Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE): genetics, mechanisms and precision therapy
In brief
Somatic SLC35A2 loss-of-function drives childhood drug-resistant MOGHE epilepsy
Recent tissue sequencing has shown that mosaic loss-of-function mutations in the Golgi transporter gene SLC35A2 underlie the newly defined malformation MOGHE, a frequent cause of infantile epileptic spasms. The disorder shows unique cortical dyslamination and oligodendroglial hyperplasia, and experimental models reveal reduced neuronal firing similar to other mTOR-related dysplasias, pointing toward future precision-targeted therapies.
- Journal
- Acta neuropathologica (Q1)
- Published
- 2 August 2026
- Study design
- Narrative review / expert opinion
- Evidence level
- Level 5, Expert Opinion (CEBM 5)
- Authors
- James Spyrou, Paul J Lockhart, Snezana Maljevic, Katherine B Howell, Christopher A Reid
- PMID
- 42542984
- DOI
- 10.1007/s00401-026-03059-6
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (paper of the day, 3 August 2026).
Abstract
Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a recently defined malformation of cortical development that is an important cause of childhood-onset drug-resistant epilepsy. Clinically, the epilepsies associated with MOGHE are heterogeneous, with infantile epileptic spasms syndrome (IESS) being the most common manifestation. Histopathologically, MOGHE demonstrates subtle cortical dyslamination, heterotopic neurons in the white matter, hypomyelination, and a distinctive increase in the density and clustering of oligodendroglial cells, features that distinguish it from other malformations of cortical development such as focal cortical dysplasia (FCD). Recent genetic analyses of epileptogenic tissue resected from individuals with MOGHE have identified somatic mosaic loss-of-function variants in SLC35A2. This gene encodes the Golgi transmembrane UDP-galactose transporter, suggesting disrupted N-glycosylation as a distinct pathogenic mechanism underlying epilepsy in this disorder. In this review, we present the current clinical, histopathological, and molecular understanding of MOGHE, with a particular focus on recent insights gained from experimental rodent and human cellular models of SLC35A2 deficiency. We contextualise these findings against established models of mTORopathies including FCD type 2, placing MOGHE within the broader malformation of cortical development spectrum. Synthesising this evidence, we observe that neuronal activity in models of both MOGHE and mTORopathies such as FCD type 2 converge on reduced action potential firing, despite their distinct genetic aetiologies. Finally, we discuss how these findings inform our understanding of epileptogenesis, especially the emergence of infantile epileptic spasms, and the development of future precision therapeutic strategies across malformations of cortical development.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.