1. The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature
- Author
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Marina Trivisano, Nicola Specchio, Chiara Pepi, Giusy Carfi-Pavia, Antonio Novelli, Francesca Diomedi Camassei, Camilla Rossi-Espagnet, Ingmar Bluemcke, Nicola Pietrafusa, Carlo Efisio Marras, Francesca Romana Lepri, Andrea Diociaiuti, Luca De Palma, Alessandro De Benedictis, and Federico Vigevano
- Subjects
Pathology ,medicine.medical_specialty ,Hippocampus ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Review ,medicine.disease_cause ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Nevus sebaceous ,Medicine ,Epilepsy surgery ,ddc:610 ,pediatric epilepsy surgery ,030304 developmental biology ,0303 health sciences ,Hippocampal sclerosis ,RAS pathway ,business.industry ,nevus sebaceous syndrome ,General Neuroscience ,Cortical dysplasia ,medicine.disease ,KRAS genetic variants ,Epileptic spasms ,hippocampal sclerosis ,KRAS ,business ,focal cortical dysplasia ,030217 neurology & neurosurgery ,RC321-571 - 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.
- Published
- 2021