WILLIAMS-BEUREN SYNDROME - PHENOTYPIC VARIABILITY AND DELETIONS OF CHROMOSOME-7, CHROMOSOME-11, AND CHROMOSOME-22 IN A SERIES OF 52 PATIENTS

Fluorescence in situ hybridisation (FISH) and conventional chromosome analysis were performed on a series of 52 patients with classical Will iams-Beuren syndrome (WBS), suspected WBS, or supravalvular aortic ste nosis (SVAS). In the classical WBS group, 22/23 (96%) had a submicrosc opic deletion of the elastin locus on chromosome 7, but-the remaining patient had a unique interstitial deletion of chromosome 11 (del(11) ( q13.5q14.2)). In the suspected WBS group 2/22 (9%) patients had elasti n deletions but a third patient had a complex karyotype including a ri ng chromosome 22 with a deletion of the long arm (r(22)(p11-->q13)). I n the SVAS group, 1/7 (14%) had an elastin gene deletion, despite havi ng normal development and minimal signs of WBS. Overall, some patients with submicroscopic elastin deletions ha ve fewer features of William s-Beuren syndrome than those with other cytogenetic abnormalities. The se results, therefore, emphasise the importance of a combined conventi onal and molecular cytogenetic approach to-diagnosis and suggest that the degree to which submicroscopic deletions of chromosome 7 extend be yond the elastin locus may explain some of the phenotypic variability found in Williams-Beuren syndrome.