ATLAS OF GENETIC DIAGNOSIS AND COUNSELING ATLAS OF GENETIC DIAGNOSIS AND COUNSELING

HAROLD CHEN, MD, FAAP, FACMG Professor of Pediatrics, Obstetrics and Gynecology, and Pathology, Louisiana State University Health Science Center, Shreveport, LA © 2006 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 humanapress.com

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Library of Congress Cataloging-in-Publication Data

Atlas of genetic diagnosis and counseling / authored by Harold Chen. p. cm. Includes bibliographical references. ISBN 1-58829-681-4 (alk. paper) 1. Genetic disorders--Diagnosis--Atlases. 2. Genetic counseling--Atlases. [DNLM: 1. Genetic Diseases, Inborn--Atlases. 2. Genetic Counseling--Atlases. 3. Prenatal Diagnosis--Atlases. QZ 17 A880383 2006] I. Chen, Harold. RB155.6.A93 2006 616'.042--dc22 2005005388 Preface

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

v Contents

Preface ...... v Cleidocranial Dysplasia ...... 185 Cloacal Exstrophy ...... 191 Acknowledgments ...... xi Collodion Baby ...... 195 Acardia ...... 1 Congenital Adrenal Hyperplasia Achondrogenesis ...... 7 (21-Hydroxylase Deficiency) ...... 198 Achondroplasia ...... 15 Congenital Cutis Laxa ...... 207 Adams-Oliver Syndrome ...... 23 Congenital Cytomegalovirus Infection ...... 212 Agnathia ...... 26 Congenital Generalized Lipodystrophy ...... 217 Aicardi Syndrome ...... 29 Congenital Hydrocephalus ...... 221 Alagille Syndrome ...... 32 Congenital Hypothyroidism ...... 227 Albinism ...... 36 Congenital Muscular Dystrophy ...... 231 Amniotic Band Syndrome ...... 42 Congenital Toxoplasmosis ...... 236 Androgen Insensitivity Syndrome ...... 50 Conjoined Twins ...... 241 Angelman Syndrome ...... 56 Corpus Callosum Agenesis/Dysgenesis ...... 247 Apert Syndrome ...... 61 Craniometaphyseal Dysplasia ...... 252 Aplasia Cutis Congenita ...... 70 Cri-Du-Chat Syndrome ...... 256 Arthrogryposis Multiplex Congenita ...... 74 Crouzon Syndrome ...... 261 Asphyxiating Thoracic Dystrophy ...... 84 Cystic Fibrosis ...... 265 Ataxia Telangiectasia ...... 92 Dandy-Walker Malformation ...... 273 Atelosteogenesis ...... 96 De Lange Syndrome ...... 276 Autism ...... 102 Del(22q11.2) Syndromes ...... 282 Beckwith-Wiedemann Syndrome ...... 109 Diabetic Embryopathy ...... 289 Behcet Disease ...... 114 Down Syndrome ...... 295 Bladder Exstrophy ...... 118 Dyschondrosteosis (Leri-Weill Syndrome) and Body Stalk Anomaly ...... 122 Langer Mesomelic Dysplasia ...... 305 Branchial Cleft Anomalies ...... 126 Dysmelia (Limb Deficiency/Reduction) ...... 312 Dysplasia Epiphysealis Hemimelica ...... 323 Campomelic Dysplasia ...... 131 Dystonia ...... 326 Cat Eye Syndrome ...... 136 Dystrophinopathies ...... 331 Cerebro-Costo-Mandibular Syndrome ...... 139 Charcot-Marie-Tooth Disease ...... 142 Ectrodactyly-Ectodermal Dysplasia-Clefting CHARGE Association ...... 149 (EEC) Syndrome ...... 339 Cherubism ...... 153 Ehlers-Danlos Syndrome ...... 342 Chiari Malformation ...... 157 Ellis-van Creveld Syndrome ...... 350 Chondrodysplasia Punctata ...... 161 Enchondromatosis (Maffucci Syndrome; Chromosome Abnormalities in Pediatric Ollier Syndrome) ...... 355 Solid Tumors ...... 169 Epidermolysis Bullosa ...... 360 Cleft Lip and/or Cleft Palate ...... 180 Epidermolytic Palmoplantar Keratoderma ...... 366

