This simple guide to neurogenetics demystifies the overwhelming amount of information on the subject so you can identify key clinical features and understand your management options. Reach relevant differential diagnoses and provide appropriate counseling to your patients using the symptom-based approach. By integrating genetic and neurological approaches to diagnoses, this book ensures that the neurological consequences of a genetic diagnosis and the genetic consequences of a neurological diagnosis are clear and explicit. Concise and portable, this book is ideal for easy reference in clinical use.
- Details the underlying basic science and clinical features of genetic disorders by taking a symptom-based approach to provide you with a comprehensive understanding of the field.
- Focuses on the clinical application of neurogenetics to be of practical use to you in the clinic.
- Clarifies the neurological consequences of a genetic diagnosis and the genetic consequences of a neurological diagnosis by integrating genetic and neurological approaches to diagnoses.
- Discusses and evaluates necessary investigations so you know when to use them and when to refer.
- Highlights diagnostic and therapeutic tips so you can learn new concepts or refine your skills in practice.
- Refers to online sources, such as Online Mendelian Inheritance in Man (OMIM) and others, to help you supplement your knowledge.
Author(s): Thomas T. Warner PhD FRCP, Simon R. Hammans MD FRCP
Edition: 1
Publisher: Saunders
Year: 2008
Language: English
Pages: 336
C
cover Page......Page 1
Copyright......Page 2
Dedication......Page 3
Contributors......Page 4
Preface......Page 5
Acknowledgments......Page 7
PATTERNS OF INHERITANCE......Page 8
NUCLEIC ACIDS AND GENES......Page 9
FROM GENE TO PROTEIN......Page 10
DNA REPLICATION AND CELL DIVISION......Page 11
IDENTIFYING DISEASE GENES......Page 12
TYPES OF MUTATION......Page 14
Huntington’s Disease (HD)......Page 15
CLINICAL APPLICATION OF DISEASE GENE MAPPING AND CLONING......Page 16
GENETIC COUNSELING......Page 18
Examination and Investigations......Page 19
Inheritance......Page 20
Autosomal Recessive (AR) Inheritance (Fig. 2.1b)......Page 21
X-linked Inheritance (Fig. 2.1c)......Page 22
Expressivity......Page 23
Genetic Testing......Page 24
Carrier Testing......Page 25
Genetic Testing in Childhood......Page 26
The Family......Page 27
Summary of Genetic Counseling and Testing Process......Page 28
REFERENCE......Page 30
Onset and Progression of Disease......Page 31
Additional Neurological Features......Page 32
Clinical Features......Page 33
mkc0003......Page 34
Treatment......Page 35
Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch Type (HCHWA-D; OMIM 609065)......Page 36
Frontotemporal Dementia (OMIM 600274)......Page 37
Clinical Features......Page 38
Genetic Advice......Page 39
Clinical Features......Page 40
Investigations......Page 41
Treatment......Page 42
Familial CJD......Page 43
BIBLIOGRAPHY......Page 44
INTRODUCTION......Page 45
With Mental Retardation, Neurodegenerative, Structural, or Metabolic Abnormalities......Page 46
Neuronal Migration Disorders......Page 47
Progressive Myoclonic Epilepsies (PMEs)......Page 49
IDIOPATHIC EPILEPSIES WITH MENDELIAN INHERITANCE......Page 50
Benign Familial Neonatal Convulsions (BFNC)......Page 51
Sibling Risk......Page 52
FEBRILE SEIZURES (FS)......Page 53
HYPEREKPLEXIA (OMIM 149400)......Page 54
REFERENCES......Page 55
Basic Facts......Page 56
Investigating Retinal and Optic Nerve Disease (Table 5.1)......Page 58
INHERITED RETINAL DEGENERATION......Page 59
Clinical Features......Page 60
ADRP (Table 5.2)......Page 61
XLRP (Table 5.4)......Page 62
Leber Congenital Amaurosis (LCA)......Page 63
Genetic Counseling for Non-Syndromic RP......Page 64
Choroideremia (OMIM 300390)......Page 72
Congenital X-linked Retinoschisis......Page 73
Bardet-Biedl Syndrome (BBS) (OMIM 209900)......Page 74
Usher Syndrome (OMIM 276900)......Page 75
Mitochondrial Disorders......Page 76
Management of Inherited Retinal Degeneration......Page 77
Primary Hereditary Optic Neuropathy......Page 78
Wolfram Syndrome (OMIM 222300)......Page 79
ABBREVIATIONS......Page 81
Clinical Manifestations......Page 82
Investigation of Ataxias......Page 83
CONGENITAL ATAXIAS......Page 85
