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Atlas of Genetic Diagnosis and Counseling Chen 1st
Edition Harold Chen Digital Instant Download
Author(s): Harold Chen
ISBN(s): 9781592599561, 1592599567
Edition: 1
File Details: PDF, 38.82 MB
Year: 2005
Language: english
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
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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
 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
2 ACARDIA

CLINICAL FEATURES 13. Cardiac

a. Absent heart tissue
1. Perinatal problems associated with acardiac twinning b. Unfolded heart tube
a. Pump-twin congestive heart failure c. Folded heart with common chamber
b. In utero fetal death of the pump fetus 14. Gastrointestinal
c. Maternal polyhydramnios a. Esophageal atresia
d. Premature rupture of membrane b. Short intestine
e. Preterm delivery c. Interrupted intestine
f. Spontaneous abortions d. Omphalocele
g. Soft tissue dystocia e. Incomplete rotation of the gut
h. Uterine rupture f. Imperforated anus
i. Postpartum hemorrhage g. Ascites
j. Increased rate of cesarean section, up to 50% 15. Liver
2. Majority of acardiac twins and their normal twin counter- a. Absent
parts are females b. Reduced
3. Nonviable 16. Kidney
4. Gross features a. Absent (bilateral)
a. Severe reduction anomalies, particularly of the upper b. Hypoplastic and/or lobulated
body 17. Other viscera
b. Characteristic subcutaneous edema a. Absent gallbladder
c. Internal organs: invariably missing b. Absent spleen
d. Absent or rudimentary cardiac development: the key c. Absent-to-reduced pancreas
diagnostic feature d. Absent adrenal
i. Pseudoacardia (rudimentary heart tissue) e. Absent-to-hypoplastic gonads
ii. Holoacardia (completely lacking a heart) f. Exstrophy of the cloaca
5. Growth abnormality g. Skin with myxedematous thickening
6. Cranial vault 18. Umbilical cord vessels
a. Absent a. Two vessels
b. Partial b. Three vessels
c. Intact 19. Severe obstetrical complications
7. Brain a. Maternal polyhydramnios
a. Absent b. Preterm labor
b. Necrotic c. Cord accidents
c. Open cranial vault d. Dystocia
d. Holoprosencephaly e. Uterine rupture
8. Facial features 20. Severe neonatal complications
a. Absent facial features a. Hydrops
b. Rudimentary facial features b. Intrauterine demise
c. Present with defects c. Prematurity
d. Anophthalmia/microphthalmia d. Heart failure
e. Cleft lip/palate e. Anemia
9. Upper limbs f. Twin-to-twin transfusion syndrome
a. Absent 21. Outcome for the normal sib in an acardiac twin pregnancy
b. Rudimentary a. Unsatisfactory
c. Radial aplasia i. Adapting to the increasing circulatory load,
d. Syndactyly/oligodactyly resulting in the following situations:
10. Lower limbs a) Intrauterine growth retardation
a. Absent b) Hydrops
b. Rudimentary/reduced c) Ascites
c. Syndactyly/oligodactyly d) Pleural effusion
d. Talipes equinovarus e) Hypertrophy of the right ventricle
11. Thorax f) Hepatosplenomegaly
a. Absent g) Severe heart failure resulting in pericardial
b. Reduced effusion and/or tricuspid insufficiency
c. Diaphragmatic defect ii. Stillbirth
12. Lungs iii. Prematurity
a. Absent iv. Neonatal death
b. Necrotic or rudimentary b. Mortality for the normal twin reported as high as 50%
c. Single midline lobe without intervention
 ACARDIA 3