vii viii CONTENTS

Faciogenital (Aarskog) Dysplasia ...... 371 Kasabach-Merritt Syndrome ...... 563 Facioscapulohumeral Muscular Dystrophy ...... 375 KID Syndrome ...... 567 Familial Adenomatous Polyposis ...... 380 Klinefelter Syndrome ...... 570 Familial Hyperlysinemia ...... 386 Klippel-Feil Syndrome ...... 575 Fanconi Anemia ...... 389 Klippel-Trenaunay Syndrome ...... 580 Femoral Hypoplasia-Unusual Facies Syndrome . . . 395 Kniest Dysplasia ...... 585 Fetal Akinesia Syndrome ...... 398 Larsen Syndrome ...... 589 Fetal Alcohol Syndrome ...... 403 LEOPARD Syndrome ...... 597 Fetal Hydantoin Syndrome ...... 407 Lesch-Nyhan Syndrome ...... 600 Fibrodysplasia Ossificans Progressiva ...... 410 Lethal Multiple Pterygium Syndrome ...... 604 Finlay-Marks Syndrome ...... 415 Lowe Syndrome ...... 613 Fragile X Syndrome ...... 417 Fraser Syndrome ...... 423 Marfan Syndrome ...... 619 Freeman-Sheldon Syndrome ...... 427 McCune-Albright Syndrome ...... 630 Frontonasal Dysplasia ...... 431 Meckel-Gruber Syndrome ...... 636 Menkes Disease (Kinky-Hair Syndrome) ...... 639 Galactosemia ...... 437 Metachromatic Leukodystrophy ...... 646 Gastroschisis ...... 442 Miller-Dieker Syndrome ...... 650 Gaucher Disease ...... 446 Möbius Syndrome ...... 655 Generalized Arterial Calcification of Infancy . . . . . 452 Mucolipidosis II (I-Cell Disease) ...... 660 Glucose-6-Phosphate Dehydrogenase Deficiency . . . 457 Mucolipidosis III (Pseudo-Hurler Polydystrophy) . 664 Glycogen Storage Disease, Type II ...... 461 Mucopolysaccharidosis I (MPS I) Goldenhar Syndrome ...... 465 (α-L-Iduronidase Deficiency): Hurler (MPS I-H), Hurler-Scheie (MPS I-H/S), Hallermann-Streiff Syndrome ...... 469 and Scheie (MPS I-S) Syndromes ...... 669 Harlequin Ichthyosis (Harlequin Fetus) ...... 473 Mucopolysaccharidosis II (Hunter Syndrome) . . . . 678 Hemophilia A ...... 476 Mucopolysaccharidosis III (Sanfilippo Syndrome) . 682 Hereditary Hemochromatosis ...... 482 Mucopolysaccharidosis IV (Morquio Syndrome) . . 687 Hereditary Multiple Exostoses ...... 487 Mucopolysaccharidosis VI (Maroteaux-Lamy Holoprosencephaly ...... 493 Syndrome) ...... 692 Holt-Oram Syndrome ...... 502 Multiple Epiphyseal Dysplasia ...... 697 Hydrops Fetalis ...... 506 Multiple Pterygium Syndrome ...... 702 Hyper-IgE Syndrome ...... 513 Myotonic Dystrophy Type 1 ...... 708 Hypochondroplasia ...... 517 Netherton Syndrome ...... 715 Hypoglossia-Hypodactylia Syndrome ...... 521 Neu-Laxova Syndrome ...... 718 Hypohidrotic Ectodermal Dysplasia ...... 524 Neural Tube Defects ...... 721 Hypomelanosis of Ito ...... 528 Neurofibromatosis I ...... 731 Hypophosphatasia ...... 532 Noonan Syndrome ...... 744 Incontinentia Pigmenti ...... 539 Infantile Myofibromatosis ...... 545 Oblique Facial Cleft Syndrome ...... 751 Ivemark Syndrome ...... 549 Oligohydramnios Sequence ...... 755 Omphalocele ...... 758 Jarcho-Levin Syndrome ...... 553 Osteogenesis Imperfecta ...... 762 Kabuki Syndrome ...... 559 Osteopetrosis ...... 773 CONTENTS ix

Pachyonychia Congenita ...... 781 Spondyloepiphyseal Dysplasia ...... 927 Pallister-Killian Syndrome ...... 784 Stickler Syndrome ...... 934 Phenylketonuria (PKU) ...... 788 Sturge-Weber Syndrome ...... 939 Pierre Robin Sequence ...... 793 Tay-Sachs Disease ...... 943 Polycystic Kidney Disease, Autosomal Dominant Type ...... 797 Tetrasomy 9p Syndrome ...... 947 Polycystic Kidney Disease, Autosomal Thalassemia ...... 950 Recessive Type ...... 803 Thanatophoric Dysplasia ...... 955 Prader-Willi Syndrome ...... 809 Thrombocytopenia-Absent Radius Syndrome . . . . . 962 Progeria ...... 815 Treacher-Collins Syndrome ...... 967 Prune Belly Syndrome ...... 821 Trimethylaminuria ...... 972 Pseudoachondroplasia ...... 826 Triploidy ...... 976 Trismus Pseudocamptodactyly Syndrome ...... 982 R(18) Syndrome ...... 831 Trisomy 13 Syndrome ...... 985 Retinoid Embryopathy ...... 835 Trisomy 18 Syndrome ...... 990 Rett Syndrome ...... 839 Tuberous Sclerosis ...... 997 Rickets ...... 844 Turner Syndrome ...... 1007 Roberts Syndrome ...... 852 Twin–Twin Transfusion Syndrome ...... 1015 Robinow Syndrome ...... 856 Rubinstein-Taybi Syndrome ...... 860 Ulnar-Mammary Syndrome ...... 1021

Schizencephaly ...... 867 VATER (VACTERL) Association ...... 1025 Schmid Metaphyseal Chondrodysplasia ...... 870 Von Hippel-Lindau Disease ...... 1029 Seckel Syndrome ...... 874 Waardenburg Syndrome ...... 1035 Severe Combined Immune Deficiency ...... 878 Williams Syndrome ...... 1040 Short Rib Polydactyly Syndromes ...... 884 Wolf-Hirschhorn Syndrome ...... 1047 Sickle Cell Disease ...... 892 Silver-Russell Syndrome ...... 899 X-Linked Ichthyosis ...... 1057 Sirenomelia ...... 903 XXX Syndrome ...... 1061 Smith-Lemli-Opitz Syndrome ...... 907 XXXXX Syndrome ...... 1064 Smith-Magenis Syndrome ...... 912 XXXXY Syndrome ...... 1068 Sotos Syndrome ...... 916 XY Female ...... 1071 Spinal Muscular Atrophy ...... 921 XYY Syndrome ...... 1075 Acknowledgments

