Skip to main content
SpringerLink
Log in

Familial Dilated Cardiomyopathy

  • Chapter
  • First Online:
Clinical Cardiogenetics

  • 967 Accesses

Abstract

Dilated cardiomyopathy (DCM) is a disorder of the ventricular myocardium characterized by normal or thinned walls, enlarged chamber volumes, and diminished systolic function. Clinically, DCM gives rise to fatigue, shortness of breath, and increased morbidity and mortality. DCM occurs in response to underlying pathologies including valvular dysfunction, hypertension, or myocarditis, or as an idiopathic disorder of the myocardium. Among patients with idiopathic DCM, approximately 25–30% have affected first-degree family members, implying a genetic etiology. 16 However, a pathogenic mutation is found in a minority of cases of familial DCM upon molecular analyses. A number of candidate genes have been identified, and these encode for proteins of the myocyte contractile apparatus, the myocyte cytoskeleton, and nuclear envelope, as well as proteins involved in calcium homeostasis. In addition, the function of a number of proteins encoded by candidate genes is still unknown. To date, over 20 genes have been shown to play a pivotal role in the origin of DCM. This diversity of genetic etiologies in DCM explains why patients sometimes exhibit additional clinical manifestations, including defects in the conduction system resulting in arrhythmias, skeletal muscle abnormalities, deafness, and endocrinologic disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 159.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 209.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Adler E, Fuster V. SCN5A – a mechanistic link between inherited cardiomyopathies and a predisposition to arrhythmias? Jama. 2005;293(4):491-493.

    Article  PubMed  CAS  Google Scholar 

  2. Arbustini E, Pilotto A, Repetto A, et al. Autosomal dominant dilated cardiomyopathy with atrioventricular block: a lamin A/C defect-related disease. J Am Coll Cardiol. 2002;39(6):981-990.

    Article  PubMed  CAS  Google Scholar 

  3. Barresi R, Di Blasi C, Negri T, et al. Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by beta sarcoglycan mutations. J Med Genet. 2000;37(2):102-107.

    Article  PubMed  CAS  Google Scholar 

  4. Beffagna G, Occhi G, Nava A, et al. Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc Res. 2005;65(2):366-373.

    Article  PubMed  CAS  Google Scholar 

  5. Bienengraeber M, Olson TM, Selivanov VA, et al. ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating. Nat Genet. 2004;36(4):382-387.

    Article  PubMed  CAS  Google Scholar 

  6. Carvajal-Huerta L. Epidermolytic palmoplantar keratoderma with woolly hair and dilated cardiomyopathy. J Am Acad Dermatol. 1998;39(3):418-421.

    Article  PubMed  CAS  Google Scholar 

  7. Chrissoheris MP, Ali R, Vivas Y, Marieb M, Protopapas Z. Isolated noncompaction of the ventricular myocardium: contemporary diagnosis and management. Clin Cardiol. 2007;30(4):156-160.

    Article  PubMed  Google Scholar 

  8. D’Adamo P, Fassone L, Gedeon A, et al. The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies. Am J Hum Genet. 1997;61(4):862-867.

    Article  PubMed  Google Scholar 

  9. Daehmlow S, Erdmann J, Knueppel T, et al. Novel mutations in sarcomeric protein genes in dilated cardiomyopathy. Biochem Biophys Res Commun. 2002;298(1):116-120.

    Article  PubMed  CAS  Google Scholar 

  10. Dalakas MC, Park KY, Semino-Mora C, Lee HS, Sivakumar K, Goldfarb LG. Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. N Engl J Med. 2000;342(11):770-780.

    Article  PubMed  CAS  Google Scholar 

  11. Durand JB, Bachinski LL, Bieling LC, et al. Localization of a gene responsible for familial dilated cardiomyopathy to chromosome 1q32. Circulation. 1995;92(12):3387-3389.

    Article  PubMed  CAS  Google Scholar 

  12. Fatkin D, MacRae C, Sasaki T, et al. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N Engl J Med. 1999;341(23):1715-1724.