DIAGNOSTIC INVESTIGATIONS 2. Amniocentesis to diagnose associated chromosome

abnormalities (about 10% of pump twins)
1. Radiography 3. Management of pregnancies complicated by an acardiac
a. Absent or rudimentary skull fetus
b. Absent or rudimentary thorax a. Conservative treatment
c. Absent or rudimentary heart i. Monitor pregnancy by serial ultrasonography
d. Vertebral anomalies ii. Conservative approach as long as there is no evi-
e. Rib anomalies dence of cardiac circulatory decompensation in
f. Limb defects, especially upper limbs the donor twin
2. Pathology b. Termination of pregnancies
a. Microcephaly c. Treatment and prevention of preterm labor by tocolytics
b. Severely rudimentary brain i. Magnesium sulphate
c. Developmental arrest of brain at the prosencephalic ii. Beta-Sympathomimetics
stage (holoprosencephaly) iii. Indomethacin
d. Hypoxic damage to the holospheric brain mantle with d. Treatment of pump fetus heart failure involving
cystic change (hydranencephaly) maternal digitalization
e. Treatment of polyhydramnios by therapeutic repeated
GENETIC COUNSELING amniocentesis
f. Selective termination of the acardiac twin
1. Recurrence risk
i. To occlude the umbilical artery of the acardiac
a. Patient’s sib: overall recurrence risk of about 1 in
twin in order to stop umbilical flow through the
10,000 (The recurrence risk is for monoamniotic
anastomosis
twinning [1% for couples who have had one set of
a) Intrafunicular injection and mechanical
monozygotic twins] times the frequency of the occur-
occlusion of the umbilical artery
rence of TRAP sequence with near-term survival
b) Embolization by steel or platinum coil, alco-
[about 1% of monozygotic twin sets])
hol-soaked suture material, or ethanol
b. Patient’s offspring: not applicable (a lethal condition)
c) Hysterotomy and delivery of acardiac twin
2. Prenatal ultrasonography
d) Ligation of the umbilical cord
a. Monochorionic placenta with a single umbilical
e) Hysterotomy and umbilical cord ligation
artery in 2/3 of cases
ii. Fetal surgery: best available treatment for acar-
b. Acardiac fetus
diac twinning
i. Unrecognizable head or upper trunk
a) Endoscopic laser coagulation of the umbili-
ii. Without a recognizable heart or a partially
cal vessels at or before 24 weeks of gestation
formed heart
b) Endoscopic or sonographic guided umbilical
iii. A variety of other malformations
cord ligation after 24 weeks of gestation
iv. Reversal of blood flow in the umbilical artery
iii. Summary of acardiac twins treated with invasive
with flow going from the placenta toward the
procedures reported in the literature
acardiac fetus (reversed arterial perfusion). Such
a) Mortality of the pump twin (13.6%)
a reversal of the blood flow in the recipient twin
b) Preterm delivery (50.3%)
can be demonstrated in utero by transvaginal
c) Delivery before 30-weeks gestation (27.2%)
Doppler ultrasound as early as 12 weeks of
d) Perinatal mortality, if untreated, is at least 50%
gestation
v. Early diagnosis by transvaginal sonography on
the following signs: REFERENCES
a) Monozygotic twin gestation (absence of the
Aggarwal N, Suri V, Saxena SV, et al.: Acardiac acephalus twins: a case report
lambda sign) and review of literature. Acta Obstet Gynecol Scand 81:983–984, 2002.
b) Biometric discordance between the twins Alderman B: Foetus acardius amorphous. Postgrad Med J 49:102–105, 1973.
c) Diffuse subcutaneous edema or morpho- Arias F, Sunderji S, Gimpelson R, et al.: Treatment of acardiac twinning.
logic anomalies of one of the twins, or Obstet Gynecol 91:818–821, 1998.
both Benirschke K, des Roches Harper V: The acardiac anomaly. Teratology
15:311–316, 1977.
d) Detection of reversed umbilical cord flow; Blaicher W, Repa C, Schaller A: Acardiac twin pregnancy: associated with tri-
cardiac activity likely to disappear as the somy 2. Hum Reprod 15:474–475, 2000.
pregnancy progresses Blenc AM, Gömez JA, Collins D, et al.: Pathologic quiz case. Pathologic diag-
e) Absence of cardiac activity, although hemi- nosis: acardiac fetus, acardius acephalus type. Arch Pathol Lab Med
cardia or pseudocardia may be present 123:974–976, 1999.
Bonilla-Musoles F, Machado LE, Raga F, et al.: Fetus acardius. Two- and three-
c. The donor fetus dimensional ultrasonographic diagnoses. J Ultrasound Med 20:1117–1127,
i. Hydrops 2001.
ii. Cardiac failure (cardiomegaly, pericardial effu- Chen H, Gonzalez E, Hand AM, Cuestas R: The acardius acephalus and
sion, and tricuspid regurgitation) monozygotic twinning. Schumpert Med Quart 1:195–199, 1983.
4 ACARDIA

