Clinical significance of prolonged QTc interval in Williams syndrome.

Williams syndrome (WS) is a congenital developmental disorder affecting the connective tissue, neurologic, and cardiovascular (CV) systems in 1 in 8,000 live births. The characteristic features of WS, including facial dysmorphisms, cognitive traits, and CV abnormalities, are known to arise from the deletion of approximately 28 genes on chromosome 7q11.23. Structural CV abnormalities occur most commonly and are present in approximately 80% of all patients with WS, and 93% of those presenting in the first year of life. The most common CV abnormalities in WS include arterial stenoses such as supravalvar aortic stenosis and peripheral pulmonary arterial stenosis, resulting from hemizygosity of the ELN gene, which encodes elastin. There is also a known increased risk for sudden cardiac death in this population that is 25-fold to 100-fold greater than in the general population. In a review of the published research, Burch et al surmised the sudden death risk to be essentially entirely the result of myocardial ischemia, especially in the setting of concomitant supravalvar aortic stenosis and stenosis of the coronary ostia. Kounis et al proposed that sudden cardiac death in WS may be related to an allergic coronary syndrome secondary to anesthetic exposure, and a recent report by Gupta et al has given credence to that hypothesis. In an attempt to evaluate potential prolongation of the corrected QT (QTc) interval noted on electrocardiography in patients with WS, and to correlate electrocardiographic findings with sudden death, we recently published the experience at the Children’s Hospital of Philadelphia in The American Journal of Cardiology. In that study, the prevalence of QTc prolongation in patients with WS was 13.6%, compared to a prevalence of 2% in healthy controls. Death occurred in 4 patients with WS, 2 of whom had evidence of QTc prolongation. An autopsy on 1 of the patients with QTc prolongation demonstrated no evidence of supravalvar aortic stenosis or stenosis of the coronary ostia; the other patient died at an outside facility, and an autopsy was not performed. A third patient with QTc prolongation sustained a sudden cardiac event but was resuscitated and placed on extracorporeal membrane oxygenation support with ultimate recovery.