Epilepsy phenotypes and responses to antiseizure medications in pediatric patients with EEF1A2-related epilepsy

Objective

To delineate the epilepsy spectrum and evaluate the response of pediatric patients with EEF1A2-related epilepsy to antiseizure medications (ASMs).

Methods

We conducted a retrospective analysis of seven pediatric patients with EEF1A2 mutations identified at our institution, combined with 69 cases from prior literature, resulting in a cohort of 76 patients. Data for age of seizure onset, seizure types, epilepsy syndromes, ASM responses, and neurodevelopmental outcomes were collected and analyzed. Epilepsy syndromes were classified following the International League Against Epilepsy guideline.

Results

Among the 76 patients, 61 (80 %) presented with epilepsy, with a median seizure onset age of 4.5 months. Of these, 56 % experienced seizure onset before the age of 12 months. Generalized seizures were predominant (67 %), including epileptic spasms, myoclonic, tonic, and tonic-clonic seizures. Developmental epileptic encephalopathy (DEE) was observed in 59 % of patients, although a range of milder epilepsy phenotypes was also present. Broad-spectrum ASMs, such as valproic acid, lamotrigine, and levetiracetam, demonstrated effectiveness in controlling seizures in 65 % of patients. Recurrent mutations such as p.Gly70Ser and p. Glu122Lys were predominantly associated with severe DEE.

Conclusions

EEF1A2-related epilepsy encompasses a broad spectrum of phenotypes, from early-onset severe syndromes to milder forms. Specific mutations within EEF1A2 seemed to be correlated with severe DEE.