Donnenfeld AE, Van de Woestijne J, Craparo F, et al.: The normal fetus of an Sanjaghsaz H, Bayram MO, Qureshi F: Twin reversed arterial perfusion
acardiac twin pregnancy: perinatal management based on echocardio- sequence in conjoined, acardiac, acephalic twins associated with a normal
graphic and sonographic evaluation. Prenat Diagn 11:235–244, 1991. triplet. A case report. J Reprod Med 43:1046–1050, 1998.
French CA, Bieber FR, Bing DH, et al.: Twins, placentas, and genetics: acar- Søgaard K, Skibsted L, Brocks V: Acardiac twins: Pathophysiology, diagnosis,
diac twinning in a dichorionic, diamniotic, monozygotic twin gestation. outcome and treatment. Six cases and review of the literature. Fetal Diagn
Hum Pathol 29:1028–1031, 1998. Ther 14:53–59, 1999.
Hanafy A, Peterson CM: Twin-reversed arterial perfusion (TRAP) sequence: Van Allen MI, Smith DW, Shepard TH: Twin reversed arterial perfusion
case reports and review of literature. Aust N Z J Obstet Gynaecol (TRAP) sequence: a study of 14 twin pregnancies with acardius. Semin
37:187–191, 1997. Perinatol 7:285–293, 1983.
Healey MG: Acardia: predictive risk factors for the co-twin’s survival.
Teratology 50:205–213, 1994.
 ACARDIA 5

Fig. 2. Radiographs of the above acardiac fetus showing a missing

head, cervical vertebrae and part of upper thoracic vertebrae, rudimen-
tal lower ribs, malformed lower thoracic and lumbar vertebrae, and
relatively well-formed lower limbs.

Fig. 1. Ventral view of an acardiac acephalus fetus (upper photo)

shows a large abdominal defect, gastroschisis (arrow), through which
small rudiments of gastrointestinal tract are seen. Dorsal view (lower
photo) shows a very underdeveloped cephalic end and relatively well-
developed lower limbs. The co-twin had major malformations consist-
ing of a large omphalocele, ectopia cordis, and absent pericardium,
incompatible with life.
Fig. 3. The head and part of the thorax of this acardiac fetus are com-
pletely missing with relatively well-formed lower limbs.
6 ACARDIA

Fig. 4. Another acardiac fetus with a missing head and part of the
upper thorax. Radiograph shows missing head, and cervical and part
of thoracic vertebrae and ribs. Pelvis and lower limbs are well formed.

Fig. 5. Acardius (second twin, 36-weeks gestation) showing spherical

body with a small amorphous mass of leptomeningeal and glial tissue
at the cephalic end. There were one deformed lower extremity and a
small arm appendage. Small intestinal loops, nodules of adrenal
glands, and testicles were present in the body. There was no heart or
lungs. The placenta was nonoamniotic monochorionic with velamen-
tous insertion of the umbilical cord. The other identical twin was free
of birth defects. Radiograph of acardius twin shows a short segment of
the spine, a femur, a tibia, and a fibula.
 Achondrogenesis

