Appendix HCM DCM MYH7 MYBPC3 TNNT2 TNNI3 TPM1 MYL2 MYL3 ACTC1 CSRP3 TNNC1 MYH6 VCL TTN DES* CRYAB* GLA^ LAMP2^* LMNA TNNT2 MYH7 TNNI3 MYBPC3 LDB3 SCN5a DES EYA4 SGCD ARVD CSRP3 TCAP ABCC9 PLN ACTC1 TMPO PSEN1 PSEN2 VCL FCMD TPM1 TNNC1 ACTN2 DSG2 NEXN MYH6 TTN CRYAB LAMP2^* PKP2 DSG2 DSC2 RYR2? DSP TMEM43 JUP @ TGF-b (continued) H.F. Baars et al. (eds.), Clinical Cardiogenetics, DOI: 10.1007/978-1-84996-471-5, Springer-Verlag London Limited 2011 443
444 Appendix NCCM LQTS CPVT SQTS BS LMNA LDB3 TAZ MYH7 MYBPC3 TNNT2 TNNI3 TPM1 ACTC1 CASQ2** PLN** LDB3 KCNQ1 KCNH2 SCN5A ANK2 KCNE1 KCNE2 KCNJ2 & CACNA1C + SCN4B AKAP9 SNTA1 RYR2 CASQ2 @ KCNH2 KCNQ1 KCNJ2 SCN5A GPD1L CACNA1C SCN1B KCNE3 SCN3B HCN4 AF IVF ATS TS JLNS PFHB1a PFH1b NSCCD CHD AD CAD FHC KCNQ1 KCNE2 NPPA KCNA5 SCN5A? DPP6 ** KCNJ8** KCJN2 CACNA1C KCNQ1 @ KCNE1 @ SCN5A TRPM4 SCN1B GATA4 NKX2-5 TNX20 MYH6 TLL1 ZIC3^^ CFC1 CRELD1 GJA1 THRAP2 LRP6 APOB ARH @ LDLR PCSK9 This table, which is not exhaustive, lists a number of genes that are associated with cardiac diseases in a more or less monogenic fashion. Some of these genes may be very infrequent causes of the disease <1%. The official gene symbols have been used (as in the OMIM Online Mendelian Inheritance in Man database).
Appendix Legenda Disease Names HCM hypertrophic cardiomyopathy, DCM dilated cardiomyopathy, ARVD arrhythmogenic right ventricular dysplasia, NCCM noncompaction cardiomyopathy, LQTS long QT syndromes, CPVT catecholaminergic polymorphic ventricular tachycardia, SQTS short QT syndrome, BS Brugada syndrome, AF atrial fibrillation, IVF idiopathic ventricular fibrillation, ATS Andersen-Tawil syndrome (cardiodysrythmic periodic paralysis/lqt7), TS Timothy syndrome (long QT syndrome with syndactyly an cognitive abnormalities/ LQT8), JLNS Jervell-Lange-Nielsen syndrome (long QT syndrome with congenital deafness), PFH1a progressive familial heart block 1a, PFH1b progressive familial heart block 1b, NSCCD non-specific conduction defect, CHD congenital heart defect (since mutations in most of these genes can lead to various different HD, they are all grouped together): GATA4, 445 NKX2-5 are mainly associated with ASD2, CRELD1 with AVSD, ZIC3 and CFC1 with laterality defects, THRAP2 with transposition of the great arteries, AD CAD autosomal dominant coronary artery disease, FHC familial hypercholesterolemia. Symbols Used * = Skeletal muscle may also be affected @ = Recessive mutations in this gene cause the disease? = Some discussion as to whether the disease caused by mutations in RyR2 cause real ARVD as defined by strict clinical criteria ** = Needs confirmation in separate studies & = LQT7 (some discussion as to whether Andersen Tawil syndrome is a genuine long QT syndrome + = Causes LQT8 also known as Timothy syndrome or long QT syndactyly syndrome ^ = X-linked recessive inheritance
A ABCA1 deficiency clinical characteristics, 318 320 diagnosis, 319 genetics, 318 management, 319 Abdominal aortic aneurysm (AAA) clinical diagnosis ruptured, 429 unruptured, 428 429 epidemiology, 423 424 follow-up, 429 430 molecular genetics association studies, 426 427 segregation and linkage analysis, 425 426 pathogenesis natural history, 424 vascular pathology, 424 425 therapy lifestyle, 430 pharmacological treatment, 430 surgical intervention, 430 431 Ablation therapy, 235 Acute coronary syndrome (ACS), 336, 338 Adenosine triphosphate (ATP) synthase, 123 AF. See Atrial fibrillation American Heart Association (AHA), 97 