelia vs., 15-28i, 15-29

Finger anomalies. See Clinodactyly; Ectrodactyly;
Polydactyly; Syndactyly.
Fluid-filled structures, normal, umbilical cord
aneurysm vs., 11-18i, 11-19
Focal adenomyosis/adenomyoma,
leiomyoma vs.,
18-11
Focal myometrial contraction. See Myometrial
contraction, focal.
Foramen ovale
aneurysm, 6-8 to 6-9
normal flap, foramen ovale aneurysm vs., 6-8i
Frontal bone concavity, isolated, Chiari II
malformation vs., 2-19
Frontal encephalocele. See Encephalocele, frontal.
Fryns syndrome, 15-18 to 15-19
Cornelia de Lange syndrome vs., 15-14i
differential diagnosis, 15-18i, 15-18 to 15-19

G
Gallbladder
duplication of, choledochal cyst vs., 8-40
umbilical cord aneurysm vs., 11-18i, 11-19
Gallstones, 8-34 to 8-8-35
differential diagnosis, 8-34i, 8-34 to 8-35
hepatic calcifications vs., 8-36i, 8-37
meconium peritonitis/pseudocyst vs., 8-20i, 8-21
Gastrointestinal ascites, differential diagnosis, 8-27
Gastrointestinal tract, 8-2 to 8-45
Gastroschisis, 7-10 to 7-12, 7-13i
amniotic band syndrome vs., 15-4i, 15-5
bladderexstrophyvs.,7-19
body stalk anomaly vs., 7-15
cloacal exstrophy vs., 7-20i
differential diagnosis, 7-1Oi, 7-11
omphalocele vs., 7-6i, 7-7
Gaucher disease
hepatic tumors vs., 8-43
hepatomegaly/splenomegaly vs., 8-39
type 2, perinatal lethal type, arthrogryposis/
akinesia sequence vs., 10-56
Genitalia
ambiguous, 9-58 to 9-60, 9-6li
differential diagnosis, 9-58i, 9-59 to 9-60
hypospadias vs., 9-62
first trimester, ambiguous genitalia vs., 9-60
normal female, ambiguous genitalia vs., 9-58i,
9-59
normal male
ambiguous genitalia vs., 9-58i, 9-59 to 9-60
hypospadias vs., 9-63
Genitourinary ascites, 8-27
Genitourinary tract anomalies, 9-6 to 9-71
Genitourinary tract obstruction, oligohydramnios
due to, biophysical profile of, 17-20i, 17-21
Germ cell tumor, incidental ovarian mass vs., 18-35

INDEX
German measles. See Rubella.
Germinal matrix
hemorrhage, tuberous sclerosis vs., 15-36i, 15-37
periventricular, tuberous sclerosis vs., 15-37
Gestational trophoblastic neoplasia. See also
Hydatidiform mole.
anembryonic pregnancy vs., 1-6i, 1-7
chorioangioma vs., 12-34i, 12-35
placenta accreta spectrum vs., 12-30i, 12-31
placental sonolucencies vs., 12-6i, 12-7
placentomegaly vs., 12-28i, 12-29
retained products of conception vs., 18-21
Glioependymal cyst, 2-76 to 2-78, 2-79i
alobar holoprosencephaly
vs., 2-43
arachnoid cyst vs., 2-72i, 2-73
central nervous system tumors vs., 2-102i, 2-103
differential diagnosis, 2-76i, 2-77
hydranencephaly vs., 2-56i, 2-57
Glioma, nasal
epignathus vs., 4-23
frontal encephalocele vs., 2-16
Glycogen storage disorder, hepatomegaly/
splenomegaly vs., 8-39
Goiter, 4-52 to 4-54, 4-55i
cervical teratoma vs., 4-56i, 4-57
differential diagnosis, 4-52i, 4-53
Goldenhar syndrome, Pierre Robin syndrome vs.,
15-27
Gray matter heterotopia, subependymal, tuberous
sclerosis vs., 15-37
Great arteries, transposition of. See Transposition
of great arteries.
Greig cephalopolysyndactyly
syndrome, syndactyly
vs.,10-47
Gut herniation, physiologic
gastroschisis vs., 7-11
omphalocelevs., 7-6i, 7-7

H
Hair, fetal, scalp masses vs., 4-44i
Hamartoma, mesenchymal, 8-42
Head, molding of, craniosynostosis vs., 2-91
Heart
abnormal position, heterotaxy vs., 6-17
anomalies/disorders, 6-6 to 6-83
dextroposition of. See Dextrocardia.
echogenic cardiac focus, 6-6 to 6-7
differential diagnosis, 6-6i, 6-7
rhabdomyoma vs., 6-80i, 6-81
hypoplastic left. See Hypoplastic left heart.
normal structures, echogenic cardiac focus vs.,
6-6i,6-7
Heart block
complete, bradyarrhythmia vs., 6-77
second degree, irregular rhythm vs., 6-70i, 6-71

Heart defects, congenital
complex, situs inversus vs., 6-14i
diabetic embryopathy vs., 18-53
ductus venosus vs., 1-36i
hydantoin syndrome vs., 18-42
pulmonary hypoplasia vs., 5-4i, 5-6
valproic acid syndrome vs., 18-42
HELLP syndrome, 18-60 to 18-62, 18-63i
Hemangioendothelioma,
hepatomegaly /
splenomegaly vs., 8-38i, 8-39
Hemangioma
cervical teratoma vs., 4-57
epignathus vs., 4-23
facial, orbital tumors vs., 4-42
gallstones vs., 8-34
lymphangioma vs., 5-29
rhabdomyoma vs., 6-81
umbilical cord, omphalocele vs., 7-8
Hemifacial microsomia, Pierre Robin syndrome vs.,
15-27
Hemihyperplasia, isolated, Beckwith-Wiedemann
syndrome vS., 15-10
Hemolysis, Elevated Liver enzymes, Low Platelets
(HELLP) syndrome, 18-60 to 18-62, 18-63i
Hemorrhage
intracranial
arachnoid cyst vS., 2-73
central nervous system tumors vs., 2-102i,
2-103
differential diagnosis, 2-65
glioependymal cyst vS., 2-77
mild ventriculomegaly vs., 2-40i
intraventricular
central nervous system tumors vs., 2-102i,
2-103
choroid plexus cyst vS., 2-69 to 2-70
perigestational, 1-10 to 1-12, 1-13i
anembryonic pregnancy vs., 1-6i, 1-7
differential diagnosis, l-lOi, 1-11
higher order multiple gestation vs., 13-30i,
13-31
postpartum, uterine rupture vs., 18-16i, 18-17
prenatal, uterine rupture vs., 18-16i, 18-17
spontaneous, HELLP syndrome vs., 18-60i, 18-61
subdural, hydranencephaly
vs., 2-57
Hepatic. See Liver.
Hepatic neoplasms. See Liver neoplasms.
Hepatic vein calcification, hepatic calcifications vS.,
8-36i,8-37
Hepatitis B, abdominal calcifications due to,
meconium peritonitis/pseudocyst
vs., 8-21
Hepatoblastoma, hepatomegaly/splenomegaly
vs.,
8-38i,8-39
Hepatocellular carcinoma, HELLP syndrome vs.,
18-61
Hepatomegaly, 8-38 to 8-39

XI

INDEX

XII

differential diagnosis, 8-38i, 8-38 to 8-39
hepatic tumors vs., 8-42i, 8-43
Hernia
diaphragmatic. See Diaphragmatic hernia,
congenital.
hiatal, esophageal atresia vs., 8-7
inguinal, testicular torsion vs., 9-66i, 9-67
inguinoscrotal, hydrocele vs., 9-64i, 9-65
umbilical, omphalocele vs., 7-7
Herniation, physiologic bowel, omphalocele vs.,
7-6i,7-7
Herpes simplex infection
abdominal calcifications due to, meconium
peritonitis/pseudocyst
vs., 8-21
cytomegalovirus infection vs., 16-2i, 16-3
parvovirus B19 infection vs., 16-6
toxoplasmosis vs., 16-8i
varicella infection vs., 16-1Oi
Heterotaxy syndromes, 6-16 to 6-18, 6-19i. See also
Atrial isomerism.
atrioventricular septal defect vs., 6-22i, 6-23
differential diagnosis, 6-16i, 6-17
situs inversus vs., 6-14i
Heterotopic pregnancy, 1-30 to 1-31
abdominal ectopic pregnancy vs., 1-26i
corpus luteum cyst vs., 18-25
differential diagnosis, 1-30i
hyperstimulation syndrome vs., 18-27
Hiatal hernia, esophageal atresia vs., 8-7
Hirschsprung disease, anal atresia vs., 8-18i, 8-19
HIV infection
cytomegalovirus infection vs., 16-3
hepatomegaly/splenomegaly
vs., 8-38
Holoprosencephaly
alobar, 2-42 to 2-44, 2-4Si
absent cavum septi pellucidi vs., 2-54
aqueductal stenosis vs., 2-22i, 2-23
differential diagnosis, 2-42i, 2-43 to 2-44
glioependymal cyst vs., 2-76i, 2-77
schizencephaly vs., 2-80i, 2-81
atelencephaly/aprosencephaly
vs., 2-87
hydranencephaly vs., 2-S6i, 2-57
lobar, 2-46 to 2-48, 2-49i
absent cavum septi pellucidi vs., 2-54
agenesis of corpus callosum vs., 2-36i, 2-37
septo-optic dysplasia vs., 2-S0i, 2-51
semilobar, 2-46 to 2-48, 2-49i
absent cavum septi pellucidi vs., 2-54, 2-S4i
differential diagnosis, 2-46i, 2-47
Smith-Lemli-Opitz syndrome vs., lS-32i, 15-33
trisomy 13 vs., 14-11
Holt-Oram syndrome, VACTERL association vs.,
lS-40i,15-41
Homozygous achondroplasia. See Achondroplasia,
homozygous.
Hydantoin syndrome, 18-42 to 18-43

