Smith's Recognizable Patterns of Human Malformation

By Kenneth Lyons Jones, MD, Professor of Pediatrics; Chief, Division of Dysmorphology and Teratology, University of California, San Diego, School of Medicine, La Jolla, CA

Marilyn Crandall Jones, MD, Professor of Clinical Pediatrics, Department of Pediatrics, University of California, San Diego School of Medicine La Jolla, California; Clinical Service Chief, Division of Genetics, Rady Children’s Hospital, San Diego, California

Miguel del Campo, MD, PhD, Assistant Professor, Ciències Experimentals i de la Salut, Universitat Pompeu Fabra; Consultant in Clinical Genetics, Programa de Medicina Molecular I Genètica, Hospital Vall d´Hebron, Barcelona, Spain

Introduction

Dysmorphology Approach and Classification

1. Recognizable Patterns of Malformation

A. Chromosomal Abnormality Syndromes Identifiable on Routine Karyotype
Down Syndrome
Trisomy 18 Syndrome
Trisomy 13 Syndrome
Trisomy 8 Syndrome
Trisomy 9 Mosaic Syndrome
Triploidy Syndrome and Diploid/Triploid Mixoploidy Syndrome
Deletion 3p Syndrome
Duplication 3q Syndrome
Deletion 4p Syndrome
Deletion 4q Syndrome
Deletion 5p Syndrome
Deletion 9p Syndrome
Duplication 9p Syndrome
Duplication 10q Syndrome
Aniridia-Wilms Tumor Association
Deletion 11q Syndrome
Deletion 13q Syndrome
Duplication 15q Syndrome
Deletion 18p Syndrome
Deletion 18q Syndrome
Cat-Eye Syndrome
XYY Syndrome
XXY Syndrome, Klinefelter Syndrome
XXXY and XXXXY Syndromes
XXX and XXXX Syndromes
XXXXX Syndrome
45X Syndrome

B. Deletion, Duplication and Microduplication Syndromes Identifiable Using Molecular Technology

1p36 Deletion Syndrome

1Q41Q42 Microdeletion Syndrome

1Q43Q44 Microdeletion Syndrome

2q31.1 Microdeletion Syndrome

2q37 Deletion Syndrome

3q29 Microdeletion Syndrome

9q34.3 Subtelomeric Deletion Syndrome

15q24 Microdeletion Syndrome

16p11.2p12.2 Microdeletion Syndrome

17q21 Microdeletion Syndrome

22q13 Deletion Syndrome

Xq Distal Duplication or Disomy

C. Very Small Stature, Not Skeletal Dysplasia

Brachmann-de Lange Syndrome
Rubinstein-Taybi Syndrome
Russell-Silver Syndrome
SHORT Syndrome
3-M Syndrome
Mulibrey Nanism Syndrome
Dubowitz Syndrome
Bloom Syndrome
Johanson-Blizzard Syndrome
Microcephalic Primordial Dwarfing Syndromes
Hallermann-Streiff Syndrome

D. Moderate Short Stature, Facial, +/- Genital

Smith-Lemli-Opitz Syndrome
Kabuki Syndrome
Williams Syndrome
Noonan Syndrome
Costello Syndrome
Cardio-Facio-Cutaneous Syndrome
Aarskog Syndrome
Robinow Syndrome
Opitz G/BBB Syndrome
Floating-Harbor Syndrome

E. Senile-Like Appearance

Progeria Syndrome
Wiedemann-Rautenstrauch Syndrome
Werner Syndrome
Cockayne Syndrome
Rothmund-Thomson Syndrome

F. Early Overgrowth with Associated Defects

Fragile X Syndrome
Sotos Syndrome
Weaver Syndrome
Marshall-Smith Syndrome
Beckwith-Wiedemann Syndrome
Simpson-Golabi-Behmel Syndrome

G. Unusual Brain and/or Neuromuscular Findings With Associated Defects

Amyoplasia Congenita Disruptive Sequence
Distal Arthrogryposis Syndrome, Type 1
Pena-Shokeir Phenotype
Cerebro-Oculo-Facio-Skeletal (COFS) Syndrome
Lethal Multiple Pterygium Syndrome
Neu-Laxova Syndrome
Restrictive Dermopathy
Meckel-Gruber Syndrome
Pallister-Hall Syndrome
Gómez-López-Hernández Syndrome
X-Linked Hydrocephalus Spectrum
Hydrolethalus Syndrome
Walker-Warburg Syndrome
Miller-Dieker Syndrome
Nablus Mask-Like Facial Syndrome
Smith-Magenis Syndrome
Ataxia-Telangiectasia Syndrome
Menkes Syndrome
Pitt-Hopkins Syndrome
Angelman Syndrome
Prader-Willi Syndrome
Cohen Syndrome
Killian/Teschler-Nicola Syndrome
1p36 Deletion Syndrome
Fryns Syndrome
Matthew-Wood Syndrome
Zellweger Syndrome
Freeman-Sheldon Syndrome
Myotonic Dystrophy Syndrome
Schwartz-Jampel Syndrome
Marden-Walker Syndrome
Schinzel-Giedion Syndrome
Acrocallosal Syndrome
3C Syndrome
Hecht Syndrome