Amyloidosis, 134 135 Anderson syndrome, 391 Angiotensin converting enzyme insertion/deletion, 360 ANP. See Atrial natriuretic peptide Antiarrhythmic drug therapy, 235 Antisense oligonucleotides (ASOs), 313 Apolipoprotein AI deficiency clinical characteristics, 317 diagnosis, 317 genetics, 317 management, 317 318 Apolipoprotein E, 359 360 Apoptosis, 377 Arrhythmias, 87, 147 148 Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) clinical presentation, 84 85 diagnosis, 85 differential diagnosis, 90 91 ECG criteria arrhythmias, 87 depolarization abnormalities, 85 87 diagnostics, 88 89 endomyocardial biopsy, 88 family history, 88 global and regional dysfunction, 87 88 modifications, 89 90 nonclassical subtypes, 90 repolarization abnormalities, 87 epidemiology, 84 molecular and genetic background autosomal dominant disease, 82 83 autosomal recessive disease, 82 desmosomal disease and dysfunction, 81 82 desmosome function, 80 81 nondesmosomal genes, 83 84 molecular genetic analysis, 91 prognosis and therapy, 91 93 Arterial thrombosis clinical relevance, 344 345 coagulation factor V and prothrombin, 339 factor VII, 337 338 factor VIII, IX and XI, 338 339 factor XII, 338 tissue factor, 338 factor XIII, 341 fibrinogen, 340 341 fibrinolysis, 341 342 fibrinolytic inhibitors, 342 hemostatic system, 332 335 polymorphisms platelet receptors, 335 336 Von Willebrand factor, 336 337 protein C pathway, 339 340 Arterial tortuosity syndrome, 276 277 ARVD/C. See Arrhythmogenic right ventricular dysplasia/cardiomyopathy Atherosclerotic plaque, 337, 338 Atrial fibrillation (AF) atrial natriuretic peptide, 218 autonomic nervous system, 219 220 clinical aspects, 220 222 H.F. Baars et al. (eds.), Clinical Cardiogenetics, DOI: 10.1007/978-1-84996-471-5, Springer-Verlag London Limited 2011 447
448 connexins, 215 216 epidemiology, 207 208 gene associations ACE, 219 GNB3, Enos, MMP-2, IL-10, 219 genome wide association studies, 218 219 molecular background, 208 210 molecular genetics, 211 mutations, 215 pathophysiology, 210 211 potassium channel KCNA5, 214 KCNE2 and KCNJ2, 212 213 KCNQ1, 212 secondary hit hypothesis, 214 215 sodium channel gain-of-function mutations, 217 218 loss-of-function mutations, 216 217 unknown loci, 218 Atrial natriuretic peptide (ANP), 218 Atrioventricular reentry tachycardia (AVRT) clinical aspects symptoms, 246 WPW syndrome, 246 247 electrocardiographic diagnosis, 247 epidemiology concealed bypasses, 244 Mahaim tachycardia, 244 Wolff Parkinson white syndrome, 243 244 genetics animal models, 249 genes, 248 249 Mahaim tachycardia, 249 pathogenesis accessory pathways (APs), 244 245 arrhythmia mechanisms, 245 246 treatment, 247 248 Atrioventricular septal defect, 289 Autopsy, 230, 231, 402, 405 406 Autosomal recessive hypercholesterolemia (ARH), 313 314 B Barth syndrome, 394 b-blocker therapy, 202 Becker muscular dystrophy, 387 Bentall procedure, 272, 273 Beta-adrenergic blockade, 158 Bicuspid aortic valves, 287 288 Bone morphogenetic proteins (BMPs), 249 Brugada syndrome (BS), 16, 404 cardiogenetics family screening, 182 183 genetic diagnosis, 181 182 cellular and ionic mechanisms, 168 169 clinical manifestations, 169 173 diagnosis ECG findings, 173 174 ECG modulators, 174 175 prognosis and risk stratification, 177 179 tools, 175 177 epidemiology, 165 166 genetics, 166 168 treatment ICD, 179 180 pharmacological options, 180 181 C CAD. See Coronary artery disease Calcium-induced calcium release (CICR), 197, 198 Cardiac