MYBPC3 (Myosin-binding protein C) founder mutations account for 35% of hypertrophic cardiomyopathy (HCM) cases in the Netherlands. We compared clinical characteristics and outcome of MYBPC3 founder mutation (FG+) HCM with nonfounder genotype-positive (G+) and genotype-negative (G-) HCM. Methods and Results - The study included 680 subjects: 271 FG+ carriers, 132 G+ probands with HCM, and 277 G- probands with HCM. FG+ carriers included 134 FG+ probands with HCM, 54 FG+ relatives diagnosed with HCM after family screening, 74 FG+/phenotype-negative relatives, and 9 with noncompaction or dilated cardiomyopathy. The clinical phenotype of FG+ and G+ probands with HCM was similar. FG+ and G+ probands were younger with less left ventricular outflow tract obstruction than G- probands, however, had more hypertrophy, and nonsustained ventricular tachycardia. FG+ relatives with HCM had less hypertrophy, smaller left atria, and less systolic and diastolic dysfunction than FG+ probands with HCM. After 8±6 years, cardiovascular mortality in FG+ probands with HCM was similar to G+ HCM (22% versus 14%; log-rank P=0.14), but higher than G- HCM (22% versus 6%; log-rank P<0.001) and FG+ relatives with HCM (22% versus 4%; P=0.009). Cardiac events were absent in FG+/phenotype-negative relatives; subtle HCM developed in 11% during 6 years of follow-up. Conclusions - Clinical phenotype and outcome of FG+ HCM was similar to G+ HCM but worse than G- HCM and FG+ HCM diagnosed in the context of family screening. These findings indicate the need for more intensive follow-up of FG+ and G+ HCM versus G- HCM and FG+ HCM in relatives.

Additional Metadata
Keywords cardiomyopathy, follow-up studies, genotype, hypertrophic, myosins, phenotype
Persistent URL dx.doi.org/10.1161/CIRCGENETICS.116.001660, hdl.handle.net/1765/101871
Journal Circulation: Cardiovascular Genetics
Citation
Van Velzen, H, Schinkel, A.F.L, Oldenburg, R.A, van Slegtenhorst, M.A, Frohn-Mulder, I.M.E, van der Velden, J, & Michels, M. (2017). Clinical Characteristics and Long-Term Outcome of Hypertrophic Cardiomyopathy in Individuals with a MYBPC3 (Myosin-Binding Protein C) Founder Mutation. Circulation: Cardiovascular Genetics, 10(4). doi:10.1161/CIRCGENETICS.116.001660