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. 1998 Mar;35(3):183–188. doi: 10.1136/jmg.35.3.183

Counselling issues in familial hypertrophic cardiomyopathy.

B Yu 1, J A French 1, R W Jeremy 1, P French 1, D R McTaggart 1, M R Nicholson 1, C Semsarian 1, D R Richmond 1, R J Trent 1
PMCID: PMC1051239  PMID: 9541100

Abstract

To illustrate the variable clinical presentations and rates of progression in familial hypertrophic cardiomyopathy (FHC), phenotypes and genotypes were compared in three FHC families with different genetic defects. In the first family, the FHC abnormality was a protein truncating mutation (Gln969X) in the cardiac myosin binding protein C gene. The second family had a missense change (Asn755Lys) in the same gene. A missense mutation (Arg453Cys) in the cardiac beta myosin heavy chain gene was present in the third family. Penetrance associated with the Gln969X defect was 27% in the age range 0 to 40 years. This was considerably less than the 93% penetrance (0 to 40 years) observed in the two families with missense mutations. The variable penetrance in FHC, as well as the unpredictability of sudden cardiac death, complicates clinical diagnosis and management, including genetic counselling. Although a genetic disease with a predominantly adult onset, there are counselling issues in FHC which set it aside from other adult onset disorders.

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Selected References

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  1. Anan R., Greve G., Thierfelder L., Watkins H., McKenna W. J., Solomon S., Vecchio C., Shono H., Nakao S., Tanaka H. Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy. J Clin Invest. 1994 Jan;93(1):280–285. doi: 10.1172/JCI116957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Autore C., Fragola P. V., Picelli A., Maccari A. M., Ruscitti G., Cannata D., Sangiorgi M. Equivocal and borderline myocardial hypertrophy in relatives of patients with hypertrophic cardiomyopathy: possible implications in genetics of the disease. Cardiology. 1988;75(5):348–356. doi: 10.1159/000174398. [DOI] [PubMed] [Google Scholar]
  3. Clarke A. The genetic testing of children. Working Party of the Clinical Genetics Society (UK) J Med Genet. 1994 Oct;31(10):785–797. doi: 10.1136/jmg.31.10.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davies M. J., McKenna W. J. Hypertrophic cardiomyopathy--pathology and pathogenesis. Histopathology. 1995 Jun;26(6):493–500. doi: 10.1111/j.1365-2559.1995.tb00267.x. [DOI] [PubMed] [Google Scholar]
  5. Fananapazir L., Epstein N. D. Genotype-phenotype correlations in hypertrophic cardiomyopathy. Insights provided by comparisons of kindreds with distinct and identical beta-myosin heavy chain gene mutations. Circulation. 1994 Jan;89(1):22–32. doi: 10.1161/01.cir.89.1.22. [DOI] [PubMed] [Google Scholar]
  6. Harper P. S., Clarke A. Should we test children for "adult" genetic diseases? Lancet. 1990 May 19;335(8699):1205–1206. doi: 10.1016/0140-6736(90)92713-r. [DOI] [PubMed] [Google Scholar]
  7. Kimura A., Harada H., Park J. E., Nishi H., Satoh M., Takahashi M., Hiroi S., Sasaoka T., Ohbuchi N., Nakamura T. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. Nat Genet. 1997 Aug;16(4):379–382. doi: 10.1038/ng0897-379. [DOI] [PubMed] [Google Scholar]
  8. MacRae C. A., Ghaisas N., Kass S., Donnelly S., Basson C. T., Watkins H. C., Anan R., Thierfelder L. H., McGarry K., Rowland E. Familial Hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3. J Clin Invest. 1995 Sep;96(3):1216–1220. doi: 10.1172/JCI118154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Maron B. J., Kragel A. H., Roberts W. C. Sudden death in hypertrophic cardiomyopathy with normal left ventricular mass. Br Heart J. 1990 May;63(5):308–310. doi: 10.1136/hrt.63.5.308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Maron B. J., Shirani J., Poliac L. C., Mathenge R., Roberts W. C., Mueller F. O. Sudden death in young competitive athletes. Clinical, demographic, and pathological profiles. JAMA. 1996 Jul 17;276(3):199–204. [PubMed] [Google Scholar]
  11. McKenna W. J., Deanfield J. E. Hypertrophic cardiomyopathy: an important cause of sudden death. Arch Dis Child. 1984 Oct;59(10):971–975. doi: 10.1136/adc.59.10.971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McKenna W. J., Spirito P., Desnos M., Dubourg O., Komajda M. Experience from clinical genetics in hypertrophic cardiomyopathy: proposal for new diagnostic criteria in adult members of affected families. Heart. 1997 Feb;77(2):130–132. doi: 10.1136/hrt.77.2.130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Poetter K., Jiang H., Hassanzadeh S., Master S. R., Chang A., Dalakas M. C., Rayment I., Sellers J. R., Fananapazir L., Epstein N. D. Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. Nat Genet. 1996 May;13(1):63–69. doi: 10.1038/ng0596-63. [DOI] [PubMed] [Google Scholar]
  14. Ryan M. P., French J., al-Mahdawi S., Nihoyannopoulos P., Cleland J. G., Oakley C. M., Harper P. S., Clarke A., Davis J., Grigg L. Genetic testing for familial hypertrophic cardiomyopathy in newborn infants. BMJ. 1995 Apr 1;310(6983):856–859. doi: 10.1136/bmj.310.6983.856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Schwartz K., Carrier L., Guicheney P., Komajda M. Molecular basis of familial cardiomyopathies. Circulation. 1995 Jan 15;91(2):532–540. doi: 10.1161/01.cir.91.2.532. [DOI] [PubMed] [Google Scholar]
  16. Smart R. V., Yu B., Le H., French J. A., Richmond D. R., Jeremy R. W., Semsarian C., Cheung L., Ross D. A., Trent R. J. DNA testing in familial hypertrophic cardiomyopathy: clinical and laboratory implications. Clin Genet. 1996 Oct;50(4):169–175. doi: 10.1111/j.1399-0004.1996.tb02621.x. [DOI] [PubMed] [Google Scholar]
  17. Spirito P., Seidman C. E., McKenna W. J., Maron B. J. The management of hypertrophic cardiomyopathy. N Engl J Med. 1997 Mar 13;336(11):775–785. doi: 10.1056/NEJM199703133361107. [DOI] [PubMed] [Google Scholar]
  18. Watkins H., McKenna W. J., Thierfelder L., Suk H. J., Anan R., O'Donoghue A., Spirito P., Matsumori A., Moravec C. S., Seidman J. G. Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. N Engl J Med. 1995 Apr 20;332(16):1058–1064. doi: 10.1056/NEJM199504203321603. [DOI] [PubMed] [Google Scholar]
  19. Watkins H., Rosenzweig A., Hwang D. S., Levi T., McKenna W., Seidman C. E., Seidman J. G. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med. 1992 Apr 23;326(17):1108–1114. doi: 10.1056/NEJM199204233261703. [DOI] [PubMed] [Google Scholar]
  20. Yu B., French J. A., Carrier L., Jeremy R. W., McTaggart D. R., Nicholson M. R., Hambly B., Semsarian C., Richmond D. R., Schwartz K. Molecular pathology of familial hypertrophic cardiomyopathy caused by mutations in the cardiac myosin binding protein C gene. J Med Genet. 1998 Mar;35(3):205–210. doi: 10.1136/jmg.35.3.205. [DOI] [PMC free article] [PubMed] [Google Scholar]

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