CART Pilot Project: Neural Basis of Autistic Spectrum Disorders in 22q11.2 Deletion Syndrome

Project summary

Defined genetic syndromes with characteristic neurobehavioral phenotypes offer a rare opportunity for investigating linkages between genes, neurobiology, and behavior. The 22q11.2 deletion syndrome (Velocardiofacial/DiGeorge syndrome) is a neurogenetic syndrome characterized by multiple central nervous system anomalies, as well as extremely high rates of autistic spectrum disorders (~14-50%). Even children with 22qDS who do not meet formal criteria for autism share many characteristics of autistic disorders, including stereotypic behaviors, sensory hyperacuity, and marked social skills deficits, and almost 100% have significant receptive and expressive language delays. However, there is considerable variability in the 22qDS phenotype, suggesting that genetic variation in the intact chromosome may modify phenotypic expression. Here we will compare children with 22qDS with and without autistic spectrum diagnoses, using novel brain imaging methods. Specifically, our aims are:

  1. To clarify the nature of information-processing abnormalities in 22q-ASD, using a comprehensive cognitive battery and functional MRI paradigm of emotion-processing, and to determine the relationship of these functional measures to brain structural anomalies
  2. To elucidate the neural bases of cognitive and quantitative behavioral traits associated with the autism phenotype.

Characterizing the structural and functional brain anomalies that distinguish children with 22qDS with autistic features from those without such features can improve our understanding of the necessary and sufficient conditions for the development of autistic spectrum disorders. These neural and cognitive differences will be examined, in future studies, in relation to variability in deletion size and to hemizygous allelic variability in genes within the deletion region. This information, in turn, will provide insights into genetic mechanisms underlying the neurodevelopmental processes that lead to the development of autistic spectrum disorders, in both individuals affected with 22qDS and in the broader population.

Primary Investigator: 
Carrie Bearden, Ph.D.