| Foreword | xvii |
| Preface | xix |
| Contributors | xxi |
| I | Classification and Terminology | 1 |
| 1 | Overview and Introduction | 3 |
| 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 |
| 2.1. | Introduction | 11 |
| 2.2. | Historical Perspective | 11 |
| 2.3. | Conclusions | 14 |
| 3 | Terminology and Classification of Facial Clefting | 17 |
| 3.1. | Introduction | 17 |
| 3.2. | Historical Classifications of Facial Clefts | 17 |
| 3.3. | Do These Classifications Really Serve a Purpose? | 19 |
| 3.4. | Back to Semantics | 21 |
| 3.5. | Is There a Useful System? | 24 |
| 3.6. | Conclusions | 27 |
| II | Embryogenesis and Etiology | 29 |
| 4 | Craniofacial Embryogenesis: Normal Developmental Mechanisms | 31 |
| 4.1. | Introduction | 31 |
| 4.2. | Early Development | 32 |
| 4.3. | Neural Crest Tissue | 35 |
| 4.4. | Craniofacial Development | 41 |
| 5 | Craniofacial Embryogenesis: Abnormal Developmental Mechanisms | 61 |
| 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 |
| 5.6. | Development Alterations in Facial Clefting with Emphasis on their Multifactorial Etiology | 86 |
| 5.7. | Abnormal Developmental Mechanisms in the Formation of Tissues and Organs | 102 |
| 5.8. | Concluding Remarks | 104 |
| 6 | Genetic Etiologies of Craniosynostosis | 125 |
| 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 |
| 7.1. | Introduction | 147 |
| 7.2. | Genetic Etiologies of Syndromic Orofacial Clefts | 147 |
| 7.3. | Genetic Etiologies of Nonsyndromic Orofacial Clefts | 151 |
| 8 | Environmental Etiologies of Orofacial Clefting and Craniosynostosis | 163 |
| 8.1. | Introduction | 163 |
| 8.2. | Nomenclature | 164 |
| 8.3. | Environmental Etiologies of Orofacial Clefts | 165 |
| 8.4. | Maternal Factors | 182 |
| 8.5. | Intrauterine Factors | 184 |
| 8.6. | Environmental Etiologies of Craniosynostosis | 186 |
| 8.7. | Summary | 188 |
| III | Animal Modeling | 207 |
| 9 | Animal Models of Craniosynostosis: Experimental, Congenital, and Transgenic Models | 209 |
| 9.1. | Introduction: The General Utility of Animal Models for Craniofacial Biology | 209 |
| 9.2. | Specific Animal Models of Cranial Vault Growth and Craniosynostosis | 213 |
| 9.3. | Conclusion | 236 |
| 10 | Animal Models of Facial Clefting: Experimental, Congenital, and Transgenic | 251 |
| 10.1. | Introduction | 251 |
| 10.2. | Midline Craniofacial Development | 252 |
| 10.3. | Midfacial and Palatal Development | 255 |
| 10.4. | Primary Palate Development | 256 |
| 10.5. | Secondary Palate Development | 261 |
| 10.6. | Transgenic Animal Models for Facial Clefting | 264 |
| IV | Cranial Vault and Cranial Base Dysmorphology and Growth Disturbances | 273 |
| 11 | Evolutionary Changes in the Cranial Vault and Base: Establishing the Primate Form | 275 |
| 11.1. | Introduction: Evolutionary Correlates of Human Neuro- and Chondrocranial Morphology | 275 |
| 11.2. | Phylogenetic Changes in Neuro- and Chondrocranial Morphology | 278 |
| 11.3. | Phylogenetic Changes in the Nervous System and its Effects on Neuro- and Chondrocranial Morphology | 281 |
| 11.4. | Skull Base Synchondroses and Comparative Growth | 285 |
| 11.5. | Conclusions | 286 |
| 12 | Cranial Base Dysmorphology and Growth in the Craniosynostoses | 295 |
| 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 |
| 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 |
