Figure 2: Genetic basis and pathogenesis of BAV and BAV associated aortopathy. The etiology of bicuspid aortic valve/of the thoracic aortic aneurysm appears to be multiple. At the onset of valvulogenesis a number of mechanisms (e.g. Genes, epigenetic factors, fluid forces) may be involved, either alone or combined, in the pathogenesis. The growth of the embryonic outflow tract (OFT, descendant of the second heart field) shortens at specific stages according to programmed cell death. During cardiac valve formation, when the heart is a simple tube, it invades the extracellular matrix to build the endocardial cushions in the OFT. Migratory cells from pharyngeal arches, i.e., neural crest cells, participate and differentiate into VSMCs that populate the interior of semilunar valves, wall of the ascending aorta, aortic arch, and head vessels. Whether mechanisms related to existing aneurysms in BAV are due to genetic heterotopy and/or wall stress induced by flow turbulence late in adulthood requires further investigation.