conduction defects (CCD) Emery-Dreifus muscular dystrophy, 225 familial defects lamin A/C mutations, 257 Lenègre disease, 255 256 molecular screening, 258 SCN5A overlap syndrome, 256 secundum atrial septal defects, 257 258 sodium channel beta1 subunit mutations, 256 TRPM4 subfamily, 254 255 observations, 253 254 Cardiac conduction system (CCS), 244, 248, 249 Cardiac ion channels, 145 Cardiogenetics ACE insertion/deletion, 360 362 adverse drug reactions, 360 apolipoprotein E, 359 360 atherosclerosis, 356 cholesterylesther transfer protein, 358 359 clinical and public health outcomes, 440 cytochrome P450, 356 delivery, dissemination, and diffusion research, 428 genomic application, 439 440 genotype phenotype correlations, 114 health care diagnostic testing, 437 438 genetic screening, 438 pharmacogenetics, 439 risk prediction, 439 HMG-CoA-reductase gene, 357 358 lipoprotein lipase, 356 357 molecular and cardiologic screening, 114 molecular strategies, 114 115 PCSK9, 358 pharmaceutics, 363 pharmacogenetics, 353 356, 364 365 polymorphisms, 363 364 thiopurine methyltransferase, 356 Cardiomyocytes, 80, 81, 88 Carnitine deficiency, 393 Carvajal syndrome, 90 Cascade screening, genetic test, 417 Catecholaminergic polymorphic ventricular tachycardia (CPVT), 404 clinical aspects diagnosis, 199 epidemiology, 198 199 etiology molecular background, 197 198 pathophysiology, 198
449 genetic diagnosis b-blocker therapy, 202 cardiogenetics, 203 204 differential diagnosis, 201 follow-up, 203 genotyping, 199 201 lifestyle modifications, 202 nonpharmacologic therapy, 203 pharmacologic therapy, 202 203 risk stratification/ indication, 203 Caveolinopathies, 388 CCD. See Cardiac conduction defects CCS. See Cardiac conduction system Cell cycle progression, 377 Central core disease, 392 Channelopathies, 166 Charcot-Marie-tooth disease, 394, 398 CHARGE syndrome, 295 Cholesteryl ester transfer protein (CETP), 358 359 clinical characteristics, 320 321 genetics, 320 Chromosomal abnormalities, 26 27 Clinical cardiogenetics Clinical genetics De Novo mutations, 32 33 founder mutations, 35 genetic isolates consanguinity, 35 36 counseling, 36 38 testing, 36 genotype phenotype correlations, 34 Hardy Weinberg equilibrium, 34 35 inherited disease, 23 24 intake family history, 22 inherited disease, 23 24 Mendelian inheritance autosomal dominant, 28 autosomal recessive, 28 X-linked dominant, 29 30 X-linked recessive, 28 29 mitosis and meiosis chromosomal abnormalities, 26 27 inheritance patterns, 27 recombination, 26 mosaicism, 33 mutation selection equilibrium, 35 non-mendelian inheritance maternal (mitochondrial), 31 32 multifactorial inheritance, 30 31 penetrance and variable expressivity, 33 predictive testing adverse consequences, 39 cardiogenetics, 43 DNA, 38 39 family members, 40 41 minors, 39 40 mutation testing, 42 43 population genetic screening, 41 42 prenatal diagnosis, 41 Congenital cardiac malformations, 106 Congenital heart defects, 105 107, 421 atrial septal defect, 288 289 atrioventricular septal defect, 289 bicuspid aortic valves, 287 288 genetic role, 285 287 monogenic disease, 285 research projects, 296 297 syndromes CHARGE, 295 Digeorge syndrome/velocardiofacial syndrome/22q11 deletion, 293 295 down syndrome/trisomy 21, 292 Holt-Oram, 295 Noonan syndrome, 293 Turner (Ullrich-Turner) syndrome, 292 293 Williams syndrome, 295 296 Connective tissue and smooth muscle disorders arterial tortuosity syndrome, 276 277 differential diagnosis, 270 272 