SLC35A2 -Related Epilepsy: Global Neuronal Consequences of a Focal Disruption in Glycosylation

Abstract

Focal cortical dysplasia is a common yet incompletely understood cause of drug-resistant focal epilepsy in adults and children.1 The newly revised classification of focal cortical dysplasia reflects the progress made in our understanding of this important pathologic entity during the last decade.2 It formally recognizes 2 forms of mild malformations of cortical development (mMCD) involving the white matter, which may account for 2%-4% of patients with drug-resistant focal epilepsy undergoing surgery.1 One form is mMCD with excessive heterotopic neurons and the other is mMCD with oligodendroglial hyperplasia in epilepsy (MOGHE). Recent work has identified somatic pathogenic variants in SLC35A2 (solute carrier family 35 member A2), a gene located at chromosome Xp11.23 as a potentially important cause of focal cortical dysplasia and especially MOGHE.2,3 Defects in SLC35A2 cause a congenital disorder of glycosylation because it encodes a transporter that brings uridine diphosphate (UDP)-galactose into Golgi apparatus from the cytosol. Neurologists should be aware of SLC35A2 because defects in this transporter provide a different mechanism for producing focal cortical dysplasia from deficits in the well-known mechanistic target of rapamycin pathway (mTOR).2