[Supravalvular aortic stenosis: clinical and genetic study of a family group]

We describe a family with a high frequency of supravalvular aortic stenosis. The family includes 5 generations and 80 subjects (prospective study in 66, on whom physical examination, ECG, M-mode and two-dimensional echocardiogram were performed, and retrospective analysis of available data in 14). This is the largest family group with this disease studied so far. Thirty-six subjects (45%) were found to be affected. On the basis of the echocardiographic image and of the haemodynamic gradient (when available), three different degrees of supravalvular aortic stenosis were identified. The disease was found to be severe in 8 subjects (22%), moderate in 6 (17%), mild in 13 (36%) and undefined in 8 (22%). In 4 cases multiple pulmonary stenoses were associated with supravalvular aortic stenosis, while in one subject multiple pulmonary stenoses were noted in the absence of aortic abnormalities. In the family we studied, the supravalvular aortic stenosis gene is transmitted with a pattern of inheritance consistent with an autosomal dominant trait with variable expressivity and penetrance (penetrance coefficient = 0.86). A high mortality rate in early childhood was observed, while symptoms and ECG abnormalities were not related to the degree of the stenosis. Furthermore, we found a high rate of mitral valve echocardiographic abnormalities, such as mitral prolapse and systolic anterior motion. The absence of Williams dysmorphic somatic features in the many generations as well as in the large number of patients we studied, appears to exclude the coexistence of Williams and Eisenberg's syndromes in the same family group.