Friedreich’s Ataxia (FA; OMIM 229300)......Page 86
Clinical Features......Page 87
Investigations......Page 88
Other Early-Onset Autosomal Recessive Cerebellar Ataxias......Page 89
Unverricht-Lundborg Disease (Baltic Myoclonus, EPM1; OMIM 254800)......Page 91
AUTOSOMAL DOMINANT CEREBELLAR ATAXIAS (ADCAs)......Page 92
Investigations......Page 93
Genetic Advice......Page 95
Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)......Page 96
TREATMENT OF ATAXIAS......Page 97
BIBLIOGRAPHY......Page 98
LEUKODYSTROPHIES......Page 99
Treatment......Page 102
Pathophysiology......Page 103
Adrenoleukodystrophy and Adrenomyeloneuropathy (ALD/AMN; OMIM 300100)......Page 104
Prognosis......Page 105
MULTIPLE SCLEROSIS (MS; OMIM 126200)......Page 106
Genetic Advice in Multiple Sclerosis......Page 107
BIBLIOGRAPHY......Page 108
DYSKINETIC MOVEMENT DISORDERS......Page 109
Clinical Features......Page 110
Differential Diagnosis and Investigations......Page 111
Genetics and Pathophysiology......Page 112
Treatment......Page 113
Genetic Advice and Testing......Page 114
Prenatal Testing......Page 115
Dystonia......Page 116
Clinical Features......Page 118
Genetics......Page 119
Genetic Advice and Testing......Page 120
Genetics......Page 121
Clinical Features......Page 122
Paroxysmal Non-Kinesigenic Dyskinesia (PNKD; OMIM 118800)......Page 123
Deafness-Dystonia-Optic Neuronopathy Syndrome (Mohr-Tranebjaerg Syndrome; OMIM 304700)......Page 124
Genetics......Page 125
Genetics......Page 126
Parkinsonism......Page 127
Investigation and Differential Diagnosis......Page 128
Genetics of PD......Page 129
PARK1 (OMIM 168601)......Page 130
PARK6 (605909)......Page 131
Genetic Advice and Testing......Page 132
Investigations......Page 133
Pathophysiology......Page 134
Clinical Features......Page 135
Clinical Features......Page 136
Disorders of Purine Metabolism......Page 137
Clinical Features......Page 138
Differential Diagnosis......Page 139
Clinical Features......Page 140
Treatment......Page 141
Genetics......Page 142
REFERENCES......Page 143
SINGLE-GENE DISORDERS ASSOCIATED WITH STROKE......Page 144
Clinical Features......Page 145
Pathophysiology......Page 147
Genetic Advice......Page 148
Clinical Features......Page 149
Management......Page 150
Familial Hemiplegic Migraine (FHM; OMIM 141500)......Page 151
Investigations and Differential Diagnosis......Page 152
Hereditary Hemorrhagic Telangiectasia (HHT; OMIM 187300)......Page 153
Moyamoya Disease (OMIM 252350)......Page 154
Stroke Susceptibility Locus (STRK1; OMIM 606799)......Page 155
REFERENCES......Page 156
Spinal Muscular Atrophy (SMA)......Page 157
SMA II (intermediate SMA; OMIM 253550)......Page 159
SMA IV (OMIM 271150)......Page 160
Genetics and Pathophysiology......Page 161
Genetic Advice......Page 162
Clinical Features......Page 163
Prognosis......Page 164
Amyotrophic Lateral Sclerosis (ALS) or Motor Neuron Disease......Page 165
Pathophysiology......Page 166
Genetics of ALS......Page 167
Other ALS Genes......Page 168
Prognosis......Page 169
Hereditary Spastic Paraplegia......Page 170
Clinical Features......Page 171
Differential Diagnosis......Page 172
Investigations......Page 173
Genetic Subtypes of HSP......Page 174
SPG4 HSP......Page 175
Autosomal Recessive Pure HSP......Page 176
X-linked HSP......Page 177
Autosomal Dominant HSP......Page 178
Spastic Paraplegia with no Family History......Page 179
Cerebral Palsy (CP)......Page 180
REFERENCE......Page 181
Investigations......Page 182
Genetic Molecular Analysis......Page 183
CHARCOT-MARIE-TOOTH DISEASE (CMT)......Page 184
Autosomal Dominant Demyelinating CMT (CMT1): PMP-22 and P0......Page 185
Clinical Features......Page 187
Investigations......Page 188
Treatment......Page 189
X-Linked Charcot-Marie-Tooth Disease......Page 190
Investigations......Page 191
Clinical Features......Page 192
Prognosis......Page 194
Hereditary Sensory and Autonomic Neuropathy......Page 195
Treatment and Genetic Advice......Page 196
Genetic Advice......Page 197
Tangier Disease (OMIM 205400)......Page 198
Management......Page 199
Acute attacks......Page 200
Investigations......Page 201
Giant Axonal Neuropathy (GAN; OMIM 256850)......Page 202
BIBLIOGRAPHY......Page 203
History......Page 204
Investigations......Page 205