Achondrogenesis is a heterogeneous group of lethal chon- e. Heart

drodysplasias. Achondrogenesis type I (Fraccaro-Houston-Harris i. Patent ductus arteriosus
type) and type II (Langer-Saldino type) were distinguished on the ii. Atrial septal defect
basis of radiological and histological criteria. Achondrogenesis iii. Ventricular septal defect
type I was further subdivided, on the basis of convincing histo- f. Protuberant abdomen
logical criteria, into type IA, which has apparently normal car- g. Limbs
tilage matrix but inclusions in chondrocytes, and type IB, i. Extremely short (micromelia), shorter than type II
which has an abnormal cartilage matrix. Classification of type ii. Flipper-like appendages
IB as a separate group has been confirmed recently by the dis- 3. Achondrogenesis type II
covery of its association with mutations in the diastrophic dys- a. Growth
plasia sulfate transporter (DTDST) gene, making it allelic with i. Lethal neonatal dwarfism
diastrophic dysplasia. ii. Mean birth weight of 2100 g
b. Craniofacial features
GENETICS/BASIC DEFECTS i. Disproportionately large head
ii. Large and prominent forehead
1. Type IA: an autosomal recessive disorder with an
iii. Midfacial hypoplasia
unknown chromosomal locus
a) Flat facial plane
2. Type IB
b) Flat nasal bridge
a. An autosomal recessive disorder
c) Small nose with severely anteverted nostrils
b. Resulting from mutations of the DTDST gene, which
iv. Normal philtrum
is located at 5q32-q33
v. Micrognathia
3. Type II
vi. Cleft palate
a. Autosomal dominant type II collagenopathy
c. Extremely short neck
b. Resulting from mutations in the COL2A1 gene, which
d. Thorax
is located at 12q13.1-q13.3
i. Short and flared thorax
ii. Bell-shaped cage
CLINICAL FEATURES
iii. Lung hypoplasia
1. Prenatal/perinatal history e. Protuberant abdomen
a. Polyhydramnios f. Extremely short limbs (micromelia)
b. Hydrops
c. Breech presentation
d. Perinatal death DIAGNOSTIC INVESTIGATIONS
2. Achondrogenesis type I 1. Radiological features
a. Growth a. Variable features
i. Lethal neonatal dwarfism b. No single obligatory feature
ii. Mean birth weight of 1200 g c. Distinction between type IA and type IB on radi-
b. Craniofacial features ographs not always possible
i. Disproportionately large head d. Degree of ossification: age dependent, and caution is
ii. Soft skull needed when comparing radiographs at different ges-
iii. Sloping forehead tational ages
iv. Convex facial plane e. Achondrogenesis type I
v. Flat nasal bridge, occasionally associated with a i. Skull: Varying degree of deficient cranial ossifi-
deep horizontal groove cation consisting of small islands of bone in
vi. Small nose, often with anteverted nostrils membranous calvaria
vii. Long philtrum ii. Thorax and ribs
viii. Retrognathia a) Short and barrel-shaped thorax
ix. Increased distance between lower lip and lower b) Thin ribs with marked expansion at costo-
edge of chin chondral junction, frequently with multiple
x. Double chin appearance fractures
c. Extremely short neck iii. Spine and pelvis
d. Thorax a) Poorly ossified spine, ischium, and pubis
i. Short and barrel-shaped thorax b) Poorly ossified iliac bones with short medial
ii. Lung hypoplasia margins

7
8 ACHONDROGENESIS

iv. Limbs and tubular bones vi. Enlarged lacunas

a) Extreme micromelia, with limbs much shorter vii. Woven bone
than in type II b. Achondrogenesis type IB
b) Prominent spike-like metaphyseal spurs i. Abnormal cartilage matrix: presence of
c) Femur and tibia frequently presenting as “demasked” coarsened collagen fibers, particu-
short bone segments larly dense around the chondrocytes, forming
v. Subtype IA (Houston-Harris type) collagen rings
a) Poorly ossified skull ii. Abnormal staining properties of cartilage
b) Thin ribs with multiple fractures a) Reduced staining with cationic dyes, such as
c) Unossified vertebral pedicles toluidine blue or Alcian blue, probably
d) Arched ilium because of a deficiency in sulfated proteo-
e) Hypoplastic but ossified ischium glycans
f) Wedged femur with metaphyseal spikes b) This distinguishes type IB from type IA, in
g) Short tibia and fibula with metaphyseal flare which the matrix is close to normal and
vi. Subtype IB (Fraccaro type) inclusions can be seen in chondrocytes, and
a) Adequately ossified skull from achondrogenesis type II, in which
b) Absence of rib fractures cationic dyes give a normal staining pattern
c) Total lack of ossification or only rudimentary c. Achondrogenesis type II
calcification of the center of the vertebral i. Cartilage
bodies a) Slightly larger than normal
d) Ossified vertebral pedicles b) Grossly distorted (lobulated and mush-
e) Iliac bones with ossification only in their upper roomed)
part, giving a crescent-shaped, “paraglider- ii. Markedly deficient cartilaginous matrix
like” appearance on X-ray iii. Severe disturbance in endochondral ossification
f) Unossified ischium iv. Hypercellular and hypervascular reserve cartilage
g) Shortened tubular bones without recognized with large, primitive mesenchymal (ballooned)
axis chondrocytes with abundant clear cytoplasm
h) Metaphyseal spurring giving the appearance (vacuoles) (“Swiss cheese-like”)
of a “thorn apple” or “acanthocyte” (a descrip- v. Overgrowth of membranous bones resulting in
tive term in hematology) cupping of the epiphyseal cartilages
i) Trapezoid femur vi. Decreased amount and altered structure of pro-
j) Stellate tibia teoglycans
k) Unossified fibula vii. Relatively lower content of chondroitin 4-sulfate
l) Poorly ossified phalanges viii. Lower molecular weight and decreased total
f. Achondrogenesis type II chondroitin sulfation
i. Skull ix. Absence of type II collagen
a) Normal cranial ossification x. Increased amounts of type I and type III collagen
b) Relatively large calvaria 3. Biochemical testing
ii. Thorax and ribs a. Lack of sulfate incorporation: cumbersome and not
a) Short and flared thorax used for diagnostic purposes
b) Bell-shaped cage b. Sulfate incorporation assay in cultured skin fibrob-
c) Shorter ribs without fractures lasts or chondrocytes: recommended in the rare
iii. Spine and pelvis: relatively well-ossified iliac instances in which the diagnosis of achondrogenesis
bones with long, crescent-shaped medial and type IB is strongly suspected but molecular genetic
inferior margins testing fails to detect SLC26A2 (DTDST) mutations
iv. Limbs and tubular bones 4. Molecular genetic studies
a) Short, broad bones, usually with some dia- a. Mutation analysis of the DTDST gene, reported in:
physeal constriction and flared, cupped i. Achondrogenesis type IB (the most severe form)
metaphyseal ends ii. Atelosteogenesis type II (an intermediate form)
b) Metaphyseal spurs, usually smaller than type I iii. Diastophic dysplasia (the mildest form)
2. Histologic features iv. Recessive multiple epiphyseal dysplasia
a. Achondrogenesis type IA b. Achondrogenesis type IB
i. Normal cartilage matrix i. Mutation analysis: testing of the following four
ii. Absent collagen rings around the chondrocytes most common SLC26A2 (DTDST) gene muta-
iii. Vacuolated chondrocytes tions (mutation detection rate about 60%)
iv. Presence of intrachondrocytic inclusion bodies a) R279W
(periodic acid-Schiff [PAS] stain positive, dia- b) IVS1+2T>C (“Finnish” mutation)
stase resistant) c) delV340
v. Extraskeletal cartilage involvement d) R178X
 ACHONDROGENESIS 9

