Craniosynostoses: Molecular Genetics, Principles of Diagnosis, and Treatment (Monographs in Human Genetics)

Contents......Page 6
Editorial......Page 8
Preface......Page 9
Foreword......Page 10
General History......Page 12
Syndromic Craniosynostosis and GeneticDiscoveries......Page 13
History of Treatment Aspects ofCraniosynostosis......Page 16
References......Page 17
Family Identification......Page 19
Functional Analyses of the Mutation......Page 21
Acknowledgement......Page 22
References......Page 23
Abstract......Page 24
Anatomy and Origins of the Cranial Vault......Page 25
Calvarial Sutures as Intramembranous Bone Growth Sites......Page 26
Transcriptional Control of Osteoblast Commitment and Differentiation......Page 27
Ephrins, Boundary Formation, and Directed Bone Growth......Page 28
Fibroblast Growth Factor Receptors in Cranial Osteoblast Proliferation and Differentiation......Page 30
Transforming Growth Factor Beta, Osteoblast Function, and Suture Maintenance......Page 35
References......Page 36
Abstract......Page 39
Suture Anatomy......Page 40
Dura Mater......Page 41
Osteogenic Fronts and Suture Mesenchyme......Page 43
Fibroblast Growth Factor (FGF) Receptors......Page 45
Eph/Ephrin Signaling......Page 47
Integration of Pathways and Mechanisms of Craniosynostosis......Page 48
References......Page 53
Abstract......Page 56
Structural and Biochemical Analysis of Mutations Leading to Ligand- Dependent Gain of Function......Page 58
Conclusion......Page 65
References......Page 66
Models to Explain Male Bias and the Paternal Age Effect......Page 69
Confirmation of High Nucleotide Substitution Germline Mutation Frequencies, Mutation Hot Spot versus Germline Selection Model......Page 70
Experimental Analysis......Page 71
By Including Selection, Computational Analysis Explains the Testis Data......Page 73
The Parental Age Effect of Apert Syndrome Occurrence Revisited......Page 74
References......Page 76
Apert Syndrome......Page 78
Crouzon Syndrome......Page 92
Pfeiffer Syndrome......Page 94
References......Page 98
Abstract......Page 100
Inheritance and Genetic Counseling......Page 101
Clinical Findings and Diagnosis......Page 102
Molecular Pathogenesis......Page 104
Acknowledgements......Page 106
References......Page 107
Phenotypic Features......Page 109
The SCS Causing Gene TWIST1......Page 113
TWIST1 Mutational Spectrum......Page 115
References......Page 116
Clinical Features......Page 118
Pattern of Inheritance......Page 120
The CFNS Causing Gene EFNB1......Page 121
EFNB1 Mutation Spectrum......Page 122
Sex- Dependent Manifestation and Proposed Pathomechanism in CFNS......Page 125
References......Page 127
Abstract......Page 130
Antley- Bixler Syndrome (MIM #207410) P450 Oxidoreductase (POR) Deficiency (MIM#201750)......Page 134
Baller- Gerold Syndrome (MIM #218600)......Page 137
Beare- Stevenson Cutis Gyrata Syndrome (MIM#123790)......Page 138
C (Opitz Trigonocephaly) Syndrome (MIM#211750) Bohring- Opitz Syndrome (MIM #605039)......Page 139
Carpenter Syndrome (MIM #201000)......Page 140
Crouzon Syndrome with Acanthosis Nigricans (MIM #612247)......Page 141
Jackson- Weiss Syndrome (MIM #123150)......Page 142
Jacobsen Syndrome (MIM #147791)......Page 143
Osteoglophonic Dysplasia (MIM #166250)......Page 145
Shprintzen- Goldberg Syndrome (MIM#182212) Loeys- Dietz Syndrome, Types IA and IB (MIM #609192, MIM #610168)......Page 147
References......Page 149
Abstract......Page 154
Case Reports......Page 155
GLI3 Pathogenesis and Mutation Spectrum......Page 159
Genetic Mouse Models for GLI3 Disorders......Page 160
References......Page 161
Abstract......Page 163
Chromosomal Alterations......Page 164
Craniosynostosis Syndromes Due to Chromosomal Deletions: 9p and 11q......Page 168
Chromosomal Rearrangements and Their Contribution to the Identification of Craniosynostotic Candidate Genes......Page 169
Conclusions......Page 170
References......Page 171
Abstract......Page 176
Scaphocephaly......Page 177
Trigonocephaly......Page 179
Anterior Plagiocephaly......Page 180
Brachycephaly......Page 181
Posterior Plagiocephaly......Page 182
Bisutural Synostosis......Page 183
Oxycephaly......Page 184
References......Page 185
Abstract......Page 188
Second Step: Genetic Workup of Craniosynostosis......Page 189
Third Step: Interpretation of Test Results and Genetic Counseling......Page 192
References......Page 194
Ultrasound Examination of the Normal Fetal Skull......Page 195
Ultrasound in Craniosynostosis......Page 197
References......Page 209
Abnormal Head Shape in the Absence of Craniosynostosis......Page 210
Abnormal Head Shape Due to Craniosynostosis......Page 211
Imaging Studies to Confirm Synostosis......Page 213
Underlying Etiology Varies by Affected Suture or Sutures......Page 214
Clinical Evaluation: Past Medical History......Page 215
Clinical Evaluation: Physical Examination......Page 217
Evaluation of Specific Organ Systems and Their Function: Central Nervous System and Neurodevelopment......Page 219
Evaluation of Specific Organ Systems and Their Function: Otolaryngologic Considerations......Page 221
Evaluation of Specific Organ Systems and Their Function: Musculoskeletal Considerations......Page 222
Differential Diagnosis and Laboratory Testing......Page 223
References......Page 224
Technical Aids of Examination......Page 227
Principles of Treatment......Page 233
Surgical Risks......Page 235
Postoperative Surveillance and Strategies......Page 237
Management of Specific Types of Craniosynostosis......Page 238
References......Page 241
Development of the Midface......Page 243
Abnormalities of the Viscerocranium in Craniosynostosis......Page 244
Principles of Maxillofacial Treatment in Patients with Craniosynostosis......Page 246
References......Page 253
Author Index......Page 255
Subject Index......Page 256