Atlas of Genetic Diagnosis and Counseling

Home , Aicardi syndrome, Alagille syndrome, Campomelic dysplasia, Dysmelia, Hypochondroplasia, Pierre Robin sequence

Harold Chen

Atlas of Genetic Diagnosis and Counseling

Second Edition

With 2427 Figures and 1 Table Harold Chen Perinatal and Clinical Genetics Department of Pediatrics LSU Health Sciences Center 1501 Kings Highway Shreveport, LA 71130 USA

ISBN 978-1-4614-1036-2 e-ISBN 978-1-4614-1037-9 Print and electronic bundle under ISBN 978-1-4614-1038-6 DOI 10.1007/978-1-4614-1037-9 Springer New York Dordrecht Heidelberg London

Library of Congress Control Number: 2011942140

The ﬁrst edition was published by # Humana Press Inc. 2006

Second Edition: # Springer Science+Business Media, LLC 2012

All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identiﬁed as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

Cover illustration: Courtesy of Harold Chen

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com) I would like to dedicate this Atlas to Children’s Hospital, Louisiana State University Health Sciences Center in Shreveport, Louisiana.

Preface to the Second Edition

It has been 5 years since the publication of the first edition of this atlas in 2006. Since then, significant progress has been made in the field of genetic diagnosis and counseling. The first edition of the atlas covered 203 chapters which were revised with current literature and addition of many illustrations, mostly in color. Fifty two new chapters have been added to this edition. Selected references have also been added to the text for the sources of the information. As with the previous edition, a detailed outline of each disorder is provided, describing the genetics, basic defects, clinical features, diagnostic investigations, and genetic counseling, including recurrence risk, prenatal diagnosis, and management. Relevant references are added in the second edition. The cases are supplemented by case history and diagnostic confirmations by imaging, cytogenetic, biochemical, and/or molecular studies. I am grateful to the following individuals for their contribution and support of this edition: Dr. Susonne Ursin, my genetic colleague and Chief of Perinatal Genetics, for case studies (Joubert syndrome, Mowatt-Wilson syndrome, otopalatodigital syndrome, rigid spine syndrome, Saethre-Chotzen syndrome, Silver-Russell syndrome); Dr. RMS Riel-Romero for megalencephalic leukoencephalopathy with subcortical cysts; Dr. Amal Anga for Duncan syndrome; Drs. Richard McCall, Phillip Gates, and Anne Hollister, Shreveport Shriners Hospital for Children; Dr. Ghali Ghali, Chairman of Oral and Maxillofacial Surgery; and Dr. Renata Pilatova, Pinecrest Development Center, for providing patients for studies and inclusion into this edition; Dr. Leonard Prouty, Ms. Rhonda Lee Young, and Mr. Jozo Ivancic, LSU Cytogenetics Laboratory for part of the karyotypes used in this edition; Mrs. Lynn Martin, Beverely Gildon, and Diane Dunki-Jacobs-Nolten for nursing care; and Ms. Ashli Daigle and Mrs. Barbara McHenry for their excellent clerical and secretarial help. My apologies in the event that I failed to mention others who have contributed to this edition. Without the patience and encouragement of my dear wife, Cheryl, this edition of the atlas would not have been possible. I would like to express my sincere appreciation to Dr. Joseph Bocchini, Chairman of the Department of Pediatrics, for his encouragement and support. I would like to dedicate this edition of the atlas to the Children’s Hospital, Louisiana State University Health Sciences Center in Shreveport, for its excellence in pediatric care and education. As previously, I would welcome comments, corrections, and criticism from readers.

Harold Chen, Shreveport, LA, USA October 2011

vii

Preface to the First Edition

This book, Atlas of Genetic Diagnosis and Counseling, reflects my experience in 38 years of clinical genetics practice. During this time, I have cared for many patients and their families and taught innumerable medical students, residents, and practicing physicians. As an academic physician, I have found that a picture is truly “worth a thousand words,” especially in the field of dysmorphology. Over the years, I have compiled photographs of my patients, which are incorporated into this book to illustrate selected genetic disorders, malformations, and malformation syndromes. A detailed outline of each disorder is provided, describing the genetics, basic defects, clinical features, diagnostic investigations, and genetic counseling, including recurrence risk, prenatal diagnosis, and management. Color photographs are used to illustrate the clinical features of patients of different ages and ethnicities. Photographs of prenatal ultrasounds, imaging, cytogenetics, and postmortem findings are included to help illustrate diagnostic strategies. The cases are supplemented by case history and diagnostic confirmation by cytogenetic, biochemical, and molecular studies, if avail- able. An extensive literature review was done to ensure up-to-date information and to provide a relevant bibliography for each disorder. This book was written in the hope that it will help physicians improve their recognition and understanding of these conditions and their care of affected individuals and their families. It is also my intention to bring the basic science and clinical medicine together for the readers. Atlas of Genetic Diagnosis and Counseling is designed for physicians involved in the evaluation and counseling of patients with genetic diseases, malformations, and malformation syndromes, including medical geneticists, genetic counselors, pediatricians, neonatologists, developmental pediatricians, perinatologists, obstetricians, neurologists, pathologists, and any physicians and health care professionals caring for handicapped children such as craniofacial surgeons, plastic surgeons, otolaryngologists, and orthopedics. I am grateful to many individuals for their invaluable help in reading and providing cases for illustration. The acknowledgments are provided on a separate page. Without the patience and encouragement of my dear wife, Cheryl, this atlas would not have been possible. I would like to dedicate this book to the Children’s Hospital, Louisiana State University Health Sciences Center in Shreveport, for its continued excellence in pediatric care and education. I would welcome comments, corrections, and criticism from readers.

