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In people with velo-cardio-facial syndrome [or 22q11.2 deletion syndrome (22qDS)], a single interstitial deletion of chromosome 22q11.2 causes a wide spectrum of cognitive deficits ranging from global learning difficulties to specific cognitive deficits. People with 22qDS are also at high risk of developing attention-deficit/hyperactivity disorder and autism spectrum disorders in childhood, and schizophrenia in adolescence or adult life. However, the neurobiology of 22qDS, and the relationship between abnormalities in brain anatomy and behaviour, is poorly understood. Thus, we studied the neuroanatomy of 22qDS children using fully automated voxel-based morphometry (VBM) and manually traced single region-of-interest (ROI) analysis. Also, we investigated whether those brain regions that differed significantly between groups were related to behavioural differences within children with 22qDS. We compared the brain morphometry of 39 children and adolescents with 22qDS (mean age: 11 years, SD +/-3, IQ = 67, SD +/-10) and 26 sibling controls (mean age: 11 years, SD +/-3, IQ = 102, SD +/-12). Using VBM, we found, after correction for IQ, that individuals with 22qDS compared with controls had a significant reduction in cerebellar grey matter, and white matter reductions in the frontal lobe, cerebellum and internal capsule. Using single ROI analysis, we found that people with 22qDS had a significant (P &lt; 0.05) reduction in bulk volume bilaterally in the occipital-parietal lobes, but a larger right caudate nucleus and lateral ventricles. Further, within people with 22qDS, there was a significant positive correlation between severity of (i) schizotypy score and grey matter volume of the temporo-occipital regions and the corpus striatum; (ii) emotional problems and grey matter volume of frontostriatal regions; and (iii) social behavioural difficulties and grey matter in frontostriatal regions. Thus, subjects with 22qDS have widespread changes in brain anatomy, particularly affecting white matter, basal ganglia and cerebellum. Also, within 22qDS, regionally specific differences in brain development may partially underpin behavioural differences. We suggest that there is preliminary evidence for specific vulnerability of the frontostriatal and cerebellar-cortical networks in 22qDS.

Brain and behaviour in children with 22q11.2 deletion syndrome: a volumetric and voxel-based morphometry MRI study