genetics

Last reviewed 02/2022

The mode of inheritance of familial hypertrophic cardiomyopathy is typically autosomal dominant with incomplete penetrance.

Linkage analysis has shown that the genetics of hypertrophic cardiomyopathy is heterogenous with four clear loci involved:

• beta myosin heavy chain on chromosome 14 (30% of cases)
• alpha-tropomyosin on chromosome 15 (3% of cases)
• cardiac troponin T on chromosome 1 (15% of cases)
• a locus on chromosome 11

There is no good correlation with the degree of myocardial hypertrophy and the risk of sudden cardiac death. Conversely there may be a good correlation between specific mutations and the risk of sudden death e.g. the Ile79Asn mutation in troponin T results in mild hypertrophy but a high risk of sudden death.

DNA screening in this disease remains complex, time consuming, mainly confined to a few research laboratories, and is not part of routine clinical evaluation.At present, genetic screening identifies the mutation in 50-60% of patients (1).

Reference:

1. BMJ 2006;332:1251-1255.
2. Oakley, C. Heart muscle disease. Medicine International 1993; 21(11):421-6.
3. Watkins, H. et al. Mutations in the genes for troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. New Engl J Med. 1995; 332:1058