Appendix CSRP3 TCAP ABCC9 PLN ACTC1 TMPO PSEN1 PSEN2 VCL FCMD TPM1 TNNC1 ACTN2 DSG2 NEXN MYH6 TTN CRYAB LAMP2^*

Átírás

1 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 TGF-b (continued) H.F. Baars et al. (eds.), Clinical Cardiogenetics, DOI: / , Springer-Verlag London Limited

2 444 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 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 SCN5A TRPM4 SCN1B GATA4 NKX2-5 TNX20 MYH6 TLL1 ZIC3^^ CFC1 CRELD1 GJA1 THRAP2 LRP6 APOB 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).

3 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 = 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

4 A ABCA1 deficiency clinical characteristics, diagnosis, 319 genetics, 318 management, 319 Abdominal aortic aneurysm (AAA) clinical diagnosis ruptured, 429 unruptured, epidemiology, follow-up, molecular genetics association studies, segregation and linkage analysis, pathogenesis natural history, 424 vascular pathology, therapy lifestyle, 430 pharmacological treatment, 430 surgical intervention, Ablation therapy, 235 Acute coronary syndrome (ACS), 336, 338 Adenosine triphosphate (ATP) synthase, 123 AF. See Atrial fibrillation American Heart Association (AHA), 97 Amyloidosis, 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, Apolipoprotein E, Apoptosis, 377 Arrhythmias, 87, Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) clinical presentation, diagnosis, 85 differential diagnosis, ECG criteria arrhythmias, 87 depolarization abnormalities, diagnostics, endomyocardial biopsy, 88 family history, 88 global and regional dysfunction, modifications, nonclassical subtypes, 90 repolarization abnormalities, 87 epidemiology, 84 molecular and genetic background autosomal dominant disease, autosomal recessive disease, 82 desmosomal disease and dysfunction, desmosome function, nondesmosomal genes, molecular genetic analysis, 91 prognosis and therapy, Arterial thrombosis clinical relevance, coagulation factor V and prothrombin, 339 factor VII, factor VIII, IX and XI, factor XII, 338 tissue factor, 338 factor XIII, 341 fibrinogen, fibrinolysis, fibrinolytic inhibitors, 342 hemostatic system, polymorphisms platelet receptors, Von Willebrand factor, protein C pathway, Arterial tortuosity syndrome, ARVD/C. See Arrhythmogenic right ventricular dysplasia/cardiomyopathy Atherosclerotic plaque, 337, 338 Atrial fibrillation (AF) atrial natriuretic peptide, 218 autonomic nervous system, clinical aspects, H.F. Baars et al. (eds.), Clinical Cardiogenetics, DOI: / , Springer-Verlag London Limited

