Genetics in bicuspid aortic valve disease: Where are we?

Abstract

Bicuspid aortic valve (BAV) is the most common congenital heart defect, found in up to 2% of the population and associated with a 30% lifetime risk of complications. BAV is inherited as an autosomal dominant trait with incomplete penetrance and variable expressivity due to a complex genetic architecture that involves many interacting genes. In this review, we highlight the current state of knowledge about BAV genetics, principles and methods for BAV gene discovery, clinical applications of BAV genetics, and important future directions.

Keywords: Aortic aneurysm; Bicuspid aortic valve; Congenital heart disease; Genetics.

Figure 1.. Cellular contributions to the formation of the outflow tract.

The outflow tract is formed by three cell lines: cardiac neural crest cells (blue), vascular smooth muscle cells (dotted yellow) and second heart field-derived myocardium (striped yellow). Inset shows endothelial (yellow oval) to mesenchymal (dark oval) transition in the endocardial cushions. Ao, aorta; PA, pulmonary artery; SHF, second heart field. Adapted from Martin et al and Kovacic et al^, .

Figure 2.. Family-based analysis

Kindred with five generations affected by bicuspid aortic valve (yellow square), coarctation of the aorta (green square) and thoracic aortic aneurysm (blue square) demonstrates reduced penetrance and variable expressivity that is characteristic of BAV pedigrees. Squares, males; circles, females; slashed, deceased family members; dark filled, affected; +, presence of mutation; −, absence of mutation. Adapted from Garg et al.