Progress in familial hypertrophic cardiomyopathy: molecular genetic analyses in the original family studied by Teare.

In this journal in 1958 Donald Teare reported the pathological findings in a series of eight unrelated young adults who died suddenly and who at necropsy had manifested gross asymmetrical hypertrophy of the heart.' In a footnote, he noted the recent sudden death of the brother of one of the original cases, thus identifying the familial nature of this condition. The subsequent report2 of two generations of the family of these two siblings showed that asymmetrical hypertrophy was inherited in a manner consistent with an autosomal dominant trait. The term "obstructive cardiomyopathy" was proposed for these and similar cases, identifying this as a heart muscle disorder. The description of this family initiated the detailed characterisation of this novel syndrome, which was later called familial hypertrophic cardiomyopathy. Demonstration of a mendelian form of inheritance implied that familial hypertrophic cardiomyopathy was the result of a single gene disorder. Despite 30 years of investigation, however, the pathogenesis of this condition is only now being revealed. Molecular biological techniques were used to identify first the location3 and later the identity4 5 of genetic defects responsible for familial hypertrophic cardiomyopathy. The identification of mutations in the cardiac myosin heavy chain (MHC) genes has made familial hypertrophic cardiomyopathy the first primary cardiac disorder to be characterised at the molecular level. An abnormality of the f myosin heavy chain gene is also responsible for disease in the original family described by Teare; we discuss here the benefits of such a genetic diagnosis.