Harold Chen, M.D., FAAP, FACMG

Biography

Harold Chen, M.D., M.S., FAAP, FACMG Dr. Chen was born in I-Lan, Taiwan, and was a graduate from the National Taiwan University School of Medicine (M.D. degree) in Taipei, Taiwan. He received M.S. degree in Human Genetics from the University of Michigan Graduate School in Ann Arbor, Michigan. He ﬁnished pediatric residency and fellowship training from Wayne State University School of Medicine in Detroit, Michigan. He had been faculty at Wayne State University (Detroit), Wright State University (Dayton, Ohio), and University of South Alabama (Mobile, Alabama). Currently, he is professor of Pediatrics, Obstetrics and Gynecology, and Pathology at the Louisiana State Univer- sity Health Sciences Center and Chief of Genetic Laboratory Services in Shreveport, Louisiana. Dr. Chen is board-certiﬁed in American Board of Pediatrics and American Board of Medical Genetics in Clinical Genetics and Clinical Cytogenetics.

Table of Contents

Acardia ...... 1 Achondrogenesis ...... 11 Achondroplasia ...... 21 Adams–Oliver Syndrome ...... 35 Agnathia ...... 41 Aicardi Syndrome ...... 49 Alagille Syndrome ...... 55 Albinism ...... 61 Alpha-Thalassemia X-linked Mental Retardation Syndrome ...... 71 Ambiguous Genitalia ...... 77 Amniotic Deformity, Adhesions, Mutilations (ADAM) Complex ...... 87 Androgen Insensitivity Syndrome ...... 99 Angelman Syndrome ...... 107 Apert Syndrome ...... 119 Aplasia Cutis Congenita ...... 135 Arthrogryposis Multiplex Congenita ...... 141 Asphyxiating Thoracic Dystrophy ...... 157 Ataxia-Telangiectasia ...... 167 Atelosteogenesis ...... 175 Autism ...... 183 Bannayan–Riley–Ruvalcaba Syndrome ...... 197 Beckwith–Wiedemann Syndrome ...... 203 Behcet Disease ...... 213 Biotinidase Deﬁciency ...... 221 Bladder Exstrophy ...... 227 Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome ...... 233

xiii xiv Table of Contents

Body Stalk Anomaly ...... 239 Brachydactyly ...... 245 Branchial Cleft Anomalies ...... 255 Calcinosis Cutis ...... 261 Campomelic Dysplasia ...... 267 Carpenter Syndrome ...... 275 Cat Eye Syndrome ...... 279 Celiac Disease ...... 285 Cerebral Palsy ...... 291 Cerebro-Costo-Mandibular Syndrome ...... 305 Charcot–Marie–Tooth Disease ...... 311 CHARGE Syndrome ...... 323 Cherubism ...... 331 Chiari Malformation ...... 337 Chondrodysplasia Punctata ...... 345 Chromosome Abnormalities in Pediatric Solid Tumors ...... 357 Cleft Lip and/or Cleft Palate ...... 377 Cleidocranial Dysplasia ...... 385 Cloacal Exstrophy ...... 395 Clubfoot ...... 401 Collodion Baby ...... 409 Congenital Adrenal Hyperplasia ...... 415 Congenital Cutis Laxa ...... 429 Congenital Cytomegalovirus Infection ...... 437 Congenital Generalized Lipodystrophy ...... 447 Congenital Hemihyperplasia ...... 455 Congenital Hydrocephalus ...... 463 Congenital Hypothyroidism ...... 471 Congenital Muscular Dystrophy ...... 479 Congenital Toxoplasmosis ...... 487 Conjoined Twins ...... 495 Corpus Callosum Agenesis/Dysgenesis ...... 507 Craniometaphyseal Dysplasia ...... 515 Table of Contents xv

