Clinical Analysis of SYNGAP1 Variant-Related Neurodevelopmental Disorders in Chinese Children

Area of Science:

• Genetics and Neurology
• Pediatric Neurodevelopmental Disorders

Background:

• SYNGAP1-related neurodevelopmental disorders (SRDs) are genetic conditions impacting brain development.
• Understanding SRD clinical phenotypes and genotype-phenotype correlations is crucial for effective management.

Purpose of the Study:

• To characterize clinical phenotypes in Chinese children with SRDs.
• To explore genotype-phenotype correlations within the SYNGAP1 gene.
• To guide optimal clinical management strategies for SRDs.

Main Methods:

• Retrospective collection of clinical data from 99 Chinese children with SRDs.
• Inclusion of genetic results, clinical features, EEG, cranial imaging, and treatment responses.
• Analysis of genotype-phenotype correlations using Pearson correlation and logistic regression.

Main Results:

• Predominant severe developmental delay (82.8%) and high autism spectrum disorder (ASD) comorbidity (60.6%) were observed.
• Epilepsy affected 68.7% of patients, with eyelid myoclonia being the most common seizure type (54.4%); ~33% developed drug-resistant epilepsy (DRE).
• Domain analysis revealed specific impacts: PH domain associated with myoclonic seizures, C2 domain with high epilepsy incidence, and SH3 domain with lower DRE incidence.

Conclusions:

• SRDs are characterized by severe developmental delay, high epilepsy incidence, and ASD comorbidity.
• Partial domain-specific genotype-phenotype associations exist, influencing clinical outcomes.
• Eyelid myoclonia is a negative prognostic indicator for epilepsy treatment response and DRE.