Hypertrophic Cardiomyopathy - Genetics

Genetics

Familial hypertrophic cardiomyopathy is inherited as an autosomal dominant trait and is attributed to mutations in one of a number of genes that encode for one of the sarcomere proteins.

About 50-60% of patients with a high index of clinical suspicion for HCM will have a mutation identified in at least 1 of 9 sarcomeric genes. Approximately 45% of these mutations occur in the β myosin heavy chain gene on chromosome 14 q11.2-3, while approximately 35% involve the cardiac myosin binding protein C gene. Since HCM is typically an autosomal dominant trait, children of an HCM parent have 50% chance of inheriting the disease-causing mutation. Whenever a mutation is identified through genetic testing, family-specific genetic testing can be used to identify relatives at-risk for the disease (HCM Genetic Testing Overview).

In individuals without a family history of HCM, the most common cause of the disease is a de novo mutation of the gene that produces the β-myosin heavy chain.

An insertion/deletion polymorphism in the gene encoding for angiotensin converting enzyme (ACE) alters the clinical phenotype of the disease. The D/D (deletion/deletion) genotype of ACE is associated with more marked hypertrophy of the left ventricle and may be associated with higher risk of adverse outcomes .

Some mutations (troponin) have much more malignant potential compared to others (β myosin heavy chain). For example, troponin T mutations are associated with a 50% mortality before the age of 40.