Ehlers Danlos syndrome, 275 276 genetic diagnosis, 269 270 genotype phenotype correlation, 270 hereditary, 263 Loeys Dietz syndrome differential diagnosis, 274 275 molecular background, 274 treatment, 275 Marfan syndrome cardiovascular system, 267 268 clinical aspects, 265 dural sac, 269 molecular genetics, 264 ocular system, 268 pathophysiology, 264 265 pulmonary system, 269 skeletal system, 265 267 skin and integuments, 269 nonsyndromic aortic aneurysms and dissections, 277 278 therapy and prognosis cardiovascular management, 272 manifestations, 273 pregnancy, 273 surgical treatment, 272 274 Connexins, 215 216 Coronary artery disease (CAD) adhesion signaling, 377 anatomy and pathology, 372 apoptosis, 377 cardiovascular system biology, 380 cell cycle progression, 377 chromosome 9p21.3 pathophysiology, 374 375 pleiotropic effects, 373 374 chromosome 21q22, 378 collagen processing, 376 coronary calcification, 377 EPC recruitment and inflammation, 376 377 family history
450 familial forms, 371 LRP6, 371 372 MEF2A, 371 predisposition, 369 risk factors, 370 genes affecting, 372 373 genome-wide association study, 373 genome-wide haplotype approach, 377 378 heritability estimates, 372 key players, 369 LDL levels translates, 375 376 LDL metabolism, 378 risk prediction, 379 380 Coronary calcification, 377 CPVT. See Catecholaminergic polymorphic ventricular tachycardia Cytoskeletal proteins desmin, 70 71 dystrophin, 71 sarcoglycans and glycoproteins, 71 72 D Danon disease, 244, 249, 393 DCM. See Dilated cardiomyopathy Death verification, 405 Denaturing high-performance liquid chromatography (DHPLC), 17 De Novo mutations, 32 33 Depolarization abnormalities, 85 87 Desmin, 70 71 Diabetic cardiomyopathy, 134 DiGeorge syndrome, 294 Dilated cardiomyopathy (DCM) epidemiology and prevalence diagnosis and clinical course, 64 genes and mutations, 66 68 genetic background, 64 66 family screening, 74molecular pathophysiology actin, 68 69 beta-myosin heavy chain, 69 70 cardiac ATP-sensitive potassium channels, 72 DCM and ventricular noncompaction cardiomyopathy, 72 73 desmin, 70 71 dystrophin, 71 lamin A/C, 70 metavincullin, 69 phospholamban, 72 sarcoglycans and glycoproteins, 71 72 SCN5A, 72 telethonin, 69 thymopoietin, 70 titin, 70 tropomyosin and troponin C, 69 troponin-i and troponin-t, 69 multiple genetic defects, 74 75 prognosis and risk stratification, 73 74 therapy, 73 DNA storage, 406 Down syndrome/trisomy 21, 292 Doxycycline, 274 Duchenne muscular dystrophy, 386, 387 Dystrophin, 71 Dystrophin-associated glycoprotein complex cardiomyopathies, 387 388 Dystrophinopathic cardiomyopathy, 385 386 E Ebstein s anomaly, 104, 106 Ehlers-Danlos syndrome, 275 276 Elastin (ELN), 296 Electrophysiological study (EPS), 177 179, 181, 184 Emery-Dreifuss muscular dystrophy (EDMD), 225, 389 Endocarditis prophylaxis, 273 Endomyocardial biopsy, 88 Endomyocardial fibrosis (EMB), 132 European Society of Cardiology (ESC), 97 F Fabry disease, 136 137 Familial amyloid polyneuropathy, 394 Familial combined hyperlipidemia (FCH), 314 Familial defective apolipoprotein B (FDB), 315 Familial dilated cardiomyopathy (FDC), 257 Familial dysbetalipoproteinemia (FD), 323 Familial hypercholesterolemia (FH), 420, 438 Familial hypertriglyceridemia (FHTG) clinical characteristics, 323 324 diagnosis, 324 management, 324 Fibrinolysis, 341 342 Fibrinolytic inhibitors, 342 Fibrosis and myocyte disarray, 48 Filamin A, 241 FHTG. See Familial hypertriglyceridemia Founder mutations, 