    Article  PubMed  CAS  Google Scholar 

  13. Felker GM, Thompson RE, Hare JM, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000;342(15):1077-1084.

    Article  PubMed  CAS  Google Scholar 

  14. Gerull B, Gramlich M, Atherton J, et al. Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy. Nat Genet. 2002;30(2):201-204.

    Article  PubMed  CAS  Google Scholar 

  15. Gillum RF. Idiopathic dilated cardiomyopathy. Epidemiology. 1994;5(3):383-385.

    Article  PubMed  CAS  Google Scholar 

  16. Grunig E, Tasman JA, Kucherer H, Franz W, Kubler W, Katus HA. Frequency and phenotypes of familial dilated cardiomyopathy. J Am Coll Cardiol. 1998;31(1):186-194.

    Article  PubMed  CAS  Google Scholar 

  17. Hermida-Prieto M, Monserrat L, Castro-Beiras A, et al. Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations. Am J Cardiol. 2004;94(1):50-54.

    Article  PubMed  Google Scholar 

  18. Hoogerwaard EM, Bakker E, Ippel PF, et al. Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in The Netherlands: a cohort study. Lancet. 1999;353(9170):2116-2119.

    Article  PubMed  CAS  Google Scholar 

  19. Ichida F, Tsubata S, Bowles KR, et al. Novel gene mutations in patients with left ventricular noncompaction or Barth syndrome. Circulation. 2001;103(9):1256-1263.

    Article  PubMed  CAS  Google Scholar 

  20. Itoh-Satoh M, Hayashi T, Nishi H, et al. Titin mutations as the molecular basis for dilated cardiomyopathy. Biochem Biophys Res Commun. 2002;291(2):385-393.

    Article  PubMed  CAS  Google Scholar 

  21. 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(6):666-671.

    Article  PubMed  CAS  Google Scholar 

  22. Kamisago M, Sharma SD, DePalma SR, et al. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N Engl J Med. 2000;343(23):1688-1696.

    Article  PubMed  CAS  Google Scholar 

  23. Knoll R, Hoshijima M, Hoffman HM, et al. The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell. 2002;111(7):943-955.

    Article  PubMed  CAS  Google Scholar 

  24. Lapidos KA, Kakkar R, McNally EM. The dystrophin glycoprotein complex: signaling strength and integrity for the sarcolemma. Circ Res. 2004;94(8):1023-1031.

    Article  PubMed  CAS  Google Scholar 

  25. Li D, Parks SB, Kushner JD, et al. Mutations of presenilin genes in dilated cardiomyopathy and heart failure. Am J Hum Genet. 2006;79(6):1030-1039.

    Article  PubMed  CAS  Google Scholar 

  26. Li D, Tapscoft T, Gonzalez O, et al. Desmin mutation responsible for idiopathic dilated cardiomyopathy. Circulation. 1999;100(5):461-464.

    Article  PubMed  CAS  Google Scholar 

  27. Lipskaia L, Pinet C, Fromes Y, et al. Mutation of delta-sarcoglycan is associated with Ca(2+) -dependent vascular remodeling in the Syrian hamster. Am J Pathol. 2007;171(1):162-171.

    Article  PubMed  CAS  Google Scholar 

  28. Mavroidis M, Panagopoulou P, Kostavasili I, Weisleder N, Capetanaki Y. A missense mutation in desmin tail domain linked to human dilated cardiomyopathy promotes cleavage of the head domain and abolishes its Z-disc localization. FASEB J. 2008;22(9):3318-3327.

    Article  PubMed  CAS  Google Scholar 

  29. 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(9221):2119-2124.

    Article  PubMed  CAS  Google Scholar 

  30. McNair WP, Ku L, Taylor MR, et al. SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation. 2004;110(15):2163-2167.

    Article  PubMed  CAS  Google Scholar 

  31. Mirabella M, Servidei S, Manfredi G, et al. Cardiomyopathy may be the only clinical manifestation in female carriers of Duchenne muscular dystrophy. Neurology. 1993;43(11):2342-2345.

    Article  PubMed  CAS  Google Scholar 

  32. Mogensen J, Murphy RT, Shaw T, et al. Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2004;44(10):2033-2040.

    Article  PubMed  CAS  Google Scholar 

  33. Mohapatra B, Jimenez S, Lin JH, et al. Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis. Mol Genet Metab. 2003;80(1–2):207-215.

