Understanding Craniofacial Anomalies: The Etiopathogenesis of Craniosynostoses and Facial Clefting

585 Pages·2002·9.041 MB·English

by  Mark P. Mooney, Michael I. Siegel

UNDERSTANDING
CRANIOFACIAL ANOMALIES
UNDERSTANDING
CRANIOFACIAL ANOMALIES
The Etiopathogenesis of Craniosynostoses
and Facial Clefting
Edited by
MARK P. MOONEY, Ph.D.
Associate Professor
Departments of Oral Medicine and Pathology, Anthropology,
Surgery-Division of Plastic and Reconstructive Surgery, and Orthodontics
Cleft Palate-Craniofacial Center
University of Pittsburgh
MICHAEL I. SIEGEL, Ph.D.
Professor
Departments of Anthropology and Orthodontics,
Associate Director of Research at Cleft Plate-Craniofacial Center
University of Pittsburgh
A JOHN WILEY & SONS, INC., PUBLICATION
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Library of Congress Cataloging-in-Publication Data:
Understanding craniofacial anomalies :etiopathogenesis of craniosynostoses and facial clefting / edited by
Mark P.Mooney,Michael I.Siegel.
p. cm.
Includes bibliographical references and index.
ISBN 0-471-38724-X (cloth :alk.paper)
1. Face—Abnormalities. 2. Skull—Abnormalities. 3. Cleft palate. 4. Craniosynostoses.
5. Face—Abnormalities—Genetic aspects. I. Mooney,Mark P. II. Siegel,Michael I.
RD763 .U53 2002
617.5¢2—dc21
2001046949
Printed in the United States of America.
10 9 8 7 6 5 4 3 2 1
We would like to dedicate this book
to our families,
to our mentors,
to our students
CONTENTS
Foreword xvii
Preface xix
Contributors xxi
I CLASSIFICATION AND TERMINOLOGY 1
1 Overview and Introduction 3
Mark P. Mooney, Ph.D. and Michael I. Siegel, Ph.D.
1.1. Introduction / 3
1.2. Normal Craniofacial Morphology / 3
1.3. Craniofacial Dysmorphology / 5
1.4. Conclusions / 7
2 Terminology and Classification of Craniosynostosis 11
Marilyn C. Jones, M.D.
2.1. Introduction / 11
2.2. Historical Perspective / 11
2.3. Conclusions / 14
3 Terminology and Classification of Facial Clefting 17
Robert J. Shprintzen, Ph.D.
3.1. Introduction / 17
3.2. Historical Classifications of Facial Clefts / 17
3.3. Do These Classifications Really Serve a Purpose? / 19
3.3.1. Etiologic Heterogeneity / 19
3.3.2. Anatomic Variability / 20
3.4. Back to Semantics / 21
3.4.1. The Language / 21
3.4.2. The Most Important Purpose and Technique for
Categorization / 21
vii
viii CONTENTS
3.4.3. Clinical Management / 21
3.4.4. Categorizing Syndromic Clefts / 22
3.4.5. Additional Anatomic Differentiation / 22
3.5. Is There a Useful System? / 24
3.5.1. Population Heterogeneity:The Instigator or Nemesis of
Classification Systems? / 25
3.5.2. The Use of Modern Databases / 26
3.6. Conclusions / 27
II EMBRYOGENESIS AND ETIOLOGY 29
4 Craniofacial Embryogenesis:
Normal Developmental Mechanisms 31
Geoffrey H. Sperber, Ph.D.
4.1. Introduction / 31
4.2. Early Development / 32
4.3. Neural Crest Tissue / 35
4.4. Craniofacial Development / 41
4.4.1. Adenohypophysial (Rathke) and Seessel Pouches / 45
4.4.2. The Mouth / 46
4.4.3. Pharyngeal Arches / 46
4.4.4. Pharyngeal Pouches and Cervical Grooves / 47
4.4.5. The Skull / 50
4.4.6. The Palate / 54
5 Craniofacial Embryogenesis: Abnormal Developmental
Mechanisms 61
Malcolm C. Johnston, D.D.S., Ph.D. and Peter T. Bronsky, D.M.D., M.S.
