Genotype and phenotype correlation in epilepsy patients with SMARCA2 variants

Area of Science:

• Genetics
• Neurology
• Epilepsy Research

Background:

• The SMARCA2 gene plays a crucial role in cellular functions.
• Epilepsy is a complex neurological disorder with diverse genetic underpinnings.
• Understanding genotype-phenotype correlations is vital for diagnosing and managing genetic epilepsy syndromes.

Purpose of the Study:

• To investigate the genotype-phenotype correlations of SMARCA2 gene variants in epilepsy patients.
• To identify specific variants and their associated clinical manifestations.
• To explore the prevalence and characteristics of SMARCA2-related epilepsy.

Main Methods:

• Analysis of genotype-phenotype data from 24 patients in a dedicated cohort.
• Evaluation of an additional 46 epilepsy patients from published literature.
• Identification and characterization of SMARCA2 variants and their clinical phenotypes, including seizure types, onset age, and associated abnormalities.

Main Results:

• Twenty-one SMARCA2 variants were identified in 24 patients, with 17 being novel and de novo.
• Seizure onset ranged from infancy to early childhood (median 15 months), with focal seizures being predominant (60.9%).
• Significant phenotypes included developmental epileptic encephalopathy (5 patients) and dental abnormalities (52.8%), such as widely spaced teeth, fused teeth, and hypodontia. Seventy-seven percent of variants were located in the SNF2-ATPase domain.
• Valproate or levetiracetam controlled seizures in 45.8% of patients.

Conclusions:

• SMARCA2 variants are associated with epilepsy, characterized by early-onset focal seizures and significant dental abnormalities.
• The SNF2-ATPase domain is a critical region for SMARCA2 variants linked to epilepsy.
• These findings contribute to understanding the genetic basis of epilepsy and highlight key clinical features for diagnosis.