    Article  PubMed  CAS  Google Scholar 

  34. Moller DV, Andersen PS, Hedley P, et al. The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy. Eur J Hum Genet. 2009;17:1241-1249.

    Article  PubMed  Google Scholar 

  35. Moric-Janiszewska E, Markiewicz-Loskot G. Genetic heterogeneity of left-ventricular noncompaction cardiomyopathy. Clin Cardiol. 2008;31(5):201-204.

    Article  PubMed  Google Scholar 

  36. Morimoto S. Sarcomeric proteins and inherited cardiomyopathies. Cardiovasc Res. 2008;77(4):659-666.

    Article  PubMed  CAS  Google Scholar 

  37. Morimoto S, Lu QW, Harada K, et al. Ca(2+)-desensitizing effect of a deletion mutation Delta K210 in cardiac troponin T that causes familial dilated cardiomyopathy. Proc Natl Acad Sci USA. 2002;99(2):913-918.

    Article  PubMed  CAS  Google Scholar 

  38. Muntoni F, Cau M, Ganau A, et al. Brief report: deletion of the dystrophin muscle-promoter region associated with X-linked dilated cardiomyopathy. N Engl J Med. 1993;329(13):921-925.

    Article  PubMed  CAS  Google Scholar 

  39. Murakami T, Hayashi YK, Noguchi S, et al. Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness. Ann Neurol. 2006;60(5):597-602.

    Article  PubMed  CAS  Google Scholar 

  40. Murphy RT, Mogensen J, Shaw A, Kubo T, Hughes S, McKenna WJ. Novel mutation in cardiac troponin I in recessive idiopathic dilated cardiomyopathy. Lancet. 2004;363(9406):371-372.

    Article  PubMed  CAS  Google Scholar 

  41. Nigro G, Comi LI, Limongelli FM, et al. Prospective study of X-linked progressive muscular dystrophy in Campania. Muscle Nerve. 1983;6(4):253-262.

    Article  PubMed  CAS  Google Scholar 

  42. Noguchi S, McNally EM, Ben Othmane K, et al. Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy. Science. 1995;270(5237):819-822.

    Article  PubMed  CAS  Google Scholar 

  43. Olson TM, Illenberger S, Kishimoto NY, Huttelmaier S, Keating MT, Jockusch BM. Metavinculin mutations alter actin interaction in dilated cardiomyopathy. Circulation. 2002;105(4):431-437.

    Article  PubMed  CAS  Google Scholar 

  44. Olson TM, Kishimoto NY, Whitby FG, Michels VV. Mutations that alter the surface charge of alpha-tropomyosin are associated with dilated cardiomyopathy. J Mol Cell Cardiol. 2001;33(4):723-732.

    Article  PubMed  CAS  Google Scholar 

  45. Olson TM, Michels VV, Thibodeau SN, Tai YS, Keating MT. Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science. 1998;280(5364):750-752.

    Article  PubMed  CAS  Google Scholar 

  46. Pasotti M, Klersy C, Pilotto A, et al. Long-term outcome and risk stratification in dilated cardiolaminopathies. J Am Coll Cardiol. 2008;52(15):1250-1260.

    Article  PubMed  Google Scholar 

  47. Paulin D, Li Z. Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle. Exp Cell Res. 2004;301(1):1-7.

    Article  PubMed  CAS  Google Scholar 

  48. Petersen SE, Selvanayagam JB, Wiesmann F, et al. Left ventricular non-compaction: insights from cardiovascular magnetic resonance imaging. J Am Coll Cardiol. 2005;46(1):101-105.

    Article  PubMed  Google Scholar 

  49. Pilotto A, Marziliano N, Pasotti M, Grasso M, Costante AM, Arbustini E. alphaB-crystallin mutation in dilated cardiomyopathies: low prevalence in a consecutive series of 200 unrelated probands. Biochem Biophys Res Commun. 2006;346(4):1115-1117.

    Article  PubMed  CAS  Google Scholar 

  50. Schmitt JP, Kamisago M, Asahi M, et al. Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science. 2003;299(5611):1410-1413.

