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Introduction Hereditary Cardiomyopathies

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Clinical Cardiogenetics

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Abstract

Cardiomyopathies are myocardial disorders in which the heart muscle is structurally and functionally abnormal in the absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease sufficient to explain the observed myocardial abnormality. We describe five main cardiomyopathy subtypes as outlined by the European Society of Cardiology: hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, restrictive cardiomyopathy and non-compaction cardiomyopathy. All show substantial overlap, both clinically and genetically. For each cardiomyopathy subtype, multiple disease genes have been identified and mutations in several genes can cause different subtypes. In addition to hereditary cardiomyopathies, several non-genetic causes can result in cardiomyopathy, which can be very difficult to distinguish clinically.

All hereditary cardiomyopathies are characterized by incomplete penetrance, meaning that some mutation carriers will remain unaffected during their entire life, and variable expression, i.e. the type and severity of the disease can vary widely, even within families. The availability of diagnostic and management guidelines for different cardiomyopathies should improve the outcome of these patients and aid the clinician to identify the many rare presentations of cardiomyopathies, that all can be part of a wider spectrum of multi-organ, systemic or syndromic diseases.

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References

  1. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, et al. Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2008;29:270–6.

    Article  PubMed  Google Scholar 

  2. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, 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;113:1807–16.

    Article  PubMed  Google Scholar 

  3. ten Cate FJ, Roelandt J. Progression to left ventricular dilatation in patients with hypertrophic obstructive cardiomyopathy. Am Heart J. 1979;97:762–5.

    Article  PubMed  Google Scholar 

  4. Sen-Chowdhry S, Morgan RD, Chambers JC, McKenna WJ. Arrhythmogenic cardiomyopathy: etiology, diagnosis, and treatment. Annu Rev Med. 2010;61:233–53.

    Article  CAS  PubMed  Google Scholar 

  5. Sen-Chowdhry S, Syrris P, Prasad SK, Hughes SE, Merrifield R, Ward D, et al. Left-dominant arrhythmogenic cardiomyopathy an under-recognized clinical entity. J Am Coll Cardiol. 2008;52:2175–87.

    Article  PubMed  Google Scholar 

  6. Jeschke B, Uhl K, Weist B, Schroder D, Meitinger T, Dohlemann C, et al. A high risk phenotype of hypertrophic cardiomyopathy associated with a compound genotype of two mutated beta-myosin heavy chain genes. Hum Genet. 1998;102:299–304.

    Article  CAS  PubMed  Google Scholar 

  7. Lekanne Deprez RH, Muurling-Vlietman JJ, Hruda J, Baars MJ, Wijnaendts LC, Stolte-Dijkstra I, et al. Two cases of severe neonatal hypertrophic cardiomyopathy caused by compound heterozygous mutations in the MYBPC3 gene. J Med Genet. 2006;43:829–32.

    Article  CAS  PubMed  Google Scholar 

  8. Wilde AA, Behr ER. Genetic testing for inherited cardiac disease. Nat Rev Cardiol. 2013;10:571–83.

    Article  CAS  PubMed  Google Scholar 

  9. Jarcho JA, McKenna W, Pare JA, Solomon SD, Holcombe RF, Dickie S, et al. Mapping a gene for familial hypertrophic cardiomyopathy to chromosome 14q1. N Engl J Med. 1989;321:1372–8.

    Article  CAS  PubMed  Google Scholar 

  10. Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, et al. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell. 1990;62:999–1006.

    Article  CAS  PubMed  Google Scholar 

  11. Authors/Task Force members, Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, et al. 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.

    Google Scholar 

  12. Rapezzi C, Arbustini E, Caforio AL, Charron P, Gimeno-Blanes J, Helio T, et al. Diagnostic work-up in cardiomyopathies: bridging the gap between clinical phenotypes and final diagnosis. A position statement from the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013;34:1448–58.