Cri-Du-Chat Syndrome ...... 521 Crouzon Syndrome ...... 529 Cutis Marmorata Telangiectatica Congenita ...... 537 Cystic Fibrosis ...... 545 Dandy–Walker Malformation ...... 559 De Lange Syndrome ...... 563 Del(18p) Syndrome ...... 577 Del(22q11.2) Syndrome ...... 583 Del(Yq) Syndrome ...... 593 Diabetic Embryopathy ...... 605 Down Syndrome ...... 613 Duncan Syndrome ...... 631 Dyschondrosteosis ...... 639 Dysmelia ...... 651 Dysplasia Epiphysealis Hemimelica ...... 669 Dystonia ...... 677 Dystrophinopathies ...... 687 Ectrodactyly-Ectodermal Dysplasia-Clefting (EEC) Syndrome ...... 699 Ehlers-Danlos Syndrome ...... 705 Ellis-van Creveld Syndrome ...... 719 Enchondromatosis ...... 725 Epidermolysis Bullosa ...... 737 Epidermolytic Palmoplantar Keratoderma ...... 749 Faciogenital (Faciodigitogenital) Dysplasia ...... 757 Facioscapulohumeral Muscular Dystrophy ...... 765 Familial Adenomatous Polyposis ...... 775 Familial Hyperlysinemia ...... 785 Familial Mediterranean Fever ...... 789 Fanconi Anemia ...... 795 Femoral Hypoplasia – Unusual Facies Syndrome ...... 805 Fetal Akinesia Deformation Sequence ...... 809 Fetal Alcohol Spectrum Disorders ...... 823 Fetal Hydantoin Syndrome ...... 831 xvi Table of Contents

Fibrodysplasia Ossificans Progressiva ...... 835 Finlay–Marks Syndrome ...... 843 Floppy Infant ...... 847 Fragile X Syndrome ...... 863 Fraser Syndrome ...... 875 Freeman–Sheldon Syndrome ...... 883 Friedreich Ataxia ...... 891 Frontonasal Dysplasia ...... 897 Galactosemia ...... 905 Gastroschisis ...... 913 Gaucher Disease ...... 919 Generalized Arterial Calcification of Infancy ...... 929 Genitopatellar Syndrome ...... 937 Giant Congenital Melanocytic Nevi ...... 945 Glucose-6-Phosphate Dehydrogenase Deficiency ...... 953 Glycogen Storage Disease, Type II ...... 961 Goldenhar Syndrome ...... 971 Gorlin Syndrome ...... 979 Greig Cephalopolysyndactyly Syndrome ...... 987 Hallermann-Streiff Syndrome ...... 993 Harlequin Ichthyosis ...... 999 Hemophilia A ...... 1005 Hereditary Hearing Loss ...... 1013 Hereditary Hemochromatosis ...... 1025 Hereditary Multiple Exostoses ...... 1033 Herlyn-Werner-Wunderlich Syndrome ...... 1041 Holoprosencephaly ...... 1045 Holt-Oram Syndrome ...... 1065 Huntington Disease ...... 1073 Hydrolethalus Syndrome ...... 1081 Hydrops Fetalis ...... 1085 Hyper-IgE Syndrome ...... 1097 Hypochondroplasia ...... 1105 Table of Contents xvii

Hypoglossia-Hypodactylia Syndrome ...... 1113 Hypohidrotic Ectodermal Dysplasia ...... 1125 Hypomelanosis of Ito ...... 1131 Hypophosphatasia ...... 1137 Hypopituitarism ...... 1147 I(1p), I(1q) Syndrome ...... 1159 Idic(Yq) Syndrome ...... 1165 Incontinentia Pigmenti ...... 1175 Infantile Myoﬁbromatosis ...... 1183 Ivemark Syndrome ...... 1189 Jarcho–Levin Syndrome ...... 1195 Joubert Syndrome ...... 1203 Kabuki Syndrome ...... 1211 Kasabach–Merritt Syndrome ...... 1219 KID Syndrome ...... 1225 Klinefelter Syndrome ...... 1231 Klippel–Feil Syndrome ...... 1241 Klippel–Trenaunay Syndrome ...... 1251 Kniest Dysplasia ...... 1259 Larsen Syndrome ...... 1265 LEOPARD Syndrome ...... 1275 Lesch–Nyhan Syndrome ...... 1281 Lethal Multiple Pterygium Syndrome ...... 1287 Loeys–Dietz Syndrome ...... 1295 Lowe Syndrome ...... 1301 Marfan Syndrome ...... 1309 McCune-Albright Syndrome ...... 1327 Meckel–Gruber Syndrome ...... 1335 Megalencephalic Leukoencephalopathy with Subcortical Cysts ...... 1341 Menkes Disease ...... 1347 Metachromatic Leukodystrophy ...... 1357 Miller–Dieker Syndrome ...... 1365 Mitochondrial Leber Hereditary Optic Neuropathy ...... 1373 xviii Table of Contents

