Sudden cardiac death in familial hypertrophic cardiomyopathy: are "benign" mutations really benign?

Pathology. 1997 Aug;29(3):305-8. doi: 10.1080/00313029700169155.

Abstract

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disorder characterised predominantly by left ventricular hypertrophy and sudden cardiac death. Mutations in the cardiac beta-myosin heavy chain gene have been identified in several families and designated as "benign" or "malignant". We describe a family (family L) with a "benign" mutation in which early sudden cardiac death has occurred. The family was studied by clinical, electrocardiographic and echocardiographic assessment. DNA analysis involved screening for the six most common cardiac beta-myosin heavy chain gene mutations using allele specific oligonucleotide probes and restriction enzyme analysis. The Val606Met missense mutation was found. This mutation has been described in four families as being "benign" since it was associated with low penetrance and a near normal life span. Sudden cardiac death was an infrequent finding. In contrast, family L has a more malignant clinical picture with one sudden death in three affected individuals. The proband died suddenly at age 14 years during exercise. Designating gene mutations in FHC as benign or malignant has major clinical implications. As these mutations have only been described in a limited number of families, caution needs to be taken when interpreting genotype-phenotype correlations in this disorder.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiomyopathy, Hypertrophic / genetics*
  • Child
  • DNA Mutational Analysis
  • Death, Sudden, Cardiac / etiology*
  • Genes, Dominant*
  • Genotype
  • Humans
  • Male
  • Myosin Heavy Chains / genetics*
  • Pedigree
  • Phenotype
  • Risk Factors

Substances

  • Myosin Heavy Chains