Researchers from Severance Children's Hospital and Severance Hospital have identified genetic markers linked to epilepsy in Koreans, which may enable the development of personalized treatment plans for epilepsy patients. 

Epilepsy is a neurological disorder that affects about 1 percent of the global population and can result from various causes, including central nervous system infections, abnormal brain development, and brain tumors.

Previous studies have linked mutations in genes such as SCN1A, SCN2A, and GABRA1 to the development and function of the central nervous system, causing pediatric epilepsy. However, most genetic epilepsy studies have focused on Western populations, leaving a gap in the genetic data for Korean patients.

To address this gap, the research team, led by Professors Kang Hoon-chul and Kim Se-hee of the Deartment of Pediatric Neurology at Severance Children's Hospital and Choi Jong-rak and Lee Seung-tae of the Department of Laboratory Medicine at Severance Hospital, conducted diagnostic exome sequencing and disease-specific next-generation sequencing (NGS) panel tests on 957 individuals showing epilepsy symptoms with unknown causes.

The analysis revealed genetic abnormalities related to epilepsy in 32 percent (310 individuals) of the participants.

Specifically, the SCN1A gene mutation was prevalent among Dravet syndrome patients, while abnormalities in the STXBP1, SCN2A, and CDKL5 genes were observed in infantile spasm patients.

Other significant genetic mutations were identified in the KCNQ2, CHD2, SLC2A1, PCDH19, MECP2, SCN8A, and PRRT2 genes, all contributing to early childhood epilepsy.

Of the 310 patients with genetic abnormalities, 145 (47 percent) exhibited mutations in one or more of the commonly identified genes, such as SCN1A, STXBP1, SCN2A, and KCNQ2. Only 47 (5%) of the total participants displayed common recurring mutations, with most patients showing rare variants.

Dravet syndrome patients predominantly had single-gene abnormalities in SCN1A, with a diagnostic rate of 87 percent, the highest among the studied conditions. In contrast, patients with Lennox-Gastaut syndrome and infantile spasms, known for severe childhood seizures, showed mutations in multiple genes with lower diagnostic rates of 33 percent and 22 percent, respectively.

The study also examined age-related epilepsy diagnosis rates, with the highest rate of 43 percent observed in newborns, while the lowest rate of 20 percent was found in children aged two to five years.

Based on genetic testing results, personalized treatment plans were possible for 111 (36 percent) of the 310 patients with identified genetic causes.

Also, some patients benefited from effective drugs or dietary therapies that were previously successful in other epilepsy cases.

"This genetic analysis will significantly advance the diagnosis and treatment of epilepsy," Professor Kim said. "Building a database of genetic variations specific to Koreans will enable us to provide tailored treatments for epilepsy patients."

The study results were published in Epilepsia.