differential diagnosis, 18-42i, 18-42 to 18-43
fetal alcohol syndrome vs., 18-4Oi
Hydatidiform mole
with coexistent twin fetus
placental sonolucencies vs., 12-7
triploidy vs., 14-18i, 14-19
complete, 12-38 to 12-40, 12-4li
anembryonic pregnancy vs., 1-6i, 1-7
chorioangioma vs., 12-35
differential diagnosis, 12-38i, 12-39 to 12-40
placenta accreta spectrum vs., 12-30i, 12-31
placental sonolucencies vs., 12-6i, 12-7
invasive, 12-42 to 12-43
anembryonic pregnancy vs., 1-6i, 1-7
chorioangioma vs., 12-35
choriocarcinoma vs., 12-44i, 12-45
differential diagnosis, 12-42i, 12-43
partial
placenta accreta spectrum vs., 12-30i, 12-31
placental sonolucencies vs., 12-7
retained products of conception vs., 18-21
Hydranencephaly, 2-56 to 2-58, 2-S9i
absent cavum septi pellucidi vs., 2-55
alobar holoprosencephaly
vs., 2-42i, 2-43
aqueductal stenosis vs., 2-22i, 2-23
atelencephaly/aprosencephaly
vs., 2-87
differential diagnosis, 2-57
schizencephaly vs., 2-80i, 2-81
trisomy 13 vs., 14-11
Hydrocele, 9-64 to 9-65
differential diagnosis, 9-64i, 9-64 to 9-65
large simple, testicular torsion vs., 9-66i, 9-67
Hydrocephalus
chronic severe, absent cavum septi pellucidi vs.,
2-55
encephalomalacia vs., 2-61
hydranencephaly
vs., 2-57
obstructive, mild ventriculomegaly vs., 2-40i,
2-41
schizencephaly vs., 2-80i, 2-81
Hydrocolpos
enteric duplication cyst vs., 8-31
ovarian cysts vs., 9-70
Hydrolethalus
polydactyly vs., 10-44
Smith-Lemli-Opitz syndrome vs., 15-33
Hydronephrosis
maternal, 18-56 to 18-58, 18-S9i
multi cystic dysplastic kidneys vs., 9-30i, 9-31
obstructive renal cystic dysplasia vs., 9-23
ovarian cysts vs., 9-69 to 9-70
Hydropic degeneration, placental, complete
hydatidiform mole vs., 12-38i, 12-39
Hydrops, 17-32 to 17-34, 17-3Si
differential diagnosis, 17-32i, 17-33
immune

INDEX
ascites vs., 8-27
hepatic tumors vs., 8-42i, 8-43
hepatomegaly/splenomegaly vs., 8-38i
macrosomia vs., 17-18i
nonimmune
ascites vs., 8-27 to 8-28
cytomegalovirus infection vs., 16-3
hepatic tumors vs., 8-42i, 8-43
hepatomegaly/splenomegaly vs., 8-38i
Rh incompatibility vs., 18-66i, 18-67
parvovirus B19 infection vs., 16-6i, 16-7
Hydrosalpinx, incidental ovarian mass vs., 18-35
Hygroma, cystic. See Cystic hygroma.
Hyperechoic bowel, meconium peritonitis/
pseudocyst vs., 8-20i, 8-21 to 8-22
Hyperextended neck, absent nasal bone vs., 4-10i
Hyperreactio luteinalis, hyperstimulation syndrome
vs., 18-27
Hyperstimulation syndrome, 18-26 to 18-28, 18-29i
differential diagnosis, 18-26i, 18-26 to 18-27
incidental ovarian mass vs., 18-35
theca lutein cysts vs., 18-31
Hypertelorism, 4-38 to 4-40, 4-4li
differential diagnosis, 4-38i, 4-40
hypotelorism vs., 4-34i, 4-36
Hypertrophic cardiomyopathy, 6-62 to 6-64, 6-6Si
differential diagnosis, 6-62i, 6-63
rhabdomyoma vs., 6-80i, 6-81
Hypochondrogenesis, achondrogenesis vs., 10-3
Hypochondroplasia
achondroplasia vs., 10-7
polydactyly vs., 10-43
Hypophosphatasia, 10-18 to 10-19
achondrogenesis vs., 10-2i, 10-3
differential diagnosis, 10-18i, 10-18 to 10-19
osteogenesis imperfecta vs., 10-20i, 10-21
Hypoplastic left heart, 6-26 to 6-28, 6-29i
aortic stenosis vs., 6-34i, 6-35
coarctation of aorta vs., 6-30i, 6-31
differential diagnosis, 6-26i, 6-27
hypertrophic cardiomyopathy vs., 6-62i, 6-63
pulmonary valve stenosis/atresia vs., 6-38i, 6-39
single ventricle vs., 6-48i
tricuspid atresia vs., 6-44i, 6-45
truncus arteriosus vs., 6-S8i, 6-59
Hypospadias, 9-62 to 9-63
Hypotelorism, 4-34 to 4-36, 4-37i
differential diagnosis, 4-34i, 4-35 to 4-36

I
Ileal atresia, 8-14 to 8-8-16, 8-17i
anal atresia vs., 8-18i, 8-18
ascites in, 8-27
cystic fibrosis vs., 15-16
differential diagnosis, 8-14i, 8-15

duodenal atresia vs., 8-10i, 8-11
volvulus vs., 8-24i
Incidental ovarian mass, 18-34 to 18-36, 18-37i
Incompetent cervix, 18-2 to 18-4, 18-Si
Increased nuchal translucency, 1-32 to 1-34, 1-3Si
Infection, 16-2 to 16-11
abdominal calcifications due to
gallstones vs., 8-34i
meconium peritonitis/pseudocyst vs., 8-21
cytomegalovirus. See Cytomegalovirus infection.
echogenic bowel in, cystic fibrosis vs., lS-16i
hepatic tumors vs., 8-43
hepatomegaly/splenomegaly vs., 8-38
herpes simplex. See Herpes simplex infection.
intracranial hemorrhage vs., 2-65
intrauterine, hydantoin syndrome vs., 18-43
parvovirus. See Parvovirus B19 infection.
postoperative, uterine rupture vs., 18-17
toxoplasmosis. See Toxoplasmosis.
triploidyvs., 14-19
in utero, hepatic calcifications vs., 8-36
Inguinal hernia, testicular torsion vs., 9-66i, 9-67
Inguinoscrotal hernia, hydrocele vs., 9-64i, 9-65
Iniencephaly, 3-10 to 3-12, 3-13i
differential diagnosis, 3-lOi, 3-11
kyphosis/scoliosis vs., 3-18i, 3-19
occipital encephalocele vs., 2-13 to 2-14
Interrupted aortic arch, aortic stenosis vs., 6-35
Interstitial ectopic pregnancy, 1-18 to 1-20, 1-2li
abdominal ectopic pregnancy vs., 1-26
differential diagnosis, 1-18i, 1-19
uterine duplication vs., 18-6i, 18-7
Intervillous thrombi, chorioangioma vs., 12-35
Intra-abdominal cysts, ovarian cysts vs., 9-68i, 9-69
Intra-abdominal neoplasms, ovarian cysts vs., 9-70
Intracranial cyst, arteriovenous fistula vs., 2-99
Intracranial hemorrhage, 2-64 to 2-66, 2-67i
arachnoid cyst vs., 2-73
central nervous system tumors vs., 2-102i, 2-103
differential diagnosis, 2-65
glioependymal cyst vs., 2-77
mild ventriculomegaly vs., 2-40i
Intracranial tumor, intracranial hemorrhage vs.,
2-64i,2-65
Intrauterine blood/clot
endometritis vs., 18-22i, 18-23
retained products of conception vs., 18-20i,
18-21
Intrauterine growth restriction
asymmetric, 17-14to 17-16, 17-17i
differential diagnosis, 17-14i, 17-15
symmetric intrauterine growth restriction vs.,
17-10i,17-11
hydantoin syndrome vs., 18-42i
Pierre Robin syndrome vs., 15-27
severe, renal agenesis vs., 9-26i, 9-27

XIII

INDEX

xiv

symmetric, 17-10 to 17-12, 17-13i
asymmetric intrauterine growth restriction
vs., 17-14i, 17-15
differential diagnosis, 17-10i, 17-11
fetal alcohol syndrome vs., 18-40
valproic acid syndrome vs., 18-42
Intrauterine infection, hydantoin syndrome vs.,
18-43
Intrauterine membrane rupture, monochorionic
monoamniotic twins vs., 13-10i, 13-12
Intrauterine pregnancy. See Pregnancy, normal
intrauterine.
Intraventricular hemorrhage
central nervous system tumors vs., 2-102i, 2-103
choroid plexus cyst vs., 2-69 to 2-70
Intussusception, volvulus vs., 8-25
Invasive hydatidiform mole. See Hydatidiform
mole, invasive.
Irregular rhythms, 6-70 to 6-71. See also
Dysrythmias.
Ischemia
bowel, cystic fibrosis vs., lS-16i
intracranial hemorrhage vs., 2-65
Ischemic infarct, hepatic, hepatic calcifications vs.,
8-37
IUGR. See Intrauterine growth restriction.