35 Friedreich s ataxia, 124, 393 394 Fukuyama congenital muscular dystrophy (FCMD), 388 389 G Gaucher disease (GD), 135 Genetic counseling cardiovascular diseases aortic dissections, 420 421 congenital heart defects, 421 familial hypercholesterolemia, 420 multidisciplinary outpatient clinics, 418 420 components, 414 415 definition, 414 evidence-based protocols and guidelines, 415 in inherited cardiovascular disease, 417 418 neurodegenerative disorders, 415 416 presymptomatic/ predictive counseling, 415 reproductive disorders, 415 screening assessment criteria, 418 Genetic heterogeneity, 11 12 Genetic screening, 417, 438 Genetic testing cascade screening, 417 diagnostic, 416 genetic population screening, 417 inherited cardiovascular disease, 417 418
451 predictive, 416 417 SCD, 406 407 screening assessment criteria, 418 Genome-wide association studies (GWAs), 218 219, 297 Genotype-phenotype correlations, 34 Genotyping, 8 10 Ghent nosology, 265, 268 269 Glycogen storage disease type II, 392 H Hardy-Weinberg equilibrium, 34 35 HCM. See Hypertrophic cardiomyopathy Health practice, evidence-based guidelines delivery, dissemination, and diffusion research, 440 genomic application, 439 440 public health outcomes, 440 Hemostatic system phosphatidylserine, 332 333 platelet activation and coagulation, 332 Hereditary neuromuscular diseases muscle disorders (see Muscle disorders) neuropathy (see Neuropathy) HERG channel, 193 High molecular weight kininogen (HMWK), 334, 338 His-Purkinje system, 253 HMG-CoA-reductase gene, 357 358 Holter monitoring, 153 Holt-Oram syndrome, 295 Hydrops fetalis, 246 Hypereosinophylic syndrome, 137 138 Hypertrophic cardiomyopathy (HCM) disease penetrance, 51 52 genetic counseling and testing, 56 57 genetics, 54 56 pathophysiology fibrosis and myocyte disarray, 48 LVH, 50 LVOTO, 51 sarcomeric proteins, 49 prevalence and diagnosis, 47 sudden cardiac death and risk stratification, 53 54 therapy, 52 53 I Idiopathic dilated cardiomyopathy (IDC), 257, 258 Idiopathic ventricular fibrillation (IVF), 229, 232 236 cardiac arrest (CA), 229 230 diagnosis clinical, 230 231 genetic, 232 233 historical, 231 232 therapy, follow-up and prognosis, 233 235 Implantable cardioverter defibrillator (ICD), 53, 54, 113 114 K Kearns-Sayre syndrome, 126 127, 393 L Lamin A/C mutations, 257 LDL-R adapting protein (LDLRAP), 313 Leber s hereditary optic neuropathy (LHON), 249 Left bundle branch block (LBBB), 255 Left cardiac sympathetic denervation (LCSD), 158, 159, 161, 203 Left dominant arrhythmogenic right ventricular dysplasia/cardiomyopathy (LDAC), 90 Left ventricular hypertrophy (LVH), 47, 49 50 Left ventricular outflow tract obstruction (LVOTO), 51, 53 Limb girdle muscular dystrophy (LGMD), 107 Lipoprotein lipase, 356 357 Lipoprotein metabolism ABCA1 deficiency clinical characteristics, 318 319 diagnosis, 319 genetics, 318 management, 319 apolipoprotein AI deficiency clinical characteristics, 317 diagnosis, 317 genetics, 317 management, 317 318 ARH, 313 314 cholesteryl ester transfer protein (CETP) clinical characteristics, 320 321 genetics, 320 endogenous synthesis, 308 exogenous and endogenous lipids, 306 308 familial combined hyperlipidemia (FCH), 314 familial defective apolipoprotein B (FDB), 313 familial dysbetalipoproteinemia (FD) clinical characteristics, 323 diagnosis, 323 genetics, 323 management, 323 familial hypercholesterolemia (FH) clinical characteristics, 310 diagnosis, 310, 312 genetics, 310 management, 311, 