Social behavioral impairments in SYNGAP1-related intellectual disability

Hajer Naveed; Maria McCormack; J Lloyd Holder Jr

doi:10.3389/fped.2023.1188117

Social behavioral impairments in SYNGAP1-related intellectual disability

Front Pediatr. 2023 Nov 29:11:1188117. doi: 10.3389/fped.2023.1188117. eCollection 2023.

Authors

Hajer Naveed¹, Maria McCormack¹, J Lloyd Holder Jr¹

Affiliation

¹ Department of Pediatrics, Division of Neurology and Developmental Neuroscience, Baylor College of Medicine and Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, United States.

Abstract

Introduction: Developmental synaptopathies are neurodevelopmental disorders caused by genetic mutations disrupting the development and function of neuronal synapses.

Methods: We administered the validated Social Responsiveness Scale, Second Edition (SRS-2) to investigate the phenotypic presentation of social-behavioral impairments for the developmental 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.

Results: 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. Surprisingly, a positive correlation between age and total score was discovered for SYNGAP1-ID participants and not found in individuals with PMD or healthy controls.

Discussion: 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.

Keywords: Phelan McDermid syndrome; SRS; SYNGAP1 gene; autism; intellectual disability.