Mutation screening of sarcomere genes established a genetic diagnosis in approximately 40% of families, with a higher yield in familial HCM (53%) compared to sporadic cases (19%).
Observational (n=451)
Does combined genetic and clinical screening improve diagnostic yield and risk stratification in families with hypertrophic cardiomyopathy compared to clinical evaluation alone?
Mutation screening in HCM families is superior to clinical investigation alone for identifying individuals not at increased risk, allowing 60% of relatives to be safely discharged from follow-up.
Absolute Event Rate: 53% vs 19%
The American Heart Association (AHA) recommends family screening for hypertrophic cardiomyopathy (HCM). We assessed the outcome of family screening combining clinical evaluation and screening for sarcomere gene mutations in a cohort of 90 Danish HCM patients and their close relatives, in all 451 persons. Index patients were screened for mutations in all coding regions of 10 sarcomere genes (MYH7, MYL3, MYBPC3, TNNI3, TNNT2, TPM1, ACTC, CSRP3, TCAP, and TNNC1) and five exons of TTN. Relatives were screened for presence of minor or major diagnostic criteria for HCM and tracking of DNA variants was performed. In total, 297 adult relatives (>18 years) (51.2%) fulfilled one or more criteria for HCM. A total of 38 HCM-causing mutations were detected in 32 index patients. Six patients carried two disease-associated mutations. Twenty-two mutations have only been identified in the present cohort. The genetic diagnostic yield was almost twice as high in familial HCM (53%) vs. HCM of sporadic or unclear inheritance (19%). The yield was highest in families with an additional history of HCM-related clinical events. In relatives, 29.9% of mutation carriers did not fulfil any clinical diagnostic criterion, and in 37.5% of relatives without a mutation, one or more criteria was fulfilled. A total of 60% of family members had no mutation and could be reassured and further follow-up ceased. Genetic diagnosis may be established in approximately 40% of families with the highest yield in familial HCM with clinical events. Mutation-screening was superior to clinical investigation in identification of individuals not at increased risk, where follow-up is redundant, but should be offered in all families with relatives at risk for developing HCM.
Andersen et al. (Tue,) conducted a observational in Hypertrophic cardiomyopathy (n=451). Mutation screening of sarcomere encoding genes vs. Clinical investigation was evaluated on Genetic diagnostic yield in familial HCM vs. sporadic or unclear inheritance. Mutation screening of sarcomere genes established a genetic diagnosis in approximately 40% of families, with a higher yield in familial HCM (53%) compared to sporadic cases (19%).