Williams-Beuren Syndrome (WBS) [Q93]
OMIM number: 194050
Dr. med. Imma Rost
The Williams-Beuren syndrome (WBS) is characterized by a combination of cardiovascular abnormalities, primarily by supravalvular aortic stenosis (SVAS) and/or (peripheral) pulmonary stenosis(es), a moderate developmental delay, typical physical and behavioural features. Furthermore, renal artery stenosis occurs with development of arterial hypertension. Based on the physical features (periorbital fullness, medial eyebrow flare, blue stellate irides, full lips, especially the lower lip, micrognathia, hoarse voice, small widely spaced teeth), a visual diagnosis is possible at an early stage. In infants and toddlers, failure to thrive and digestive disorders are frequently observed. Hernias as well as hyperextensibility of the joints are signs of connective tissue weakness. 50% of all patients exhibit a temporary hypercalcemia. Despite their developmental delay, WBS patients show remarkable skills and behavioural patterns. As children, they are rather shy, later very sociable and articulative with good musical skills. They have weaknesses especially in visuo-motoric coordination such as the recognizing of patterns.
WBS is caused by a microdeletion of 1.5 to 1.8 mb in size within the long arm of chromosome 7 (7q11.23). This area contains 28 genes. The haploinsufficiency of the elastin gene is responsible for the cardiovascular signs such as SVAS. The loss of the genes LIMK1, CLIP2, GTF2IRD1 und GTF2I is thought to cause the characteristic physical and cognitive features. The microdeletion and therefore the WBS usually occurs sporadically; however, occasionally there are parent-to-child transmissions that follow an autosomal dominant inheritance. Frequency is 1:7,500 to 1:20,000.