The extent to which the phenotype of children comorbid for velocardiofacial syndrome (VCFS) and autism spectrum disorders (ASD) differs from that of VCFS-only has not been studied. The sample consisted of 41 children (20 females) with VCFS, ranging in age from 6.5 years to 15.8 years. Eight children with VCFS met formal DSM-IV diagnostic criteria for autism based upon the ADI-R. These eight plus an additional nine participants met diagnostic criteria for an autistic spectrum disorder (VCFS + ASD). Ninety-four percent of the children with VCFS + ASD had a co-occurring psychiatric disorder while 60% of children with VCFS had a psychiatric disorder. Children with VCFS + ASD had larger right amygdala volumes. All other neuroanatomic regions of interest were statistically similar between the two groups.

Ninety-two children with velocardiofacial syndrome (VCFS), a genetic disorder caused by a microdeletion of chromosome 22q11.2 and an age, race and gender-ratio comparable sample of 59 control participants were included in the project. Participants received a MRI as well as a comprehensive neuropsychological battery; the primary outcome measure in the current report is the Rey-Osterrieth Complex Figure (ROCF). Children with VCFS performed less well on the ROCF and have lower whole brain volume compared to controls. After controlling for whole brain volume differences, children with VCFS have bilaterally less parietal lobe gray and white matter yet more frontal lobe white matter. Brain -behavior relationships include: (a) for both groups, parietal volumes (both gray and white matter) predicted ROCF Copy Organization performance and frontal volumes (both gray and white matter) predicted ROCF Copy Accuracy performance; (b) for controls, frontal white matter also predicted ROCF Copy Organization performance; (c) ROCF Recall Organization performance was best predicted by frontal gray matter volume only in our controls; ROCF Recall Accuracy performance was best predicted by frontal gray matter volume in both groups; and (d) in children with VCFS, performance on the ROCF-Copy Structural Elements Accuracy scale was predicted by right hemisphere white matter volume. Our hypotheses were also retested using IQmatched and whole brain volume-matched subsamples. Identical results were obtained in these analyses. Assumptions about the organization of and the localization of the brain structures that subserve specific cognitive functions in the typically developing brain may not apply in the abnormally developing brain. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptVelocardiofacial syndrome (VCFS), a chromosomal deletion disorder of 22q11.2 (3 Mb, 25-30 genes) affects 1 in 2000-5000 individuals . The deletion syndrome is associated with multiple congenital anomalies, including cardiac malformations, hearing loss, hypocalcaemia, velopharyngeal insufficiency and cleft palate (Ryan et al., 1997). Phenotypic facial abnormalities include a long face, pear-shaped nose, small ears with overfolded helicies, and vertically narrow eyes (Antshel et al., 2005). VCFS is associated with cognitive and developmental delays and the vast majority of children with VCFS experience academic difficulties, especially in math (Simon et al., 2002;Swillen et al., 1997;Swillen et al., 1999). Executive functioning deficits including difficulties shifting attention and a poorly developed working memory have also been indicated (Woodin et al., 2000). Most, but not all, children with VCFS exhibit deficits in abstract and nonverbal reasoning and visuospatial abilities (Moss et al., 1999). Some have hypothesized that VCFS is an exemplar of the nonverbal learning disability (NLD; Rourke et al., 2002;Swillen et al., 1999).The VCFS behavioral phenotype includes poor social skills, introversion, disinhibition, impulsivity, anxiet...