Dilation of the Aorta Ascendens Forms Part of the Clinical Spectrum of HCN4 Mutations

Dilation of the ascending aorta was detected in 20 of 26 (77%) HCN4 mutation-positive patients in whom we could obtain images with diagnostic quality sufficient to assess the ascending aorta. Because our data suggested that dilation of the aorta in HCN4 mutation carriers displays an age-dependent penetrance, this was subsequently tested. Because aortic diameter is correlated with age in the general population (where the aortic diameter increases with 0.19 mm/year; p < 2e-16) (4) we used a multiple regression model to assess whether there was an additive effect of HCN4 mutation carriership on increase in aortic dilation with increasing age. [...]we here report on multiple families harboring HCN4 mutations, who show significant dilation of the aorta ascendens, besides the recently established combined phenotype of bradycardia, NCCM, and mitral valve disease.