To gain insight into the specificity of cerebellar vermian abnormalities reported in autism, we conducted a magnetic resonance imaging (MRI) study of boys with either of two conditions associated with autism, Down syndrome and fragile X syndrome, compared with boys with idiopathic autism and controls. The subjects, ranging in age from 3 to 9 years, included 16 boys with Down syndrome + autism and 11 boys with Down syndrome only; 13 boys with fragile X syndrome + autism and 9 boys with fragile X syndrome only; 10 boys with idiopathic autism; and 22 controls. Diagnosis of autism was based on DSM-IV criteria, confirmed primarily by the Autism Diagnostic Interview. T1-weighted midsagittal MRIs were used to measure midline structures. Intracranial area, reflecting brain size, was significantly smaller in subjects with Down syndrome. Therefore, all vermian measures were expressed as ratios to intracranial area. Analysis of covariance (covarying for age and IQ) demonstrated that posterior vermi (lobules VI-VII and VIII-X) were markedly smaller in both Down syndrome groups and those with fragile X syndrome only, whereas only lobules VI-VII were reduced in idiopathic autism. Factorial analyses of variance tested interactions between autism factor and the diagnosis of Down syndrome or fragile X syndrome. The size of lobules VI-VII/intracranial area was dependent on autism status only in fragile X syndrome, with ratios significantly larger in fragile X syndrome with autism with respect to fragile X syndrome only. We conclude that selective posterior vermis hypoplasia is seen not only in idiopathic autism but also in Down syndrome and some individuals with fragile X syndrome. However, reductions in vermian lobules VI and VII appear to be specific to idiopathic autism, whereas increased size of lobules VI and VII is associated with autism in fragile X syndrome. The latter results are consistent with MRI studies showing lobules VI-VII hyperplasia in a subset of subjects with idiopathic autism and cerebral and hippocampal enlargements in fragile X syndrome.

Our data suggest that in RTT, autistic behaviour persists after the period of regression. It also demonstrated that neurological and behavioural impairments, including autistic features, are relatively independent of one another. Consistent with previous reports of the RTT phenotype, individual MECP2 mutations demonstrate complex associations with autistic features. Evidence of persistent autistic behaviour throughout childhood, and of a link between hand function and social skills, has important implications not only for research on the RTT behavioural phenotype, but also for the clinical management of the disorder.

BACKGROUND AND PURPOSE:Previous studies have examined volumetric abnormalities in Rett syndrome (RTT), using MR imaging and focusing on selective changes. However, these studies preceded the identification of MECP2 as the gene mutated in most RTT cases. We studied regional brain volume changes as noted by MR imaging in girls with RTT who had mutations in the MECP2 gene and more or less severe clinical outcomes to further characterize the neuroanatomy of RTT and its correlations with clinical severity.

Using voxel-based (VBA) and region-of-interest (ROI) diffusion tensor imaging (DTI) analyses, we examined white matter (WM) organization in 7 children with dyslexia and 6 age-matched controls. Both methods demonstrated reduced fractional anisotropy (FA) in the left superior longitudinal fasciculus (SLF) and abnormal orientation in the right SLF in dyslexics. Application of this complementary dual DTI approach to dyslexia, which included novel analyses of fiber orientation, demonstrates its usefulness for analyzing mild and complex WM abnormalities.