Atlas of Genetic Diagnosis and Counseling

1069 Pages·2006·37.01 MB·English

by  Harold Chen MD, FAAP, FACMG (auth.)

A G D C
TLAS OF ENETIC IAGNOSIS AND OUNSELING
A G
TLAS OF ENETIC
D
IAGNOSIS
C
AND OUNSELING
H C , , ,
AROLD HEN MD FAAP FACMG
Professor of Pediatrics, Obstetrics and Gynecology, and Pathology,
Louisiana State University Health Science Center, Shreveport, LA
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e-ISBN 1-59259-956-7
Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1
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 Counselingis 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;
Ollier Syndrome) . . . . . . . . . . . . . . . . . . . . . . . . . 355
Chromosome Abnormalities in Pediatric
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
Marfan Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . 619
Fraser Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
McCune-Albright Syndrome . . . . . . . . . . . . . . . . . . 630
Freeman-Sheldon Syndrome . . . . . . . . . . . . . . . . . . 427
Meckel-Gruber Syndrome . . . . . . . . . . . . . . . . . . . . 636
Frontonasal Dysplasia . . . . . . . . . . . . . . . . . . . . . . . 431
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
Oblique Facial Cleft Syndrome . . . . . . . . . . . . . . . . 751
Infantile Myofibromatosis . . . . . . . . . . . . . . . . . . . . 545
Oligohydramnios Sequence . . . . . . . . . . . . . . . . . . . 755
Ivemark Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . 549
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
Tetrasomy 9p Syndrome . . . . . . . . . . . . . . . . . . . . . 947
Dominant Type . . . . . . . . . . . . . . . . . . . . . . . . . . 797
Thalassemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 950
Polycystic Kidney Disease,Autosomal
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 HIROKOTANIAI, MD • A case of Finlay-Marks syndrome
and help in searching of references for the Atlas.
DIANA BIENVENU, MD • A case of Marfan syndrome
with apical bleb rupture. THEODORETHURMON, MD • Comments on the Atlas
and cases on achondrogenesis, arthrogryposis,
SAMI BAHNA, MD • Comments on del(22q11.2), hyper
cleidocranial dysplasia, chondrodysplasia punctata,
IgE syndrome, Netherton syndrome, and severe
de Lange syndrome, Crouzon syndrome, cutis laxa,
combined immunodeficiency.
Freeman-Sheldon syndrome, hypophosphatasia,
JOSEPH BOCCHINI, JR. MD • Comments on congenital
multiple epiphyseal dysplasia, omphalocele,
cytomegalovirus infection and congenital
prune belly syndrome, Sturge-Weber syndrome,
toxoplasmosis and encouragement and support
and Treacher-Collins syndrome.
throughout preparation of the Atlas.
CHUNG-HO CHANG, MD • Cases on Duchenne muscular CATHYTUCK-MULLER,PhD•Akaryotype on Roberts
dystrophy and congenital toxoplasmosis. syndrome.
SAU CHEUNG, PhD • FISH on a case of STS deficiency. SUSONNE URSIN, MD • Cases of galactosemia
and Gaucher disease and helps covering patient care
JAMES GANLEY, MD • Cases on ophthalmology
for me during the last stage of preparing the Atlas.
(Behcet disease, Lisch nodule in NF1, cherry spot
in Tay-Sachs disease, and retinal changes in WLADIMIRWERTELECKI, 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 SAMUELYANG,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
band syndrome,anencephaly,asphyxiating thoracic
WILLIAM HOFFMAN, MD • Comments on topics
dystrophy,body stalk anomaly,cebocephaly,
of endocrinological interest and cases on androgen
campomelic dysplasia,Chiari malformation,colon
insensitivity and hypophosphatemic rickets.
polyposis,congenital cytomegalovirus infection,
RACHEL FLAMHOLZ, MD • Peripheral blood smears on
congenital toxoplasmosis,cyclopia,cystic fibrosis,
sickle cell anemia and thalassemia.
Duchenne muscular dystrophy,Ellis van Creveld
MAJED JEROUDI, MD • A case of sickle cell anemia
syndrome,gastroschisis,hypophosphatasia,I-cell
dactylitis.
disease,Kniest syndrome,polycystic kidney diseases,
DANIEL LACEY, MD • Comments on dystrophinopathy,
premaxillary agenesis,prune belly syndrome,SED
spinal muscular atrophy, neural tube defects,
congenita,sirenomelia,short rib polydactyly
and holoprosencephaly.
syndromes,Tay-Sachs disease,thanatophoric
MARYLOWERY,MD•Comments on the Atlas and cases
dysplasia,twin-twin transfusion placentas,VATER
on molecular cytogenetics/pathology (FISH on trisomy
association,and Werdnig-Hoffman syndrome).
21,trisomy 13,trisomy 18,X/XXX,Williams syndrome,
and neuroblastoma; mutation analysis on cystic CHENGW. YU, PhD • Karyotypes/FISH on pediatric
fibrosis and hereditary hemochromatosis). tumors (meningioma,Wilms tumor), Cri-du-chat
syndrome, and Wolf-Hirschhorn syndrome.
LYNN MARTIN, LPN • Help in caring for the patients
including obtaining the photographs of patients
Institutions
and searching for clinical information of the old
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
Acardia
Acardia is a bizarre fetal malformation occurring only in b) Presence of rudimentary nerve tissue in
twins or triplets. It is also called acardius acephalus, acardiac addition to anatomical features in acardius
twinning,or twin reversed arterial perfusion (TRAP) syndrome amorphous
or sequence. This condition is very rare and occurs 1 in 35,000 iii. Acardius acephalus
deliveries, 1 in 100 monozygotic twins, rarely in triplet preg- a) The most common type
nancy,and even in quintuplet gestations. b) Missing head, part of the thorax, and upper
extremities
GENETICS/BASIC DEFECTS
c) May have additional malformations in the
1. Etiology remaining organs
a. Rare complication of monochorionic twinning, pre- iv. Acardius anceps
sumably resulting from the fused placentation of a) Presence of a partially developed fetal head,
monochorionic twins a thorax,abdominal organs,and extremities
b. Represents manifestation of abnormal embryonic and b) Lacks even a rudimentary heart
fetal blood flow rather than a primary defect of car- v. Acardius acormus
diac formation a) The rarest type
c. Heterogeneous chromosomal abnormalities are present b) Lacks thorax
in nearly 50% of the cases,although chromosome errors c) Presence of a rudimentary head only
are not underlying pathogenesis of the acardiac anomaly. d) The umbilical cord inserts in the head and
i. 45,XX,t(4;21)del(4p) connects directly to the placenta
ii. 46,X,i(Xp) 4. The acardia
iii. 47,XX,+2 a. Characterized by the absence of a normally function-
iv. 47,XX,+11 ing heart
v. 47,XY,+G b. Acardia as a recipient of twin transfusion sequence
vi. 47,XXY i. Reversal of blood flow in various types of acar-
vii. 69,XXX dia,hence the term “twin reversed arterial perfu-
viii. 70,XXX,+15 sion (TRAP) sequence”has been proposed
ix. 94,XXXXYY ii. Receiving the deoxygenated blood from an
2. Pathogenesis:reversal of fetal arterial perfusion umbilical artery of its co-twin through the sin-
a. First hypothesis gle umbilical artery of the acardiac twin and
i. A primary defect in the development of the heart returning to its umbilical vein. Therefore, the
ii. Survival of the acardiac twin as a result of the circulation is entirely opposite to the normal
compensatory anastomoses that develop direction
b. Second hypothesis c. Usually the severe reduction anomalies occur in the
i. The acardiac twin beginning life as a normal fetus upper part of the body
ii. The reversal of the arterial blood flow resulting d. May develop various structural malformations
in atrophy of the heart and the tributary organs i. Growth retardation
3. Classification of TRAP sequence (syndrome) ii. Anencephaly
a. Classification according to the status of the heart of iii. Holoprosencephaly
the acardiac twin iv. Facial defects
i. Hemiacardius (with incompletely formed heart) v. Absent or malformed limbs
ii. Holoacardius (with completely absent heart) vi. Gastrointestinal atresias
b. Morphologic classification of the acardiac twin vii. Other abnormalities of abdominal organs
i. Acardius amorphous 5. The co-twin
a) The least differentiated form; no resem- a. Also known as the “pump twin or donor twin”
blance to classical human form b. The donor “pump”twin perfuses itself and its recipi-
b) Anatomical features: presence of only ent acardiac twin through abnormal arterial anasto-
bones,cartilage,muscles,fat,blood vessels, mosis in the fused placenta
and stroma c. Increased cardiac workload often leads to cardiac fail-
ii. Acardius myelacephalus ure and causes further poor perfusion and oxygena-
a) Resembles the amorphous type, except for tion of the acardiac co-twin
the presence of rudimentary limb formation d. May develop various malformations (about 10%)
1