We report a whole-brain MRI morphometric survey of asymmetry in children with high-functioning autism and with developmental language disorder (DLD). Subjects included 46 boys of normal intelligence aged 5.7-11.3 years (16 autistic, 15 DLD, 15 controls). Imaging analysis included grey-white segmentation and cortical parcellation. Asymmetry was assessed at a series of nested levels. We found that asymmetries were masked with larger units of analysis but progressively more apparent with smaller units, and that within the cerebral cortex the differences were greatest in higher-order association cortex. The larger units of analysis, including the cerebral hemispheres, the major grey and white matter structures and the cortical lobes, showed no asymmetries in autism or DLD and few asymmetries in controls. However, at the level of cortical parcellation units, autism and DLD showed more asymmetry than controls. They had a greater aggregate volume of significantly asymmetrical cortical parcellation units (leftward plus rightward), as well as a substantially larger aggregate volume of right-asymmetrical cortex in DLD and autism than in controls; this rightward bias was more pronounced in autism than in DLD. DLD, but not autism, showed a small but significant loss of leftward asymmetry compared with controls. Right : left ratios were reversed, autism and DLD having twice as much right- as left-asymmetrical cortex, while the reverse was found in the control sample. Asymmetry differences between groups were most significant in the higher-order association areas. Autism and DLD were much more similar to each other in patterns of asymmetry throughout the cerebral cortex than either was to controls; this similarity suggests systematic and related alterations rather than random neural systems alterations. We review these findings in relation to previously reported volumetric features in these two samples of brains, including increased total brain and white matter volumes and lack of increase in the size of the corpus callosum. Larger brain volume has previously been associated with increased lateralization. The sizeable right-asymmetry increase reported here may be a consequence of early abnormal brain growth trajectories in these disorders, while higher-order association areas may be most vulnerable to connectivity abnormalities associated with white matter increases.

Background Segmental duplications at breakpoints (BP4–BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or EEG abnormalities. Patients DNA samples from 1,445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children’s Hospital Boston and DNA samples from 1,441 individuals with Autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository. Results We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4–BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4–BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, ADHD, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4–BP5 covers ~1.5Mb (chr15:28.719–30.298Mb) and includes 6 reference genes and 1 miRNA gene, while the smaller duplications cover ~500 kb (chr15:28.902–29.404 Mb) and contain 3 reference genes and one miRNA gene. The BP4–BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG. Conclusions The phenotype of chromosome 15q13.2q13.3 BP4–BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying etiology of this syndrome.

Autism is a neurodevelopmental disorder affecting cognitive, language, and social functioning. Although language and social communication abnormalities are characteristic, prior structural imaging studies have not examined languagerelated cortex in autistic and control subjects. Subjects included 16 boys with autism (aged 7-11 years), with nonverbal IQ greater than 80, and 15 age-and handedness-matched controls. Magnetic resonance brain images were segmented into gray and white matter; cerebral cortex was parcellated into 48 gyral-based divisions per hemisphere. Asymmetry was assessed a priori in language-related inferior lateral frontal and posterior superior temporal regions and assessed post hoc in all regions to determine specificity of asymmetry abnormalities. Boys with autism had significant asymmetry reversal in frontal language-related cortex: 27% larger on the right in autism and 17% larger on the left in controls. Only one additional region had significant asymmetry differences on post hoc analysis: posterior temporal fusiform gyrus (more left-sided in autism), whereas adjacent fusiform gyrus and temporooccipital inferior temporal gyrus both approached significance (more right-sided in autism). These inferior temporal regions are involved in visual face processing. In boys with autism, language and social/face processing-related regions displayed abnormal asymmetry. These structural abnormalities may relate to language and social disturbances observed in autism.

Objective To evaluate the role of copy number abnormalities detectable by chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center. Methods We identified patients with ICD-9 codes for epilepsy or seizures and clinical CMA testing performed between October 2006 and February 2011 at Boston Children’s Hospital. We reviewed medical records and included patients meeting criteria for epilepsy. We phenotypically characterized patients with epilepsy-associated abnormalities on CMA. Results Of 973 patients who had CMA and ICD-9 codes for epilepsy or seizures, 805 patients satisfied criteria for epilepsy. We observed 437 copy number variants (CNVs) in 323 patients (1–4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). Excluding full chromosome trisomies, CNV size ranged from 18 kb to 142 Mb, and 34% were over 500 kb. In at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or “hotspots.” We observed numerous recurrent CNVs including 10 involving loss or gain of Xp22.31, a region described in patients with and without epilepsy. Interpretation Copy number abnormalities play an important role in patients with epilepsy. Given that the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy.