The uneven landscape of cognitive domains in 22q11.2 deletion syndrome: A large consortium study

22q11.2 deletion syndrome (22q11DS) is strongly associated with aberrant neurodevelopment, including decreased cognitive functioning and schizophrenia spectrum disorders (SSDs). While the different core domains of IQ have distinct clinical ramifications, their collective profile has not been well-characterized in 22q11DS. Here, in the largest 22q11DS sample to date, we elucidate the overall IQ profile, including Verbal and Performance IQ (VIQ and PIQ), Processing Speed (PS), and Working Memory (WM), including associations with developmental stage and SSDs.

We included 1,328 individuals with 22q11DS from the International Brain and Behavior Consortium. We derived an overall IQ profile using VIQ, PIQ, PS, and WM scores at initial assessment, from age-appropriate Wechsler scales. Using both cross-sectional and longitudinal IQ data from a subset (n = 496; 37.35%) of individuals, we examined IQ profiles across three age groups and compared profiles between individuals with and without SSDs.

IQ profiles in 22q11DS exhibited differences between IQ domains (p < 0.001), ranked from relatively strongest to weakest: PS > WM > VIQ > PIQ. This profile was similar across age groups, with scores highest in children, lower in adolescents, and lowest in adults. Individuals without SSDs had higher IQ scores than those with SSDs (p < 0.001), with no significant domain-specific effects.

The results indicate a tendency toward a characteristic IQ profile in 22q11DS, regardless of SSD status. A clinical implication of these divergent IQ domains, in particular the relative weakness in PIQ, is that functional expectations are likely to be overestimated. The domain-specific differences across age-groups highlight the need for repeated and comprehensive cognitive assessments in this high-risk population, and may suggest differing underlying mechanisms that require further investigation.