Executive dysfunction and the relation with behavioral problems in children with 47,XXY and 47,XXX

Abstract

Neuroimaging studies have shown that having an extra X chromosome is associated with abnormal structure and function of brain areas in the frontal lobe, which is crucially involved in executive functioning. However, there is little of knowledge of the type and severity of executive dysfunction, and the impact on emotional and behavioral problems. The present study aims to provide in this. In total, 40 children (23 boys with 47,XXY and 17 girls with 47,XXX) with an extra X chromosome and 100 non-clinical controls (47 boys and 53 girls) participated in the study. The participants were 9-18 years old. Processing speed and executive functioning were assessed using the Amsterdam Neuropsychological Testbattery (ANT) and the Dysexecutive Questionnaire (DEX). Problems in emotional and behavioral functioning were assessed with the Childhood Behavior Checklist (CBCL). Children with an extra X chromosome showed deficits in inhibition, mental flexibility, sustained attention and visual working memory. Parental report showed high levels of everyday manifestations of executive dysfunction. More severe inhibition difficulties were associated with higher levels of thought problems, aggression and rule breaking behavior. Boys and girls with an extra X chromosome could not be differentiated based on severity of executive dysfunction, however, girls had lower information processing speed than boys. These findings suggest that executive dysfunction may be part of the phenotype of children with an extra X chromosome, impacting the ability to function adequately in everyday life. Furthermore, children with impairments in inhibition may have more problems in regulating their thinking, emotions and behavior.

A review of neurocognitive functioning of children with sex chromosome trisomies: Identifying targets for early intervention

“…The third study used both computerized performance-based tasks as well as parent reports to assess EF in 23 boys with XXY and 17 girls with XXX all aged between 9 and 18 years. 27 This study found no significant differences between the extra X groups and a group of controls on information processing speed, focused attention, or verbal working memory. However, significant group differences were found on measures of sustained attentional control, inhibition, mental flexibility, visual working memory, and daily life EF (as reported by parents).…”

Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders

“…For instance, genes on the sex chromosome may influence neurological diseases by altering the basic differentiation process of the neurons [278], encoding proteins [279], neurotransmitter biosynthesis [26,280] and synaptic transmission [281]. Moreover, sex chromosome abnormalities can influence neurodevelopment and often result in impairments in attention, working memory, verbal skills and executive function [282]. Therefore, the study of sex chromosomes in brain disorders may provide a new angle to understand the sex differences in the pathogeneses of neurodevelopmental and degenerative diseases.…”

Advances in the Interdisciplinary Care of Children with Klinefelter Syndrome

“…Recent research in KS has also linked decreased EF and inhibition to increased behavioral difficulties including aggression, rule-breaking behavior, and thought problems. 92 Neuropsychological and educational assessment in KS should include direct evaluation of EF, and parents and teachers should be educated about behavioral manifestations of EF difficulties, as well as effective interventions and supports, which should be included as part of a comprehensive educational plan.…”

“…5,56,69,92,97–100 As with other associated features, there is broad variability in the presence and severity of these symptoms between individuals with KS. Behavioral and emotional concerns should be screened for routinely, with referrals made for further psychological evaluation and therapy/counseling as needed.…”