Background Bicuspid aortic valve (BAV) is the commonest valvular congenital heart defect, affecting around 1% of the population. BAV shows strong familial clustering and is thought to be inherited as an oligogenic, autosomal dominant trait with incomplete penetrance. Guidelines recommend cascade screening of first degree relatives of patients with BAV using echocardiography but the effectiveness of this approach is unknown. Incomplete penetrance can negatively influence screening programs leading to non-detection of silent carriers.
Aim To assess the prevalence of incomplete penetrance of BAV among families with the familial form of the disease.
Methods Consecutive patients with a diagnosis of BAV presenting to Glenfield Hospital, Leicester were recruited. First degree relatives were screened for the presence of BAV using transthoracic echocardiography. In families with at least two affected individuals, screening was extended to second-degree relatives.
Results 425 participants were recruited to the study (298 with BAV, 127 unaffected relatives). 16 multigenerational pedigrees with multiple affected subjects were identified. Incomplete penetrance was observed in three of sixteen pedigrees (19%), meaning that echocardiographic screening demonstrated the absence of BAV in a particular generation and the presence of BAV in the subsequent generation of the same lineage
Conclusions Incomplete penetrance is common in pedigrees with familial forms of BAV. This phenomenon may reduce the effectiveness of cascade screening for BAV using echocardiography alone as it fails to identify silent carriers. A better understanding of the genetics of familial BAV might lead to improvements in the effectiveness of cascade screening programmes for the condition.
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