J
Jackson-Weiss syndrome, craniosynostosis vs., 2-91
Jarcho-Levin syndrome
iniencephaly vs., 3-11
VACTERLassociation vs., 15-42
Jejunal atresia, 8-14 to 8-8-16, 8-17i
differential diagnosis, 8-14i, 8-15
duodenal atresia vs., 8-10i, 8-11
volvulus vs., 8-24i
Jeune syndrome. See Asphyxiating thoracic
dysplasia.
Joubert syndrome, 15-20 to 15-21
classic Dandy-Walker continuum vs., 2-27
differential diagnosis, lS-20i, 15-20 to 15-21
polydactylyvs., 1O-42i, 10-43
rhombencephalosynapsis vs., 2-34, 2-34i
variant Dandy-Walker continuum vs., 2-31

K
Kidney(s). See also Renal entries.
agenesis. See Renal agenesis.
anomalies
bilateral, oligohydramnios due to,
biophysical profile of, 17-21
congenital, pulmonary hypoplasia vs., S-4i,
5-5 to 5-6

collecting system. See Renal collecting system,
duplicated.
crossed fused ectopic, mesoblastic nephroma vs.,
9-38i,9-39
cystic dysplasia. See Renal cystic dysplasia.
cysts. See also Polycystic kidney disease.
maternal hydronephrosis vs., 18-58
simple, multicystic dysplastic kidneys vs., 9-31
developmental variants of, 9-6 to 9-8, 9-9i
duplication, mild pelviectasis vs., 9-14i
enlarged, causes of, 9-10i, 9-11
extralobar sequestration, neuroblastoma vs.,
9-42i,9-43
masses, renal developmental variants vs., 9-6i,
9-7

multicystic dysplastic. See Multicystic dysplastic
kidneys.
obstruction, maternal hydronephrosis vs., 18-57
obstructive cystic dysplasia. See Renal cystic
dysplasia, obstructive.
polycystic disease. See Polycystic kidney disease.
tumors, mesoblastic nephroma vs., 9-39
Kidney stones
acute abdomen vs., 18-49
maternal hydronephrosis vs., 18-S6i
Klippel-Feil syndrome, iniencephaly vs., 3-11
Klippel Trenaunay Weber syndrome,
lymphangioma vs., 5-29
Kyphomelic dysplasia, campomelic dysplasia vs.,
1O-16,10-16i
Kyphosis, 3-18 to 3-20, 3-2li
differential diagnosis, 3-18i, 3-19
isolated, spina bifida vs., 3-6i, 3-7

L
Large for gestational age. See Macrosomia.
Laryngeal cyst, congenital, goiter vs., 4-53
Left ventricle. See Ventricle(s).
Leiomyoma, 18-10 to 18-12, 18-13i
cervical, cervical ectopic pregnancy vs., 1-22i,
1-23
degenerated, incidental ovarian mass vs.,
18-34i, 18-35
differential diagnosis, 18-10i, 18-11
infarction of, acute abdomen vs., 18-48i, 18-49
oligohydramnios vs., 17-6i, 17-8
pedunculated, incidental ovarian mass vs.,
18-34i, 18-35
placental abruption vs., 12-18i, 12-19
submucosal, chorioangioma vs., 12-35
uterine duplication vs., 18-6i, 18-7
Lemon shaped head, in Chiari II malformation,
craniosynostosis vs., 2-92
Limb-body-wall complex. See Body stalk anomaly
(limb-body-wall complex).

INDEX
Limb-mammary syndrome, ectrodactyly vs., 10-53
Limb reduction defect
amelia vs., 10-lOi
Cornelia de Lange syndrome vs., 15-15
ectrodactyly vs., lO-S2i, 10-53
varicella infection vs., 16-10
Liver. See also Hepatic or Hepato entries.
calcifications, 8-36 to 8-37
cysts, choledochal cyst vs., 8-40
echogenicities, gallstones vs., 8-34
enlarged. See Hepatomegaly.
fatty liver of pregnancy, acute, HELLPsyndrome
vs., 18-61
ischemic infarct, hepatic calcifications vs., 8-37
trauma, HELLPsyndrome vs., 18-60i, 18-61
Liver neoplasms, 8-42 to 8-44, 8-4Si
bleeding, HELLPsyndrome vs., 18-60i, 18-61
hepatic calcifications vs., 8-36i
hepatoblastoma, hepatomegaly/splenomegaly
vs., 8-38i, 8-39
hepatocellular carcinoma, HELLPsyndrome vs.,
18-61
hepatomegaly/splenomegaly vs., 8-38i, 8-39
hepatomegaly vs., 8-42i, 8-43
Lobar holoprosencephaly. See Holoprosencephaly,
alobar.
Lower extremity malformations, sirenomelia vs.,
15-29
Lung, hyperechoic mass of, tracheal atresia vs., 5-27
Lymphangioma, 5-28 to 5-30, S-31i. See also
Mesenteric cyst.
body/trunk, cystic hygroma vs., 4-48i, 4-50
chest wall
pleural effusion vs., S-20i, 5-21
Turner (XO) syndrome vs., 14-15
differential diagnosis, 5-28i, 5-29
goiter vs., 4-53
macroglossia vs., 4-19
teratoma of chest vs., S-24i, 5-25

M
Macroglossia, 4-18 to 4-20, 4-2li
Macrosomia, 17-18 to 17-19
diabetic, Beckwith-Wiedemann syndrome vs.,
lS-lOi
diabetic embryopathy vs., 18-53
differential diagnosis, 17 -18i, 17-18 to 17-19
Rh incompatibility vs., 18-66i
Majewski syndrome. See also Mohr syndrome.
polydactyly vs., 10-43
Marginal sinus previa, vasa previa vs., 11-24, 11-24i
Maternal conditions in pregnancy, 18-2 to 18-69
MCADoppler, 17-24toI7-26,17-27i
MCDK. See Multicystic dysplastic kidneys.

Measurement technique, erroneous, increased
nuchal translucency vs., 1-32i, 1-34
Meckel-Gruber syndrome, 15-22 to 15-24, lS-2Si
autosomal recessive polycystic kidney disease vs.,
9-34i,9-35
differential diagnosis, lS-22i, 15-23
polydactyly vs., lO-42i, 10-43
Smith-Lemli-Opitz syndrome vs., 15-33
trisomy 13 vs., 14-10i, 14-11
Meconium ileus, jejunal/ileal atresia vs., 8-14i, 8-15
Meconium peritonitis, 8-20 to 8-22, 8-23i
ascites vs., 8-27
differential diagnosis, 8-20i, 8-21 to 8-22
echogenic bowel vs., 8-2i, 8-3
gallstones vs., 8-34i, 8-35
hepatic calcifications vs., 8-36i
Meconium pseudocyst, 8-20 to 8-22, 8-23i
ascites vs., 8-26i, 8-27
choledochal cyst vs., 8-40
differential diagnosis, 8-20i, 8-21 to 8-22
enteric duplication cyst vs., 8-30i, 8-31
mesenteric cyst vs., 8-33
ovarian cysts vs., 9-69
umbilical cord aneurysm vs., 11-19
Mega-cisterna magna, 2-32 to 2-2-33
classic Dandy-Walker continuum vs., 2-26i, 2-27
differential diagnosis, 2-32i, 2-32 to 2-2-33
Joubert syndrome vs., lS-2Oi
variant Dandy-Walker continuum vs., 2-30,
2-3Oi
Megacystis-microcolon
posterior urethral valves vs., 9-47
prune belly syndrome vs., 9-50
Megaureter
congenital
duplicated renal collecting system vs., 9-11
ureterocele vs., 9-53
multicystic dysplastic kidneys vs., 9-30i
Membrane rupture
intrauterine, monochorionic mono amniotic
twins vs., 13-10i, 13-12
premature. See Premature rupture of membranes.
Meningeal tumor, scalp masses vs., 4-45
Meningocele, sacrococcygeal teratoma vs., 3-22i,
3-23
Mesenteric cyst, 8-32 to 8-33
choledochal cyst vs., 8-40
differential diagnosis, 8-32i, 8-32 to 8-33
duodenal atresia vs., 8-10i, 8-11
enteric duplication cyst vs., 8-30i
meconium peritonitis/pseudocyst vs., 8-21
ovarian cysts vs., 9-69
Mesoblastic nephroma, 9-38 to 9-40, 9-4li
Beckwith-Wiedemann syndrome vs., lS-lOi
differential diagnosis, 9-38i, 9-39
neuroblastoma vs., 9-43

xv

INDEX

xvi

renal developmental variants vs., 9-6i, 9-7
renal enlargement due to, 9-10i, 9-11
Metopic ridge
occipital encephalocele vs., 2-12i, 2-14
without synostosis, craniosynostosis vs., 2-92
Microcephaly, 2-84 to 2-85
differential diagnosis, 2-84i, 2-84 to 2-85
severe
anencephaly/exencephaly vs., 2-6i, 2-7
atelencephaly/aprosencephalyvs.,
2-86i, 2-87
Micrognathia, 4-14 to 4-16, 4-17i
differential diagnosis, 4-14i, 4-15
ear anomalies vs., 4-26i
isolated, Pierre Robin syndrome vs., lS-26i
Micrognathia-glossoptosis, macroglossia vs., 4-18i
Micromelia, 10-10 to 10-12, lO-13i
Micropenis, hypospadias vs., 9-62i, 9-62 to 9-63
Microsomia, hemifacial, Pierre Robin syndrome vs.,
15-27
Middle cerebral artery Doppler, 17-24 to 17-26,
17-27i
errors in, 17-24i, 17-25
Midface anomalies, 4-30 to 4-32, 4-33i
Midface mass, midface anomalies vs., 4-30i, 4-32
Midgut volvulus. See also Volvulus.
ascites in, 8-27
jejunal/ileal atresia vs., 8-15
Minor antigen alloimmune syndromes, Rh
incompatibility vs., 18-66
Moderator band muscles, normal, echogenic
cardiac focus vs., 6-6i, 6-7
Mohr syndrome. See also Majewski syndrome.
polydactyly vs., 10-43
short rib-polydactyly syndrome vs., 10-25
Molar tooth malformation. See Joubert syndrome.
Mole. See Hydatidiform mole.
Monochorionic diamniotic twins, 13-6 to 13-8,
13-9i
dichorionic diamniotic twins vS., 13-2i, 13-3
differential diagnosis, 13-6i, 13-7, 13-6i, 13-7
Monochorionic mono amniotic twins, 13-10 to 1312,13-13i
conjoined twins vs., 13-26i, 13-27
dichorionic diamniotic twins vs., 13-2i, 13-3
differential diagnosis, 13-10i, 13-11 to 13-12
monochorionic diamniotic twins vs., 13-6i, 13-7
Monosomy 13q, partial, atelencephaly/
aprosencephaly vs., 2-87
Monosomy 21, 14-22 to 14-23
Muenke craniosynostosis, craniosynostosis vs., 2-91
Multicystic dysplastic kidneys, 9-30 to 9-32, 9-33i
bilateral
autosomal recessive polycystic kidney disease
vs., 9-34i, 9-35
renal agenesis vs., 9-26i, 9-27
differential diagnosis, 9-30i, 9-31 to 9-32