H. Facial Defects As Major Feature

Moebius Sequence
Blepharophimosis-Ptosis-Epicanthus Inversus Synrome
Robin Sequence
Cleft Lip Sequence
Van Der Woude Syndrome
Frontonasal Dysplasia Sequence
Fraser Syndrome
Melnick-Fraser Syndrome
Branchio-Oculo-Facial Syndrome
Donnai-Barrow Syndrome
CHARGE Syndrome
Waardenburg Syndrome
Treacher Collins Syndrome
Mandibulofacial Dysostosis with Microcephaly
Marshall Syndrome
Cervico-Oculo-Acoustic Syndrome

I. Facial-Limb Defects as Major Feature

Miller Syndrome
Nager Syndrome
Townes-Brocks Syndrome
Laurin-Sandrow Syndrome
Oral-Facial-Digital Syndrome
Mohr Syndrome
22q11.2 Microdeletion Syndrome
Oculodentodigital Syndrome
Lenz Microphthalmia Syndrome
Oto-Palato-Digital Syndrome, Type I
Oto-Palato-Digital Syndrome, Type II
Coffin-Lowry Syndrome
X-Linked ?-Thalassemia/Mental Retardation Syndrome
FG Syndrome
Stickler Syndrome
Catel-Manzke Syndrome
Langer-Giedion Syndrome
Tricho-Rhino-Phalangeal Syndrome, Type I
Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome
Hay-Wells Syndrome of Ectodermal Dysplasia
Roberts Syndrome

J. Limb Defect as Major Feature

Poland Sequence
Ulnar-Mammary Syndrome
Popliteal Pterygium Syndrome
Escobar Syndrome
CHILD Syndrome
Femoral Hypoplasia-Unusual Facies Syndrome
Tibial Aplasia-Ectrodactyly Syndrome
Adams-Oliver Syndrome
Holt-Oram Syndrome
Levy-Hollister Syndrome
Okihiro Syndrome
Fanconi Pancytopenia Syndrome
Radial Aplasia-Thrombocytopenia Syndrome
Aase Syndrome

K. Osteochondrodysplasias

Achondrogenesis, Types IA And IB
Type II Achondrogenesis-Hypochondrogenesis
Fibrochondrogenesis
Atelosteogenesis, Type I
Boomerang Dysplasia
Short Rib-Polydactyly Syndromes
Thanatophoric Dysplasia
Jeune Thoracic Dystrophy
Campomelic Dysplasia
Achondroplasia
Hypochondroplasia
Pseudoachondroplasia
Acromesomelic Dysplasia
Spondyloepiphyseal Dysplasia Congenita
Kniest Dysplasia
Dyggve-Melchior-Clausen Syndrome
Smith-McCort Dysplasia
Spondylometaphyseal Dysplasia, Kozlowski Type
Metatropic Dysplasia
Geleophysic Dysplasia
Chondroectodermal Dysplasia (Ellis-van Creveld Syndrome)
Diastrophic Dysplasia
X-Linked Recessive Spondyloepiphyseal Dysplasia Tarda
Multiple Epiphyseal Dysplasia
Metaphyseal Dysplasia, Schmid Type
Metaphyseal Dysplasia, McKusick Type
Chondrodysplasia Punctata, X-Linked Dominant Type
Autosomal Recessive Chondrodysplasia Punctata
Hypophosphatasia
Hajdu-Cheney Syndrome
Craniometaphyseal Dysplasia
Sensenbrenner Syndrome
Frontometaphyseal Dysplasia

L. Osteochondrodysplasia with Osteopetrosis

Osteopetrosis: Autosomal Recessive-Lethal
Lenz-Majewski Hyperostosis Syndrome
Pyknodysostosis
Cleidocranial Dysostosis

M. Craniosynostosis Syndromes

Saethre-Chotzen Syndrome
Pfeiffer Syndrome
Apert Syndrome
Crouzon Syndrome
FGFR3- Associated Coronal Synostosis Syndrome
Curry-Jones Syndrome
Craniofrontonasal Dysplasia
Carpenter Syndrome
Greig Cephalopolysyndactyly Syndrome
Antley-Bixler Syndrome
Baller-Gerold Syndrome

