Genetik der Kardiomyopathien

Abstract

Cardiomyopathies are myocardial diseases, which are divided into different phenotypes: Dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic rechtventricular cardiomyopathy (ARVC), left-ventricular-non-compaction cardiomyopathy (LVNC) and restrictive cardiomyopathy (RCM). While gene mutations are responsible for considerable proportions of DCM and RCM, the other cardiomyopathies HCM, ARVC and LVNC are considered to be solely caused genetically. HCM is characterized by mutations of genes encoding sarcomeric proteins, ARVC is a disease of the desmosome while DCM, RCM and LVNC have diverse genetic causes.

Kernaussagen

• Kardiomyopathien sind Herzmuskelerkrankungen, die sich in verschiedenen Phänotypen als dilatative Kardiomyopathie (DCM), hypertrophe Kardiomyopathie (HCM), arrhythmogene rechtsventrikuläre Kardiomyopathie (ARVC), linksventrikuläre Non-Compaction-Kardiomyopathie (LVNC) und restriktive Kardiomyopathie (RCM) widerspiegeln.

• Während Genmutationen einen wesentlichen Anteil an den dilatativen und restriktiven Kardiomyopathien ausmachen, sind die HCM, die ARVC und die LVNC ausschließlich genetisch definierte Erkrankungen.

• Die HCM ist durch Mutationen in Genen sarkomerischer Proteine charakterisiert.

• Die ARVC kann als eine Erkrankung des Desmosoms definiert werden.

• Die DCM, die RCM und die LVNC haben divergente genetische Ursachen.

• Literatur

• 1 Jarcho JA, McKenna W, Pare JA et al. Mapping a gene for familial hypertrophic cardiomyopathy to chromosome 14q1. N Engl J Med 1989; 321: 1372-1378
• 2 Watkins H, Ashrafian H, Redwood C. Inherited cardiomyopathies. N Engl J Med 2011; 364: 1643-1656
• 3 Lopes LR, Elliott PM. Genetics of heart failure. Biochim Biophys Acta 2013; 1832: 2451-2461
• 4 Felker GM, Shaw LK, O’Connor CM. A standardized definition of ischemic cardiomyopathy for use in clinical research. J Am Coll Cardiol 2002; 39: 210-218
• 5 Maron BJ, Towbin JA, Thiene G et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006; 113: 1807-1816
• 6 Gersh BJ, Maron BJ, Bonow RO. American College of Cardiology Foundation/American Heart Association Task Force on Practice G et al. 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2011; 58: e212-260
• 7 Elliott PM, Anastasakis A, Borger MA et al. Authors/Task Force 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014; 35: 2733-2779
• 8 Maron BJ, Maron MS, Semsarian C. Genetics of hypertrophic cardiomyopathy after 20 years: clinical perspectives. J Am Coll Cardiol 2012; 60: 705-715
• 9 Gersh BJ, Nishimura RA. Management of symptomatic hypertrophic cardiomyopathy: pills, alcohol, or the scalpel?. Rev Esp Cardiol (Engl Ed) 2014; 67: 341-344
• 10 Monserrat L, Gimeno-Blanes JR, Marin F et al. Prevalence of fabry disease in a cohort of 508 unrelated patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2007; 50: 2399-2403
• 11 Roma-Rodrigues C, Fernandes AR. Genetics of hypertrophic cardiomyopathy: advances and pitfalls in molecular diagnosis and therapy. Appl Clin Genet 2014; 7: 195-208
• 12 Thiene G. The research venture in arrhythmogenic right ventricular cardiomyopathy: a paradigm of translational medicinedagger. Eur Heart J 2015; Jan 29. pii: ehu 493 [Epub ahead of print]
• 13 McKoy G, Protonotarios N, Crosby A et al. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 2000; 355: 2119-2124
• 14 Norgett EE, Hatsell SJ, Carvajal-Huerta L et al. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet 2000; 9: 2761-2766
• 15 Guzzo-Merello G, Cobo-Marcos M, Gallego-Delgado M et al. Alcoholic cardiomyopathy. World J Cardiol 2014; 6: 771-781
• 16 Mordente A, Meucci E, Silvestrini A et al. New developments in anthracycline-induced cardiotoxicity. Curr Med Chem 2009; 16: 1656-1672
• 17 McMurray JJ, Adamopoulos S, Anker SD et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012; 33: 1787-1847
• 18 Grunig E, Tasman JA, Kucherer H et al. Frequency and phenotypes of familial dilated cardiomyopathy. J Am Coll Cardiol 1998; 31: 186-194
• 19 Lee DS, Pencina MJ, Benjamin EJ et al. Association of parental heart failure with risk of heart failure in offspring. N Engl J Med 2006; 355: 138-147
• 20 Hershberger RE, Morales A, Siegfried JD et al. Clinical and genetic issues in dilated cardiomyopathy: a review for genetics professionals. Genet Med 2010; 12: 655-667
• 21 Hassel D, Dahme T, Erdmann J et al. Nexilin mutations destabilize cardiac Z-disks and lead to dilated cardiomyopathy. Nat Med 2009; 15: 1281-1288
• 22 Herman DS, Lam L, Taylor MR et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med 2012; 366: 619-628
• 23 Morita H, Seidman J, Seidman CE. Genetic causes of human heart failure. J Clin Invest 2005; 115: 518-526
• 24 van Spaendonck-Zwarts KY, van Hessem L, Jongbloed JD et al. Desmin-related myopathy. Clin Genet 2011; 80: 354-366
• 25 Schonberger J, Wang L, Shin JT et al. Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss. Nat Genet 2005; 37: 418-422
• 26 Bendig G, Grimmler M, Huttner IG et al. Integrin-linked kinase, a novel component of the cardiac mechanical stretch sensor, controls contractility in the zebrafish heart. Genes Dev 2006; 20: 2361-2372
• 27 Oechslin EN, Attenhofer JostCH, Rojas JR et al. Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol 2000; 36: 493-500
• 28 Lofiego C, Biagini E, Pasquale F et al. Wide spectrum of presentation and variable outcomes of isolated left ventricular non-compaction. Heart 2007; 93: 65-71
• 29 Mogensen J, Kubo T, Duque M et al. Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. J Clin Invest 2003; 111: 209-216