Mo¨bius Syndrome ...... 1383 Mowat–Wilson Syndrome ...... 1391 Mucopolysaccharidosis I (MPS I) ...... 1395 Mucopolysaccharidosis II ...... 1409 Mucopolysaccharidosis III ...... 1417 Mucopolysaccharidosis IV ...... 1425 Mucopolysaccharidosis VI ...... 1433 Mucolipidosis II ...... 1441 Mucolipidosis III ...... 1449 Multiple Endocrine Neoplasia Syndromes ...... 1457 Multiple Epiphyseal Dysplasia ...... 1467 Multiple Pterygium Syndrome ...... 1479 Myotonic Dystrophy Type I ...... 1487 Nail-Patella Syndrome ...... 1499 Neonatal Herpes Simplex Infection ...... 1505 Nephrogenic Diabetes Insipidus ...... 1511 Netherton Syndrome ...... 1515 Neu–Laxova Syndrome ...... 1521 Neural Tube Defects ...... 1527 Neuroﬁbromatosis I ...... 1545 Neuroﬁbromatosis 2 ...... 1571 Noonan Syndrome ...... 1577 Oblique Facial Cleft Syndrome ...... 1587 Oligohydramnios Sequence ...... 1595 Omphalocele ...... 1601 Oral–Facial–Digital Syndrome ...... 1607 Osteogenesis Imperfecta ...... 1619 Osteopetrosis ...... 1641 Osteopoikilosis ...... 1655 Otopalatodigital Spectrum Disorders ...... 1661 Pachyonychia Congenita ...... 1671 Pallister–Killian Syndrome ...... 1677 Phenylketonuria ...... 1683 Table of Contents xix

Pierre Robin Sequence ...... 1693 Polycystic Kidney Disease, Autosomal Dominant Type ...... 1699 Polycystic Kidney Disease: Autosomal Recessive Type ...... 1709 Popliteal Pterygium Syndrome ...... 1717 Prader–Willi Syndrome ...... 1723 Progeria ...... 1735 Prune Belly Syndrome ...... 1743 Pseudoachondroplasia ...... 1751 R(18) Syndrome ...... 1759 Retinoid Embryopathy ...... 1767 Rett Syndrome ...... 1773 Rickets ...... 1783 Rigid Spine Syndrome ...... 1797 Roberts Syndrome ...... 1805 Robinow Syndrome ...... 1811 Rubinstein-Taybi Syndrome ...... 1817 Saethre-Chotzen Syndrome ...... 1825 Sagittal Craniosynostosis Associated with Chromosome Abnormalities with a Brief Review on Craniosynostosis ...... 1833 Schizencephaly ...... 1845 Schmid Metaphyseal Chondrodysplasia ...... 1853 Seckel Syndrome ...... 1857 Severe Combined Immune Deﬁciency ...... 1863 Short Rib–Polydactyly Syndromes ...... 1873 Sickle Cell Disease ...... 1887 Silver–Russell Syndrome ...... 1899 Sirenomelia ...... 1907 Smith-Lemli-Opitz Syndrome ...... 1913 Smith-Magenis Syndrome ...... 1923 Sotos Syndrome ...... 1929 Spinal Muscular Atrophy ...... 1937 Spondyloepiphyseal Dysplasia ...... 1947 Stickler Syndrome ...... 1959 xx Table of Contents

Sturge-Webber Syndrome ...... 1967 Tay-Sachs Disease ...... 1973 Tetrasomy 9p Syndrome ...... 1981 Thalassemia ...... 1987 Thanatophoric Dysplasia ...... 1997 Thrombocytopenia-Absent Radius Syndrome ...... 2007 Treacher-Collins Syndrome ...... 2017 Trimethylaminuria ...... 2025 Triploidy ...... 2031 Trismus-Pseudocamptodactyly Syndrome ...... 2043 Trisomy 8 Mosaicism Syndrome ...... 2051 Trisomy 13 Syndrome ...... 2057 Trisomy 18 Syndrome ...... 2069 Tuberous Sclerosis ...... 2081 Turner Syndrome ...... 2097 Twin–Twin Transfusion Syndrome ...... 2115 Ulnar-Mammary Syndrome ...... 2123 Urofacial Syndrome ...... 2127 VATER (VACTERL) Association ...... 2131 Von Hippel–Lindau Disease ...... 2137 Waardenburg Syndrome ...... 2145 Weill–Marchesani Syndrome ...... 2151 Williams Syndrome ...... 2155 Wolf-Hirschhorn Syndrome ...... 2165 X-Linked Agammaglobulinemia ...... 2179 X-Linked Ichthyosis ...... 2185 XX Male ...... 2191 XXX Syndrome ...... 2197 XXXXX Syndrome ...... 2203 XXXXY Syndrome ...... 2209 XY Female ...... 2213 XYY Syndrome ...... 2221