    Article  PubMed  CAS  Google Scholar 

  51. Schonberger J, Levy H, Grunig E, et al. Dilated cardiomyopathy and sensorineural hearing loss: a heritable syndrome that maps to 6q23-24. Circulation. 2000;101(15):1812-1818.

    Article  PubMed  CAS  Google Scholar 

  52. 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(4):418-422.

    Article  PubMed  Google Scholar 

  53. Syrris P, Ward D, Evans A, et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. Am J Hum Genet. 2006;79(5):978-984.

    Article  PubMed  CAS  Google Scholar 

  54. Taylor MR, Fain PR, Sinagra G, et al. Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. J Am Coll Cardiol. 2003;41(5):771-780.

    Article  PubMed  CAS  Google Scholar 

  55. Taylor MR, Ku L, Slavov D, et al. Danon disease presenting with dilated cardiomyopathy and a complex phenotype. J Hum Genet. 2007;52(10):830-835.

    Article  PubMed  Google Scholar 

  56. Taylor MR, Slavov D, Gajewski A, et al. Thymopoietin (lamina-associated polypeptide 2) gene mutation associated with dilated cardiomyopathy. Hum Mutat. 2005;26(6):566-574.

    Article  PubMed  CAS  Google Scholar 

  57. Tsubata S, Bowles KR, Vatta M, et al. Mutations in the human delta-sarcoglycan gene in familial and sporadic dilated cardiomyopathy. J Clin Invest. 2000;106(5):655-662.

    Article  PubMed  CAS  Google Scholar 

  58. van Berlo JH, Duboc D, Pinto YM. Often seen but rarely recognised: cardiac complications of lamin A/C mutations. Eur Heart J. 2004;25(10):812-814.

    Article  PubMed  Google Scholar 

  59. van Essen AJ, Busch HF, te Meerman GJ, ten Kate LP. Birth and population prevalence of Duchenne muscular dystrophy in The Netherlands. Hum Genet. 1992;88(3):258-266.

    PubMed  Google Scholar 

  60. van Langen IM, Birnie E, Leschot NJ, Bonsel GJ, Wilde AA. Genetic knowledge and counselling skills of Dutch cardiologists: sufficient for the genomics era? Eur Heart J. 2003;24(6):560-566.

    Article  PubMed  Google Scholar 

  61. Vasile VC, Will ML, Ommen SR, Edwards WD, Olson TM, Ackerman MJ. Identification of a metavinculin missense mutation, R975W, associated with both hypertrophic and dilated cardiomyopathy. Mol Genet Metab. 2006;87(2):169-174.

    Article  PubMed  CAS  Google Scholar 

  62. Vatta M, Mohapatra B, Jimenez S, et al. Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction. J Am Coll Cardiol. 2003;42(11):2014-2027.

    Article  PubMed  CAS  Google Scholar 

  63. Watkins H, McKenna WJ, Thierfelder L, et al. Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. N Engl J Med. 1995;332(16):1058-1064.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands

    G. Aernout Somsen

  2. Cardiologie Centra Nederland / Cardiology Centers of The Netherlands, Amsterdam, The Netherlands

    G. Aernout Somsen

Authors
  1. G. Aernout Somsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Kees Hovingh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. I. Tulevski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jon Seidman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christine E. Seidman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Aernout Somsen .

Editor information

Editors and Affiliations

  1. University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, 3508 GA, Netherlands

    H.F. Baars

  2. University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, 3508 GA, Netherlands

    P.A.F.M. Doevendans

  3. University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, 3508 GA, Netherlands

    J.J. van der Smagt

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag London Limited

About this chapter

Cite this chapter

Somsen, G.A., Hovingh, G.K., Tulevski, I.I., Seidman, J., Seidman, C.E. (2011). Familial Dilated Cardiomyopathy. In: Baars, H., Doevendans, P., van der Smagt, J. (eds) Clinical Cardiogenetics. Springer, London. https://doi.org/10.1007/978-1-84996-471-5_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-84996-471-5_4

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-84996-470-8

  • Online ISBN: 978-1-84996-471-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation