PHENOTYPE OF THE WILLIAMS-BEUREN SYNDROME-ASSOCIATED WITH HEMIZYGOSITY AT THE ELASTIN LOCUS

To correlate presence or absence of a 7q11 microdeletion with the clin ical picture of the Williams-Beuren syndrome (WBS), we investigated 29 patients with a clinical diagnosis of WBS or WBS-like features, aged 1-30 years, using molecular analysis and/or fluorescent in situ hybrid ization (FISH). Deletions at 7q11 were found in 75% of the patients (2 2 out of 29). Nine deletions occurred on a paternal, and ten on a mate rnal chromosome; three deletions were demonstrated by FISH only, and p arental origin could thus not be determined. All deletion patients age d between 2 years and puberty displayed a distinct pattern of facial f eatures (including periorbital fullness, short nose with flat bridge, wide mouth, and full lips and cheeks), the characteristic outgoing soc ial behaviour, as well as moderate growth and mental retardation. Two- thirds (15 out of 22) had a cardiovascular malformation, but only one third (7 of 22) had supravalvular aortic stenosis (SVAS). A stellate i ris pattern was also present in one-third of the patients only. In the four adult patients with 7q11 deletions, there was prominence of the lower lip whereas fullness of cheeks and periorbital tissue was not se en. Conclusion This study confirms that WBS has a unique clinical pict ure which can be diagnosed clinically, but also shows that the relativ e frequency of individual features may have been overemphasized in the past, and that a minority of patients may exist who are clinically in distinguishable from WBS but who appear to have no deletion at 7q11.