Early Development in Agenesis of the Corpus Callosum

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Project Summary Neurodevelopmental disorders are abnormalities of brain function and structure resulting from pathologies affecting brain development during fetal development or early life. They may affect behaviour, learning, and motor skills, and are associated with an increased risk of epileptic seizures. The incidence of neurodevelopmental disorders is high in industrialised countries, with around 1 in 6 children affected by resulting conditions, including cerebral palsy, epilepsy, attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability and learning disabilities. Research suggests that the prevalence of certain neurodevelopmental disorders has been increasing over the last four decades, with significant costs to both the individual and society. Although earlier identification and intervention leads to improved outcomes for children with neurodevelopmental disorders, many of these conditions cannot be diagnosed until behavioral symptoms appear, thereby limiting opportunities to study early development and early interventions. To overcome this barrier, we are proposing to study infants with agenesis of the corpus callosum (AgCC) diagnosed prior to 6 months of age. The overarching aim of this application is to characterize the developmental trajectory of behavior during the first 3 years of life in children with AgCC, using this information to identify phenotypic factors associated with increased risk of developmental delays, autism spectrum disorder (ASD), and/or familial distress. 1 in 2000 children is diagnosed with AgCC by 12 months of age, and many of these children receive the diagnosis in utero. AgCC is defined only by neuroanatomy, but about 30% of individuals with AgCC will develop social cognitive deficits consistent with ASD. Because AgCC can be diagnosed before birth, it presents a unique opportunity to learn about early development of social cognitive deficits observed in ASD and related conditions, and the relationship of these developing behaviors to early organization of the corpus callosum. Insights regarding increased risk or protection conferred by early neural and behavioral development in AgCC may inform etiological models of impairment and potentially improve prognostic predictions and treatment options for children at risk for social cognitive deficits including ASD. In addition to their potential contributions to research and treatment of ASD and other forms of social impairment, the studies in this application offer significant public health benefit specific to a heretofore understudied population, children with AgCC and their families. Currently, no published research describes early behavioral development in a large cohort of children with AgCC, despite the fact that it could provide critical information to parents who are determining the future of their unborn fetus with AgCC or determining how to support the development of a child with AgCC. Cohort studies of adults with AgCC reveal a broad range of cognitive and adaptive functioning. These variations appear to be substantially informed by the presence or absence or other neurological abnormalities, but may also be influenced by developmental factors. However, in the absence of research on early behavioral development in children with AgCC, it is not possible to identify risk factors or potential interventions relevant to AgCC, leaving parents with the psychological stress of having a neurologically disabled child whose developmental trajectory is unpredictable. The proposed research will provide practical information for clinicians and parents regarding phenotypic variations in AgCC and suggest areas for potential intervention, as well as novel scientific insights regarding callosal involvement in development of social cognitive deficits.