Meckel-Gruber syndrome vs., IS-22i, 15-23
mesoblastic nephroma vs., 9-39
obstructive renal cystic dysplasia vS., 9-22i, 9-23
ovarian cysts vs., 9-68i, 9-70
renal enlargement due to, 9-10i, 9-11
ureteropelvic junction obstruction vs., 9-18i,
9-19
Multiple gestation, 13-2 to 13-33
Multiple pterygium syndrome, 10-58 to 10-59
arthrogryposis/akinesia sequence vs., 10-55
differential diagnosis, 1O-S8i, 10-58 to 10-59
lethal type of, differential diagnosis, 10-58
MURCS association, VACTERLassociation vs., 15-41
Musculoskeletal system anomalies, 10-1 to 10-59
Myelomeningocele
caudal regression syndrome vs., 3-15
sacrococcygeal teratoma vs., 3-22i, 3-23
Myoblastoma, epignathus vs., 4-23
Myocardium
calcification, hypertrophic cardiomyopathy vs.,
6-62i,6-63
normal peripheral, pericardial effusion vs.,
6-lOi,6-11
Myofibromatosis
cervical teratoma vs., 4-S6i, 4-57
epignathus vs., 4-23
Myoma, subplacental
invasive hydatidiform mole vs., 12-42i, 12-43
placentomegaly vs., 12-28i, 12-29
Myometrial contraction, focal
incompetent cervix vS., 18-3
leiomyoma vs., 18-10i, 18-11
placenta previa vs., 12-12i, 12-13
placental abruption vs., 12-18i, 12-19
succenturiate lobe vs., 12-22i, 12-23
Myometrium, abnormal, uterine rupture vs., 18-17
Myxoma, rhabdomyoma vs., 6-81

N
Nabothian cyst
cervical ectopic pregnancy vs., 1-22i, 1-23
incompetent cervix vs., 18-2i, 18-3
Nasal bone
absent, 4-10 to 4-12, 4-13i
normal, absent nasal bone vs., 4-10i, 4-11
Nasal glioma
epignathus vs., 4-23
frontal encephalocele vs., 2-16
Nasal teratoma, frontal encephalocele vs., 2-16i,
2-17
Nasopharyngeal teratoma, orbital tumors vs., 4-42i
Neck, hyperextended, absent nasal bone vs., 4-10i
Neck masses, cystic, goiter vs., 4-S2i, 4-53
Neoplasms. See Tumors; specific neoplasms.
Nephroma, mesoblastic. See Mesoblastic nephroma.

INDEX
Neu-Laxova syndrome, triploidy vs., 14-19
Neural tube defect
amniotic band syndrome vs., 15-5
craniosynostosis vs., 2-92
diabetic embryopathy vs., 18-53
isolated, OElS syndrome vs., 7-22
valproic acid syndrome vs., l8-42i
Neuroblastoma, 9-42 to 9-44, 9-4Si
bronchopulmonary sequestration vs., 5-17
cervical, goiter vs., 4-S2i, 4-53
differential diagnosis, 9-42i, 9-43
Neuromuscular anomalies, pulmonary hypoplasia
vs.,5-6
Nonimmune hydrops. See Hydrops, nonimmune.
Noonan syndrome, Turner (XO) syndrome vs.,
14-15
Nuchal cystic hygroma, lymphangioma vs., S-28i,
5-29
Nuchal fold, increased, cystic hygroma vs., 4-49
Nuchal translucency, increased, 1-32 to 1-34, l-3Si
Nuchal umbilical cord, 11-26 to 11-27
differential diagnosis, 11-26i
goiter vs., 4-S2i, 4-53
scalp masses vs., 4-44i

o
Obstructive cystic dysplasia. See Renal cystic
dysplasia, obstructive.
Obstructive hydrocephalus, mild ventriculomegaly
vs., 2-40i, 2-41
Occipital encephalocele, 2-12 to 2-14, 2-lSi
cystic hygroma vs., 4-48i, 4-50
differential diagnosis, 2-l2i, 2-13 to 2-14
Joubert syndrome vs., lS-20i, 15-21
Oculodentodigital syndrome, syndactyly vs., 10-47
OElS syndrome, 7-22 to 7-23
body stalk anomaly vs., 7-l4i, 7-15
differential diagnosis, 7-22i
Oligohydramnios, 17-6to 17-8, l7-9i
conditions causing, pulmonary hypoplasia vs.,
S-4i, 5-5 to 5-6
differential diagnosis, 17-6i, 17-7 to 17-8
micrognathia vs., 4-l4i
Pierre Robin syndrome vs., 15-27
secondary to fetal anomaly, biophysical profile
of, l7-20i, 17-21
severe, renal developmental variants vs., 9-6i,
9-7

twin-twin transfusion syndrome vs., l3-l8i,
13-19
Omphalocele, 7-6 to 7-8, 7-9i
amniotic band syndrome vs., 15-5
bladder exstrophy vs., 7-18
body stalk anomaly vs., 7-15
differential diagnosis, 7-6i, 7-7 to 7-8

gastroschisis vs., 7-11
isolated
Beckwith-Wiedemann syndrome vs., lS-lOi
cloacal exstrophy vs., 7-20i
OElS syndrome vs., 7-22i
pentalogy of Cantrell vs., 7-24
urachal anomalies vs., 9-56
Orbital tumors, 4-42 to 4-43
Osteogenesis imperfecta, 10-20 to 10-22, 1O-23i
achondrogenesis vs., 10-2i, 10-3
achondroplasia vs., 10-6i, 10-7
acrania vs., 2-l0i, 2-11
campomelic dysplasia vs., 10-16, 10-16i
differential diagnosis, 1O-20i, 10-21
hypophosphatasia vs., 10-18, 10-18i
thanatophoric dysplasia vs., 1O-26i, 10-27
type II, micromelia vs., 10-10i, 10-12
Outflow tract obstruction
coarctation of aorta vs., 6-30i, 6-31
dilated cardiomyopathy vs., 6-66i, 6-67
left ventricular, hypertrophic cardiomyopathy
vs.,6-63
rhabdomyoma vs., 6-81
Ovarian carcinoma. See also Ovarian neoplasms.
epithelial, incidental ovarian mass vs., 18-35
Ovarian cysts, 9-68 to 9-70, 9-7li
choledochal cyst vs., 8-40
differential diagnosis, 9-68i, 9-69 to 9-70
duodenal atresia vs., 8-11
enteric duplication cyst vs., 8-30i
meconium peritonitis/pseudocyst vs., 8-22
mesenteric cyst vs., 8-32
paraovarian, incidental ovarian mass vs., 1834i,18-35
rupture of, ascites vs., 8-26i, 8-27
tubal ectopic pregnancy vs., 1-14i, 1-15
umbilical cord aneurysm vs., ll-l8i, 11-19
urachal anomalies vs., 9-S6i
Ovarian hyperstimulation syndrome. See
Hyperstimulation syndrome.
Ovarian mass, incidental, 18-34 to 18-36, 18-37i
Ovarian neoplasms
corpus luteum cyst vs., l8-24i
cystic, hyperstimulation syndrome vs., 18-27
epithelial carcinoma, incidental ovarian mass
vs.,18-35
metastatic, incidental ovarian mass vs., 18-36
tubal ectopic pregnancy vs., l-14i, 1-16
Ovarian vein thrombosis, 18-64 to 18-65

