Congenitally bicuspid aortic valves. Clinicogenetic study of 41 families.

Abstract

SUMMARYThe families of 41 patients with surgically proved isolated bicuspid aortic valves were examined. There were 275 first degree relatives of whom 220 were living, and 188 (85.5%) of thesewere examined. Seven first degree relatives were found to have aortic valve disease, and in a further 11 there was 'doubtful' evidence of bicuspid aortic valves. In 6 families there was more than 1 affected member and in an additional 7 families there was 1 or more 'doubtful' first degree relative. The minimum family incidence was therefore 14-6 per cent, or 31-7 per cent if 'doubtful' cases were included. The inheritance is most probably multifactorial, but occasionally the condition may occur as an autosomal dominant.The difficulties of diagnosing bicuspid aortic valves before the development of obstruction of left ventricular outflow were encountered and are discussed. The association of a bicuspid aortic valve with asymmetric septal hypertrophy, hypertrophic cardiomyopathy, and Marfan's syndrome was also noted. Peacock (1866) was the first to recognise the role of congenitally bicuspid aortic valves in the development of aortic stenosis, but he neither appreciated the frequency of this lesion nor realised that most cases of isolated aortic stenosis were congenital. The delay in recognition of the prevalence of bicuspid aortic valves has been partly caused by difficulty in diagnosis before the development of stenosis with the clinical signs of obstruction to left ventricular outflow; this may not occur until the third or fourth decade or even later, by which time the bicuspid nature of the valve has often become obscured by calcification. Koletsky (1941) reported a frequency of 0-54 per cent from 3300 consecutive necropsies and Roberts (1970) 0 9 per cent from 1440 necropsies. These figures, if representative, suggest that the incidence for all types of congenital heart disease in the population usually quoted as between 0 7 and 1-0 per cent may be an underestimate 'Present address:

Whole Exome Sequencing for Familial Bicuspid Aortic Valve Identifies Putative Variants

“…On the basis of large multiplex families with BAV, autosomal dominant inheritance with reduced penetrance has been proposed, [15][16][17] but only 2 genes, KCNJ2 18 and NOTCH1, 19 that account for <5% of BAV cases have been identified. Reasons to explain this apparent lack of success include that there are many genes involved in cardiac valve development (genetic heterogeneity), a focus on protein-changing variants in known candidate genes, and mounting evidence that BAV exhibits complex inheritance (ie, may not be because of a single genetic variant).…”

Diagnosis and Treatment of Bicuspid Aortic Valve Disease

“…Generally, a genetic multifactorial inheritance and an autosomal dominant condition are observed. Emanuel et al (11) determined the minimum familial incidence of bicuspid aorta to be 14.6%. Latest studies have shown that the prevalence in the immediate family of an individual with BAV is 9.1%.…”

Clinical and Genetic Aspects of Bicuspid Aortic Valve: A Proposed Model for Family Screening Based on a Review of Literature

“…39 The first systematic study on cardiological screening in asymptomatic relatives of BAV patients, to our knowledge, was published in 1978. 40 The authors screened 188 first-degree relatives of 41 BAV patients by auscultation and eccentricity index. BAV was diagnosed in 3.7-9.6% of the relatives and was familial in 14.6-31.7% of the 41 families (depending on the inclusion of doubtful cases).…”