Abstract 20016: Genetic Anticipation in Familial Hypertrophic Cardiomyopathy

Introduction: To identify HCM at the earliest time possible, estimating the onset of disease based on diagnostic criteria is vital in timing the initiation of screening and interventions. Hypothesis: Clinic observations indicate an early diagnose of HCM in second generation of most affected families. From the pedigrees with or without mutations in beta-myosin heavy chain gene (MYH7) affected in two or more generations with hypertrophic cardiomyopathy (HCM), ages and maximal wall thickness (MWT) of left ventricles at diagnosis were evaluated to investigate the potential genetic anticipation in patients with familiar HCM (FHCM). Methods: 56 individuals from 25 families were analyzed. Linear mixed effects models were adopted to prevent misinterpretation resulting from the cohort effect. Published data containing 9 sarcomere mutations (181 individuals in 52 families) also were extracted. Results: MYH7 mutations were detected in 9 of the 25 probands, The median age of HCM diagnosis was 24 in the younger generation and 55 in the older (p < 0.001). In the parametric model, the estimated change in the expected age at diagnosis for the entire cohort was 25.8 years (p <0.001). Statistically significant earlier ages at diagnoses were also observed within subgroups of MYH7+ and MYH7- mutations, and probands older and younger than 30 years old. Although the estimated change in MWT at diagnosis for the entire cohort was only 2.161 mm (p =0.212), the subgroup of probands in the younger generation aged less than 30 years had 10.393 mm (p=0.018) thicker MWT and showed a significant reverse correlation with age. Analysis of published data also supports these findings. Conclusions: Genetic anticipation was observed in patients with FHCM. FHCM is prone to be diagnosed at an earlier age in younger generations. Patients who are younger with relatives affected by HCM, especially those who are diagnosed before 30 years of age, should continue to be tracked to offer appropriate screening modalities as earlier as possible.