p
Palate
cleft. See Cleft lip, palate.
intact, cleft palate vs., 4-6i

XVII

INDEX

xviii

Pallister-Killian syndrome
Cornelia de Lange syndrome vs., 15-14
Fryns syndrome vs., 15-18
Pancreatitis, acute, acute abdomen vs., 18-49
Papillary muscles, normal, echogenic cardiac focus
vs., 6-6i, 6-7
Papilloma, choroid plexus
choroid plexus cyst vs., 2-68i, 2-69
intracranial hemorrhage vs., 2-64i, 2-65
Paraovarian cyst, incidental ovarian mass vs.,
18-34i, 18-35
Para pelvic cysts, maternal hydronephrosis vs.,
18-S6i, 18-58
Parvovirus B19 infection, 16-6 to 16-7
abdominal calcifications due to, meconium
peritonitis/pseudocyst vs., 8-21
cytomegalovirus infection vs., 16-2
differential diagnosis, 16-6i, 16-6 to 16-7
hepatic tumors vs., 8-43
hepatomegaly/splenomegaly vs., 8-38
Rh incompatibilityvs., 18-67
toxoplasmosis vs., 16-8i
varicella infection vs., 16-10
Pelviectasis, mild. See Renal pelviectasis, mild.
Pena-Shokeir syndrome
Pierre Robin syndrome vs., 15-27
trisomy 18 vs., 14-6i, 14-7
Pentalogy of Cantrell, 7-24 to 25
body stalk anomaly vs., 7-14i, 7-15
cloacal exstrophy vs., 7-20i
differential diagnosis, 7-24i, 7-24 to 25
omphalocele vs., 7-7
Pericardial effusion, 6-10 to 6-12, 6-13i
differential diagnosis, 6-lOi, 6-11
isolated, hydrops vs., 17-32i, 17-33
Pericardial fluid, normal, pericardial effusion vs.,
6-11
Perigestational hemorrhage, 1-10 to 1-12, 1-13i
anembryonic pregnancy vs., 1-6i, 1-7
differential diagnosis, 1-10i, 1-11
higher order multiple gestation vs., 13-30i, 13-31
Perimembranous ventricular septal defect, tetralogy
of Fallot vs., 6-S0i, 6-51
Peritonitis, meconium. See Meconium peritonitis.
Periventricular germinal matrix, tuberous sclerosis
vs.,15-37
.'
Periventricular nodular heterotopia, bilateral,
tuberous sclerosis vs., 15-37
Permanent junctional reciprocating tachycardia,
tachyarrhythmia vs., 6-73
Persistent right umbilical vein, 11-22 to 11-23
Pfeiffer syndrome
Apert syndrome vs., IS-8i
Carpenter syndrome vs., IS-12i, 15-13
craniosynostosis vs., 2-90i, 2-91
syndactylyvs.,10-47

Philtrum, normal, cleft lip, cleft palate vs., 4-6i, 4-7
Phocomelia/amelia, isolated, amelia vs., 10-11
Pierre Robin syndrome, 15-26 to 15-27
Placenta, 12-6 to 12-47
battledore, 12-26 to 12-27
differential diagnosis, 12-26i, 12-26 to 12-27
velamentous cord vs., 12-16i, 12-16 to 12-17
circumvallate, 12-24 to 12-25
differential diagnosis, 12-24i, 12-24 to 12-25
uterine synechia vs., 18-14i
hemorrhage, chorioangioma vs., 12-34i, 12-35
hydropic degeneration
complete hydatidiform mole vs., 12-38i,
12-39
with fetal demise, triploidy vs., 14-18i, 14-19
pseudomole of, triploidy vs., 14-19
succenturiate lobe, 12-22 to 12-23
thickened (placentomegaly), 12-28 to 12-29
Placenta accreta spectrum, 12-30 to 12-32, 12-33i
differential diagnosis, 12-30i, 12-31
invasive hydatidiform mole vs., 12-42i, 12-43
uterinerupturevs.,
18-16i, 18-17
Placenta percreta
invasive hydatidiform mole vs., 12-42i, 12-43
uterine rupture vs., 18-16i, 18-17
Placenta previa, 12-12 to 12-14, 12-1Si
differential diagnosis, 12-12i, 12-13
marginal sinus, velamentous cord vs., 12-16i,
12-17
placental abruption vs., 12-19
uncomplicated, placenta accreta spectrum vs.,
12-30i, 12-31
uterine rupture vs., 18-16i, 18-17
Placental abruption, 12-18 to 12-20, 12-2li
acute, succenturiate lobe vs., 12-22i, 12-23
acute abdomen vs., 18-48i
chorioangioma vs., 12-34i, 12-35
differential diagnosis, 12-18i, 12-19
leiomyoma vs., 18-10i, 18-11
placenta previa vs., 12-12i, 12-13
placental sonolucencies vs., 12-6i, 12-7 to 12-8
placentomegaly vs., 12-28i, 12-29
uterine rupture vs., 18-16i, 18-17
Placental insufficiency
ductus venosus vs., 1-36i
symmetric intrauterine growth restriction vs.,
17-10i,17-11
Placental lakes. See Placental sonolucencies.
Placental sonolucencies, 12-6 to 12-12-8, 12-9i
chorioangioma vs., 12-34i, 12-35
complete hydatidiform mole vs., 12-38i, 12-39
differential diagnosis, 12-6i, 12-7 to 12-8
placenta accreta spectrum vs., 12-30i, 12-31
triploidyvs., 14-18i, 14-19
Placentomegaly, 12-28 to 12-29

INDEX
Plagiocephaly, deformational, craniosynostosis vs.,
2-91
Pleural effusion, 5-20 to 5-22, S-23i
differential diagnosis, S-20i, 5-21
pericardial effusion vs., 6-10i, 6-11
Polycystic kidney disease
autosomal dominant
autosomal recessive polycystic kidney disease
vs.,9-35
maternal hydronephrosis vs., 18-S6i, 18-58
multicystic dysplastic kidneys vs., 9-31 to 9-32
autosomal recessive, 9-34 to 9-36, 9-37i
differential diagnosis, 9-34i, 9-35
Meckel-Gruber syndrome vs., lS-22i, 15-23
mesoblastic nephroma vs., 9-38i, 9-39
multicystic dysplastic kidneys vs., 9-31
obstructive renal cystic dysplasia vs., 9-24
pulmonary hypoplasia vs., S-4i, 5-6
renal agenesis vs., 9-26i, 9-27
renal enlargement due to, 9-11
twin-twin transfusion syndrome vs., 13-18i,
13-19
Polycystic ovarian syndrome, hyperstimulation
syndrome vs., 18-26i, 18-27
Polydactyly, 10-42 to 10-44, 1O-4Si. See also Short
rib-polydactyly syndrome.
clinodactyly vs., lO-SOi, 10-51
differential diagnosis, 1O-42i, 10-43 to 10-44
valproic acid syndrome vs., 18-42i
Polyhydramnios, 17-2 to 17-4, 17 -Si
Popliteal pterygium syndrome, multiple pterygium
syndrome vs., 10-58, 1O-S8i
Porencephalic cyst
arachnoid cyst vs., 2-73
glioependymal cyst vs., 2-77
schizencephaly vs., 2-81
Porencephaly
alobar holoprosencephaly
vs., 2-43
aqueductal stenosis vs., 2-24
vein of Galen malformation vs., 2-94i, 2-95
'Portal vein calcification, hepatic calcifications vs.,
8-36i,8-37
Posterior urethral valves. See Urethral valves,
posterior.
Postpartum fever, endometritis vs., 18-23
Pregnancy
ectopic. See Ectopic pregnancy.
first trimester, 1-6 to 1-39
heterotopic. See Heterotopic pregnancy.
maternal conditions in, 18-2 to 18-69
normal intrauterine
abdominal ectopic pregnancy vs., 1-26
anembryonic pregnancy vs., 1-7
interstitial ectopic pregnancy vs., 1-18i, 1-19
low uterine implantation, cervical ectopic
pregnancy vs., 1-23

tubal ectopic pregnancy vs., 1-15
Premature atrial contractions
blocked, bradyarrhythmia
vs., 6-76i, 6-77
irregular rhythm vs., 6-70
Premature rupture of membranes
monochorionic
monoamniotic twins vs.,
13-10i,13-11
renal agenesis vs., 9-27
twin-twin transfusion syndrome vs., 13-18i,
13-19
Premature ventricular contraction, irregular rhythm
vs.,6-71
Proboscis, orbital tumors vs., 4-42i, 4-43
Products of conception, retained. See Retained
products of conception.
Proptosis
hypertelorism vs., 4-38i, 4-40
hypotelorism vs., 4-34i, 4-36
Prune belly syndrome, 9-50 to 9-51
differential diagnosis, 9-S0i
posterior urethral valves vs., 9-46i, 9-47
Pseudo-warfarin embryopathy, warfarin
(coumadin) embryopathy vs., 18-46
Pseudocardiomegaly, dilated cardiomyopathy vs.,
6-66i,6-67
Pseudochondroplasia,
achondroplasia vs., 10-7
Pseudomicrognathia,
micrognathia vs., 4-15
Pseudomole, complete hydatidiform mole vs.,
12-38i, 12-39
Pseudoprosencephaly, atelencephaly /
aprosencephaly vs., 2-87
Pseudotrisomy 13, Smith-Lemli-Opitz syndrome vs.,
15-33
Pseudotrisomy 18. See Pena-Shokeir syndrome.
Pterygia, isolated, multiple pterygium syndrome vs.,
10-59
Pterygium colli, multiple pterygium syndrome vs.,
1O-S8i, 10-59
Pterygium syndrome
multiple, 10-58 to 10-59
arthrogryposis/akinesia
sequence vs., 10-55
differential diagnosis, 1O-S8i, 10-58 to 10-59
lethal type of, differential diagnosis, 10-58
popliteal, multiple pterygium syndrome vs., 1058,1O-S8i
Pulmonary atresia
dilated cardiomyopathy vs., 6-66i, 6-67
Ebstein anomaly, tricuspid dysplasia vs., 6-42i,
6-43

hypertrophic cardiomyopathy vs., 6-62i, 6-63
with intact ventricular septum, tricuspid atresia
vs.,6-44i
rhabdomyoma vs., 6-80i, 6-81
with ventricular septal defect
tetralogy of Fallot vs., 6-S0i, 6-51
truncus arteriosus vs., 6-59

xix

INDEX
Pulmonary hypoplasia, 5-4 to 5-6, S-7i
Pulmonary valve stenosis, atresia, 6-38 to 6-40,
6-4li
differential diagnosis, 6-38i, 6-39
hypertrophic cardiomyopathy vs., 6-62i, 6-63
rhabdomyoma vs., 6-80i, 6-81
PUV. See Urethral valves, posterior.
Pyelonephritis
acute abdomen vs., 18-49
maternal hydronephrosis vs., 18-58
ovarian vein thrombosis vs., 18-64i, 18-65