5 448 connexins, epidemiology, gene associations ACE, 219 GNB3, Enos, MMP-2, IL-10, 219 genome wide association studies, molecular background, molecular genetics, 211 mutations, 215 pathophysiology, potassium channel KCNA5, 214 KCNE2 and KCNJ2, KCNQ1, 212 secondary hit hypothesis, sodium channel gain-of-function mutations, loss-of-function mutations, unknown loci, 218 Atrial natriuretic peptide (ANP), 218 Atrioventricular reentry tachycardia (AVRT) clinical aspects symptoms, 246 WPW syndrome, electrocardiographic diagnosis, 247 epidemiology concealed bypasses, 244 Mahaim tachycardia, 244 Wolff Parkinson white syndrome, genetics animal models, 249 genes, Mahaim tachycardia, 249 pathogenesis accessory pathways (APs), arrhythmia mechanisms, treatment, Atrioventricular septal defect, 289 Autopsy, 230, 231, 402, Autosomal recessive hypercholesterolemia (ARH), B Barth syndrome, 394 b-blocker therapy, 202 Becker muscular dystrophy, 387 Bentall procedure, 272, 273 Beta-adrenergic blockade, 158 Bicuspid aortic valves, Bone morphogenetic proteins (BMPs), 249 Brugada syndrome (BS), 16, 404 cardiogenetics family screening, genetic diagnosis, cellular and ionic mechanisms, clinical manifestations, diagnosis ECG findings, ECG modulators, prognosis and risk stratification, tools, epidemiology, genetics, treatment ICD, pharmacological options, 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, molecular screening, 258 SCN5A overlap syndrome, 256 secundum atrial septal defects, sodium channel beta1 subunit mutations, 256 TRPM4 subfamily, observations, Cardiac conduction system (CCS), 244, 248, 249 Cardiac ion channels, 145 Cardiogenetics ACE insertion/deletion, adverse drug reactions, 360 apolipoprotein E, atherosclerosis, 356 cholesterylesther transfer protein, clinical and public health outcomes, 440 cytochrome P450, 356 delivery, dissemination, and diffusion research, 428 genomic application, genotype phenotype correlations, 114 health care diagnostic testing, genetic screening, 438 pharmacogenetics, 439 risk prediction, 439 HMG-CoA-reductase gene, lipoprotein lipase, molecular and cardiologic screening, 114 molecular strategies, PCSK9, 358 pharmaceutics, 363 pharmacogenetics, , polymorphisms, 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, etiology molecular background, pathophysiology, 198

6 449 genetic diagnosis b-blocker therapy, 202 cardiogenetics, differential diagnosis, 201 follow-up, 203 genotyping, lifestyle modifications, 202 nonpharmacologic therapy, 203 pharmacologic therapy, 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), clinical characteristics, genetics, 320 Chromosomal abnormalities, Clinical cardiogenetics Clinical genetics De Novo mutations, founder mutations, 35 genetic isolates consanguinity, counseling, testing, 36 genotype phenotype correlations, 34 Hardy Weinberg equilibrium, inherited disease, intake family history, 22 inherited disease, Mendelian inheritance autosomal dominant, 28 autosomal recessive, 28 X-linked dominant, X-linked recessive, mitosis and meiosis chromosomal abnormalities, inheritance patterns, 27 recombination, 26 mosaicism, 33 mutation selection equilibrium, 35 non-mendelian inheritance maternal (mitochondrial), multifactorial inheritance, penetrance and variable expressivity, 33 predictive testing adverse consequences, 39 cardiogenetics, 43 DNA, family members, minors, mutation testing, population genetic screening, prenatal diagnosis, 41 Congenital cardiac malformations, 106 Congenital heart defects, , 421 atrial septal defect, atrioventricular septal defect, 289 bicuspid aortic valves, genetic role, monogenic disease, 285 research projects, syndromes CHARGE, 295 Digeorge syndrome/velocardiofacial syndrome/22q11 deletion, down syndrome/trisomy 21, 292 Holt-Oram, 295 Noonan syndrome, 293 Turner (Ullrich-Turner) syndrome, Williams syndrome, Connective tissue and smooth muscle disorders arterial tortuosity syndrome, differential diagnosis, Ehlers Danlos syndrome, genetic diagnosis, genotype phenotype correlation, 270 hereditary, 263 Loeys Dietz syndrome differential diagnosis, molecular background, 274 treatment, 275 Marfan syndrome cardiovascular system, clinical aspects, 265 dural sac, 269 molecular genetics, 264 ocular system, 268 pathophysiology, pulmonary system, 269 skeletal system, skin and integuments, 269 nonsyndromic aortic aneurysms and dissections, therapy and prognosis cardiovascular management, 272 manifestations, 273 pregnancy, 273 surgical treatment, Connexins, 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, pleiotropic effects, chromosome 21q22, 378 collagen processing, 376 coronary calcification, 377 EPC recruitment and inflammation, family history

