SUDDEN CARDIAC DEATH IN FAMILIAL HYPERTROPHIC CARDIOMYOPATHY - ARE BENIGN MUTATIONS REALLY BENIGN

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant di sorder characterised predominantly by left ventricular hypertrophy and sudden cardiac death. Mutations in the cardiac beta-myosin heavy chai n gene have been identified in several families and designated as ''be nign'' or ''malignant''. We describe a family (family L) with a ''beni gn'' mutation in which early sudden cardiac death has occurred. The fa mily was studied by clinical, electrocardiographic and echocardiograph ic 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 penetran ce 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 i n FHC as benign or malignant has major clinical implications. As these mutations have only been described in a limited number of families, c aution needs to be taken when interpreting genotype-phenotype correlat ions in this disorder.