5.1. Introduction / 61
5.2. Some Relevant Aspects of Craniofacial Evolution and
Development / 62
5.3. The Holoprosencephalies and Germ Layer Formation / 65
5.4. Otocephalies / 69
5.5. Syndromes with Major Crest Cell Involvement / 72
5.5.1. Normal Neural Crest Cell Involvement in Craniofacial
Malformations / 72
5.5.2. Retinoic Acid Syndrome / 75
5.5.3. Other Malformations with Major Crest Cell Involvement / 77
5.5.4. Summary of the Otofacial Malformations / 85
5.6. Development Alterations in Facial Clefting with Emphasis on their
Multifactorial Etiology / 86
5.6.1. Primary Palate Formation and Cleft Lip with or without
Cleft Palate / 87
5.6.2. Secondary Palate Formation and Cleft Palate / 99
CONTENTS ix
5.7. Abnormal Developmental Mechanisms in the Formation of Tissues
and Organs / 102
5.7.1. Abnormalities of Tooth Formation / 102
5.7.2. Development of Cartilage and Bone / 102
5.8. Concluding Remarks / 104
6 Genetic Etiologies of Craniosynostosis 125
Ethylin Wang Jabs, M.D.
6.1. Introduction / 125
6.2. Genetic Epidemiology of Craniosynostoses / 125
6.3. Phenotypes and Genotypes of Craniosynostoses / 126
6.4. Fibroblast Growth Factor Receptors / 126
6.5. Crouzon Syndrome and FGFR2 Extracellular
Domain Mutations / 128
6.6. Apert Syndrome and FGFR2 Ser252Trp and Pro253Arg
Mutations / 129
6.7. Pfeiffer Syndrome and FGFR2 Extracellular Mutations and
Paralogous Mutations in FGFR1 and FGFR3 / 133
6.8. Jackson-Weiss Syndrome and FGFR2 Extracellular Domain
Mutations / 134
6.9. Beare-Stevenson Cutis Gyrata Syndrome and FGFR2 Juxta- or
Transmembrane Domain Mutations / 135
6.10. Crouzon Syndrome with Acanthosis Nigricans or
Crouzonodermoskeletal Syndrome and FGFR3 Ala391Glu
Transmembrane Domain Mutation / 135
6.11. FGFR3 Pro250Arg-Associated Coronal Synostosis Syndrome
or Muenke Syndrome or Craniosynostosis Adelaide Type / 136
6.12. Pathophysiology of FGFR Mutations in Craniosynostosis / 136
6.13. Saethre Chotzen Syndrome and Robinow-Sorauf Syndrome and
TWIST Mutations / 137
6.14. Craniosynostosis,Boston Type,and MSX2 Pro148His
Mutation / 139
6.15. Integration of Developmental,Clinical,and Molecular Genetics
of Craniosynostoses / 139
7 Genetic Etiologies of Facial Clefting 147
Mary L. Marazita, Ph.D., F.A.C.M.G.
7.1. Introduction / 147
7.2. Genetic Etiologies of Syndromic Orofacial Clefts / 147
7.2.1. Terms Used in Syndromology / 147
7.2.2. Association of Orofacial Clefts with Other
Anomalies / 148
7.2.3. Chromosomal Rearrangements / 149
7.2.4. Single-Gene Etiologies / 150
7.2.5. Summary / 150
x CONTENTS
7.3. Genetic Etiologies of Nonsyndromic Orofacial Clefts / 151
7.3.1. Family Studies / 151
7.3.2. Linkage/Association Studies / 152
7.3.3. Summary / 155
8 Environmental Etiologies of Orofacial Clefting and
Craniosynostosis 163
Vandana Shashi, M.D. and Thomas C. Hart, D.D.S., Ph.D.
8.1. Introduction / 163
8.2. Nomenclature / 164
8.3. Environmental Etiologies of Orofacial Clefts / 165
8.3.1. Medications / 165
8.3.2. Recreational Drugs / 173
8.3.3. Toxins / 177
8.3.4. Hyperthermia / 181
8.4. Maternal Factors / 182
8.4.1. Vitamin Deficiency / 182
8.4.2. Maternal Hormone Influences / 184
8.5. Intrauterine Factors / 184
8.5.1. Amniotic Bands / 184
8.5.2. Fetal Constraint / 186
8.6. Environmental Etiologies of Craniosynostosis / 186
8.6.1. Rickets / 186
8.6.2. Hyperthyroidism / 187
8.6.3. Teratogens / 187
8.6.4. Fetal Constraint / 188
8.7. Summary / 188
III ANIMAL MODELING 207
9 Animal Models of Craniosynostosis: Experimental, Congenital,
and Transgenic Models 209
Mark P. Mooney, Ph.D., Michael I. Siegel, Ph.D., and
Lynne M. Opperman, Ph.D.
