Bicuspid Aortic Valve: a Review with Recommendations for Genetic Counseling

Abstract

Bicuspid aortic valve (BAV) is the most common congenital heart defect and falls in the spectrum of left-sided heart defects, also known as left ventricular outflow tract obstructive (LVOTO) defects. BAV is often identified in otherwise healthy, asymptomatic individuals, but it is associated with serious long term health risks including progressive aortic valve disease (stenosis or regurgitation) and thoracic aortic aneurysm and dissection. BAV and other LVOTO defects have high heritability. Although recommendations for cardiac screening of BAV in at-risk relatives exist, there are no standard guidelines for providing genetic counseling to patients and families with BAV. This review describes current knowledge of BAV and associated aortopathy and provides guidance to genetic counselors involved in the care of patients and families with these malformations. The heritability of BAV and recommendations for screening are highlighted. While this review focuses specifically on BAV, the principles are applicable to counseling needs for other LVOTO defects.

Clinical and pathophysiological aspects of bicuspid aortic valve disease

“…The final development of the semilunar valves is a complex interplay between the second heart field cells and the neural crest cells, where the rudimentary aortic valve leaflets are shaped by neural crest cells that create "cavities" in the rudimentary valve. 4,6 If the cavities are not created, the cusps will be fused. 4,6 It is hypothesised that right coronary and non-coronary cusp fusion is caused by defective morphogenesis of the outflow tract tissue before "valve cavitation", whereas perturbations in the neural crest cell behaviour result in the lack of "cavitation" and thereby right and left coronary cusp fusion occurs.…”

Bicuspid aortic valve syndrome: a multidisciplinary approach for a complex entity

“…In cardiac valve morphogenesis there are multiple signaling pathways involved, such as members of the TGF-β superfamily, VEGF, Notch, Wnt/β-catenin, bx20, and Gata4 (32). Many other genes, including genes involved in connective tissue disorders, cell signaling, and the extracellular matrix, have also been associated to BAV.…”

“…Many other genes, including genes involved in connective tissue disorders, cell signaling, and the extracellular matrix, have also been associated to BAV. The alteration of these pathways may produce or be related to BAV and studies developed in mouse models are contributing to clarify the new BAV candidate genes role (32).…”

Sudden cardiac death and valvular pathology

“…With age, degenerative alterations may aggravate the valve deformation, causing stenosis and/or insufficiency. Both the valvulopathy and the aortopathy may lead to unexpected sudden death [1,[13][14][15][16][17].…”