Genotype and phenotype correlation in epilepsy patients with SMARCA2 variants

Area of Science:

• Genetics
• Neurology
• Epilepsy Research

Background:

• Epilepsy is a complex neurological disorder with diverse genetic underpinnings.
• The SMARCA2 gene plays a crucial role in cellular processes, and its variants are increasingly implicated in neurodevelopmental disorders.

Purpose of the Study:

• To investigate genotype-phenotype correlations of SMARCA2 gene variations in epilepsy patients.
• To identify common clinical features associated with SMARCA2 mutations.

Main Methods:

• Analysis of genotype-phenotype data from 24 patients in a dedicated cohort.
• Evaluation of an additional 46 epilepsy patients from published literature.

Main Results:

• Twenty-one SMARCA2 variants were identified in 24 patients, with 17 being novel and de novo.
• Seizure onset typically occurred in infancy (median 15 months), with focal seizures being predominant (60.9%).
• Dental abnormalities (e.g., widely spaced teeth, hypodontia) were observed in 52.8% of patients; 77.3% of variants were in the SNF2-ATPase domain.

Conclusions:

• SMARCA2 variants are associated with epilepsy, characterized by early-onset focal seizures.
• Dental anomalies represent a significant phenotype in SMARCA2-related epilepsy.
• Most pathogenic SMARCA2 variants cluster within the SNF2-ATPase domain, suggesting functional importance.