Genetic Basis of Familial Valvular Heart Disease

Abstract

Valvular heart disease (VHD) is a major cause of morbidity and premature death from cardiovascular diseases, making it an important clinical entity. Despite a dramatic decline in the incidence of rheumatic heart disease in industrialized countries, VHD remains highly prevalent. Although many VHDs are acquired during adult life, familial clustering and heritability have been noted for common heart valve defects, such as bicuspid aortic valve and myxomatous mitral valve prolapse, denoting an underlying genetic basis. Over the past decade, advances in our understanding of the genetic basis of familial VHD have been made through the unraveling of gene network and molecular mechanisms regulating normal valve development. Important progress has also arisen from a series of elegant studies that have focused on linkage analyses of large families with VHD, transgenic animal models, in vitro studies, and, more recently, microRNA and transcriptomic assessment of diseased tissues. Identification of the genes and molecular pathways responsible for the development of VHD has important implications in terms of improving current therapeutic strategies, as well as guiding the management of at-risk family members, with the ultimate aim to reduce the health burden of VHD. This article will summarize the current state of knowledge regarding the genetic basis of 2 common familial VHDs, namely mitral valve prolapse and bicuspid aortic valve, and highlight some of the recent findings that shed light on the pathogenesis of these diseases. Valvular heart disease (VHD) is a major cause of disability, diminished quality of life, and premature death from cardiovascular disease,1 making it an important clinical entity. Despite a dramatic decline in the incidence of rheumatic heart disease in industrialized countries, VHD remains highly prevalent.2 Although many VHDs are acquired during adult life, congenital forms present with abnormal valve structures at birth, yet may not manifest as valvular dysfunction …