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 < 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.

Adults with ASD have significant differences from controls in the anatomy of brain regions implicated in behaviours characterizing the disorder, and this differs according to clinical subtype.

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Women with autistic-spectrum disorder have significant differences in brain anatomy from controls, in brain regions previously reported as abnormal in adult men with the disorder. Some anatomical differences may be related to clinical symptoms.

Turner syndrome (TS) is a model for X-chromosome influences on neurodevelopment because it is most commonly caused by absence of one X-chromosome, and associated with altered brain structure and function. However, all prior in vivo magnetic resonance imaging studies of the brain in TS have either used manual approaches or voxel-based-morphometry (VBM) to measure cortical volume (CV). These methods, unlike surface-based-morphometry (SBM), cannot measure the two neurobiologically distinct determinants of CV– cortical thickness (CT) and surface area (SA) – which have differing genetic determinants, and may be independently altered. Therefore, in 24 adults with X-monosomy and 19 healthy female controls, we used SBM to compare (i) lobar CV, CT and SA, (ii) an index of hemispheric gyrification (iii) CT throughout the cortical sheet, and (iv) CT correlation between cortical regions. Compared to controls, females with TS had (i) significantly increased CT and decreased SA in parietal and occipital lobes (resulting in no significant difference in lobar CV), (ii) reduced hemispheric gyrification bilaterally, (iii) foci of significantly increased CT involving inferior-temporal, lateral-occipital, intraparietal sulcus (IPS), cingulate, and orbito-frontal cortices, (iv) significantly reduced CT correlation between the left IPS and cortical regions including supramarginal and lateral-occipital gyri. Our findings suggest that females with TS have complex, sometimes ‘opposing’, abnormalities in SA/gyrification (decreased) and CT (increased); which can result in no overall detectable differences in CV. Thus haploinsufficiency of X-chromosome genes, may differentially impact the distinct mechanisms shaping SA (e.g. cortical folding) and CT (e.g. dendritic arborization/pruning). CT disruptions are maximal within and between cortical regions previously implicated in the TS cognitive phenotype.