The Neurodevelopmental and Behavioral Phenotyping Service provides a resource to the NIH Clinical Center, as well as to specific NIH research projects, by conducting over 200 neurodevelopmental assessments yearly. Assessments provide data on a variety of rare genetic conditions associated with neurodevelopmental disorders, including Intellectual Disability and Autism Spectrum Disorder. The service enrolls patients into a protocol that includes behavioral assessments (NCT00271622) and a collaborative protocol that includes assessment of specific rare genetic conditions (NCT02461420). We have also added a protocol that specifically enrolls adults with Phelan-McDermid Syndrome, to study the behavioral phenotype of this condition throughout the lifespan (NCT03426059). In addition, we participate in several other studies that are conducting behavioral phenotyping of conditions that have yet to have their natural histories fully explored, including Williams Syndrome, Moebius Syndrome, propionic acidemia, creatine transport deficiency, Smith-Lemli-Opitz Syndrome, congenital disorders of glycosylation and other diagnosed and undiagnosed conditions that affect neurodevelopment early in life. These characterization studies are necessary for understanding 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. This past year, we continued to explore data on samples of ASD and at-risk populations collected through the NIMH intramural research program, as well as from several large-scale repositories and epidemiologic studies. Collaborative efforts included contributing to large-scale ASD collections, and analyzing data to answer questions about sex differences and developmental milestone attainment differences in subpopulations. We are specifically focused on the rates and phenotypic expression 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 is building on the work of research on existing standardized autism diagnostic instruments by analyzing data on how these measures function over time, and on how measurements differ within specific genetic disorders. We are also testing out newly updated versions of tests with different psychometric properties, to analyze their more fine-grained data for the detection of potential changes in skills over time. Given that the field is moving towards genetics-first approaches in general, we also use data from 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 are currently working to improve upon existing measures for this population, and are collaborating with others to develop new tools and improve upon the capabilities of instruments such as the NIH Toolbox to be used in treatment trials for specific neurodevelopmental conditions. A goal here is to establish feasibility and validity of measures that will truly capture clinically meaningful changes that directly contribute to improvement in core symptoms of conditions such as Intellectual Disability. Similarly, another goal 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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Scientific Cores Intramural Research (ZIC)
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Khan, Omar I; Zhou, Xiangping; Leon, Jill et al. (2018) Prospective longitudinal overnight video-EEG evaluation in Phelan-McDermid Syndrome. Epilepsy Behav 80:312-320
Farmer, Cristan A; Chilakamarri, Priyanka; Thurm, Audrey E et al. (2018) Spindle activity in young children with autism, developmental delay, or typical development. Neurology 91:e112-e122
Mitz, Andrew R; Philyaw, Travis J; Boccuto, Luigi et al. (2018) Identification of 22q13 genes most likely to contribute to Phelan McDermid syndrome. Eur J Hum Genet 26:293-302
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Farmer, Cristan; Swineford, Lauren; Swedo, Susan E et al. (2018) Classifying and characterizing the development of adaptive behavior in a naturalistic longitudinal study of young children with autism. J Neurodev Disord 10:1
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Anderson, Afrouz A; Smith, Elizabeth; Chowdhry, Fatima A et al. (2017) Prefrontal Hemodynamics in Toddlers at Rest: A Pilot Study of Developmental Variability. Front Neurosci 11:300
Ory, Daniel S; Ottinger, Elizabeth A; Farhat, Nicole Yanjanin et al. (2017) Intrathecal 2-hydroxypropyl-?-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1-2 trial. Lancet 390:1758-1768
Soorya, Latha; Leon, Jill; Trelles, M Pilar et al. (2017) Framework for assessing individuals with rare genetic disorders associated with profound intellectual and multiple disabilities (PIMD): the example of Phelan McDermid Syndrome. Clin Neuropsychol :1-30

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