9.1. Introduction:The General Utility of Animal Models for
Craniofacial Biology / 209
9.1.1. Levels of Hypothesis Testing and Appropriate Animal
Model Choice / 209
9.1.2. Comparative Animal Model Growth Pattern
Assessment / 213
9.2. Specific Animal Models of Cranial Vault Growth and
Craniosynostosis / 213
9.2.1. Historical Perspectives / 213
CONTENTS xi
9.2.2. Levels of Appropriate Animal Models to Study
Craniosynostosis / 215
9.3. Conclusion / 236
10 Animal Models of Facial Clefting: Experimental,
Congenital, and Transgenic 251
Virginia M. Diewert, D.D.S., M.Sc. and Scott Lozanoff, Ph.D.
10.1. Introduction / 251
10.2. Midline Craniofacial Development / 252
10.2.1. Early Midline Craniofacial Development / 252
10.2.2. BrMouse as a Model for Median Cleft Face / 253
10.3. Midfacial and Palatal Development / 255
10.4. Primary Palate Development / 256
10.4.1. Primary Palate Development and Cleft Lip Malformation
in the Mouse Model / 256
10.4.2. Craniofacial Growth During Primary Palate
Formation / 258
10.4.3. Development of the Internal Components of the Primary
Palate / 258
10.4.4. Primary Choanae Opening:The Critical Threshold
Period / 260
10.5. Secondary Palate Development / 261
10.5.1. Craniofacial Growth During Secondary Palate
Development / 261
10.5.2. Cleft Palate Observations / 262
10.6. Transgenic Animal Models for Facial Clefting / 264
IV CRANIAL VAULTAND CRANIAL BASE DYSMORPHOLOGY
AND GROWTH DISTURBANCES 273
11 Evolutionary Changes in the Cranial Vault and Base:
Establishing the Primate Form 275
Mark P. Mooney, Ph.D., Michael I. Siegel, Ph.D., Timothy D. Smith, Ph.D.,
and Annie M. Burrows, Ph.D., D.P.T.
11.1. Introduction:Evolutionary Correlates of Human Neuro- and
Chondrocranial Morphology / 275
11.1.1. Bipedalism,Bracephalization,and Skull Base
Kyphosis / 275
11.1.2. Neural Spatial Packing,Brachycephalization,and Skull
Base Kyphosis / 276
11.1.3. Synchondrosal Fusion Timing,Brachycephalization,
and Skull Base Kyphosis / 277
11.2. Phylogenetic Changes in Neuro- and Chondrocranial
Morphology / 278
xii CONTENTS
11.2.1. The Chondrocranial Template / 278
11.2.2. Derivatives of the Chondrocranial Template and
Neurocranium in Vertebrates / 278
11.2.3. The Chondrocranial Template and Neurocranium of
Mammals / 279
11.3. Phylogenetic Changes in the Nervous System and its Effects on
Neuro- and Chondrocranial Morphology / 281
11.3.1. Cephalization / 281
11.3.2. Cerebralization / 282
11.3.3. Gyrification of the Cerebral Cortex and Spatial
Packing / 282
11.3.4. Evolutionary Changes in the Special Sense Organ
Capsules / 283
11.4. Skull Base Synchondroses and Comparative Growth / 285
11.5. Conclusions / 286
12 Cranial Base Dysmorphology and Growth in the
Craniosynostoses 295
Alphonse R. Burdi, Ph.D.
12.1. Historical Perspective / 295
12.2. The Etiopathogenesis of Cranial Base Abnormalities / 296
12.3. Cranial Base Growth Patterns in Craniosynostosis / 300
12.4. Conclusions / 302
13 Cranial Base Dysmorphology and Growth in Facial Clefting 307
Timothy D. Smith, Ph.D., Mark P. Mooney, Ph.D.,
Annie M. Burrows, Ph.D., and Michael I. Siegel, Ph.D.
13.1. Introduction / 307
13.2. Prenatal Development of the Cranial Base in Cleft Samples / 307
13.3. Postnatal Development of the Cranial Base in Cleft Samples / 310
13.4. Mechanisms for Basicranial Influences on Clefting / 316
13.5. Conclusions / 317
14 Cranial Vault Dysmorphology and Growth in Craniosynostosis 321
Joan T. Richtsmeier, Ph.D.
14.1. Introduction / 321
14.2. The Relevant Questions / 323
14.3. Soft Tissue–Hard Tissue Interactions as an Explanation for
Craniofacial Dysmorphology and Growth / 324
14.4. Formation and Growth of Calvarial Bones and the Cranial Vault / 326
14.5. Lessons from Evolution and Development / 328
14.6. The Genetic Basis of Craniofacial (Dys)Morphology / 330
14.7. Conclusions:Some Preliminary Answers and New Questions / 333