Bicuspid aortic valve (BAV) is the most common congenital valvular heart defect with an overall frequency of 0.5%–1.2%. BAVs result from abnormal aortic cusp formation during valvulogenesis, whereby adjacent cusps fuse into a single large cusp resulting in two, instead of the normal three, aortic cusps. Individuals with BAV are at increased risk for ascending aortic disease, aortic stenosis and coarctation of the aorta. The frequent occurrence of BAV and its anatomically discrete but frequent co-existing diseases leads us to suspect a common cellular origin. Although autosomal-dominant transmission of BAV has been observed in a few pedigrees, notably involving the gene NOTCH1, no single-gene model clearly explains BAV inheritance, implying a complex genetic model involving interacting genes. Several sequencing studies in patients with BAV have identified rare and uncommon mutations in genes of cardiac embryogenesis. But the extensive cell-cell signaling and multiple cellular origins involved in cardiac embryogenesis preclude simplistic explanations of this disease. In this review, we examine the series of events from cellular and transcriptional embryogenesis of the heart, to development of the aortic valve.
Bibliographical noteFunding Information:
This work was supported by a National Institutes of Health grants 1R01HL114823 (SCB), 1P30GM103342 (RAN), 8P20GM103444-07 (RAN), R01HL127692 (RAN, DM), American Heart Association 15GRNT25080052 (RAN).
© 2015 by the authors; licensee MDPI, Basel, Switzerland.
- Aortic incompetence
- Aortic stenosis
- Aortic valve
- Bicuspid aortic valve
- Congenital heart disease
- Heart development
PubMed: MeSH publication types
- Journal Article