Central Core Disease (CCD; OMIM 117000)......Page 206
Clinical Features......Page 207
Genetic Advice......Page 208
Genetics......Page 209
Nemaline Rod Myopathies......Page 210
Myotonic Dystrophy (DM1; OMIM 160900)......Page 211
Genetics......Page 213
Management......Page 214
Clinical Features......Page 215
Manifesting Female Carriers......Page 216
Treatment......Page 217
Genetic Advice......Page 218
Autosomal Recessive LGMD (Table 12.8)......Page 219
Approach to Diagnosis in LGMD......Page 221
Clinical Features......Page 222
Investigations......Page 224
Scapuloperoneal Syndromes (OMIM 181430, 181400, 309660)......Page 225
Clinical Features......Page 226
Management......Page 227
Pathophysiology......Page 228
Prognosis......Page 229
CONGENITAL MUSCULAR DYSTROPHIES......Page 230
Investigations......Page 231
Congenital Absence or Weakness of Muscles......Page 232
CONGENITAL MYASTHENIC SYNDROMES......Page 233
Investigations......Page 234
REFERENCES......Page 235
Periodic Paralyses......Page 236
Investigations......Page 237
Prognosis......Page 238
Hyperkalemic Periodic Paralysis (HyperPP; OMIM 170500: and PMC; OMIM 168300)......Page 239
Diagnosis and Investigations......Page 240
Diagnosis......Page 241
Investigations......Page 242
Other Disorders with Myotonia and Cramps......Page 243
MALIGNANT HYPERTHERMIA......Page 244
Glycogen Storage Myopathies......Page 245
Pathophysiology......Page 246
Diagnosis......Page 247
Lipid Myopathies......Page 248
Diagnosis......Page 250
REFERENCES......Page 251
Overview of Clinical Diagnosis......Page 252
Progressive External Ophthalmoplegia (PEO; OMIM 530000)......Page 254
Mitochondrial Encephalomyopathies: Myoclonic Epilepsy and Ragged Red Fibers (MERRF; OMIM 590060)......Page 255
Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE; OMIM 603041)......Page 256
Investigation of Mitochondrial Disease (Table 14.2)......Page 257
Muscle Biopsy (Table 14.3)......Page 258
Single mtDNA Deletions......Page 259
Mitochondrial Myopathies Without Identified Genetic Cause......Page 260
Leigh’s Syndrome (LS; OMIM 256000)......Page 261
Leber’s Hereditary Optic Neuropathy (LHON)......Page 262
Genetic Advice......Page 263
MtDNA Depletion (OMIM 251880)......Page 264
TREATMENT FOR MITOCHONDRIAL DISEASE......Page 265
REFERENCES......Page 266
Clinical Features and Family History......Page 267
Annual Surveillance (Affected Individuals and Those at 50% Risk)......Page 270
Genetic Advice......Page 271
Differential Diagnosis......Page 272
Pathophysiology......Page 273
Prognosis......Page 274
Clinical Features......Page 275
Pathophysiology......Page 276
Treatment......Page 277
Skin Lesions......Page 278
Visceral Lesions......Page 279
Pathophysiology......Page 280
Genetic Advice......Page 281
REFERENCES......Page 282
CLINICAL MANIFESTATIONS AND INVESTIGATION......Page 283
Neonatal Presentation (<28 days)......Page 284
mkc0016sec4......Page 285
Childhood Presentation (>3 years)......Page 286
Tay-Sachs Disease (TS; OMIM 272800)......Page 287
Lysosomal Disease - Mucopolysaccharidoses (MPS)......Page 291
Neuropathology and Genetics......Page 292
Sialiuria......Page 294
Oligosaccharidoses......Page 295
Pathology and Genetics......Page 296
Investigations......Page 297
DISORDERS OF AMINO ACID AND ORGANIC ACID CATABOLISM......Page 298
Treatment......Page 299
Homocystinuria (OMIM 236200)......Page 300
Investigations......Page 301
Maple Syrup Urine Disease (MSUD; OMIM 248600/248611/248610)......Page 302
Investigations......Page 303
Canavan’s Disease (OMIM 271900)......Page 304
Neuropathology and Genetics......Page 305
Clinical Features......Page 306
CARBOHYDRATE DISORDERS......Page 307
Investigations......Page 308
Neuropathology and Genetics......Page 310
Clinical Features......Page 311
Neuronal Ceroid Lipofuscinoses (NCL or Batten Disease)......Page 312
Genetics......Page 313
Rett Syndrome (RS; OMIM 312750)......Page 314
Genetics......Page 315
Treatment......Page 316
INTRODUCTION......Page 317
Genetic Advice......Page 318
Fragile X Syndrome (OMIM 300624)......Page 320
Adult Males......Page 321
Management......Page 322
BIBLIOGRAPHY......Page 326
A......Page 327
C......Page 328
D......Page 329
G......Page 330
H......Page 331
M......Page 332
P......Page 334
S......Page 335
Z......Page 336
