Genome rearrangements detected by SNP microarrays in individuals with intellectual disability referred with possible Williams syndrome.

Background: Intellectual disability (ID) affects 2-3% of the population and may occur with or without multiple congenital anomalies (MCA) or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for approximately 50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge.

Alpha 1 antitrypsin deficiency alleles are associated with joint dislocation and scoliosis in Williams syndrome.

Elastin haploinsufficiency is responsible for a significant portion of the Williams syndrome (WS) phenotype including hoarse voice, supravalvar aortic stenosis (SVAS), hernias, diverticuli of bowel and bladder, soft skin, and joint abnormalities. All of the connective tissue signs and symptoms are variable in the WS population, but few factors other than age and gender are known to influence the phenotype. We examined a cohort of 205 individuals with WS for mutations in SERPINA1, the gene that encodes alpha-1-antitrypsin (AAT), the inhibitor of elastase.

Inversion of the Williams syndrome region is a common polymorphism found more frequently in parents of children with Williams syndrome.

Williams syndrome (WS) is a multisystem disorder caused by deletion of about 1.55 Mb of DNA (including 26 genes) on chromosome 7q11.23, a region predisposed to recombination due to its genomic structure.