Q
Quadruplets,

13-30 to 13-32, 13-33i

R

xx

Radial ray malformation, 10-38 to 10-40, 1O-4li
differential diagnosis, 1O-38i, 10-39
valproic acid syndrome vs., 18-42i
Radial-ulnar deficiencies, ectrodactyly vs., 10-S2i,
10-53
Redundant skin, hydrops vs., 17-32i, 17-33
Reflux
duplicated renal collecting system vs., 9-11
vesicoureteral. See Vesicoureteral reflux.
Renal. See also Kidney entries.
Renal agenesis, 9-26 to 9-28, 9-29i
autosomal recessive polycystic kidney disease vs.,
9-34i
differential diagnosis, 9-26i, 9-27 to 9-28
oligohydramnios
due to, biophysical profile of,
17-20i,17-21
pulmonary hypoplasia vs., S-4i, 5-5
sirenomelia vs., lS-28i, 15-29
twin-twin transfusion syndrome vs., 13-18i,
13-19
Renal collecting system, duplicated, 9-10 to 9-12,
9-13i
differential diagnosis, 9-10i, 9-11
maternal hydronephrosis vs., 18-S6i, 18-58
mesoblastic nephroma vs., 9-38i, 9-39
mild pelviectasis vs., 9-15
neuroblastoma vs., 9-42i, 9-43
Renal cystic dysplasia
obstructive, 9-22 to 9-24, 9-2Si
differential diagnosis, 9-22i, 9-23 to 9-24
multicystic dysplastic kidneys vs., 9-30i, 9-31
renal developmental variants vs., 9-6i, 9-7
secondary to aneuploidy/syndromes,
obstructive
renal cystic dysplasia vs., 9-24
Renal cysts. See also Polycystic kidney disease; Renal
cystic dysplasia.
maternal hydronephrosis vs., 18-58
simple, multicystic dysplastic kidneys vs., 9-31

Renal developmental variants, 9-6 to 9-8, 9-9i
Renal hilum vessels, mild pelviectasis vs., 9-15 to
9-16
Renal masses, renal developmental variants vs., 96i,9-7
Renal pelviectasis, mild, 9-14 to 9-16, 9-17i
differential diagnosis, 9-14i, 9-15 to 9-16
ureteropelvic junction obstruction vs., 9-18i, 919 to 9-20
Renal pyramids, normal
obstructive renal cystic dysplasia vs., 9-22i, 9-24
ureteropelvic junction obstruction vs., 9-18i,
9-20
Renal stones
acute abdomen vs., 18-49
maternal hydronephrosis vs., 18-S6i
Restrictive dermopathy, arthrogryposis/akinesia
sequence vs., 10-56
Retained products of conception, 18-20 to 18-21
anembryonic pregnancy vs., 1-7
choriocarcinoma vs., 12-44i, 12-45
differential diagnosis, 18-20i, 18-20 to 18-21
endometritis vs., 18-22i
invasive hydatidiform mole vs., 12-42i, 12-43
uterine rupture vs., 18-16i, 18-17
Retroperitoneal teratoma, mesoblastic nephroma
vs., 9-39
Reversed atrial flap, foramen ovale aneurysm vs.,
6-8i
Rh incompatibility, 18-66 to 18-68, 18-69i
differential diagnosis, 18-66i, 18-66 to 18-67
parvovirus B19 infection vs., 16-6i
Rhabdomyoma, 6-80 to 6-82, 6-83i
differential diagnosis, 6-80i, 6-81
echogenic cardiac focus vs., 6-6i, 6-7
hypertrophic cardiomyopathy vs., 6-62i, 6-63
Rhabdomyosarcoma
cervical teratoma vs., 4-57
epignathus vs., 4-22i, 4-23
midface anomalies vs., 4-32
Rhombencephalosynapsis,
2-34 to 2-35
Right heart enlargement, coarctation of aorta vs.,
6-30i,6-31
Right ventricle. See Ventricle(s).
Roberts syndrome/Roberts sacrococcygeal syndrome
amelia vs., 10-10 to 10-11
VACTERLassociation vs., 15-42
Rockerbottom foot, 10-34 to 10-35
clubfoot vs., 1O-30i, 10-31
differential diagnosis, 1O-34i, 10-35
Rubella
abdominal calcifications due to, meconium
peritonitis/pseudocyst
vs., 8-21
cytomegalovirus infection vs., 16-3
parvovirus B19 infection vs., 16-6

INDEX

s
Sacrococcygeal teratoma, 3-22 to 3-24, 3-25i
Chiari II malformation vs., 2-19
differential diagnosis, 3-22i, 3-23
kyphosis/scoliosis vs., 3-18i, 3-19
spina bifida vs., 3-6i, 3-7
SADDAN syndrome, achondroplasia vs., 10-7
Saethre-Chotzen syndrome
Apert syndrome vs., 15-8 to 15-9
Carpenter syndrome vs., 15-13
craniosynostosis vs., 2-91
with mental retardation, craniosynostosis vs.,
2-91
Sandal gap foot, 10-36 to 10-37
SC teratoma. See Sacrococcygeal teratoma.
Scalp edema, scalp masses vs., 4-44i
Scalp masses, 4-44 to 4-46, 4-47i
differential diagnosis, 4-44i, 4-45
occipital encephalocele vs., 2-12i, 2-13
Schizencephaly, 2-80 to 2-82, 2-83i
absent cavum septi pellucidi vs., 2-54i, 2-55
arachnoid cyst vs., 2-72i, 2-73
differential diagnosis, 2-80i, 2-81
encephalomalacia vs., 2-60i, 2-61
glioependymal cyst vs., 2-76i, 2-77
hydranencephaly vs., 2-56i, 2-57
semilobar/lobar holoprosencephaly vs., 2-46i,
2-47
septo-optic dysplasia vs., 2-50i, 2-51
Scoliosis, 3-18 to 3-20, 3-2li
differential diagnosis, 3-18i, 3-19
isolated, spina bifida vs., 3-6i, 3-7
Seckel syndrome, Pierre Robin syndrome vs., 15-27
Segmental spinal dysgenesis, caudal regression
syndrome vs., 3-15
Semilobar holoprosencephaly. See
Holoprosencephaly, semilobar.
Septate uterus
circumvallate placenta vs., 12-24i, 12-25
interstitial ectopic pregnancy vs., 1-18i, 1-19
Septo-optic dysplasia, 2-50 to 2-53, 2-54i
.
absent cavum septi pellucidi vs., 2-54, 2-541
agenesis of corpus callosum vs., 2-36i, 2-37
differential diagnosis, 2-50i, 2-51
semilobar/lobar holoprosencephaly vs., 2-46i,
2-47
Sequestration. See Bronchopulmonary
sequestration.
Sex cord stromal tumor, incidental ovarian mass
vs., 18-35
Short rib-polydactyly syndrome, 10-24 to 10-25
achondrogenesis vs., 10-3
asphyxiating thoracic dysplasia vs., 10-14,
1O-14i
differential diagnosis, 1O-24i, 10-25

polydactyly vs., 1O-42i, 10-43
types I and II, micromelia vs., 10-12
Sigmoid colon, mass effect from, ureterocele vs.,
9-53
Simpson-Golabi-Behmel syndrome, BeckwithWiedemann syndrome vs., 15-10
Single umbilical artery, 11-10 to 11-11-12, 11-13i
Single ventricle, 6-48 to 49
.
Sinus bradycardia, transient, bradyarrhythmla vs.,
6-76i,6-77
Sinus previa, marginal, vasa previa vs., 11-24,
11-24i
Sinus tachycardia, tachyarrhythmia vs., 6-73
Sirenomeli a, 15-28 to 15-30, 15-3li
caudal regression syndrome vs., 3-15
differential diagnosis, 15-28i, 15-29
renal agenesis vs., 9-27
Situs inversus, 6-14 to 6-15
Skin, redundant, hydrops vs., 17 -32i, 17-33
Skull vault tumor, scalp masses vs., 4-45
Small for gestational age, symmetric intrauterine
growth restriction vs., 17-11
.
Smith-Lemli-Opitz syndrome, 15-32 to 15-34, 15-351
differential diagnosis, 15-32i, 15-32 to 15-33
polydactyly vs., 10-43
trisomy 18 vs., 14-7
Spaulding sign
atelencephaly/aprosencephaly
vs., 2-86i, 2-87
craniosynostosis vs., 2-90i, 2-92
Spina bifid a, 3-6 to 3-8, 3-9i. See also Chiari II
malformation.
Spinal dysgenesis, segmental, caudal regression
syndrome vs., 3-15
Spinal muscular atrophy, arthrogryposis/akinesia
sequence vs., 10-55
Spine and spinal cord anomalies, 3-6 to 3-25
Splenomegaly, 8-38 to 8-39
Split hand-split foot malformation
ectrodactyly vs., 10-52
with long bone deficiency, ectrodactyly vs.,
10-53
syndactyly vs., 10-48
Spondyloepiphyseai dysplasia, achondroplasia vs./
10-7
Spontaneous abortion, cervical ectopic pregnancy
vs., 1-22i, 1-23
Stargazer malformation. See Iniencephaly.
Sternum, cleft, pentalogy of Cantrell vs., 7-24
Steroidogenesis, abnormal, craniosynostosis vs.,
2-91
Stickler syndrome, Pierre Robin syndrome vs., 15-26
Stomach bubble, abnormal, heterotaxy vs., 6-17
Strawberry shaped head
craniosynostosis vs., 2-90i, 2-92
microcephaly vs., 2-84i
"Stuck" twin. See Twins, anomalous (stuck).

