Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Cardiomyopathy, familial hypertrophic form (HCM) [I42.1, I42.2]

OMIM numbers: 192600, 160760 (MYH7), 115195, 191045 (TNNT2), 115197, 600958 (MYBPC3), 613690, 191044 (TNNI3)

Dr. rer. nat. Christoph Marschall

Scientific Background

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant, structural disease of the heart muscle and has a prevalence of approx. 1 in 500 within the Caucasian population. The disease is usually associated with an asymmetrical increase in muscle mass of the left ventricle with the interventricular septum being involved. The consequence is characteristic changes in ECG (q-wave, ST segment, p-wave). The phenotype ranges from benign forms, forms with reduced penetrance to malignant forms with a high risk of sudden cardiac death occurring already during childhood. The average life expectancy is 66 years; however, the prognosis depends on the underlying molecular cause.

So far, approx. 650 mutations in 15 different genes have been identified to cause HCM. All except two of them encode cardiac sarcomeric proteins. More than 85% of all mutations described so far are located in the genes for the ß-myosin heavy chain (MYH7), the myosin binding protein C (MYBPC3), troponin T (TNNT2) and troponin I (TNNI3). Approx. 50% of all mutations can be detected during the first step of the diagnostic procedure, which comprises a search for mutations in 16 exons. The current routine diagnostics enable detection of mutations in approx. 60% of all HCM cases. Deletions of single exons or entire genes are very rare (< 1% of all cases) and are therefore not analyzed.