7 450 familial forms, 371 LRP6, MEF2A, 371 predisposition, 369 risk factors, 370 genes affecting, genome-wide association study, 373 genome-wide haplotype approach, heritability estimates, 372 key players, 369 LDL levels translates, LDL metabolism, 378 risk prediction, Coronary calcification, 377 CPVT. See Catecholaminergic polymorphic ventricular tachycardia Cytoskeletal proteins desmin, dystrophin, 71 sarcoglycans and glycoproteins, D Danon disease, 244, 249, 393 DCM. See Dilated cardiomyopathy Death verification, 405 Denaturing high-performance liquid chromatography (DHPLC), 17 De Novo mutations, Depolarization abnormalities, Desmin, Diabetic cardiomyopathy, 134 DiGeorge syndrome, 294 Dilated cardiomyopathy (DCM) epidemiology and prevalence diagnosis and clinical course, 64 genes and mutations, genetic background, family screening, 74molecular pathophysiology actin, beta-myosin heavy chain, cardiac ATP-sensitive potassium channels, 72 DCM and ventricular noncompaction cardiomyopathy, desmin, dystrophin, 71 lamin A/C, 70 metavincullin, 69 phospholamban, 72 sarcoglycans and glycoproteins, SCN5A, 72 telethonin, 69 thymopoietin, 70 titin, 70 tropomyosin and troponin C, 69 troponin-i and troponin-t, 69 multiple genetic defects, prognosis and risk stratification, therapy, 73 DNA storage, 406 Down syndrome/trisomy 21, 292 Doxycycline, 274 Duchenne muscular dystrophy, 386, 387 Dystrophin, 71 Dystrophin-associated glycoprotein complex cardiomyopathies, Dystrophinopathic cardiomyopathy, E Ebstein s anomaly, 104, 106 Ehlers-Danlos syndrome, Elastin (ELN), 296 Electrophysiological study (EPS), , 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, 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, diagnosis, 324 management, 324 Fibrinolysis, Fibrinolytic inhibitors, 342 Fibrosis and myocyte disarray, 48 Filamin A, 241 FHTG. See Familial hypertriglyceridemia Founder mutations, 35 Friedreich s ataxia, 124, Fukuyama congenital muscular dystrophy (FCMD), G Gaucher disease (GD), 135 Genetic counseling cardiovascular diseases aortic dissections, congenital heart defects, 421 familial hypercholesterolemia, 420 multidisciplinary outpatient clinics, components, definition, 414 evidence-based protocols and guidelines, 415 in inherited cardiovascular disease, neurodegenerative disorders, presymptomatic/ predictive counseling, 415 reproductive disorders, 415 screening assessment criteria, 418 Genetic heterogeneity, Genetic screening, 417, 438 Genetic testing cascade screening, 417 diagnostic, 416 genetic population screening, 417 inherited cardiovascular disease,

8 451 predictive, SCD, screening assessment criteria, 418 Genome-wide association studies (GWAs), , 297 Genotype-phenotype correlations, 34 Genotyping, 8 10 Ghent nosology, 265, Glycogen storage disease type II, 392 H Hardy-Weinberg equilibrium, HCM. See Hypertrophic cardiomyopathy Health practice, evidence-based guidelines delivery, dissemination, and diffusion research, 440 genomic application, public health outcomes, 440 Hemostatic system phosphatidylserine, 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, Holter monitoring, 153 Holt-Oram syndrome, 295 Hydrops fetalis, 246 Hypereosinophylic syndrome, Hypertrophic cardiomyopathy (HCM) disease penetrance, genetic counseling and testing, genetics, pathophysiology fibrosis and myocyte disarray, 48 LVH, 50 LVOTO, 51 sarcomeric proteins, 49 prevalence and diagnosis, 47 sudden cardiac death and risk stratification, therapy, I Idiopathic dilated cardiomyopathy (IDC), 257, 258 Idiopathic ventricular fibrillation (IVF), 229, cardiac arrest (CA), diagnosis clinical, genetic, historical, therapy, follow-up and prognosis, Implantable cardioverter defibrillator (ICD), 53, 54, K Kearns-Sayre syndrome, , 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, Left ventricular outflow tract obstruction (LVOTO), 51, 53 Limb girdle muscular dystrophy (LGMD), 107 Lipoprotein lipase, Lipoprotein metabolism ABCA1 deficiency clinical characteristics, diagnosis, 319 genetics, 318 management, 319 apolipoprotein AI deficiency clinical characteristics, 317 diagnosis, 317 genetics, 317 management, ARH, cholesteryl ester transfer protein (CETP) clinical characteristics, genetics, 320 endogenous synthesis, 308 exogenous and endogenous lipids, 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, diagnosis, 324 management, 324 familial LCAT deficiency and fish eye disease clinical characteristics, diagnosis, 320 genetics, 319 management, 320 HDL metabolism, LPL-deficiency and Apo-CII deficiency, 322 sitosterolemia, 315 structure, 306 Tangier disease clinical characteristics, diagnosis, 319 genetics, 318 management, 319 Loeys-Dietz syndrome differential diagnosis, molecular background, 274 treatment, 275 Long QT syndrome (LQTS)