ii. Sequence analysis of the SLC26A2 (DTDST) b) Possible presence of asymptomatic carriers
coding region (mutation detection rate over 90%) in families of an affected patient
a) Private mutations c) Prenatal diagnosis possible if the mutation
b) Common mutations has been characterized in the affected family
c. Achondrogenesis type II: mutation analysis of the 3. Management
COL2A1 gene a. Supportive care
b. No treatment available for the underlying lethal
disorder
GENETIC COUNSELING
1. Recurrence risk
a. Patient’s sib REFERENCES
i. Achondrogenesis type IA and type IB (autoso- Balakumar K: Antenatal diagnosis of Parenti-Fraccaro type achondrogenesis.
Indian Pediatr 27:496–499, 1990.
mal recessive disorders)
Bonafé L, Ballhausen D, Superti-Furga A: Achondrogenesis type 1B. Gene
a) Recurrence risk: 25% reviews, 2004. http://www.genetests.org
b) Unaffected sibs of a proband: 2/3 chance of Borochowitz Z, Lachman R, Adomian GE, et al.: Achondrogenesis type I:
being heterozygotes delineation of further heterogeneity and identification of two distinct sub-
ii. Achondrogenesis type II groups. J Pediatr 112:23–31, 1988.
Borochowitz Z, Ornoy A, Lachman R, et al.: Achondrogenesis II-hypochondro-
a) Usually caused by a new dominant muta- genesis: variability versus heterogeneity. Am J Med Genet 24:273–288,
tion, in which case recurrence risk is not sig- 1986.
nificantly increased Benacerraf B, Osathanondh R, Bieber FR: Achondrogenesis type I: ultrasound
b) Asymptomatic carrier parent (germline diagnosis in utero. J Clin Ultrasound 12:357–359, 1984.
mutation for a dominant mutation) may be Chen H: Achondrogenesis. Emedicine, 2001. http://www.emedicine.com
Chen H: Skeletal dysplasia. Emedicine, 2002. http://www.emedicine.com
present in the families of affected patients, in Chen H, Liu CT, Yang SS: Achondrogenesis: a review with special considera-
which case recurrence risk is 50% tion of achondrogenesis type II (Langer-Saldino). Am J Med Genet
b. Patient’s offspring: lethal entities not surviving to 10:379–394, 1981.
reproduction Faivre L, Le Merrer M, Douvier S, et al.: Recurrence of achondrogenesis type
2. Prenatal diagnosis II within the same family: Evidence for germline mosaicism. Am J Med
Genet 126A:308–312, 2004.
a. Ultrasonography Godfrey M, Hollister DW: Type II achondrogenesis-hypochondrogenesis: identi-
i. Polyhydramnios fication of abnormal type II collagen. Am J Hum Genet 43:904–913, 1988.
ii. Fetal hydrops Horton WA, Machado MA, Chou JW, et al.: Achondrogenesis type II, abnor-
iii. Disproportionally big head malities of extracellular matrix. Pediatr Res 22:324–329, 1987.
Körkkö J, Cohn DH, Ala-Kokko L, et al.: Widely distributed mutations in the
iv. Nuchal edema
COL2A1 gene produce achondrogenesis type II/hypochondrogenesis.
v. Cystic hygroma Am J Med Genet 92:95–100, 2000.
vi. A narrow thorax Langer LO, Jr, Spranger JW, Greinacher I, et al.: Thanatophoric dwarfism. A
vii. Short limbs condition confused with achondroplasia in the neonate, with brief com-
viii. Poor ossification of vertebral bodies and limb ments on achondrogenesis and homozygous achondroplasia. Radiology
92:285–294 passim, 1969.
tubular bones (leading to difficulties in determin- Meizner I, Barnhard Y: Achondrogenesis type I diagnosed by transvaginal ultra-
ing their length) sonography at 13 weeks’ gestation. Am J Obstet Gynecol 173:1620–1622,
ix. Suspect achondrogenesis type I 1995.
a) An extremely echo-poor appearance of the Molz G, Spycher MA: Achondrogenesis type I: light and electron-microscopic
skeleton studies. Eur J Pediatr 134:69–74, 1980.
Mortier GR, Wilkin DJ, Wilcox WR, et al.: A radiographic, morphologic, bio-
b) A poorly mineralized skull chemical and molecular analysis of a case of achondrogenesis type II
c) Short limbs resulting from substitution for a glycine residue (Gly691>Arg) in the type
d) Rib fractures II collagen trimer. Hum Mol Genet 4:285–288, 1995.
b. Molecular genetic studies Ornoy A, Sekeles E, Smith P, et al.: Achondrogenesis type I in three sibling
i. Prenatal diagnosis of achondrogenesis type IB fetuses. Scanning and transmission electron microscopic studies. Am J
Pathol 82:71–84, 1976.
and type II by mutation analysis of chorionic vil- Smith WL, Breitweiser TD, Dinno N: In utero diagnosis of achondrogenesis,
lus DNA or amniocyte DNA in the first or sec- type I. Clin Genet 19:51–54, 1981.
ond trimester Soothill PW, Vuthiwong C, Rees H: Achondrogenesis type 2 diagnosed by trans-
ii. Achondrogenesis type IB vaginal ultrasound at 12 weeks’ gestation. Prenat Diagn 13:523–528, 1993.
Spranger J: International classification of osteochondrodysplasias. Eur J
a) Characterize both alleles of DTDST before-
Pediatr 151:407–415, 1992.
hand Spranger J, Winterpacht A, Zabel B: The type II collagenopathies: a spectrum
b) Identify the source parent of each allele of chondrodysplasias. Eur J Pediatr 153:56–65, 1994.
c) Theoretically, analysis of sulfate incorpora- Superti-Furga A: Achondrogenesis type 1B. J Med Genet 33:957–961, 1996.
tion in chorionic villi might be used for pre- Superti-Furga A, Hästbacka J, Wilcox WR, et al.: Achondrogenesis type IB is
caused by mutations in the diastrophic dysplasia sulphate transporter
natal diagnosis, but experience is lacking gene. Nat Genet 12:100–102, 1996.
iii. Achondrogenesis type II Superti-Furga A, Rossi A, Steinmann B, et al.: A chondrodysplasia family pro-
a) The affected fetus usually with a new domi- duced by mutations in the diastrophic dysplasia sulfate transporter gene:
nant mutation of the COL2A1 gene genotype/phenotype correlations. Am J Med Genet 63:144–147, 1996.
10 ACHONDROGENESIS

