Social Behavioral Impairments in SYNGAP1-related Intellectual Disability (P11-9.003)

Abstract

<h3>Objective:</h3> The goal of this study is to characterize the prevalence and severity of social impairments for children with <i>SYNGAP1</i>-related intellectual disability (<i>SYGNAP1</i>-ID), and to compare the severity of social impairment between patients with <i>SYNGAP1</i>-ID and, the phenotypically similar, Phelan-McDermid Syndrome (PMD). <h3>Background:</h3> Synaptopathies are neurodevelopmental disorders caused by genetic mutations disrupting the development and function of neuronal synapses. <i>SYNGAP1</i>-related intellectual disability is due to either de novo loss-of-function single nucleotide variants in <i>SYNGAP1</i> or a hemizygous deletion of the chromosome 6p21.3. Phenotypic presentations of <i>SYNGAP1</i>-ID can include epilepsy, intellectual disability, autism, speech impairments, sleep abnormalities, global developmental delays, and behavioral issues. <h3>Design/Methods:</h3> We utilized the validated Social Responsiveness Scale, Second Edition (SRS-2) to investigate the phenotypic presentation of social-behavioral impairments for two synaptopathies—<i>SYNGAP1</i>-ID (n=32) and PMD (n=19). The short form SRS-2, derived for populations with severe intellectual disability by Sturm et al., was also utilized. The short form SRS-2 limits the influence of age, expressive language, behavioral problems, and nonverbal IQ on survey scores, while maintaining a unidimensional factor structure. <h3>Results:</h3> For the full form analysis, both <i>SYNGAP1</i>-ID and PMD had significantly elevated total and subcategory T-scores as compared to controls, with no significant difference between <i>SYNGAP1</i>-ID and PMD. Similarly, the short form analysis showed significantly elevated total scores for both <i>SYNGAP1</i>-ID and PMD as compared to healthy controls, with no significant difference between the two synaptopathies. <h3>Conclusions:</h3> The survey data showed 87.5% of <i>SYNGAP1</i>-ID and 100% of PMD individuals met the criteria for mild to severe deficiencies in reciprocal social behavior—with majority falling within the “Severe” category (68.8%, <i>SYNGAP1</i>-ID; 73.7%, PMD). Survey item completion data suggests improved utility of the Sturm et al. short form assessment for this patient population. <b>Disclosure:</b> Ms. Naveed has nothing to disclose. Maria McCormack has nothing to disclose. Dr. Holder has received personal compensation in the range of $0-$499 for serving as a Consultant with Stoke Pharmaceutical.