Ann Child Neurol.  2022 Jul;30(3):88-94. 10.26815/acn.2022.00073.

Epilepsy with SLC35A2 Brain Somatic Mutations in Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE)

• Kang HJ
• Kim DS
• Kim SH
• Lee JH
• Ko A
• Kim SH
• Lee JS
• Kim HD
• Kang HC

• KMID: 2548645
• DOI: http://doi.org/10.26815/acn.2022.00073

Abstract

Purpose
This study presents the characteristics of patients with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) with SLC35A2 somatic variants in the brain who underwent epilepsy surgery and showed clinical improvement in seizures.
Methods
We collected 10 patients with SLC35A2 somatic mutations in the brain who underwent surgery to treat drug-resistant epilepsy at Severance Children’s Hospital from 2014 to 2019 and retrospectively reviewed their genetic profiles, neuropathologic results, clinical features, pre-operative evaluations, and post-operative outcomes.
Results
Six of the 10 patients with SCL35A2 somatic mutations in the brain had Lennox Gastaut syndrome (LGS) evolving from infantile spasms (IS), three had LGS, and one had IS. The median value of variant allele frequencies (VAFs) was 5.7% (1.7% to 5.8%; range, 1.4% to 22.9%). Nonsense mutations were the most common (50%), followed by missense mutations (40%) and a splicing site mutation (10%). Eight patients (80%) had good post-operative outcomes, with freedom from disabling seizures in five (Engel class I) and rare disabling seizures in three (Engel class II). Four of the eight patients who could be assessed for social quotient (SQ) after surgery showed SQ improvements by 12.2±6.4. Although all patients were finally diagnosed with MOGHE, seven (70%) were initially diagnosed with gliosis, two with mild malformation of cortical development, and one with no abnormality.
Conclusion
All patients with SCL35A2 brain somatic mutations, even with low VAFs, had refractory epilepsy such as LGS or IS, and were finally diagnosed with MOGHE. This report is the first in Korea to our knowledge.

Keyword

Malformations of cortical development; Drug resistant epilepsy; Lennox Gastaut syndrome