Tongsong T, Srisomboon J, Sudasna J: Prenatal diagnosis of Langer-Saldino Yang SS, Bernstein J: Achondrogenesis type I. Arch Dis Child 52:253–254,
achondrogenesis. J Clin Ultrasound 23:56–58, 1995. 1977.
van der Harten HJ, Brons JT, Dijkstra PF, et al.: Achondrogenesis-hypochon- Yang SS, Gilbert-Barnes E: Skeletal system. In: Gilbert-Barness E (ed):
drogenesis: the spectrum of chondrogenesis imperfecta. A radiological, Potter’s Pathology of the Fetus and Infant. St Louis: Mosby, 1997, pp
ultrasonographic, and histopathologic study of 23 cases. Pediatr Pathol 1423–1478.
8:571–597, 1988. Yang SS, Brough AJ, Garewal GS, et al.: Two types of heritable lethal achon-
Yang SS, Bernstein J: Letter: Proposed readjustment of eponyms for achondro- drogenesis. J Pediatr 85:796–801, 1974.
genesis. J Pediatr 87:333–334, 1975. Yang SS, Heidelberger KP, Bernstein J: Intracytoplasmic inclusion bodies in
Yang S-S, Heidelberger KP, Brough AJ, et al.: Lethal short-limbed chondrodys- the chondrocytes of type I lethal achondrogenesis. Hum Pathol
plasia in early infancy. Persp Pediatr Pathol 3:1–40, 1976. 7:667–673, 1976.
ACHONDROGENESIS 11

Fig. 1. A neonate with achondrogenesis type I showing large head,

short trunk, and extreme micromelia. Radiograph shows unossified
calvarium, vertebral bodies and some pelvic bones. The remaining
bones are extremely small. There are multiple rib fractures. The sagit-
tal section of the femora and the humeri are similar. An extremely
small ossified shaft is capped by a relatively large epiphyseal cartilage
at both ends. Photomicrographs of resting cartilage with high magni-
fication show many chondrocytes that contain large cytoplasmic
inclusions which are within clear vacuoles (Diastase PAS stain).
Electron micrograph shows inclusion as a globular mass of electron
dense material. It is within a distended cistern of rough endoplasmic
reticulum.
12 ACHONDROGENESIS

Fig. 2. Achondrogenesis type II. As in type I, this neonate shows large

head, short trunk, and micromelia. Sagittal section of the femur shows
much better ossification of the shaft than type I. The cartilage lacks glis-
tering appearance due to cartilage matrix deficiency. Photomicrograph
of the entire cartilage shows severe deficiency of cartilage matrix. The
cartilage canals are large, fibrotic, and stellate in shape. Physeal growth
zone is severely retarded.
 ACHONDROGENESIS 13

Fig. 3. Two infants with achondrogenesis type II showing milder spec-

trum of manifestations, bordering the type II and spondyloepiphyseal
congenita.
Another Random Scribd Document
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 Psychology - Revision Notes
Second 2025 - Division

