The future in hypertrophic cardiomyopathy: important clues and potential advances from an understanding of the genotype phenotype relationship.

Hypertrophic cardiomyopathy is a familial heart muscle disorder caused by sarcomeric contractile protein gene abnormalities, nine of which have been recognised to date. The condition has been defined clinically and pathologically as a syndrome of unexplained myocardial hypertrophy, which is associated with characteristic pathophysiological (diastolic dysfunction, ischaemia, altered vascular responses) and pathological (myocyte disarray, increased loose connective tissue, small vessel disease) abnormalities. Disease expression is variable. Preliminary observations suggest that the marked clinical and pathological heterogeneity, which has long caused controversy in hypertrophic cardiomyopathy, is at least, in part, a function of the disease-causing gene. The clinical syndrome of hypertrophic cardiomyopathy can then be seen as nine or more different, but related diseases. Greater understanding of these diseases will require broader application of DNA diagnostic testing, as well as careful and accurate evaluation of the clinical/pathological phenotype of hypertrophic cardiomyopathy.