    Article  PubMed  Google Scholar 

  13. Wicks EC, Elliott PM. Genetics and metabolic cardiomyopathies. Herz. 2012;37:598–610.

    Article  CAS  PubMed  Google Scholar 

  14. Gelb BD, Roberts AE, Tartaglia M. Cardiomyopathies in Noonan syndrome and the other RASopathies. Prog Pediatr Cardiol. 2015;39:13–9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012;126:1286–300.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bos JM, Will ML, Gersh BJ, Kruisselbrink TM, Ommen SR, Ackerman MJ. Characterization of a phenotype-based genetic test prediction score for unrelated patients with hypertrophic cardiomyopathy. Mayo Clin Proc. 2014;89:727–37.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mestroni L, Rocco C, Gregori D, Sinagra G, Di Lenarda A, Miocic S, et al. Familial dilated cardiomyopathy: evidence for genetic and phenotypic heterogeneity. Heart Muscle Disease Study Group. J Am Coll Cardiol. 1999;34:181–90.

    Article  CAS  PubMed  Google Scholar 

  18. Felker GM, Thompson RE, Hare JM, Hruban RH, Clemetson DE, Howard DL, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000;342:1077–84.

    Article  CAS  PubMed  Google Scholar 

  19. Herman DS, Lam L, Taylor MR, Wang L, Teekakirikul P, Christodoulou D, et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012;366:619–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Arbustini E, Pilotto A, Repetto A, Grasso M, Negri A, Diegoli M, et al. Autosomal dominant dilated cardiomyopathy with atrioventricular block: a lamin A/C defect-related disease. J Am Coll Cardiol. 2002;39:981–90.

    Article  CAS  PubMed  Google Scholar 

  21. Taylor MR, Slavov D, Ku L, Di Lenarda A, Sinagra G, Carniel E, et al. Prevalence of desmin mutations in dilated cardiomyopathy. Circulation. 2007;115:1244–51.

    Article  CAS  PubMed  Google Scholar 

  22. Van der Zwaag PA, van Rijsingen IA, Asimaki A, Jongbloed JD, van Veldhuisen DJ, Wiesfeld AC, et al. Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy. Eur J Heart Fail. 2012;14:1199–207.

    Google Scholar 

  23. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, 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;33:1787–847.

    Article  PubMed  Google Scholar 

  24. van Rijsingen IA, Arbustini E, Elliott PM, Mogensen J, Hermans-van Ast JF, van der Kooi AJ, et al. Risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers a European cohort study. J Am Coll Cardiol. 2012;59:493–500.

    Article  PubMed  Google Scholar 

  25. van Rijsingen IA, van der Zwaag PA, Groeneweg JA, Nannenberg EA, Jongbloed JD, Zwinderman AH, et al. Outcome in phospholamban R14del carriers: results of a large multicentre cohort study. Circ Cardiovasc Genet. 2014;7:455–65.

    Article  PubMed  Google Scholar 

  26. Marcus FI, Fontaine GH, Guiraudon G, Frank R, Laurenceau JL, Malergue C, et al. Right ventricular dysplasia: a report of 24 adult cases. Circulation. 1982;65:384–98.

    Article  CAS  PubMed  Google Scholar 

  27. Corrado D, Basso C, Thiene G, McKenna WJ, Davies MJ, Fontaliran F, et al. Spectrum of clinicopathologic manifestations of arrhythmogenic right ventricular cardiomyopathy/dysplasia: a multicenter study. J Am Coll Cardiol. 1997;30:1512–20.

    Article  CAS  PubMed  Google Scholar 

  28. Sen-Chowdhry S, Syrris P, Ward D, Asimaki A, Sevdalis E, McKenna WJ. Clinical and genetic characterization of families with arrhythmogenic right ventricular dysplasia/cardiomyopathy provides novel insights into patterns of disease expression. Circulation. 2007;115:1710–20.

    Article  PubMed  Google Scholar 

  29. Basso C, Corrado D, Marcus FI, Nava A, Thiene G. Arrhythmogenic right ventricular cardiomyopathy. Lancet. 2009;373:1289–300.

    Article  PubMed  Google Scholar 

  30. McKenna WJ, Thiene G, Nava A, Fontaliran F, Blomstrom-Lundqvist C, Fontaine G, et al. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology. Br Heart J. 1994;71:215–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur Heart J. 2010;31:806–14.