Prepared by: Researcher Davis

Date: July 28, 2025

Unit 1: Best practices and recommendations

Learning Objective 1: Historical development and evolution
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Learning Objective 2: Ethical considerations and implications
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Learning Objective 3: Ethical considerations and implications
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Learning Objective 4: Key terms and definitions
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Learning Objective 5: Case studies and real-world applications
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 5: Literature review and discussion
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 6: Critical analysis and evaluation
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 7: Interdisciplinary approaches
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Best practices and recommendations
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 9: Diagram/Chart/Graph]
Example 9: Experimental procedures and results
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Discussion 2: Comparative analysis and synthesis
Note: Best practices and recommendations
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
[Figure 11: Diagram/Chart/Graph]
Example 11: Interdisciplinary approaches
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Literature review and discussion
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Note: Assessment criteria and rubrics
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Historical development and evolution
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 15: Literature review and discussion
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Example 16: Practical applications and examples
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 17: Current trends and future directions
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Important: Key terms and definitions
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 19: Diagram/Chart/Graph]
Remember: Best practices and recommendations
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Discussion 3: Interdisciplinary approaches
Remember: Study tips and learning strategies
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 21: Diagram/Chart/Graph]
Key Concept: Fundamental concepts and principles
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Critical analysis and evaluation
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 23: Interdisciplinary approaches
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Assessment criteria and rubrics
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Ethical considerations and implications
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Best practices and recommendations
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Statistical analysis and interpretation
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 28: Diagram/Chart/Graph]
Example 28: Best practices and recommendations
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Historical development and evolution
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Chapter 4: Statistical analysis and interpretation
Remember: Experimental procedures and results
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 31: Learning outcomes and objectives
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 32: Diagram/Chart/Graph]
Key Concept: Current trends and future directions
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Note: Experimental procedures and results
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Note: Comparative analysis and synthesis
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 35: Diagram/Chart/Graph]
Important: Comparative analysis and synthesis
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 36: Ethical considerations and implications
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Theoretical framework and methodology
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Practice Problem 38: Research findings and conclusions
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Statistical analysis and interpretation
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Summary 5: Study tips and learning strategies
Important: Interdisciplinary approaches
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Case studies and real-world applications
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Practice Problem 42: Learning outcomes and objectives
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Definition: Literature review and discussion
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 44: Diagram/Chart/Graph]
Definition: Assessment criteria and rubrics
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Theoretical framework and methodology
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Learning outcomes and objectives
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 47: Experimental procedures and results
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Important: Learning outcomes and objectives
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 49: Diagram/Chart/Graph]
Note: Problem-solving strategies and techniques
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 50: Diagram/Chart/Graph]
Topic 6: Current trends and future directions
Definition: Problem-solving strategies and techniques
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Problem-solving strategies and techniques
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 52: Diagram/Chart/Graph]
Note: Key terms and definitions
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Theoretical framework and methodology
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Interdisciplinary approaches
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Ethical considerations and implications
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Practice Problem 56: Case studies and real-world applications
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 57: Historical development and evolution
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 58: Critical analysis and evaluation
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Definition: Literature review and discussion
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Quiz 7: Experimental procedures and results
Important: Experimental procedures and results
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Remember: Practical applications and examples
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Critical analysis and evaluation
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Definition: Critical analysis and evaluation
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 64: Diagram/Chart/Graph]
Note: Learning outcomes and objectives
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Important: Theoretical framework and methodology
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 66: Current trends and future directions
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Interdisciplinary approaches
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Best practices and recommendations
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Definition: Best practices and recommendations
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 70: Diagram/Chart/Graph]
Exercise 8: Fundamental concepts and principles
Definition: Current trends and future directions
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Literature review and discussion
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Experimental procedures and results
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
[Figure 73: Diagram/Chart/Graph]
Definition: Historical development and evolution
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Note: Comparative analysis and synthesis
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Definition: Ethical considerations and implications
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Definition: Historical development and evolution
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Learning outcomes and objectives
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Historical development and evolution
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Literature review and discussion
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Unit 9: Interdisciplinary approaches
Key Concept: Assessment criteria and rubrics
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Practice Problem 81: Critical analysis and evaluation
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 82: Learning outcomes and objectives
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 83: Ethical considerations and implications
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Remember: Learning outcomes and objectives
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 85: Diagram/Chart/Graph]
Example 85: Learning outcomes and objectives
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Practice Problem 86: Assessment criteria and rubrics
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Fundamental concepts and principles
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Example 88: Comparative analysis and synthesis
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 89: Diagram/Chart/Graph]
Remember: Assessment criteria and rubrics
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Test 10: Current trends and future directions
Note: Practical applications and examples
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Remember: Current trends and future directions
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Important: Historical development and evolution
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 93: Fundamental concepts and principles
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Note: Critical analysis and evaluation
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 95: Fundamental concepts and principles
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 96: Diagram/Chart/Graph]
Important: Learning outcomes and objectives
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Definition: Learning outcomes and objectives
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 98: Diagram/Chart/Graph]
Practice Problem 98: Best practices and recommendations
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Experimental procedures and results
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Discussion 11: Practical applications and examples
Key Concept: Learning outcomes and objectives
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Critical analysis and evaluation
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Ethical considerations and implications
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Note: Fundamental concepts and principles
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Interdisciplinary approaches
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Best practices and recommendations
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 106: Diagram/Chart/Graph]
Important: Interdisciplinary approaches
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Historical development and evolution
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 108: Diagram/Chart/Graph]
Remember: Ethical considerations and implications
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 109: Fundamental concepts and principles
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 110: Diagram/Chart/Graph]
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