Clinical Utility of Genetic Diagnosis in Drug-Resistant Epilepsy: Refining Classification and Guiding Therapy in an...

Recent advances in epilepsy genetics have revolutionized the diagnosis and management of patients. This study was conducted to evaluate the clinical significance of molecular diagnosis in Egyptian patients with pediatric-onset drug-resistant epilepsy (DRE). All patients lacked electro-clinic-radiological concordant lesions and therefore were not candidates for surgical intervention. More than 70% of cases had variable degrees of cognitive impairment, and about 25% had different forms of movement disorders. Exome sequencing was able to unravel potential genetic defects in 40 patients across 31 genes. The study identified 15 novel variants, including those in MYCBP2 and BAZ2B, which were recently linked to genetic epilepsy. Genetic diagnosis refined classification and guided therapy in several patients, particularly those with ion channelopathies, progressive myoclonic epilepsy, infantile convulsions, choreoathetosis syndrome, and glucose transporter Type 1 deficiency. Our findings underscore the importance of genetic testing for patients with DRE, improving clinical classifications beyond electroclinical assessments and supporting better outcomes.