Bicuspid Aortic Valve and Thoracic Aortic Aneurysm: Three Patient Populations, Two Disease Phenotypes, and One Shared Genotype

Figure 5

Hypothetical model of shared complex genotype in BAV-TAA. Multiple susceptibility genes exist for both BAV and TAA, and some of these genes are common to both phenotypes (yellow letters, Normal). An unaffected genotype might have 8 BAV susceptibility genes (a–d, j–m) and 8 TAA susceptibility genes (j–m, w–z), 4 in common (j–m). If the manifestation of each phenotype is dependent on a liability threshold of predisposing variants, for example, greater than or equal to 3 variants, then there are multiple ways in which an individual may realize an affected status (BAV, TAA, BAV-TAA), and the specific pattern of variants may contribute to phenotypic variability. Importantly, this model does not take into account the likely importance of additional insults (epigenetic modifiers, environmental factors) that may be necessary for phenotype manifestation.