313 familial hypertriglyceridemia (FHTG) clinical characteristics, 323 324 diagnosis, 324 management, 324 familial LCAT deficiency and fish eye disease clinical characteristics, 319 320 diagnosis, 320 genetics, 319 management, 320 HDL metabolism, 308 309 LPL-deficiency and Apo-CII deficiency, 322 sitosterolemia, 315 structure, 306 Tangier disease clinical characteristics, 318 319 diagnosis, 319 genetics, 318 management, 319 Loeys-Dietz syndrome differential diagnosis, 274 275 molecular background, 274 treatment, 275 Long QT syndrome (LQTS)
452 arrhythmia, 147 148 cardiac action potential, 143 145 cardiac ion channels, 145 clinical presentation, 148 diagnosis, 149 150 differential diagnosis, 154 epidemiology and prevalence, 146 epinephrine stress test, 153 154 exercise testing, 153 family screening, 160 161 genotype phenotype correlations, 148 149 genotypes, 156 Holter monitoring, 153 molecular genetic diagnosis, 154 155 molecular genetics, 146 147 QT-dispersion, 153 QT-interval, 150 151 risk factors LQTS genotypes, 156 mutation, 156 postpartum period, 156 symptoms, 157 risk stratification gender, 155 QTc duration, 155 time-dependent syncope, 155 156 sinus node dysfunction, 153 therapy and prognosis asymptomatic patients, 160 beta-adrenergic blockade, 158 general lifestyle measures, 157 158 genotype specific measures, 159 160 ICD, 158 159 LCSD, 158 pacemaker therapy, 158 T wave alternans, 153 morphology, 151 152 Low-density-lipoprotein cholesterol (LDL-C) levels clinical characteristics, 310 diagnosis, 310, 312 genetics, 310 management, 311, 313 LVH. See Left ventricular hypertrophy LVOTO. See Left ventricular outflow tract obstruction Lysosomal glycogenosis danon disease, 393 Pompe s disease/glycogen storage disease type II, 392 M Mahaim tachycardia, 244 245, 247, 249 Marfan syndrome, 239 cardiovascular system, 267 268 clinical aspects, 265 dural sac, 269 molecular genetics, 264 ocular system, 268 pathophysiology, 264 265 pulmonary system, 269 skeletal system, 265 267 skin and integuments, 269 MELAS syndrome, 125 126 Mendelian inheritance autosomal dominant, 28 autosomal recessive, 28 X-linked dominant, 29 30 X-linked recessive, 28 29 Metallo-matrix proteinases (MMPs), 425 Metavincullin, 69 MFM. See Myofibrillar myopathies Mitochondrial cardiomyopathy Friedreich s ataxia, 124 heteroplasmy, 123 Kearns Sayre syndrome, 126 127 MELAS syndrome, 125 126 mitochondrial diseases, 127 OXPHOS, 123 Mitochondrial disorders Barth syndrome, 394 carnitine deficiency, 393 Friedreich s ataxia, 393 394 Kearns-Sayre syndrome, 393 Mitochondrial DNA mutations, 72 Mitral valve prolapse (MVP) epidemiology, 239 genetic aspects, 241 pathophysiology and clinical aspects, 239 241 MLPA. See Multiplex ligation dependent probe amplification MMPs. See Metallo-matrix proteinases Molecular genetics analysis, 91 DNA diagnostics, 12 15 eukaryotic genes, 4 genetic heterogeneity, 11 genotyping, 8 10 linkage and risk haplotype analysis, 15 16 meiosis, 6 mutations, 6 8 Sanger sequencing, 16 scanning methods, 16 17 technologies, 17 19 genetic testing, 3 Mucopolysaccharidoses (MPS), 135 136 Multifactorial inheritance, 30 31 Multiple wavelet hypothesis, 210, 212, 214 Multiplex ligation dependent probe amplification (MLPA), 13, 15, 18 Muscular disorders congenital myopathies CCD, 392 myosin storage myopathy, 392 nemaline rod myopathy, 392 enzymatic activity FCMD, 388 389 LGMD2I/MDC1C, 388 inner nuclear membrane proteins autosomal dominant EDMD/LGMD1B, 390 EDMD, 389 X-linked emery dreifuss muscular dystrophy, 389 390
