Medical overview and genetics of Williams-Beuren syndrome

Williams-Beuren syndrome (WBS) is a multisystem genetic disorder caused by a microdeletion on chromosome 7. The majority of patients demonstrate cardiovascular pathology, most commonly supravalvular aortic and/or other vascular stenoses. Progressive stenosis can occur and, furthermore, ∼ 50% of WBS patients develop hypertension. Although the absolute risk for life-threatening cardiovascular complications is low, certain constellations of problems such as severe biventricular outflow disease increase the relative risk of adverse outcomes. Many additional medical problems complicate WBS such as feeding difficulties, colic and irritability, slow physical growth, abnormal dentition, constipation, and a variety of endocrine abnormalities. All patients with WBS have intellectual handicaps. Most patients function in the range of moderate mental retardation and also demonstrate a characteristic cognitive profile of strengths and weaknesses; notably most individuals with WBS develop anxieties and phobias. The typical, albeit subtle, facial dysmorpology of WBS in conjunction with one or more of the above problems should prompt fluorescence in situ hybridization (FISH) laboratory testing to confirm deletion of one copy of the elastin gene. Almost all WBS patients have the same size microdeletion on one chromosome 7 resulting in loss of one copy of ∼ 20 genes. The role these genes play in causing the complex WBS phenotype is actively being studied in several research laboratories. Patients with WBS require long-term care and guidelines for medical management and anticipatory guidance are offered.