Heredity of bicuspid aortic valve: is family screening indicated?

Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation with a prevalence of 1% and occurs when the aortic valve has only two cusps instead of the normal three.1 BAV is a common cause of adult valve disease and accounts for the majority of acquired valvular disease in industrialised countries.2 In cases of BAV, the normally thin aortic valve cusps often prematurely calcify leading to valvular thickening and stenosis.3 These malformed valves may also present with aortic regurgitation and are at increased risk for infective endocarditis.4 BAV not only affects valvular function but is also associated with aortic and pulmonary root dilatation.5 Thoracic aorta aneurysm (TAA) is found in up to 50% of people with a BAV and may result in the development of aortic dissection.6 BAV is thus becoming increasingly recognised as an important contributor to adult cardiovascular disease, and the genetic basis of the BAV is actively being investigated. Cardiac valve development begins when the heart is a simple tube, and at this time the extracellular matrix thickens to form the endocardial cushions in the common outflow tract. The endocardial cushions with a contribution from migrating cardiac neural crest cells undergo remodelling to form the aortic and pulmonary valves together with the proximal aortic and pulmonary walls. These initial stages of valve formation involve multiple signalling molecules including members of the TGFβ, Ras, Wnt/β-catenin, VEGF and NOTCH signalling families.7 The leaflet primordia then divide into three separate cusps for each great vessel. When this process goes awry in the aorta, two leaflet primordia do not separate or remain fused, resulting in BAV. Fusion between the right and left coronary cusps occurs most frequently while fusion of the right coronary and non-coronary cusps is the next most common location …