The role of kras mutations in cortical malformation and epilepsy surgery: A novel report of nevus sebaceous syndrome and review of the literature

Pepi C, De Palma L, Trivisano M, Pietrafusa N, Lepri FR, Diociaiuti A, Camassei FD, Carfi-Pavia G, De Benedictis A, Rossi-Espagnet C, Vigevano F, Marras CE, Novelli A, Blümcke I, Specchio N (2021)

Publication Type: Journal article, Review article

Publication year: 2021

Journal

Brain Sciences MDPI

Book Volume: 11

Article Number: 793

Journal Issue: 6

DOI: 10.3390/brainsci11060793

Abstract

The rare nevus sebaceous (NS) syndrome (NSS) includes cortical malformations and drug-resistant epilepsy. Somatic RAS-pathway genetic variants are pathogenetic in NS, but not yet described within the brain of patients with NSS. We report on a 5-year-old boy with mild psychomotor delay. A brown-yellow linear skin lesion suggestive of NS in the left temporo-occipital area was evident at birth. Epileptic spasms presented at aged six months. EEG showed continuous left temporo-occipital epileptiform abnormalities. Brain MRI revealed a similarly located diffuse cortical malformation with temporal pole volume reduction and a small hippocampus. We performed a left temporo-occipital resection with histopathological diagnosis of focal cortical dysplasia type Ia in the occipital region and hippocampal sclerosis type 1. Three years after surgery, he is seizure-and drug-free (Engel class Ia) and showed cognitive improvement. Genetic examination of brain and skin specimens revealed the c.35G > T (p.Gly12Val) KRAS somatic missense mutation. Literature review suggests epilepsy surgery in patients with NSS is highly efficacious, with 73% probability of seizure freedom. The few histological analyses reported evidenced disorganized cortex, occasionally with cytomegalic neurons. This is the first reported association of a KRAS genetic variant with cortical malformations associated with epilepsy, and suggests a possible genetic substrate for hippocampal sclerosis.

Authors with CRIS profile

Ingmar Blümcke Lehrstuhl für Neuropathologie

Involved external institutions

Ospedale Pediatrico Bambino Gesu IT Italy (IT) Istituto di ricovero e cura a carattere scientifico (IRCCS) IT Italy (IT)

How to cite

APA:

Pepi, C., De Palma, L., Trivisano, M., Pietrafusa, N., Lepri, F.R., Diociaiuti, A.,... Specchio, N. (2021). The role of kras mutations in cortical malformation and epilepsy surgery: A novel report of nevus sebaceous syndrome and review of the literature. Brain Sciences, 11(6). https://doi.org/10.3390/brainsci11060793

MLA:

Pepi, Chiara, et al. "The role of kras mutations in cortical malformation and epilepsy surgery: A novel report of nevus sebaceous syndrome and review of the literature." Brain Sciences 11.6 (2021).

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