Abstract 5717: Cardiovascular Abnormalities and Outcomes in a Large Williams Syndrome Cohort
Background: Williams syndrome (WS) is a congenital developmental disorder caused by microdeletion of approximately 28 genes on chromosome 7q11.23, affecting the vascular, connective tissue, and central nervous systems of 1 in 8,000 live births. Previous reports have reported high frequencies of cardiovascular abnormalities (CVA) in small cohorts of patients with WS.
Methods: A retrospective review was undertaken of patients (pts) with WS evaluated at the Children’s Hospital of Philadelphia from 1/1/1980 through 12/31/2007. WS was diagnosed by the clinical phenotype assessed by an experienced medical geneticist and/or by fluorescence in situ hybridization. Congenital CVA were diagnosed by echocardiography and/or cardiac catheterization. Freedom from intervention was determined using Kaplan-Meier analysis.
Results: Two hundred and seventy two pts were identified and constituted the study group. Pts presented to our center at 5.2 ± 8.2 yrs with an average length of follow-up of 8.2 ± 7.8 yrs (0 – 43 yrs). Congenital CVA were present in 220/272 (81%) pts. The commonest lesions were supravalvar (SV) aortic stenosis (AS) in 120/272 (44%) and branch pulmonary stenosis (PS) in 84/272 (31%); 44/272 (16%) had both. Other common lesions included mitral valve prolapse and regurgitation in 32/272 (12%), VSD in 30/272 (11%), and SVPS in 29/272 (11%). A number of other CVA occurred with frequencies less than 10%. Surgical or catheter-based interventions were performed in 55/220 (25%) pts with CVA. SVAS most commonly required intervention (28/120 pts, 23%). Branch PS was second with 13/84 (15%). Freedom from intervention in all pts with CVA was 91, 78, 75, 69, and 66% at 1, 5, 10, 20, and 40 years, respectively. Death occurred in 7 pts with an average of 1 death per 345 pt-yrs.
Conclusion: Though CVA are common in WS, in this, the largest cohort ever reported analyzing CVA and outcomes, SVAS and branch PS occur less frequently than previously reported. In WS pts with CVA, interventions are commonly required and usually occur by 5 years of age. Most WS pts do not require intervention on long-term follow-up and overall mortality in these pts is low.