Ronen Durst, M.D., Cardiology Department, Hadassah Hebrew University Medical Center. Jerusalem, Israel
Valve diseases are very common and are the cause of considerable morbidity and mortality. Some of these diseases were shown to have a strong heritability index. Such is the case for mitral valve prolapse (MVP) and bicuspid aortic valve (BAV) which together affect approximately 3.5% of the population. Both demonstrate mostly autosomal dominant inheritance with variable penetrance. Both BAV and MVP demonstrate considerable functional changes that may lead to regurgitation, arrhythmias, bacterial endocarditis, congestive heart failure, and even sudden death. In spite of being very common diseases very little is known on the pathophysiology and underlying mechanisms of valve diseases. The only treatment for these diseases is surgical in nature, which may lead to considerable lifelong complications.
Valvular diseases may be part of a more generalized syndromes. Such is the case of Marfan's disease and MVP and Turner's syndrome and BAV. The genetic etiology of non-syndromic BAV and MVP is beginning to be understood by familial based positional cloning studies and GWAS. Major pathways related to valve disease development were discovered this way. TGF ß signaling pathway mutation has been linked to MVP pathophysiology. Notch1 signaling has been related to BAV.
Clinically, it is important to understand the genetic etiology of valve diseases because they may suggest that familial cascade screening is advisable to detect early undiagnosed cases and potentially prevent complications. Currently, only surgical interventions are proven efficacious in treating valve disease. However, better understanding of valve disease aetiology may suggest new therapeutic targets that may be approach pharmacologically.