From the Guidelines
Genetic testing is a crucial component in the management of hypertrophic obstructive cardiomyopathy (HOCM), as it facilitates the identification of disease-causing mutations, guides clinical care, and informs family screening and preventive strategies. According to the most recent guidelines, genetic testing is beneficial for patients with HOCM to elucidate the genetic basis of the disease and to identify family members at risk of developing HOCM 1. The initial tier of genes tested should include those with strong evidence of being disease-causing in HOCM, such as MYH7, MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, and ACTC1 1.
Key Points to Consider
- Genetic testing can confirm the diagnosis, enable preclinical diagnosis, and guide reproductive decisions in patients with HOCM 1.
- Cascade genetic testing in the family can identify those who carry the disease-causing variant and require ongoing surveillance, while those who do not carry the variant can be released from lifelong clinical surveillance 1.
- Pretest and posttest genetic counseling are essential to ensure that patients understand the benefits and potential harms of genetic testing, as well as the implications of the results for themselves and their family members 1.
- Genetic testing can provide prognostic insights, as certain mutations correlate with disease severity, risk of sudden cardiac death, and response to treatments 1.
Recommendations for Clinical Practice
- Genetic testing should be offered to patients with HOCM to identify specific genetic variants and guide clinical care.
- First-degree relatives of patients with HOCM should undergo clinical screening and cascade genetic testing if a pathogenic or likely pathogenic variant has been identified in the proband 1.
- Genetic counseling should be provided before and after genetic testing to help patients understand the implications of the results and to discuss the potential benefits and harms of testing 1.
From the Research
Role of Genetic Testing in HOCM
- Genetic testing is a valuable tool in the diagnosis and management of patients and families with hypertrophic cardiomyopathy (HCM) 2, 3, 4.
- It can help identify causative variants in 30 to >60% of patients, with the probability of a positive test varying with baseline characteristics such as known family history of HCM 2.
- Genetic testing can inform diagnosis and differentiate HCM from other disorders that also result in increased left ventricular wall thickness, directly impacting treatment 3.
- Positive genetic testing can clarify diagnosis and assist in family screening, and if a pathogenic or likely pathogenic variant is identified, predictive genetic testing is recommended for at-risk relatives 2, 3, 4.
Challenges and Considerations
- Interpreting test results can be complex and requires expertise in understanding human genetic variation and clinical manifestations of the disease 2, 3.
- Genetic testing results can have psychological and other implications for patients and their families, emphasizing the importance of genetic counseling before and after genetic testing 3.
- Determining the clinical relevance of genetic testing results is also complex and requires a multidisciplinary team approach 2.
Risk Stratification and Management
- Genetic testing can play a role in guiding risk stratification and management, with emerging evidence suggesting a role for prognosis and patient management 4.
- Genotype may play a greater role in risk stratification, management, treatment, and prognosis in the future, offering improved outcomes for patients and their families with HCM 4.
- Patients with HCM should be assessed for their risk of sudden death, regardless of severity of symptoms or morphology, and factors predictive of risk should be considered 5.