xxi

INDEX

xxii

Subdural hemorrhage, hydranencephaly vs., 2-57
Subependymal gray matter heterotopia, tuberous
sclerosis vs., 15-37
Subplacental myoma
invasive hydatidiform mole vs., 12-42i, 12-43
placentomegaly vs., 12-2Si, 12-29
Succenturiate lobe, 12-22 to 12-23
Supraventricular tachycardia
irregular rhythm vs., 6-70i, 6-71
tachyarrhythmia vs., 6-72i, 6-73
Sutures, overlapping, with demise, atelencephaly/
aprosencephaly vs., 2-87
Swallowed debris, echogenic bowel vs., S-2i, 8-4
Swallowing, abnormal, esophageal atresia vs., 8-7
Syndactyly, 10-46 to 10-48, lO-49i
clinodactyly vs., lO-SOi, 10-51
differential diagnosis, lO-46i, 10-48 to 10-48
ectrodactyly vs., lO-S2i, 10-53
non-syndromal, syndactylyvs., 10-47
sandal gap foot vs., 10-37
Syndromes, 15-2 to 15-43. See also specific
syndrome.
Synechia. See Uterine synechia.
Syntelencephaly, semilobar/lobar
holoprosencephaly vs., 2-47
Syphilis
abdominal calcifications due to, meconium
peritonitis/pseudocyst vs., 8-21
cytomegalovirus infection vs., 16-2i, 16-3
hepatomegaly/splenomegaly vs., 8-38
parvovirus B19 infection vs., 16-6

T
Tachyarrhythmia, 6-72 to 74, 6-7Si
Tachycardia
permanent junctional reciprocating,
tachyarrhythmia vs., 6-73
sinus, tachyarrhythmia vs., 6-73
supraventricular
irregular rhythm vs., 6-70i, 6-71
tachyarrhythmia vs., 6-72i, 6-73
ventricular, tachyarrhythmia vs., 6-73
Talipes equinovarus. See Clubfoot.
Teratoma
arachnoid cyst vs., 2-73
cervical. See Cervical teratoma.
chest, 5-24 to 5-25
chorioangioma vs., 12-34i, 12-35
congenital diaphragmatic hernia vs., S-Si, 5-9
cystic adenomatoid malformation vs., 5-13
facial. See Epignathus.
glioependymal cystvs., 2-76i, 2-77
hepatic calcifications vs., 8-36i
intracranial hemorrhage vs., 2-64i
midface anomalies vs., 4-30i, 4-32

nasal, frontal encephalocele vs., 2-16i, 2-17
nasopharyngeal, orbital tumors vs., 4-42i
neuroblastoma vs., 9-42i, 9-43
pericardial, bronchopulmonary sequestration
vs., S-16i, 5-17
retroperitoneal, mesoblastic nephroma vs., 9-39
rhabdomyoma vs., 6-S0i, 6-81
sacrococcygeal. See Sacrococcygeal teratoma.
Testicular torsion, 9-66 to 9-67
differential diagnosis, 9-66i, 9-66 to 9-67
hydrocele vs., 9-64i
Testicular tumor, testicular torsion vs., 9-67
Tetra-amelia, amelia vs., 10-11
Tetralogy of Fallot, 6-50 to 6-52, 6-S3i
differential diagnosis, 6-S0i, 6-51
double outlet right ventricle vs., 6-46i
pulmonary valve stenosis/atresia vs., 6-38i, 6-39
transposition of great arteries vs., 6-S4i, 6-55
truncus arteriosus vs., 6-59
Thalidomide embryopathy, amelia vs., 10-11
Thanatophoric dysplasia, 10-26 to 10-28, lO-29i
absent nasal bone vs., 4-10i, 4-11
achondrogenesis vs., 10-2i, 10-3
achondroplasia vs., lO-6i, 10-7
Apert syndrome vs., 15-9
Carpenter syndrome vs., IS-12i, 15-13
craniosynostosis vs., 2-91
differential diagnosis, lO-26i, 10-27
osteogenesis imperfecta vs., lO-20i, 10-21
warfarin (coumadin) embryopathy vs., IS-46i
Theca lutein cysts, 18-30 to 18-32, IS-33i
differential diagnosis, IS-30i, 18-31
hyperstimulation syndrome vs., IS-26i
incidental ovarian mass vs., 18-34
Thoracic anomalies, 5-4 to 5-31
Thoracic dysplasia, asphyxiating. See Asphyxiating
thoracic dysplasia.
Thoracoabdominal syndrome, Fryns syndrome vs.,
15-19
Thrombocytopenia-absent
radius syndrome
amelia vs., 10-11
VACTERLassociation vs., 15-41
Thrombosis
umbilical artery
abnormal cord Doppler ultrasound vs., 11-6i
single umbilical artery vs., ll-IOi, 11-11
umbilical vein, single umbilical artery vs., 11lOi,l1-l1
Thrombus, intervillous, chorioangioma vs., 12-35
Thumbs
adducted, radial ray malformation vs., 10-3Si,
10-39
hypoplastic, radial ray malformation vs.,
10-3Si, 10-39
Thyroglossal duct cyst, goiter vs., 4-53

INDEX
Toe anomalies. See Clinodactyly; Ectrodactyly;
Polydactyly; Syndactyly.
Tongue
cysts of, macroglossia vs., 4-19
normal, macroglossia vs., 4-18i
Torsion
adnexal/tuboovarian, 18-38 to 18-39
acute abdomen vs., I8-48i, 18-49
differential diagnosis, I8-38i, 18-39
testicular, 9-66 to 9-67
differential diagnosis, 9-66i, 9-66 to 9-67
hydrocele vs., 9-64i
Townes-Brock syndrome, VACTERLassociation vs.,
15-42
Toxoplasmosis, 16-8 to 16-9
abdominal calcifications due to
differential diagnosis, I6-8i
gallstones vs., 8-34i
meconium peritpnitis/pseudocyst vs., 8-20i,
8-21
cytomegalovirus infection vs., I6-2i, 16-2 to 16-3
differential diagnosis, I6-8i
hepatic tumors vs., 8-43
hepatomegaly/splenomegaly vs., 8-38
parvovirus B19 infection vs., 16-6
varicella infection vs., I6-IOi
Tracheal atresia, 5-26 to 5-27
cystic adenomatoid malformation vs., 5-I2i,
5-13
differential diagnosis, S-26i, 5-27
Transposition of great arteries, 6-54 to 6-56, 6-S7i
differential diagnosis, 6-S4i, 6-55
double outlet right ventricle vS., 6-46i
Treacher Collins syndrome, Pierre Robin syndrome
vs., 15-26 to 15-27
Tricuspid atresia, 6-44 to 6-45
differential diagnosis, 6-44i, 6-44 to 6-45
pulmonary valve stenosis/atresia vs., 6-38i, 6-39
single ventricle vs., 6-48i, 6-49
Tricuspid dysplasia, 6-42 to 6-43
Triplets, 13-30 to 13-32, 13-33i
Triploidy, 14-18 to 14-20, I4-2li
chorioangioma vs., 12-35
complete hydatidiform mole vs., 12-38i, 12-39
to 12-40
differential diagnosis, I4-I8i, 14-19
Pierre Robin syndrome vs., IS-26i
Smith-Lemli-Opitz syndrome vs., lS-32i, 15-32
to 15-33 .
syndactyly vs., 10-46i, 10-47
trisomy 18 vS., 14-8
Trisomy 13, 14-10 to 14-12, I4-13i
autosomal recessive polycystic kidney disease vs.,
9-35
differential diagnosis, I4-IOi, 14-11 to 14-12
Meckel-Gruber syndrome vs., IS-22i, 15-23

monosomy 21 vS., 14-22
polydactyly vs., 1O-42i, 10-43
Smith-Lemli-Opitz syndrome vs., IS-32i
triploidy vs., 14-19
trisomy 18 vS., 14-8
trisomy 21 vs., I4-2i, 14-4
Trisomy 18, 14-6 to 14-8, I4-9i
arthrogryposis/akinesia sequence vs., 10-S4i,
10-55
Cornelia de Lange syndrome vs., IS-14i
craniosynostosis vs., 2-90i, 2-92
differential diagnosis, I4-6i, 14-7 to 14-8
ductus venosus vs., I-36i, 1-37
Fryns syndrome vs., IS-18i
Pierre Robin syndrome vs., IS-26i
Smith-Lemli-Opitz syndrome vs., IS-32i
triploidy vs., 14-19
trisomy 13 vS., 14-12
trisomy 21 vs., I4-2i, 14-3
VACTERLassociation vs., IS-40i, 15-41
Trisomy 21, 14-2 to 14-4, I4-Si
differential diagnosis, I4-2i, 14-3 to 14-4
ductus venosus vs., I-36i, 1-37
echogenic bowel in, cystic fibrosis vs., IS-16i
hepatomegaly/splenomegaly vs., 8-38 to 8-39
isolated minor markers, 14-3
monosomy 21 vS., 14-22, I4-22i
parvovirus B19 infection vs., I6-6i
Turner (XO) syndrome vs., I4-I4i, 14-15
warfarin (coumadin) embryopathy vs., I8-46i
Truncus arteriosus, 6-58 to 6-60, 6-6li
Tubal ectopic pregnancy, 1-14 to 1-16, I-17i
abdominal ectopic pregnancy vs., I-26i
differential diagnosis, I-14i, 1-15 to 1-16
interstitial ectopic pregnancy vs., 1-19
Tuberous sclerosis, 15-36 to 15-38
autosomal recessive polycystic kidney disease vs.,
9-35
differential diagnosis, IS-36i, 15-37
Tuboovarian torsion. See Torsion, adnexal/
tuboovarian.
Tumors. See also specific type of tumor;neoplasm.
abdominal calcifications due to
gallstones vs., 8-34
meconium peritonitis/pseudocyst vs., 8-21
central nervous system, 2-102 to 2-104, 2-I0Si
chest
pleural effusion vs., S-20i, 5-21
pulmonary hypoplasia vs., 5-5
fibroid. See Leiomyoma.
germ cell, incidental ovarian mass vs., 18-35
hepatic. See Liver neoplasms.
hyperextension of head due to, iniencephaly
vs., 3-11
intracranial, intracranial hemorrhage vs., 2-64i,
2-65

