Estudo clínico-genético em adolescentes e adultos jovens com Síndrome de Williams

Abstract

INTROUCTION: Williams syndrome (WS) is a contiguous gene syndrome with estimated incidence of 1:10,000 births. It happens due to partial loss of a specific region containing about 27 genes on chromosome 7q11.23. Clinical differences among patients with different parental origin or different size of this anomaly have been reported in the literature. PURPOSE: To identify whether clinical or laboratory variability of patients with Williams syndrome correlate with parental origin and size of the loss of genetic material. METHODS: A clinical inventory was developed and applied in 8 patients with Williams syndrome diagnosed by genotyping microsatellite technique to identify size and parental origin of gene loss. RESULTS: The majority of patients have an average loss of 1.55 Mb DNA at 7q11.23, genome area containing some genes with known functions in hemizygosity associated with clinical components of Williams Syndrome. Stand out among these genes, the ELN gene, associated with structural heart disease, the LIMK1 gene, related to visuospatial cognitive deficit, the BAZ1B gene, linked to hypercalcemia, and the STX1A gene, contributing to the predisposition to diabetes in adult patients with syndrome Williams. We identified an atypical case of WS, maintaining biallelism for GTF2IRD1 gene, which is expressed on bone tissue in the embryonic period. The presence of hyperactivity disorder were more frequent in patients with deletion of paternal origin, but the sample size limitation does not allow us to rule out stochastic events. The presence of atypical digital dermatoglyphics in the patient with GTF2IRD1 biallelism may suggest a specific correlation. CONCLUSION: The size and parental origin of genomic abnormality causing the Williams Syndrome can affect the clinical expression of the disease. More reviews of genotype-phenotype correlation for this condition are needed.