SETBP1 Haploinsufficiency and Related Disorders Clinical and Neurobehavioral Phenotype Study

Author:

Oyler Haley O.ORCID,Hudac Caitlin M.ORCID,Chung Wendy K.ORCID,Snyder LeeAnne G.,Robertson StephanieORCID,Srivastava SiddharthORCID,Geye TrinaORCID

Abstract

AbstractTo comprehensively investigate the neurodevelopmental profile and clinical characteristics associated with SETBP1 haploinsufficiency disorder (SETBP1-HD) and SETBP1-related disorders (SETBP1-RD). We reported genetic results on 34 individuals, with behavior and clinical data from 22 with SETBP1-HD and 5 with SETBP1-RD, by assessing results from medical history interviews and standardized adaptive, clinical, and social measures provided from Simons Searchlight. All individuals with SETBP1-HD and SETBP1-RD exhibited neurological impairments including intellectual disability/developmental delay (IDD), attention- deficit/hyperactivity disorder, autism spectrum disorder, and/or seizures, as well as speech and language delays. While restricted interests and repetitive behaviors present challenges, a relative strength was observed in social motivation within both cohorts. Individuals with SETBP1-RD reported a risk for heart issues and compared to SETBP1-HD greater risks for orthopedic and somatic issues with greater difficulty in bowel control. Higher rates for neonatal feeding difficulties and febrile seizures were reported for individuals with SETBP1-HD. Additional prominent characteristics included sleep, vision, and gastrointestinal issues, hypotonia, and high pain tolerance. This characterization of phenotypic overlap (IDD, speech challenges, autistic and attention deficit traits) and differentiation (somatic and heart issue risks for SETBP1-RD) between the distinct neurodevelopmental disorders SETBP1-HD and SETBP1- RD is critical for medical management and diagnosis.

Publisher

Cold Spring Harbor Laboratory

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