SUPRAVALVULAR AORTIC STENOSIS WITHOUT WILLIAMS SYNDROME

Supravalvular aortic stenosis (SVAS) is the major cardiac lesion of Williams Syndrome (WS). WS also has features of mental retardation (MR), characteristic facies and variable hypercalcemia in infancy. Most cases of WS probably represent new autosomal dominant (AD) mutations. Isolated SVAS ± peripheral pulmonic stenosis can occur sporadically, however, when reported to occur in more than one family member, it has been assumed by some (McKusick #19405) to be a mild expression of WS. This has major implications for genetic counseling, cardiac evaluation and for the prognosis of the patient and family. We evaluated 21 members of a 3-generation, 34-member family in which 12 have SVAS documented by ultrasound (US). Four others have SVAS by report of cardiac US done elsewhere. The pedigree was compatible with AD inheritance with high penetrance and variable expression. In 5 tested individuals, the IQ ranged from 102-107; all other members were of normal intelligence by personal observation and interview. No family member had the characteristic facies or other associated findings of WS. This family study, the largest studied to our knowledge, illustrates that isolated SVAS without WS can be inherited as an AD disorder. Although allelic heterogeneity can not be excluded, this family demonstrates that SVAS and WS are separate clinical entities. Relatives of patients with isolated SVAS should be evaluated for mild signs of disease, and families with SVAS can be reassured that occurrence of MR with WS is unlikely to occur.