Epidemiology and Pathophysiology of Mitral Valve Prolapse

Mitral valve (MV) prolapse (MVP) is a common disorder, afflicting 2% to 3% of the general population.1,2 It is characterized by typical fibromyxomatous changes in the mitral leaflet tissue with superior displacement of 1 or both leaflets into the left atrium.3,4 With a prevalence of 2% to 3%, MVP is expected to affect ≈7.8 million individuals in the United States and >176 million people worldwide. MVP can be associated with significant mitral regurgitation (MR), bacterial endocarditis, congestive heart failure, and even sudden death.5–7 MVP is a clinical entity that is not fully understood, despite being known for more than a century. A “midsystolic click” was first described in 1887 by Cuffer and Barbillon.8 In 1963, Barlow and Pocock9 demonstrated the presence of MR by angiography in patients with the “click-murmur” syndrome. Criley et al10 subsequently coined the term MVP. MVP may be familial or sporadic. Despite being the most common cause of isolated MR requiring surgical repair,11 little is known about the genetic mechanisms underlying the pathogenesis and progression of MVP. Studies on the heritable features of MVP have been limited by the analysis of relatively small pedigrees and by self-referral and selection biases, including a preponderance of data from hospital-based cohorts.12,13 Nonetheless, the majority of data favor an autosomal-dominant pattern of inheritance in a large proportion of individuals with MVP.12,13 Despite the variability in clinical features, familial MVP might be considered a prevalent mendelian cardiac abnormality in humans. Although filamin-A has been identified as causing an X-linked form of MVP,14 the causative genes for the more common form of autosomal-dominant MVP have yet to be defined. In this review, we summarize our current knowledge of the diagnosis, epidemiology, prognosis, …