This past year the Neurodevelopmental and Behavioral Phenotyping Service conducted over 200 neurodevelopmental assessments and focused on collection and analyses of data from a variety of rare genetic disorders associated with intellectual disability and autism spectrum disorder. Much of the data analyzed has been collected through a protocol that includes behavioral assessments (NCT00271622) and a collaborative protocol that includes assessment of specific rare genetic conditions (NCT02461420). We are investigators on these and several other multi-site studies that are conducting behavioral phenotyping of conditions that have yet to have their natural histories fully explored, including Phelan-McDermid Syndrome, Williams Syndrome, Moebius Syndrome, propionic acidemia, creatine transport deficiency, holoprocencephaly, congenital disorders of glycosylation and other diagnosed and undiagnosed conditions that affect neurodevelopment early in life. These characterization studies are necessary for beginning to understand the breadth and depth of syndromes that cause lifelong impairments, based on developmental delays that often lead to Intellectual Disability and Autism Spectrum Disorder (ASD). Related to these goals, we seek to take advantage of gains made in identification of genetic abnormalities in those already diagnosed with ASD or Intellectual Disability, by exploring whether genotypic differences may be reflected in behavioral phenotype differences in cohorts of children diagnosed with these conditions. As such, we engaged in collaborative efforts to analyze genotype-phenotype data from large scale ASD collections and identified phenotypic profiles of children with ASD identified with specific genetic abnormalities. Such analyses allow us to refine our understanding of when and how symptoms of neurodevelopmental disorders present if genetic etiologies such as 16p11.2 duplications or deletions are identified. We are specifically focused on the rates and types of Intellectual Disability and ASD profiles within rare genetic conditions, given the implications of these diagnoses on lifelong disability and the need for potential treatment targets and appropriate outcome measures. Our collection of data using standardized autism diagnostic instruments (e.g. the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule) and traditional measures of intellectual functioning and adaptive behavior allows us to conduct analyses on how use of these measures differs within specific genetic disorders, to gain an understanding of how ASD and neurocognitive profiles may present differently based on specific etiology. Given that the field is moving towards such genetic first approaches, we also use our unique study populations to explore the limitations of our current measures and terminology for fully characterizing individuals who are minimally verbal or severely intellectually impaired. This group of children are particularly important for inclusion in potential treatment trials of rare genetic conditions, but for which few tools have been developed with adequate representation in standardization samples. We also plan to use such data to improve upon existing measures, and collaborate with others to develop new tools. Our goal here is to participate in the creation of tools that capture the full range of social-communication development, including the ability to capture profiles of those with early onset of neurologic conditions. We seek to create measures that capture growth and differences that may be important for recognizing change based on treatment as well as loss of skills that often accompanies both neurodevelopmental and neurodegenerative conditions.
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