xxiii

INDEX

xxiv

nasal glioma
epignathus vs., 4-23
frontal encephalocele vs., 2-16
ovarian. See Ovarian neoplasms.
pulmonary hyperechoic mass, tracheal atresia
vs., 5-27
sex cord stromal tumor, incidental ovarian mass
vs., 18-35
solid, sacrococcygeal teratoma vs., 3-23
teratoma. See Teratoma.
vascular, arteriovenous fistula vs., 2-99
Turbulence artifact, intracranial hemorrhage vs.,
2-64i
Turner (XO) syndrome, 14-14 to 14-16, 14-17i
differential diagnosis, 14-14i, 14-15
parvovirus B19 infection vs., 16-6i
trisomy 21 vs., 14-2i, 14-3
Twin anomaly, monochorionic monoamniotic
twins vs., 13-11
Twin demise
discordant twin growth vs., 13-14i, 13-15
monochorionic monoamniotic twins vs., 13-11
twin reversed arterial perfusion vs., 13-22i, 13-23
twin-twin transfusion syndrome vs., 13-18i,
13-19
Twin reversed arterial perfusion, 13-22 to 13-24,
13-25i
conjoined twins vs., 13-26i, 13-27
differential diagnosis, 13-22i, 13-23
Twin-twin transfusion syndrome, 13-18 to 13-19,
13-2Oi
absent bladder in, renal agenesis vs., 9-26i, 9-27
bladder exstrophy vs., 7-18i
differential diagnosis, 13-18i, 13-19
discordant twin growth vs., 13-14i, 13-15
monochorionic monoamniotic twins vs., 13-11
Twins, 13-2 to 13-29
anomalous (stuck)
mimicking of acardiac twin in, 13-22i, 13-23
monochorionic monoamniotic twins vs.,
13-1Oi
twin-twin transfusion syndrome vs., 13-18i,
13-19
bicornuate, heterotopic pregnancy vs., 1-30i
conjoined, 13-26 to 13-28, 13-29i
differential diagnosis, 13-26i, 13-27
monochorionic mono amniotic twins vs.,
13-10i,13-11
twin reversed arterial perfusion vs., 13-22i,
13-23
diamniotic. See Diamniotic twins.
dichorionic diamniotic, 13-2 to 13-4, 13-Si
differential diagnosis, 13-2i, 13-3
monochorionic diamniotic twins vs., 13-6i,
13-7
discordant growth, 13-14 to 13-16, 13-17i

higher order multiple gestation vs., 13-30i, 13-31
hydatidiform mole with
placental sonolucencies vs., 12-7
triploidyvs., 14-18i, 14-19
monochorionic diamniotic, 13-6 to 13-8, 13-9i
dichorionic diamniotic twins vs., 13-2i, 13-3
differential diagnosis, 13-6i, 13-7
monochorionic monoamniotic, 13-10 to 13-12,
13-13i
dichorionic diamniotic twins vs., 13-2i, 13-3
differential diagnosis, 13-10i, 13-11 to 13-12
monochorionic diamniotic twins vs., 13-6i,
13-7
uterine synechia vs., 18-15
TWIST mutation associated craniosynostosis,
craniosynostosis vs., 2-91

u
Umbilical artery(ies)
fused, single umbilical artery vs., 11-11
single, 11-10 to 11-12, 11-13i
thrombosis
abnormal cord Doppler ultrasound vs., 11-6i
single umbilical artery vs., 11-lOi, 11-11
Umbilical cord, 11-6 to 11-27
abnormal cord Doppler ultrasound, 11-6 to 11-8,
11-9i
adjacent, battledore placenta vs., 12-26i, 12-27
adjacent to neck, nuchal umbilical cord vs., 1126 to 11-27
aneurysm. See Umbilical cord aneurysm.
compression, abnormal cord Doppler
ultrasound vs., 11-6i, 11-7
cyst. See Umbilical cord cyst.
hemangioma, omphalocele vs., 7-8
nuchal. See Nuchal umbilical cord.
presentation of, vasa previa vs., 11-24, 11-24i
resolving hematoma of, umbilical cord cyst vs.,
11-16
supernumerary vessels of, umbilical cord cyst vs.,
11-16
velamentous insertion. See Velamentous cord.
Umbilical cord aneurysm, 11-18 to 11-20, 11-2li
differential diagnosis, 11-18i, 11-19
umbilical cord cyst vs., 11-14i, 11-15
Umbilical cord cyst, 11-14 to 11-16, 11-17i
differential diagnosis, 11-14i, 11-15 to 11-16
omphalocele vs., 7-6i, 7-7
umbilical cord aneurysm vs., 11-18i, 11-19
Umbilical hernia, omphalocele vs., 7-7
Umbilical vein
normal, persistent right umbilical vein vs., 1122i,l1-23
persistent right, 11-22 to 11-23

INDEX
thrombosis, single umbilical artery vs., ll-IOi,
11-11
varix
choledochal cyst vs., 8-40i
persistent right umbilical vein vs., 11-22i,
11-23
umbilical cord aneurysm vs., 11-18i
UPJ. See Ureteropelvic junction obstruction.
Urachal anomalies, 9-56 to 9-57
Urachal cyst
enteric duplication cyst vs., 8-31
meconium peritonitis/pseudocyst
vs., 8-22
mesenteric cyst vs., 8-33
ovarian cysts vs., 9-68i, 9-69
umbilical cord aneurysm vs., 11-19
Ureter
dilated, multicystic dysplastic kidneys vs., 9-32
enlarged. See Megaureter.
Ureteral distention
mild pelviectasis vs., 9-15
ureteropelvic junction obstruction vs., 9-19
Ureterectasis, jejunal/ileal atresia vs., 8-15
Ureteric filling defect, maternal hydronephrosis vs.,
18-57
Ureterocele, 9-52 to 9-54, 9-SSi
differential diagnosis, 9-S2i, 9-53 to 9-54
simple, duplicated renal collecting system vs.,
9-11
Ureteropelvic junction obstruction, 9-18 to 9-20,
9-21i
ascites vS., 8-27
differential diagnosis, 9-18i, 9-19 to 9-20
duplicated renal collecting system vs., 9-lOi,
9-11
maternal hydronephrosis vS., 18-57
mild pelviectasis vS., 9-14i, 9-15
obstructive cystic dysplasia vS., 9-22i
ovarian cysts vs., 9-68i
prune belly syndrome vs., 9-S0i
ureterocele vs., 9-S2i, 9-53
Ureterovesical obstruction, ascites vs., 8-27
Urethral atresia, posterior urethral valves vs., 9-46i,
9-47
Urethral valves, posterior, 9-46 to 9-48, 9-49i
ascites vs., 8-26i, 8-27
autosomal recessive polycystic kidney disease vs.,
9-34i
differential diagnosis, 9-46i, 9-47
mild pelviectasis vs., 9-14i, 9-15
prune belly syndrome vS., 9-S0i
pulmonary hypoplasia vs., S-4i, 5-6
urachal anomalies vs., 9-S6i
ureterocele vs., 9-S2i
Urinary ascites, differential diagnosis, 8-27
Uterine artery Doppler, 17-28 to 17-30, 17-3li
pitfalls in, 17-28i, 17-29

Uterine contraction. See Myometrial contraction,
focal.
Uterine duplication, 18-6 to 18-8, 18-9i
differential diagnosis, 18-6i, 18-7
heterotopic pregnancy vs., 1-3Oi
interstitial ectopic pregnancy vs., 1-18i, 1-19
oligohydramnios vS., 17-6i, 17-8
polyhydramnios vs., 17-2i, 17-4
Uterine fibroids. See Leiomyoma.
Uterine rupture, 18-16 to 18-18, 18-19i
acute abdomen vs., 18-48i
differential diagnosis, 18-16i, 18-17 to 18-18
Uterine septum, synechia vs., 18-14i, 18-14 to 18-15
Uterine synechia, 18-14 to 18-15
chorioamniotic separation vS., 12-10i, 12-11
circumvallate placenta vs., 12-24i
differential diagnosis, 18-14i, 18-14 to 18-15
Uterine vessel, near cervix, vasa previa vs., 11-24i,
11-25
Uterus
atonic, retained products of conception vs.,
18-20
bicornuate
heterotopic pregnancy vs., 1-30i
interstitial ectopic pregnancy vs., 1-18i, 1-19
blood/clot in
endometritis vS., 18-22i, 18-23
retained products of conception vs., 18-20i,
18-21
infection
hepatic calcifications vs., 8-36
hydantoin syndrome vs., 18-43
normal postpartum, retained products of
conception vs., 18-20
ruptured. See Uterine rupture.
septate
circumvallate placenta vs., 12-24i, 12-25
interstitial ectopic pregnancy vs., 1-18i, 1-19

v
VACTERLassociation, 15-40 to 15-42, IS-43i
caudal regression syndrome vs., 3-14i, 3-15
differential diagnosis, IS-40i, 15-41 to 15-42
sirenomelia vs., 15-29
VACTERLwith hydrocephalus, VACTERL
association vs., 15-42
Vaginal air, incompetent cervix vs., 18-2i, 18-3
Valproic acid syndrome, 18-44 to 18-45
differential diagnosis, 18-44i
hydantoin syndrome vs., 18-42i
Varicella infection, 16-10 to 16-11
abdominal calcifications due to
gallstones vS., 8-34i
meconium peritonitis/pseudocyst
vS., 8-21
cytomegalovirus infection vs., 16-2i, 16-3

xxv