453 ion channel disorder Anderson syndrome, 391 metabolic disorders lysosomal glycogenosis, 392 393 mitochondrial disorders, 393 394 myofibrillar myopathies (MFM), 391 nucleotide repeat disorders dystrophia myotonica, 390 391 myotonic dystrophy type 2 (DM2) (see Proximal myotonic myopathy (PROMM)) sarcolemma-associated proteins Becker muscular, 387 caveolinopathies, 388 Duchenne muscular, 386, 387 dystrophin-associated glycoprotein complex cardiomyopathies, 387 388 dystrophinopathic cardiomyopathy, 385 386 X-linked dilated cardiomyopathy, 387 Myofibrillar myopathies (MFM), 391 Myosin storage myopathy, 392 Myotonic dystrophy, 390 391 N Naxos disease, 90 NCCM. See Noncompaction cardiomyopathy NCLVM. See Noncompaction of the left ventricular myocardium Nemaline rod myopathy, 392 Neuromuscular disease, 107 108 Neuropathy Charcot-Marie-tooth disease, 394, 398 familial amyloid polyneuropathy, 394 Refsum s disease, 398 Noncompaction cardiomyopathy (NCCM), 72 73 asymptomatic disease, 115 116 cardiogenetics genotype phenotype correlations, 114 molecular and cardiologic screening, 114 molecular strategies, 114 115 clinical aspects, 111 112 coincidental etiologies, 111 congenital heart disease, 105 107 differential diagnosis, 112 epidemiology, 102 etiology and molecular genetics, 102 104 implantable cardioverter defibrillator, 113 114 isolation, 104 105 mitochondrial disorders, 108 111 neuromuscular disease, 107 108 nonisolation, 105 pathology macroscopy, 99 101 microscopy, 101 102 prognosis, 113 syndromes, 108 111 therapy and follow-up, 113 trabeculations, 98 99 Noncompaction of the left ventricular myocardium (NCLVM), 97 Nondesmosomal genes, 83 84 Non-Mendelian inheritance maternal (mitochondrial), 31 32 multifactorial inheritance, 30 31 Noonan syndrome, 293 Nuclear envelope proteins, 70 O Ocular system, 268 Osteogenesis imperfecta, 279 Outpatient clinics genetic counseling (see Genetic counseling) genetic testing cascade screening, 417 diagnostic, 416 genetic population screening, 417 predictive, 416 417 Oxidative phosphorylation (OXPHOS), 123, 125 OXPHOS. See Oxidative phosphorylation P Pacemaker therapy, 158 PCCD. See Progressive cardiac conduction defect PCR. See Polymerase chain reaction Permanent junctional reciprocating tachycardia (PJRT), 244, 245 Persistent ductus arteriosus (PDA), 285 Pharmacogenetics, 353 356, 364 365, 427 Phospholamban, 72 Poison polypeptide, 104 Polygenic threshold theory, 285 Polymerase chain reaction (PCR), 12 15 Pompe disease, 244, 249, 392 Potassium channel KCNA5, 214 KCNE2 and KCNJ2, 212 213 KCNQ1, 212 Preparticipation screening, 409 Progressive cardiac conduction defect (PCCD), 253, 256, 258 Protein C pathway, 339 340 Protein kinase A (PKA), 198 Proximal myotonic myopathy (PROMM), 391 Pseudoxanthoma elasticum (PXE), 134 Q Quinidine, 169, 172, 182, 184 R Radiofrequency catheter ablation (RFCA), 248, 250 Refsum s disease, 398 Repolarization abnormalities, 87 Restrictive cardiomyopathy (RCM), 97 clinical aspects, 131 diagnosis, 131 132 differential diagnosis, 132 endomyocardial causes endomyocardial fibrosis, 137 hypereosinophylic syndrome, 137 138 idiopatic and familial restrictive cardiomyopathy, 132 133 infiltrative
