Parental Education Predicts Longitudinal IQ Trajectories in 22q11.2 Deletion Syndrome: A Three-Cohort European Study.

Background: 22q11.2 deletion syndrome (22q11DS) is a genetic disorder characterised by a wide range of physical, cognitive, and psychiatric symptoms. Current knowledge on 22q11DS highlights considerable variation in cognitive outcomes, but the role of environmental factors in shaping these trajectories over time remains poorly understood.

Aims: This study investigates how environmental factors contribute to variability in intelligence quotient (IQ) among individuals with 22q11DS across three European cohorts. By examining these influences over time, the research aims to identify potential drivers of IQ differences and uncover modifiable factors that may support improved cognitive outcomes in individuals with 22q11DS.

Methods: Data were collected from 297 individuals with 22q11DS across three European cohorts. Cognitive assessments included full-scale IQ (FSIQ), verbal IQ (VIQ) and performance IQ (PIQ). Environmental measures encompassed parental education, sleep, stress and substance use, gathered through questionnaires and interviews. Baseline associations between environmental measures and IQ were evaluated with ANOVA at the first assessment. To examine within-person IQ change across three visits, we used linear mixed-effects models.

Results: We found a significant decline in FSIQ, VIQ and PIQ over time, with linear trends observed for all three measures. Parental education, particularly the father's education, explained a significant proportion of the variance of all IQ-based measures.

Conclusions: Parental education emerged as a key predictor of IQ, suggesting that socioeconomic factors contribute to cognitive performance variability in individuals with 22q11DS. Even in high-penetrance genetic variants, such as the 22q11.2 deletion, environmental factors and gene-environment interactions may make significant contributions to the severity of phenotypes.