Autism in patients with Williams-Beuren syndrome: A re-evaluation of 31 Tunisian patients’ phenotype

Abstract

Background Williams Beuren Syndrome is a multisystemic disorder manifested by congenital heart defects associated with dysmorphic features, intellectual delay, and a particular behavioural profile due to a microdeletion in 7q11.2. Methods To establish a genotype-phenotype correlation; we carried out a molecular cytogenetic analysis on 31 Tunisian WBS patients using the CGH-array and FISH techniques. Results 6 patients were investigated by CGH-array. All of them had a typical WBS deletion ranging from 1.4Mb to 1.7Mb. Curiously in 2 patients autistic spectrum disorders were noted in contrast to the behavioural profile generally observed in the other patients which are characterized by good contact. If we analyse the distal region of the generally deleted region, we found that the HIP1 gene is included. HIP1 encodes a central nervous system expressed protein and is considered the candidate gene for autism in this region. Conclusion Considering the presence of autism, a CGH analysis is essential to determine the exact etiology of this disorder, which seems strange for this syndrome, but is becoming progressively frequent. We suggest that alteration of the HIP1 gene could be indirectly responsible for autism, but specific environmental factors might act as risk factors triggering the development of this trait...