Individuals HIROKO TANIAI, MD • A case of Finlay-Marks syndrome DIANA BIENVENU, MD • A case of Marfan syndrome and help in searching of references for the Atlas. with apical bleb rupture. THEODORE THURMON, MD • Comments on the Atlas SAMI BAHNA, MD • Comments on del(22q11.2), hyper and cases on achondrogenesis, arthrogryposis, IgE syndrome, Netherton syndrome, and severe cleidocranial dysplasia, chondrodysplasia punctata, combined immunodeficiency. de Lange syndrome, Crouzon syndrome, cutis laxa, JOSEPH BOCCHINI,JR. MD • Comments on congenital Freeman-Sheldon syndrome, hypophosphatasia, cytomegalovirus infection and congenital multiple epiphyseal dysplasia, omphalocele, toxoplasmosis and encouragement and support prune belly syndrome, Sturge-Weber syndrome, throughout preparation of the Atlas. and Treacher-Collins syndrome. CHUNG-HO CHANG, MD • Cases on Duchenne muscular CATHY TUCK-MULLER, PhD • A karyotype on Roberts dystrophy and congenital toxoplasmosis. syndrome. SAU CHEUNG, PhD • FISH on a case of STS deficiency. SUSONNE URSIN, MD • Cases of galactosemia JAMES GANLEY, MD • Cases on ophthalmology and Gaucher disease and helps covering patient care (Behcet disease, Lisch nodule in NF1, cherry spot for me during the last stage of preparing the Atlas. in Tay-Sachs disease, and retinal changes in WLADIMIR WERTELECKI, MD • Enjoy working together congenital toxoplasmosis, von-Hippel Lindal disease, on birth defects and congenital malformations and Waardenburg syndrome). and appreciate friendship and encouragement. ENRIQUE GONZALEZ, MD • Valuable comments SAMUEL YANG, MD • Meticulous reading and editing on pathological aspects of clinical entities and cases of the whole manuscript from the start to the end on acardius, agnathia, cloacal exstrophy, congenital during his retirement and encouragement throughout cytomegalovirus infection, omphalocele, pediatric the preparation of the Atlas. Special thanks to solid tumors (meningioma, neuroblastoma, contribution of his life-time collection of cases retinoblastoma, and Wilms tumor), phocomelia, sickle on skeletal dysplasias and malformation syndromes cell anemia, thalassemia, and Gaucher disease. (acardius, achondrogenesis, achondroplasia, amniotic WILLIAM HOFFMAN, MD • Comments on topics band syndrome, anencephaly, asphyxiating thoracic of endocrinological interest and cases on androgen dystrophy, body stalk anomaly, cebocephaly, insensitivity and hypophosphatemic rickets. campomelic dysplasia, Chiari malformation, colon RACHEL FLAMHOLZ, MD • Peripheral blood smears on polyposis, congenital cytomegalovirus infection, sickle cell anemia and thalassemia. congenital toxoplasmosis, cyclopia, cystic fibrosis, MAJED JEROUDI, MD • A case of sickle cell anemia Duchenne muscular dystrophy, Ellis van Creveld dactylitis. syndrome, gastroschisis, hypophosphatasia, I-cell DANIEL LACEY, MD • Comments on dystrophinopathy, disease, Kniest syndrome, polycystic kidney diseases, spinal muscular atrophy, neural tube defects, premaxillary agenesis, prune belly syndrome, SED and holoprosencephaly. congenita, sirenomelia, short rib polydactyly MARY LOWERY, MD • Comments on the Atlas and cases syndromes, Tay-Sachs disease, thanatophoric on molecular cytogenetics/pathology (FISH on trisomy dysplasia, twin-twin transfusion placentas, VATER 21, trisomy 13, trisomy 18, X/XXX, Williams syndrome, association, and Werdnig-Hoffman syndrome). and neuroblastoma; mutation analysis on cystic CHENG W. YU, PhD • Karyotypes/FISH on pediatric fibrosis and hereditary hemochromatosis). tumors (meningioma, Wilms tumor), Cri-du-chat LYNN MARTIN, LPN • Help in caring for the patients syndrome, and Wolf-Hirschhorn syndrome. including obtaining the photographs of patients and searching for clinical information of the old Institutions files. Louisiana State University Health Sciences Center LEONARD PROUTY, PhD • Reading of several topics in the in Shreveport, Louisiana (Drs. Joseph Bocchini, Jr., Atlas. David Lewis, Rose Brouillette, Rodney Wise) DAN SANUSI, MD • A case of X-linked ichthyosis. Pinecrest Developmental Center in Pineville, Louisiana TOHRU SONODA, MD • Cases on chondrodysplasia (Drs. Gaylon Bates, Tony Hanna, Renata Pilat) punctata, del(22q11.2), Kabuki syndrome, Klippel- Shreveport Shriner’s Hospital for Children (Dr. Richard Trenaunay syndrome, and tuberous sclerosis. McCall) xi