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The National Institute of Health (NIH) Undiagnosed Diseases Program (UDP) is an NIH project with the goal of providing both a comprehensive diagnosis and a better understanding of the many mechanisms of disease for patients with rare and undiagnosed conditions. Patients accepted to the program receive a careful review of their medical records and a tailored inpatient evaluation at the NIH Clinical Center in Bethesda, MD. For the pediatric population, systematic neurodevelopmental phenotypic evaluations are included. Here we report neurodevelopmental phenotyping data on pediatric participants enrolled in the NIH UDP from 2009 to 2019, with genetic findings reported through 2025. Results for 219 pediatric participants included a high rate of intellectual disability, with 27% of the sample in the severe-to-profound range. The phenotype often included multisystemic involvement, with motor impairments as well as vision and hearing concerns. For the 46% for whom a genetic diagnosis was made, there was greater impairment, including more severe intellectual disability and more frequent motor impairments as well as minimal verbal status. This study documented that severe neurodevelopmental impairments are frequently present in the unique pediatric undiagnosed patients enrolled in NIH UDP; the diagnosis of a genetic condition was associated with greater impairment.