Does Hypertrophic Cardiomyopathy Run in Families?
Yes, hypertrophic cardiomyopathy (HCM) is definitively a familial disease that runs in families, inherited in an autosomal dominant pattern with a 50% risk of transmission from an affected parent to each offspring. 1
Genetic Basis
HCM is caused by autosomal dominant mutations in genes encoding sarcomere proteins. 1 Eight genes are definitively known to cause HCM: beta myosin heavy chain, myosin binding protein C, troponin T, troponin I, alpha tropomyosin, actin, regulatory light chain, and essential light chain. 1
- A single mutation in one allele is sufficient to cause disease 1
- Approximately 5% of patients have two mutations in the same or different genes 1
- Genetic testing identifies pathogenic mutations in 60-70% of patients with a positive family history and 10-50% of those without a documented family history 1
Clinical Implications for Family Members
All first-degree relatives of HCM patients require systematic screening, as they have a 50% risk of inheriting the disease-causing mutation. 1
Screening Strategy for Relatives
When genetic testing identifies a mutation in the index patient:
- Mutation-positive relatives have substantial (95%) lifetime risk of developing clinical HCM and require ongoing surveillance 1
- Mutation-negative relatives have no risk of developing HCM and do not need further evaluation 1
When genetic testing is not performed or inconclusive, clinical screening intervals are: 1
- Age <12 years: Optional screening unless there is malignant family history, competitive athletics, symptoms, or clinical suspicion 1
- Age 12-18/21 years: Every 12-18 months 1
- Age >18-21 years: At symptom onset or at least every 5 years (more frequently in families with malignant clinical course or late-onset HCM) 1
Important Caveats
HCM shows incomplete penetrance and age-related expression, meaning relatives can develop the disease well into adulthood even after normal adolescent screening. 2 Recent data shows that approximately 5% of child first-degree relatives will meet diagnostic criteria for HCM, with 72% diagnosed by age 12 years. 3 However, late-onset disease occurs, necessitating continued surveillance into mid-life. 2
The diagnostic yield of family screening is approximately 26% at baseline evaluation, with an additional 4% developing HCM during an average of 7 years of follow-up. 4
Genetic Counseling
Genetic counseling should precede genetic testing of family members. 1 This increases understanding of medical and familial implications, enables informed decision-making, and reduces potential psychological responses to learning mutation status. 1
Sporadic Cases
While HCM can appear sporadic (isolated cases), this may reflect inaccurate family history, incomplete penetrance in family members, or de novo mutations that can initiate new familial disease. 1 The true frequency of genuinely sporadic HCM remains unresolved. 1