Comparing phenotypes in patients with idiopathic autism to patients with velocardiofacial syndrome (22q11 DS) with and without autism.

At least three research groups have reported that autism is diagnosed in up to 20% of children with velocardiofacial syndrome (VCFS). However the degree of phenotypic overlap between VCFS-affected children with autism and those with idiopathic autism has not been established. The purpose of this study was to define and differentiate the behavioral phenotype of autism in samples of children with either (VCFS) or idiopathic autism. Five groups of children ages 5-15 were included in the between-group design. Parent report of autism behaviors (based on the Autism Diagnostic Interview-Revised, ADI-R) were compared between children with VCFS, children with VCFS and autism (VCFS + autism), siblings of the children with VCFS, a community control group, and a group of children with idiopathic autism. Autism diagnoses were based according to the ADI-R. Parental responses to the ADI-R indicated that relative to children with VCFS-only, children with idiopathic autism and children with VCFS + autism exhibited less make believe play and more rituals, motor stereotypies and repetitive use of objects. However several other core autism behaviors, including difficulties sharing attention, deficits in gestural communication and initiating conversation, and presence of circumscribed interests, appear to be phenotypic VCFS behaviors, characterizing children with VCFS regardless of an autism diagnosis. Accordingly, the autism phenotype in VCFS differs to some extent from that of idiopathic autism. Several features of idiopathic autism are spared in VCFS, and other features appear to be a function of the VCFS phenotype independent of autism. These findings carry implications for clinicians who diagnose and treat VCFS or autism, and for researchers who study genotype-phenotype associations in autism.

Autistic spectrum disorders in velo-cardio facial syndrome (22q11.2 deletion).

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.

Frontal and caudate alterations in velocardiofacial syndrome (deletion at chromosome 22q11.2).

This study investigated the morphology of the frontal lobe and the caudate nucleus in velocardiofacial syndrome, a neurogenetic disorder caused by a microdeletion at chromosome 22q11.2 and frequently associated with severe psychiatric disturbances. Volumes of the caudate nucleus and subregions of the frontal lobe were compared on magnetic resonance images of 10 children with velocardiofacial syndrome and 10 age- and gender-matched controls. Frontal deep white matter was reduced significantly (by about 23%) in subjects with velocardiofacial syndrome relative to controls. Frontal and prefrontal volumes were also reduced in subjects with velocardiofacial syndrome, although not disproportionately to whole brain volume. The volume of the right caudate nucleus was increased in children with velocardiofacial syndrome. Associations between right caudate and right frontal regions were noted in controls but not in children with velocardiofacial syndrome. These findings suggest frontostriatal dysfunction in children with velocardiofacial syndrome. Insofar as up to 30% of adults with velocardiofacial syndrome (also known as chromosome 22q11 deletion syndrome) develop schizophrenia and frontostriatal dysfunction has been noted in schizophrenia, the findings support the hypothesis that velocardiofacial syndrome might represent a neurodevelopmental model of schizophrenia.

Neuroanatomic variation in monozygotic twin pairs discordant for the narrow phenotype for autism.

OBJECTIVE: The broader autism phenotype includes relatives of individuals with autism who display social and language deficits that are qualitatively similar to those of autism but less severe. In previous studies of monozygotic twins discordant for autism, more than 75% of the twins without autism displayed the broader phenotype. Differences in neuroanatomy between discordant monozygotic twins might be associated with the narrow and broader behavioral phenotypes. The authors examined the relationship of twin pair differences in clinical phenotype to differences in neuroanatomic phenotype. METHOD: The subjects were 16 monozygotic twin pairs between the ages of 5 and 14 years and 16 matched singleton comparison subjects. Seven twin pairs were clinically concordant and nine twin pairs were clinically discordant for strictly defined autism. After magnetic resonance imaging, a semiautomated procedure was applied to images in which the brain tissue was subdivided into neurofunctional regions and segmented into gray, white, and ventricular compartments. RESULTS: Both the concordant and discordant twin pairs exhibited concordance in cerebral gray and white matter volumes. However, only the clinically concordant pairs exhibited concordance in cerebellar gray and white matter volumes. Within the discordant twin pairs, both the twins with autism and their co-twins exhibited frontal, temporal, and occipital white matter volumes that were lower than those of the comparison subjects. CONCLUSIONS: These findings support the role and the limits of genetic liability in autism. Continuing to clarify the neuroanatomic pathways in autistic spectrum disorders could illuminate the etiology of autism and, ultimately, contribute to treatments.