N. Other Skeletal Dysplasias

Multiple Synostosis Syndrome
Spondylocarpotarsal Synostosis Syndrome
Larsen Syndrome
Multiple Exostoses Syndrome
Nail-Patella Syndrome
Meier-Gorlin Syndrome
Cantú Syndrome
Leri-Weill Dyschondrosteosis
Acrodysostosis
Albright Hereditary Osteodystrophy
Yunis-Varón Syndrome
Desbuquois Syndrome

O. Storage Disorders

Leroy I-Cell Syndrome
Mucopolysaccharidosis I H, I H/S, I S
Hunter Syndrome
Sanfilippo Syndrome
Morquio Syndrome
Mucopolysaccharidosis VII

P. Connective Tissue Disorders

Marfan Syndrome
Beals Syndrome
Shprintzen-Goldberg Syndrome
Ehlers-Danlos Syndrome
Vascular Ehlers-Danlos Syndrome (EDS IV)
Loeys-Dietz Syndrome
Osteogenesis Imperfecta Syndrome, Type I
Osteogenesis Imperfecta Syndrome, Type II
Fibrodysplasia Ossificans Progressiva Syndrome

Q. Hamartoses

Sturge-Weber Sequence
Neurocutaneous Melanosis Sequence
Linear Sebaceous Nevus Sequence
Incontinentia Pigmenti Syndrome
Hypomelanosis of Ito
Tuberous Sclerosis Syndrome
Neurofibromatosis Syndrome
McCune-Albright Syndrome
Klippel-Trenaunay Syndrome
Macrocephaly-Capillary Malformation Syndrome
Proteus Syndrome
Encephalocraniocutaneous Lipomatosis
Maffucci Syndrome
Peutz-Jeghers Syndrome
Bannayan-Riley-Ruvalcaba Syndrome
Hereditary Hemorragic Telangiectasia
Multiple Endocrine Neoplasia, Type 2B
Gorlin Syndrome
Multiple Lentigines Syndrome
Goltz Syndrome
Microphthalmia-Linear Skin Defects Syndrome

R. Ectodermal Dysplasias

Hypohidrotic Ectodermal Dysplasia
Rapp-Hodgkin Ectodermal Dysplasia
Tricho-Dento-Osseous Syndrome
Clouston Syndrome
Cranioectodermal Dysplasia
GAPO Syndrome
Pachyonychia Congenita Syndrome
Xeroderma Pigmentosa Syndrome
Senter-KID Syndrome

S. Environmental Agents

Fetal Alcohol Syndrome
Fetal Hydantoin Syndrome
Fetal Valproate Syndrome
Fetal Warfarin Syndrome
Fetal Aminopterin/Methotrexate Syndrome
Retinoic Acid Embryopathy
Methimazole/Carbimazole Embryopathy
Mycophenolate Mofetil Embryopathy
Fetal Varicella Syndrome
Hyperthermia-Induced Spectrum of Defects

T. Miscellaneous Syndromes

Coffin-Siris Syndrome
Börjeson-Forssman-Lehmann Syndrome
Alagille Syndrome
Melnick-Needles Syndrome
Bardet-Biedl Syndrome
Axenfeld-Rieger Syndrome
Rieger Syndrome
Peters' -Plus Syndrome
Toriello-Carey Syndrome
Finlay-Marks Syndrome
Mowat-Wilson Syndrome
Cerebro-Costo-Mandibular Syndrome
Jarcho-Levin Syndrome
Mandibuloacral Dysplasia
Berardinelli-Seip Congenital Lipodystrophy Syndrome
Distichiasis-Lymphedema Syndrome
Vici Syndrome

U. Miscellaneous Sequences

Laterality Sequences
Holoprosencephaly Sequence
Meningomyelocele, Anencephaly, Iniencephaly Sequences
Occult Spinal Dysraphism Sequence
Septo-Optic Dysplasia Sequence
Klippel-Feil Sequence
Early Urethral Obstruction Sequence
Exstrophy of Bladder Sequence
Exstrophy of Cloaca Sequence
Urorectal Septum Malformation Sequence
Oligohydramnios Sequence
Sirenomelia Sequence
Caudal Dysplasia Sequence
Amnion Rupture Sequence
Limb-Body Wall Complex

V. Spectra Of Defects

Oculo-Auriculo-Vertebral Spectrum
Oromandibular-Limb Hypogenesis Spectrum
Congenital Microgastria-Limb Reduction Complex
Sternal Malformation-Vascular Dysplasia Spectrum
Monozygotic Twinning And Structural Defects- General

W. Miscellaneous Associations

VATER Association
MURCS Association

2. Morphogenesis and Dysmorphogenesis

3. Genetics, Genetic Counseling, and Prevention

4. Minor Anomalies: Clues to More Serious Problems and to the Recognition of Malformation Syndromes

5. Normal Standards

Appendix I

Pattern of Malformation Differential Diagnosis by Anomalies