9 452 arrhythmia, cardiac action potential, cardiac ion channels, 145 clinical presentation, 148 diagnosis, differential diagnosis, 154 epidemiology and prevalence, 146 epinephrine stress test, exercise testing, 153 family screening, genotype phenotype correlations, genotypes, 156 Holter monitoring, 153 molecular genetic diagnosis, molecular genetics, QT-dispersion, 153 QT-interval, risk factors LQTS genotypes, 156 mutation, 156 postpartum period, 156 symptoms, 157 risk stratification gender, 155 QTc duration, 155 time-dependent syncope, sinus node dysfunction, 153 therapy and prognosis asymptomatic patients, 160 beta-adrenergic blockade, 158 general lifestyle measures, genotype specific measures, ICD, LCSD, 158 pacemaker therapy, 158 T wave alternans, 153 morphology, 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, , 247, 249 Marfan syndrome, 239 cardiovascular system, clinical aspects, 265 dural sac, 269 molecular genetics, 264 ocular system, 268 pathophysiology, pulmonary system, 269 skeletal system, skin and integuments, 269 MELAS syndrome, Mendelian inheritance autosomal dominant, 28 autosomal recessive, 28 X-linked dominant, X-linked recessive, Metallo-matrix proteinases (MMPs), 425 Metavincullin, 69 MFM. See Myofibrillar myopathies Mitochondrial cardiomyopathy Friedreich s ataxia, 124 heteroplasmy, 123 Kearns Sayre syndrome, MELAS syndrome, mitochondrial diseases, 127 OXPHOS, 123 Mitochondrial disorders Barth syndrome, 394 carnitine deficiency, 393 Friedreich s ataxia, Kearns-Sayre syndrome, 393 Mitochondrial DNA mutations, 72 Mitral valve prolapse (MVP) epidemiology, 239 genetic aspects, 241 pathophysiology and clinical aspects, MLPA. See Multiplex ligation dependent probe amplification MMPs. See Metallo-matrix proteinases Molecular genetics analysis, 91 DNA diagnostics, eukaryotic genes, 4 genetic heterogeneity, 11 genotyping, 8 10 linkage and risk haplotype analysis, meiosis, 6 mutations, 6 8 Sanger sequencing, 16 scanning methods, technologies, genetic testing, 3 Mucopolysaccharidoses (MPS), Multifactorial inheritance, 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, LGMD2I/MDC1C, 388 inner nuclear membrane proteins autosomal dominant EDMD/LGMD1B, 390 EDMD, 389 X-linked emery dreifuss muscular dystrophy,

10 453 ion channel disorder Anderson syndrome, 391 metabolic disorders lysosomal glycogenosis, mitochondrial disorders, myofibrillar myopathies (MFM), 391 nucleotide repeat disorders dystrophia myotonica, 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, dystrophinopathic cardiomyopathy, X-linked dilated cardiomyopathy, 387 Myofibrillar myopathies (MFM), 391 Myosin storage myopathy, 392 Myotonic dystrophy, N Naxos disease, 90 NCCM. See Noncompaction cardiomyopathy NCLVM. See Noncompaction of the left ventricular myocardium Nemaline rod myopathy, 392 Neuromuscular disease, Neuropathy Charcot-Marie-tooth disease, 394, 398 familial amyloid polyneuropathy, 394 Refsum s disease, 398 Noncompaction cardiomyopathy (NCCM), asymptomatic disease, cardiogenetics genotype phenotype correlations, 114 molecular and cardiologic screening, 114 molecular strategies, clinical aspects, coincidental etiologies, 111 congenital heart disease, differential diagnosis, 112 epidemiology, 102 etiology and molecular genetics, implantable cardioverter defibrillator, isolation, mitochondrial disorders, neuromuscular disease, nonisolation, 105 pathology macroscopy, microscopy, prognosis, 113 syndromes, therapy and follow-up, 113 trabeculations, Noncompaction of the left ventricular myocardium (NCLVM), 97 Nondesmosomal genes, Non-Mendelian inheritance maternal (mitochondrial), multifactorial inheritance, 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, 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, , , 427 Phospholamban, 72 Poison polypeptide, 104 Polygenic threshold theory, 285 Polymerase chain reaction (PCR), Pompe disease, 244, 249, 392 Potassium channel KCNA5, 214 KCNE2 and KCNJ2, KCNQ1, 212 Preparticipation screening, 409 Progressive cardiac conduction defect (PCCD), 253, 256, 258 Protein C pathway, 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, differential diagnosis, 132 endomyocardial causes endomyocardial fibrosis, 137 hypereosinophylic syndrome, idiopatic and familial restrictive cardiomyopathy, infiltrative

11 454 cardiac amyloidosis, Gaucher disease, 135 mucopolysaccharidoses, molecular background, non-infiltrative restrictive cardiomyopathy diabetic cardiomyopathy, 134 pseudoxanthoma elasticum, 134 scleroderma/systemic sclerosis, prognosis, 132 storage diseases Fabry disease, 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, Sarcoidosis, 135 Sarcolemma-associated proteins Becker muscular, 387 caveolinopathies, 388 Duchenne muscular, 386, 387 dystrophin-associated glycoprotein complex cardiomyopathies, dystrophinopathic cardiomyopathy, X-linked dilated cardiomyopathy, 387 Sarcomere proteins, 49 actin, beta-myosin heavy chain, 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), SCN5A overlap syndrome, 256 Secondary hit hypothesis, Secundum atrial septal defects, Short QT syndrome (SQTS) cardiogenetics, 195 clinical presentation, 191 diagnosis, differential diagnosis, 193 epidemiology and prevalence, 190 ICD therapy, 194 molecular and genetic background, pathophysiology, pharmacologic therapy, risk stratification and indication, Short QT syndrome pharmacologic therapy, 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, loss-of-function mutations, Somatic mutation, 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, cardiogenetic clinic, 406 causes, 404 definitions, demographics, family history, 50 first-degree relatives, genetic testing, incidence, 403 postmortem diagnosis, preparticipation screening, 409 subset, 53 Sudden infant death syndrome (SIDS), Sudden unexplained death (SUD), , 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, 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

12 455 TRPM4 subfamily, Turner (Ullrich-Turner) syndrome, U Unexplained cardiac arrest (UCA), 230, 232 V Ventricular tachyarrhythmia, 195 Von Willebrand factor, W Williams syndrome, 278 Wolff Parkinson White syndrome, , X Xenopus laevis, 213, 217 X-linked dilated cardiomyopathy, 387 X-linked emery dreifuss muscular dystrophy,