Cognitive, Behavioral, and Adaptive Profiles in Williams Syndrome With and Without Loss of GTF2IRD2

Williams syndrome (WS) is a neurodevelopmental disorder that results from a heterozygous microdeletion on chromosome 7q11.23. Most of the time, the affected region contains similar to 1.5 Mb of sequence encoding approximately 24 genes. Some 5-8% of patients with WS have a deletion exceeding 1.8 Mb, thereby affecting two additional genes, including GTF2IRD2. Currently, there is no consensus regarding the implications of GTF2IRD2 loss for the neuropsychological phenotype of WS patients. Objectives: The present study aimed to identify the role of GTF2IRD2 in the cognitive, behavioral, and adaptive profile of WS patients. Methods: Twelve patients diagnosed with WS participated, four with GTF2IRD2 deletion (atypical WS group), and eight without this deletion (typical WS group). The age range of both groups was 7-18 years old. Each patient's 7q11.23 deletion scope was determined by chromosomal microarray analysis. Cognitive, behavioral, and adaptive abilities were assessed with a battery of neuropsychological tests. Results: Compared with the typical WS group, the atypical WS patients with GTF2IRD2 deletion had more impaired visuospatial abilities and more significant behavioral problems, mainly related to the construct of social cognition. Conclusions: These findings provide new evidence regarding the influence of the GTF2IRD2 gene on the severity of behavioral symptoms of WS related to social cognition and certain visuospatial abilities.