ILAE genetic literacy series: Focal cortical dysplasia

Abstract

Focal cortical dysplasia (FCD) is a common cause of drug-resistant focal epilepsy in children and young adults and is often surgically remediable. The genetics of FCD are increasingly understood due to the ability to perform genomic testing including deep sequencing of resected FCD tissue specimens. There is clear evidence that FCD type II occurs secondary to both germline and somatic mTOR pathway variants, while emerging literature supports the role of SLC35A2, a glycosylation gene, in mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE). Herein, we provide a review of FCDs focusing on their clinical phenotypes, genetic basis, and management considerations when performing genetic testing in this patient group.

Keywords: GATOR1; bottom‐of‐sulcus dysplasia; familial focal epilepsy; focal epilepsy genetics; mTOR.

FIGURE 1

T1 axial MP2RAGE of the 4‐year‐old boy with a bottom‐of‐sulcus focal cortical dysplasia type II described in the clinical case shows blurring of the gray‐white junction at the bottom of a sulcus in the right middle frontal gyrus (A). 18F‐FDG‐PET co‐registered to axial T1 MRI of the same patient demonstrates localized focal cortical hypometabolism restricted to the bottom of the same sulcus (B). An example of mild malformation with oligodendroglial hyperplasia and epilepsy (MOGHE) is also shown (C and D). A T2 axial MRI performed in a 15‐month‐old presenting with infantile spasms shows an increased T2 signal at the corticomedullary junction characteristic of MOGHE (arrowheads) (C). An 18F‐FDG‐PET co‐registered to axial T1 MRI of the same patient shows extensive cortical hypometabolism affecting the frontal, temporal, and parietal lobes (arrowheads) (D).