    Article  PubMed  PubMed Central  Google Scholar 

  32. McKoy G, Protonotarios N, Crosby A, Tsatsopoulou A, Anastasakis A, Coonar A, et al. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet. 2000;355:2119–24.

    Article  CAS  PubMed  Google Scholar 

  33. Norgett EE, Hatsell SJ, Carvajal-Huerta L, Cabezas JC, Common J, Purkis PE, et al. Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet. 2000;9:2761–6.

    Article  CAS  PubMed  Google Scholar 

  34. Merner ND, Hodgkinson KA, Haywood AF, Connors S, French VM, Drenckhahn JD, et al. Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene. Am J Hum Genet. 2008;82:809–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Corrado D, Wichter T, Link MS, Hauer R, Marchlinski F, Anastasakis A, et al. Treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia: an international task force consensus statement. Eur Heart J. 2015;36:3227–37.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Mogensen J, Arbustini E. Restrictive cardiomyopathy. Curr Opin Cardiol. 2009;24:214–20.

    Article  PubMed  Google Scholar 

  37. Kushwaha SS, Fallon JT, Fuster V. Restrictive cardiomyopathy. N Engl J Med. 1997;336:267–76.

    Article  CAS  PubMed  Google Scholar 

  38. Adams MJ, Lipsitz SR, Colan SD, Tarbell NJ, Treves ST, Diller L, et al. Cardiovascular status in long-term survivors of Hodgkin's disease treated with chest radiotherapy. J Clin Oncol. 2004;22:3139–48.

    Article  PubMed  Google Scholar 

  39. Mogensen J, Kubo T, Duque M, Uribe W, Shaw A, Murphy R, et al. Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. J Clin Invest. 2003;111:209–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kaski JP, Syrris P, Burch M, Tome-Esteban MT, Fenton M, Christiansen M, et al. Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes. Heart. 2008;94:1478–84.

    Article  CAS  PubMed  Google Scholar 

  41. Mogensen J, Hey T, Lambrecht S. A systematic review of phenotypic features associated with cardiac troponin I mutations in hereditary cardiomyopathies. Can J Cardiol. 2015;31:1377–85.

    Article  PubMed  Google Scholar 

  42. Arbustini E, Pasotti M, Pilotto A, Pellegrini C, Grasso M, Previtali S, et al. Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects. Eur J Heart Fail. 2006;8:477–83.

    Article  CAS  PubMed  Google Scholar 

  43. Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart. 2001;86:666–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hoedemaekers YM, Caliskan K, Michels M, Frohn-Mulder I, van der Smagt JJ, Phefferkorn JE, et al. The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy. Circ Cardiovasc Genet. 2010;3:232–9.

    Article  PubMed  Google Scholar 

  45. Arbustini E, Narula N, Dec GW, Reddy KS, Greenberg B, Kushwaha S, et al. The MOGE(S) classification for a phenotype-genotype nomenclature of cardiomyopathy: endorsed by the World Heart Federation. J Am Coll Cardiol. 2013;62:2046–72.

    Article  PubMed  Google Scholar 

  46. Hazebroek MR, Moors S, Dennert R, van den Wijngaard A, Krapels I, Hoos M, et al. Prognostic relevance of gene-environment interactions in patients with dilated cardiomyopathy: applying the MOGE(S) classification. J Am Coll Cardiol. 2015;66:1313–23.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Paul A. van der Zwaag

  2. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Maarten P. van den Berg

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  1. Paul A. van der Zwaag
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Correspondence to Paul A. van der Zwaag .

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Editors and Affiliations

  1. Department of Cardiology, St. Elisabeth-TweeSteden Ziekenhuis, Tilburg, The Netherlands

    Hubert F. Baars

  2. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands

    Pieter A. F. M. Doevendans

  3. Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands

    Arjan C. Houweling

  4. Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands

    J. Peter van Tintelen

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van der Zwaag, P.A., van den Berg, M.P. (2016). Introduction Hereditary Cardiomyopathies. In: Baars, H., Doevendans, P., Houweling, A., van Tintelen, J. (eds) Clinical Cardiogenetics. Springer, Cham. https://doi.org/10.1007/978-3-319-44203-7_3

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  • DOI: https://doi.org/10.1007/978-3-319-44203-7_3

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