Cardiovascular manifestations of Williams syndrome: Imaging findings

Summary

Williams syndrome is a relatively common (1 in 10,000 live births) genetic disorder caused by a deletion involving chromosome 7 that results in a variety of clinically significant abnormalities, including developmental delay, behavioral changes, hypercalcemia, and a distinct “elfin” facial appearance. Congenital cardiovascular disease that presents in childhood is responsible for most of the morbidity and mortality associated with this disorder. The purpose of this pictorial essay is to review imaging findings of some of the more common cardiovascular manifestations of Williams syndrome and to highlight some of the unique anatomic variations that can be seen in these patients.

Introduction

Williams-Beuren syndrome, also known as Williams syndrome (WS), is a genetic disorder that affects approximately 1 in every 10,000 live births and involves a wide range of organ systems.¹ It typically presents in childhood with a number of phenotypic abnormalities, including a distinct facial appearance, developmental delay, behavioral changes, and hypercalcemia. However, congenital cardiovascular disease is responsible for most of the morbidity associated with this disorder.¹

The syndrome is the result of a deletion on the long arm of chromosome 7. The affected region of this chromosome includes the elastin gene, which encodes for elastin protein.¹ The ensuing decrease in the synthesis of elastin leads to a number of histologic changes in the vascular wall, including decreased elasticity, thickening of the tunica media, and smooth muscle cell hypertrophy. These changes result in several classic cardiovascular manifestations; the most common of these are supravalvular aortic stenosis (SVAS), hypoplasia of the aortic arch, and pulmonary artery stenosis (PAS).² However, nearly any arterial vessel can be affected. It should be noted that many patients with WS present with multiple vascular anomalies.³

The cardiovascular sequelae of this syndrome put these patients at a significantly increased risk of adverse events and are the principal cause of mortality.1, 4 In fact, a cohort study of 293 patients found a 25 to 100 times higher risk of sudden death in the WS population than with controls.⁴ Surgical treatment is often required in these patients, particularly in patients with significant SVAS.¹ Accordingly, cardiovascular imaging techniques are often required to determine the anatomic characteristics and severity of the lesions seen in these patients.

Although most of these patients are initially evaluated with echocardiography, additional imaging of the coronary and extracardiac anatomy is often warranted to assist in clinical management. Cardiovascular CT angiography (CTA) is an excellent imaging modality for these purposes. Cardiovascular CTA is well validated for visualization and characterization of the coronary and thoracic vasculature and can often be performed rapidly without sedation. Our purpose is to briefly describe the utility of cardiovascular CTA in patients with WS and to review imaging findings of some of the most common cardiovascular manifestations seen in these patients.