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This study aims to characterize the clinical phenotypes of children with SYNGAP1-related neurodevelopmental disorders (SRDs), explore the genotype-phenotype correlation, and guide optimal clinical management. Clinical data of 99 Chinese children with SRDs were retrospectively collected, including genetic results, clinical features, electroencephalogram (EEG), cranial imaging, and treatment responses. The correlation between clinical phenotype and genotype was analyzed using Pearson correlation and logistic regression analyses. All children with SRDs exhibited varying degrees of developmental delay, with severe developmental delay being predominant (82/99, 82.8%). The comorbidity rate of autism spectrum disorder (ASD) was high (60/99, 60.6%), and muscle tone abnormalities (21/99, 21.2%), as well as sleep and feeding problems, were also common. Epilepsy occurred in 68.7% of patients, with a mean onset age of 2.14 ± 0.99 years. The most common seizure type was eyelid myoclonia (37/68, 54.4%), and approximately one-third of the children developed drug-resistant epilepsy (DRE). For most phenotypes, no significant differences were observed between truncating and missense mutations. However, domain analysis indicated a significantly higher proportion of myoclonic seizures in the PH domain (9/14, 64.3%), an extremely high epilepsy incidence in the C2 domain (92.3%), and the lowest incidence of DRE in the SH3 domain (2/13, 15.4%), suggesting mutations in different functional regions may have specific clinical impacts. Antiseizure medication (ASM) treatment was generally effective, with 39.7% of children achieving seizure freedom. Eyelid myoclonia was identified as an independent risk factor for poor ASM response and DRE. The severity of developmental delay was negatively correlated with epilepsy onset age. Significant EEG abnormalities and ASD comorbidity were significant risk factors for severe developmental delay. In conclusion, SRDs exhibit a clinical profile centered on severe developmental delay, high epilepsy incidence, and ASD comorbidity. Partial domain-specific genotype-phenotype associations exist. Eyelid myoclonia is an important negative prognostic indicator for epilepsy. This study provides clinical evidence based on a Chinese population for the early diagnosis, prognosis assessment, and individualized treatment of SRDs.