Cognitive, adaptive and behavioral profile in Sotos syndrome children with 5q35 microdeletion or intragenic variants

Sotos syndrome (SoS) is a congenital overgrowth syndrome with variable degree of intellectual disability caused in the 90% of cases by pathogenetic variants of the Nuclear receptor binding SET Domain protein1 (NSD1) gene. NSD1 gene functions can be abrogated by different genetic alterations (i.e., small intragenic pathogenic variants like deletions/insertions, nonsense/missense pathogenic variants, partial gene deletions and whole deletions or microdeletion of 5q35 chromosomal region). Therefore, correlation of the genotype–phenotype with a possible contribution of more implicated genes to the medical, cognitive and behavioral profile is a topic of great interest. Although a more severe learning disability has been described in individuals with 5q35 microdeletion when compared to individuals with NSD1 intragenic pathogenic variants a fully delineated cognitive and behavioral phenotype has not been described yet. The importance of providing clinical characterization in relation to the genotype comes from the necessity to early identify children more at risk of developing psychopathological disorders. We characterize the cognitive, adaptive and behavioral phenotype of a pediatric sample of 64 individuals affected by SoS, performing a standardized neuropsychological evaluation. Secondly, we compare cognitive‐behavioral profiles of SoS individuals carrying and not carrying the 5q35 microdeletion. SoS participants were characterized by a mild cognitive impairment of both Intellectual Quotient and adaptive skills in association to borderline symptoms of attention deficit. Our results suggest that the 5q35 microdeletion is associated with lower scores specifically concerning the cognitive, adaptive functioning and behavioral domains. However, longitudinal studies are necessary to confirm these findings and delineate a developmental trajectory of SoS.