Authors :
Presenting Author: Seok-Jin Lee, MD, PhD – Department of Pediatric Neurology, Severance Children’s Hospital, Yonsei University College of Medicine
Won Seok Chang, M.D., Ph.D. – Department of Neurosurgery, Severance Hospital, Yonsei University College of Medicine; Hoon-Chul Kang, M.D., Ph.D. – Department of Pediatric Neurology, Severance Children’s Hospital, Yonsei University College of Medicine; Heung Dong Kim, M.D., Ph.D. – Department of Pediatric Neurology, Severance Children’s Hospital, Yonsei University College of Medicine; Se Hee Kim, M.D., Ph.D. – Department of Pediatric Neurology, Severance Children’s Hospital, Yonsei University College of Medicine; Ara Ko, M.D., Ph.D. – Department of Pediatric Neurology, Severance Children’s Hospital, Yonsei University College of Medicine; Jeong Ho Lee, M.D., Ph.D. – Graduate school of medical science and engineering, KAIST
Rationale:
A significant portion of children with focal epilepsy who undergo epilepsy surgery have brain somatic variants leading to malformation of cortical development as the etiology. Somatic variants in mTOR pathway genes cause hemimegalencephaly and focal cortical dysplasia (FCD) type II, while somatic SLC35A2 variants result in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). Distinguishing between these conditions is challenging using brain imaging alone. This study aims to compare the clinical characteristics of FCD type II patients with somatic mTOR pathway gene mutations and MOGHE patients with somatic SLC35A2 mutations.
Methods:
A brain somatic variant gene panel was routinely performed on brain specimens from patients undergoing epilepsy surgery at Severance Children’s Hospital. Patients with structural etiology due to previous injury, confirmed germline mutations, hippocampal sclerosis, or those who did not consent to genetic analysis were excluded. Among 253 patients tested with the somatic gene panel, pathogenic variants were detected in 29.2% of cases, including MTOR (33.8%) and SLC35A2 (32.4%). Clinical characteristics were retrospectively reviewed for 31 FCD type II patients with mTOR pathway somatic mutations and 24 MOGHE patients with SLC35A2 mutations, including age at seizure onset, syndromic diagnosis, brain imaging findings, and developmental status.
Results:
Comparison between the two groups revealed a significantly higher incidence of developmental and epileptic encephalopathy in MOGHE patients. MOGHE patients also had earlier seizure onset and poorer development compared to FCD type II patients with mTOR pathway mutations. A considerable number of MOGHE patients had received corpus callosotomy prior to epilepsy surgery, indicating challenges in localizing the epileptogenic focus. More MOGHE patients required multilobar resection, suggesting wider lesions or greater difficulty in localizing the epileptogenic focus. The prognosis was also poorer in MOGHE patients, with a 50.0% seizure recurrence rate after 2 years of epilepsy surgery.
Conclusions:
MOGHE patients with brain somatic SLC35A2 mutations are more likely to present with developmental and epileptic encephalopathy, such as West syndrome or Lennox-Gastaut syndrome, compared to FCD type II patients with brain somatic mTOR pathway mutations. Additionally, a higher proportion of MOGHE patients experience seizure recurrence after epilepsy surgery, emphasizing the need for careful planning during pre-surgical evaluation.
Funding: No external funding received