Social Behavioral Impairments inSYNGAP1-Related Intellectual Disability

ABSTRACT Synaptopathies are neurodevelopmental disorders caused by genetic mutations disrupting the development and function of neuronal synapses. We administered the validated Social Responsiveness Scale, Second Edition (SRS-2) to investigate the phenotypic presentation of social-behavioral impairments for the synaptopathy— SYNGAP1 -related Intellectual Disability ( SYNGAP1 -ID) (n=32) compared with a phenotypically similar disorder Phelan-McDermid Syndrome (PMD) (n=27) and healthy controls (n=43). A short form SRS-2 analysis (n=85) was also conducted. Both SYNGAP1 -ID and PMD had significantly elevated total and subcategory T-scores, with no significant score differences between SYNGAP1 -ID and PMD, consistent between the full and short form. Mild to severe deficiencies in reciprocal social behavior were found in 100% of PMD individuals and 87.1% of SYNGAP1 -ID individuals. Additionally, the short form demonstrated greater utility for SYNGAP1- ID participants due to lower item-omission rates. In conclusion, significant impairment in reciprocal social behaviors is highly prevalent in SYNGAP1 -ID.