To analyze the incidence and severity of cardiovascular disease in patients with Williams syndrome (WS) and to identify factors contributing to its variable expression.

Clinical data on patients with WS were collected from several WS centers. Elastin gene deletions were confirmed in all patients. Age at diagnosis, growth data, and cardiovascular diagnoses were recorded retrospectively. Cardiac diagnoses were made on the basis of echocardiographic data. The severity of supravalvular aortic stenosis was recorded by using a 4-step scale (none, mild, moderate, severe).

Statistical analysis of the data revealed that the severity of both supravalvular aortic stenosis and total cardiovascular disease was significantly greater in male patients than female patients (P < .002 and P < .002, respectively; Kruskal-Wallis rank-sum test). This difference was not accounted for by differences in height, weight, body mass index, or head circumference. The clinical diagnosis of WS was made at a significantly younger age in male patients (P < .01, Student t test). Earlier diagnosis was partly because of increased incidence and severity of cardiovascular disease. Another determinant of early diagnosis was low body mass index.

Penetrance and severity of the elastin arteriopathy in patients with WS is affected by sex. We hypothesize that differences by sex in arterial stenoses may be related to prenatal hormonal effects. Future epidemiologic and in vitro studies may provide additional insight into the pathogenetic mechanisms of these observed differences. (J Pediatr 2001;139:849-53)