Velo-cardio-facial Syndrome (VCFS) is a genetic disorder caused by the deletion of part of chromosome 22. It occurs in approximately one in 4000 births and there are now more than 100 physical phenotypic features reported. VCFS affects every major system in the body and this is the first book to describe its full clinical impact. It has been authored by leading international VCFS clinicians/researchers. The focus is on clinical issues with chapters devoted to psychiatric disorders (with the sufferer showing very high levels of schizophrenia), neuroimaging, speech and language disorders, as well as cardiac, ENT, gastrointestinal, ophthalmic and urological manifestations. Molecular genetics, immunodeficiency and genetic counselling are also covered, and practical approaches to diagnosis and treatment described. As VCFS is seen as a paradigm for other microdeletion disorders, this book will not just appeal to clinicians seeing VCFS patients, but also to those with interests in other genetic disorders.
Author(s): Kieran C. Murphy, Peter J. Scambler
Edition: 1
Publisher: Cambridge University Press
Year: 2005
Language: English
Pages: 257
Cover......Page 1
Half-title......Page 3
Title......Page 5
Copyright......Page 6
Contents......Page 7
Abbreviations......Page 9
Contributors......Page 10
Foreword......Page 13
1 Historical overview......Page 15
Speech disorders and VCFS......Page 17
Immune and endocrine disorders......Page 18
Congenital heart anomalies......Page 19
Development of interest in the 1990s......Page 21
Psychiatric manifestations......Page 22
Secondary sequences......Page 23
Other syndromes associated with 22q11.2 deletions......Page 26
Nosology in the historical context......Page 27
Spreading information......Page 29
References......Page 30
Prenatal diagnosis of the 22q11 deletion......Page 33
A molecular genetic approach......Page 34
DGCR6......Page 35
DGCR2 (aliases IDD, LAN, Sez 12)......Page 36
CLTCL1......Page 37
UFD1l......Page 38
GP1Bbeta......Page 39
ARVCF......Page 40
USP18 (UBP43)......Page 41
CRKL......Page 42
Mechanism of deletion......Page 43
Mouse models......Page 45
Neural crest involvement......Page 47
TBX1 mutations are rare in non-deletion VCFS/DGS......Page 49
Chromosome 10p deletion syndromes......Page 50
The future......Page 51
References......Page 52
3 Congenital cardiovascular disease and velocharater-cardio-facial syndrome......Page 61
Tetralogy of Fallot......Page 63
Pulmonary atresia with ventricular septal defect......Page 64
Persistent truncus arteriosus......Page 67
Interrupted aortic arch......Page 68
Ventricular septal defect......Page 72
Other cardiovascular defects......Page 76
Common findings......Page 77
Clinical implications......Page 79
Surgical implications......Page 80
Tetralogy of Fallot......Page 81
Pulmonary atresia with ventricular septal defect......Page 82
Truncus arteriosus......Page 83
Isolated aortic arch anomalies......Page 84
Perioperative policy......Page 85
References......Page 86
Defining the palatal phenotype in VCFS......Page 97
Surgical management of cleft palate: timing......Page 101
Surgical management of cleft palate: technique......Page 102
Anatomy and physiology of the velopharyngeal valve......Page 105
Nature of velopharyngeal dysfunction in VCFS......Page 107
Assessment of velopharyngeal function......Page 108
Surgical management of velopharyngeal insufficiency......Page 111
References......Page 115
Nephro-urological anomalies in VCFS......Page 119
Pathogenesis of congenital nephro-urological malformations......Page 120
Prenatal presentation of uropathies......Page 122
Gastrointestinal findings......Page 123
Normal development......Page 124
VCFS......Page 125
Normal development......Page 126
VCFS......Page 127
VCFS......Page 128
Breastfeeding in VCFS......Page 129
Ophthalmic findings......Page 130
Acknowledgements......Page 132
References......Page 133
Overview......Page 137
A multidisciplinary approach......Page 138
Overview of the immunodeficiency......Page 139
The immunodeficiency is independent of other phenotypic features......Page 141
Natural history of the immunodeficiency......Page 142
Consequences of the immunodeficiency......Page 143
Management......Page 144
References......Page 146
Behavioral and psychiatric disorder in children with VCFS......Page 149
Psychiatric disorder in adults with VCFS......Page 150
Is the frequency of schizophrenia increased in VCFS individuals?......Page 152
Is there increased frequency of VCFS in people with schizophrenia?......Page 153
Is there a susceptibility locus for schizophrenia mapping to 22q11?......Page 154
Assessment and treatment of psychiatric disorders in individuals with VCFS......Page 155
Adults......Page 156
Children and adolescents......Page 157
References......Page 158
Introduction......Page 161
Intelligence......Page 162
Intellectual profile......Page 163
Academic achievement......Page 164
Mathematics and numerical skills......Page 165
Memory......Page 167
Executive functions (EF)......Page 168
Attention......Page 169
Communication skills and language......Page 170
VCFS and non-verbal learning disability (NVLD)......Page 171
Discussion and future directions......Page 172
References......Page 175
Qualitative MRI studies in VCFS......Page 179
Quantitative MRI studies of children and adolescents with VCFS......Page 180
Quantitative MRI studies of VCFS adults......Page 184
Effects of imprinting......Page 187
Discussion......Page 188
References......Page 190
Language......Page 195
Speech......Page 198
Voice......Page 199
Resonance......Page 201
Articulation......Page 206
Summary......Page 209
References......Page 210
11 Genetic counseling......Page 214
Parent of origin......Page 216
Recurrence risk......Page 218
Genetic counseling......Page 220
Guidelines for prenatal diagnosis......Page 223
References......Page 229
The mother......Page 233
The grandparents......Page 234
Social implications......Page 235
Personality......Page 236
Communication and education......Page 237
How physicians can help individuals with VCFS and their families......Page 239
How else might the physician help?......Page 240
Support services......Page 241
Conclusions......Page 242
Index......Page 244