454 cardiac amyloidosis, 134 135 Gaucher disease, 135 mucopolysaccharidoses, 135 136 molecular background, 129 130 non-infiltrative restrictive cardiomyopathy diabetic cardiomyopathy, 134 pseudoxanthoma elasticum, 134 scleroderma/systemic sclerosis, 133 134 prognosis, 132 storage diseases Fabry disease, 136 137 glycogen storage disease, 137 hemochromatosis, 136 treatment, 132 RFCA. See Radiofrequency catheter ablation Right bundle branch block (RBBB), 254, 255 RNA polymerase, 5 S SAM. See Systolic anterior motion Sanger sequencing, 16 Sarcoglycans and glycoproteins, 71 72 Sarcoidosis, 135 Sarcolemma-associated proteins Becker muscular, 387 caveolinopathies, 388 Duchenne muscular, 386, 387 dystrophin-associated glycoprotein complex cardiomyopathies, 387 388 dystrophinopathic cardiomyopathy, 385 386 X-linked dilated cardiomyopathy, 387 Sarcomere proteins, 49 actin, 68 69 beta-myosin heavy chain, 69 70 metavincullin, 69 telethonin and troponin-t, 69 titin, 70 tropomyosin, 69 troponin-i and troponin-c, 69 Sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA), 198 SCD. See Sudden cardiac death Scleroderma/Systemic sclerosis (SSc), 133 134 SCN5A overlap syndrome, 256 Secondary hit hypothesis, 214 215 Secundum atrial septal defects, 257 258 Short QT syndrome (SQTS) cardiogenetics, 195 clinical presentation, 191 diagnosis, 192 193 differential diagnosis, 193 epidemiology and prevalence, 190 ICD therapy, 194 molecular and genetic background, 189 190 pathophysiology, 190 191 pharmacologic therapy, 193 194 risk stratification and indication, 194 195 Short QT syndrome pharmacologic therapy, 193 194 SIDS. See Sudden infant death syndrome Single nucleotide polymorphisms (SNPs), 285, 287, 297, 426 Sinus node dysfunction, 153 Sitosterolemia, 315 Smooth muscle disorders. See Connective tissue and smooth muscle disorders Sodium channel gain-of-function mutations, 217 218 loss-of-function mutations, 216 217 Somatic mutation, 215 216 Southern blot analysis, 12, 15 SQTS. See Short QT syndrome Stickler syndrome, 279 Sudden arrhythmic death syndrome, 402 Sudden cardiac death (SCD), 11 arrhythmia, 54 athletes screening, 408 409 cardiogenetic clinic, 406 causes, 404 definitions, 401 403 demographics, 404 405 family history, 50 first-degree relatives, 407 408 genetic testing, 406 407 incidence, 403 postmortem diagnosis, 405 406 preparticipation screening, 409 subset, 53 Sudden infant death syndrome (SIDS), 401 403 Sudden unexplained death (SUD), 229 236, 402 Sudden unexplained death syndrome (SUDS), 166, 170 SUDS. See Sudden unexplained death syndrome Supravalvular aortic stenosis (SVAS), 296 Supraventricular arrhythmias, 170, 174, 182 Supraventricular tachycardia (SVT), 243 Systolic anterior motion (SAM), 51 T Tangier disease clinical characteristics, 318 319 diagnosis, 319 genetics, 318 management, 319 Telethonin, 69 Tetralogy of Fallot (TOF), 294, 295 Thiopurine methyltransferase, 356 Thoracic aortic aneurysms and aortic dissections (TAAD) aortic dilatation, 277 autosomal dominant manner, 277 familial dilatation, 277 genetic heterogeneity, 277 Marfan-related disorders, 279 mutations, 274 phenotypic manifestations, 263 thoracic aneurysms, 278 Thrombosis. See Arterial thrombosis Thymopoietin, 70 Tissue factor, 338 Titin, 70 Transforming growth factor-b (TGF-b), 241 Tropomyosin and troponin C, 69
455 TRPM4 subfamily, 254 255 Turner (Ullrich-Turner) syndrome, 292 293 U Unexplained cardiac arrest (UCA), 230, 232 V Ventricular tachyarrhythmia, 195 Von Willebrand factor, 336 337 W Williams syndrome, 278 Wolff Parkinson White syndrome, 243 244, 246 247 X Xenopus laevis, 213, 217 X-linked dilated cardiomyopathy, 387 X-linked emery dreifuss muscular dystrophy, 389 390