Familial thoracic aortic dilation and bicommissural aortic valve: a prospective analysis of natural history and...

The autosomal dominant inheritance of bicommissural aortic valve (BAV) (Online Mendelian Inheritance in Man #109730) in some families is well-documented; however, the inheritance of BAV with thoracic aortic aneurysm (TAA) is less clear. Whether the aneurysm is secondary to hemodynamic perturbation related to the valve abnormality or a primary manifestation of the disorder remains controversial. Guidelines are needed regarding the follow-up and treatment of these patients and their families. Thirteen families with at least one individual with TAA and BAV (BAV/TAA) were evaluated prospectively by standard echocardiographic methods or clinical history. Affected status was determined by the presence of BAV or TAA or a history of dissection, rupture, or surgical repair. Six of 13 families had at least two family members with both BAV and TAA, often in successive generations. Informatively, all 13 families had at least one family member with TAA in the absence of BAV. Thirty-five percent (39/110) of family members had BAV/TAA or TAA, and the majority of families (11/13) had maximal dilatation above the sinotubular junction (STJ). Vascular dissection or rupture occurred in seven of 13 families and in individuals with structurally normal aortic valves. Two families had non-manifesting, obligate carriers. Three families have members with other left heart outflow tract anomalies. This study confirms autosomal dominant inheritance with incomplete penetrance for BAV/TAA in these families. Furthermore, our data suggest that the component features, BAV and TAA, are independent manifestations of a single gene defect. To avoid the risk of early death, it is essential that all first-degree relatives receive echocardiographic follow-up at regular intervals regardless of the presence or absence of a BAV. This assessment must include imaging of the aortic region above the STJ.