Abstract 840: Genetic Screening Adds Important Clinical Benefits To Clinical Screening Of Adult Relatives In Families With Hypertrophic Cardiomyopthy
BACKGROUND Family screening is recommended for hypertrophic cardiomyopathy (HCM). We assessed the outcome of family screening by combining clinical investigation and screening for sarcomere gene mutations in a cohort of ninety Danish HCM index patients and their close relatives, a total of 451 persons.
METHODS Index patients were screened for mutations by single strand conformation polymorphism analysis and DNA sequencing in all coding regions of 10 sarcomere genes (MYH7, MYBPC3, TNNT2, TPM1, TNNI3, MYL2, MYL3, ACTC, TCAP, CSRP3) and 5 exons of titin (TTN). Relatives were screened for minor or major diagnostic criteria for HCM.
RESULTS Thirty-eight HCM-causing mutations were detected in 32 index patients. Six patients carried two disease-associated mutations. In a total of 297 adult relatives (>18 years), 51.2% fulfilled one or more criteria for HCM (Table⇓). The genetic diagnostic yield was 53% in familial HCM vs. 19% in HCM of sporadic or unclear inheritance. The yield was highest in families with a history of HCM-related clinical events. Of relatives from carrier families 59% had no mutation and could be reassured and further follow-up ceased. Thirty percent of relatives carrying a mutation did not fulfil any clinical diagnostic criterion. In addition, 37.5% of relatives without a mutation fulfilled one or more criterion.