Familial Williams–Beuren syndrome ascertained by screening rather than targeted diagnosis

Abstract

Williams-Beuren syndrome (WBS), a contiguous gene deletion syndrome, mostly occurs sporadically. Although a few cases of familial WBS have been reported in the literature, molecular confirmation of the deletion has not been carried out in all of them. Here, we report on the eighth clinically and molecularly confirmed inherited WBS detected in a family with 'familial mental retardation.' A comprehensive screening approach to mental retardation that included stepwise karyotyping, assessment for fragile-X syndrome, subtelomeric rearrangements and known microdeletion/microduplication syndromes, and a genome-wide array-CGH study was applied. The father, the mother, and their daughter were all mentally handicapped with nonspecific clinical manifestations and dysmorphic features. The first child of the family died from multiple congenital anomalies. The father and his daughter, who had never been suspected to have WBS, were diagnosed as having a deletion of the WBS critical region. No other abnormalities were detected in the family. Unlike other previously reported cases, in which the disease was ascertained on the basis of clinical manifestations, the present report represents an example of the detection of cryptic chromosomal abnormalities in mental retardation patients by the stepwise application of high-throughput screening methods.