| 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 |
| V | Midfacial and Mandibular Dysmorphology and Growth Disturbances | 343 |
| 15 | Evolutionary Changes in the Midface and Mandible: Establishing the Primate Form | 345 |
| 15.1. | Introduction | 345 |
| 15.2. | General Principles of Midfacial Ontogeny | 346 |
| 15.3. | Anatomic Features of the Primate Midface | 348 |
| 15.4. | General Principles of Evolutionary Biology | 367 |
| 15.5. | General Principles of Craniofacial and Midfacial Evolution | 369 |
| 15.6. | Summary | 372 |
| 16 | Facial Dysmorphology in the Craniosynostoses: Clinical Implications | 379 |
| 16.1. | Introduction | 379 |
| 16.2. | Theories of Craniosynostosis Etiopathogenesis | 380 |
| 16.3. | Clinical Management of Craniosynostosis | 382 |
| 16.4. | Patterns of Dysmorphogenesis | 383 |
| 16.5. | Experimental Studies | 385 |
| 16.6. | Conclusions | 388 |
| 17 | Midfacial and Mandibular Dysmorphology and Growth in Facial Clefting: Clinical Implications | 391 |
| 17.1. | Introduction | 391 |
| 17.2. | Cleft Lip/Cleft Palate | 391 |
| 17.3. | Other Facial Clefts | 415 |
| 17.4. | Summary and Conclusions | 416 |
| VI | Regional Dysmorphology and Growth Disturbances | 423 |
| 18 | Dental Development and Anomalies in Craniosynostoses and Facial Clefting | 425 |
| 18.1. | Introduction | 425 |
| 18.2. | Tooth Number | 426 |
| 18.3. | What to Measure and Improving Technologies | 427 |
| 18.4. | Tooth Crown Formation | 430 |
| 18.5. | Tooth Size | 434 |
| 18.6. | Diminished Postnatal Growth with CLP | 436 |
| 18.7. | Bilateral Asymmetry | 439 |
| 18.8. | Types of Asymmetry | 441 |
| 18.9. | Dental Age | 444 |
| 18.10. | Syndromic Craniosynostoses | 449 |
| 18.11. | Dental Response to Stress | 451 |
| 18.12. | CLP: A Developmental Model | 451 |
| 18.13. | Perspective | 453 |
| 19 | Vocal Tract Anatomy and Functional Consequences in Cleft Lip/Palate and Syndromes of Craniosynostosis | 469 |
| 19.1. | Introduction | 469 |
| 19.2. | Normal Anatomy of the Vocal Tract | 469 |
| 19.3. | Congenital Anomalies of the Human Supralaryngeal Vocal Tract | 477 |
| 19.4. | Summary | 489 |
| VII | Molecular Biology Studies and Future Directions | 495 |
| 20 | Molecular Studies of Craniosynostosis: Factors Affecting Cranial Suture Morphogenesis and Patency | 497 |
| 20.1. | Introduction: Regulation of Suture Morphogenesis and Patency | 497 |
| 20.2. | Molecular Regulation of Suture Morphogenesis and Patency | 499 |
| 20.3. | Interactions Between Growth and Transcription Factors in Regulating Suture Morphogenesis and Patency | 510 |
| 20.4. | Conclusions, Future Studies, and Directions | 511 |
| 21 | Molecular Studies of Facial Clefting: From Mouse to Man | 519 |
| 21.1. | Introduction | 519 |
| 21.2. | Etiology of Nonsyndromic Oral Clefts | 519 |
| 21.3. | Investigating the Fraser-Juriloff Paradigm | 521 |
| 21.4. | IGF-IIR/TGF-[beta]2 Epigenetic Network | 531 |
| 21.5. | Conclusion | 542 |
| 22 | Molecules and Faces: What is on the Horizon? | 549 |
| 22.1. | Introduction | 549 |
| 22.2. | Molecular Advances in Craniofacial Morphogenesis | 552 |
| 22.3. | Biomimetics for Repair and Regeneration of Craniofacial Tissues | 557 |
| 22.4. | Possibilities For Craniofacial and Skeletal Growth Modifications | 557 |
| 22.5. | Prospectus for the 21st Century | 558 |
| Index | 561 |
Format: Hardcover, 584 pages
