The 25-year genetic era in hypertrophic cardiomyopathy: revisited.

Abstract

Genomics in hypertrophic cardiomyopathy (HCM) are now 25 years old.1,2 The article of Li et al3 in this issue of the journal provides an opportunity to revisit and place into perspective several important principles related to the clinical application of genetic testing to the HCM patient population, thereby assessing progress in understanding this heterogeneous condition, the most common of the inherited heart diseases.4,5 Article see p 416 ### Genetic Testing Perhaps, most important is recognizing the current role achieved by genetic testing in contemporary HCM patient management and family screening. This technology has been available commercially in the United States since 2003, now with 4 fee-for-service companies that have brought advances in genomics for HCM and other genetic diseases out of the research laboratory, and widely available to clinicians.1,2 As a result, the landscape of HCM has changed in several ways. Notable in this regard is the emergence of a new patient subgroup known as gene positive-phenotype negative (ie, genetically affected family members without left ventricular hypertrophy).6 Recognition of relatives who are gene carriers and, therefore, at risk for developing clinical disease demonstrates the power of HCM mutational analysis not otherwise possible. However, the precise likelihood of incurring clinical disease, or the age at which phenotype conversion could occur, remain uncertain with the possibility that some patients will achieve advanced age without developing left ventricular hypertrophy. The most clinically impactful outcome of predictive family screening is the possibility of excluding those relatives without the family mutation from the risk of developing HCM and further clinical consideration.2 However, for such an initiative to be actionable, a pathogenic (disease-causing) mutation must be identified in a family member with clinically expressed HCM (ie, with left ventricular hypertrophy).2 Figure 1. Top , Distribution of genetic test …