The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature
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-yello...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/11/6/793 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Chiara Pepi Luca de Palma Marina Trivisano Nicola Pietrafusa Francesca Romana Lepri Andrea Diociaiuti Francesca Diomedi Camassei Giusy Carfi-Pavia Alessandro De Benedictis Camilla Rossi-Espagnet Federico Vigevano Carlo Efisio Marras Antonio Novelli Ingmar Bluemcke Nicola Specchio |
| spellingShingle |
Chiara Pepi Luca de Palma Marina Trivisano Nicola Pietrafusa Francesca Romana Lepri Andrea Diociaiuti Francesca Diomedi Camassei Giusy Carfi-Pavia Alessandro De Benedictis Camilla Rossi-Espagnet Federico Vigevano Carlo Efisio Marras Antonio Novelli Ingmar Bluemcke Nicola Specchio 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 KRAS genetic variants nevus sebaceous syndrome pediatric epilepsy surgery hippocampal sclerosis focal cortical dysplasia RAS pathway |
| author_facet |
Chiara Pepi Luca de Palma Marina Trivisano Nicola Pietrafusa Francesca Romana Lepri Andrea Diociaiuti Francesca Diomedi Camassei Giusy Carfi-Pavia Alessandro De Benedictis Camilla Rossi-Espagnet Federico Vigevano Carlo Efisio Marras Antonio Novelli Ingmar Bluemcke Nicola Specchio |
| author_sort |
Chiara Pepi |
| title |
The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature |
| title_short |
The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature |
| title_full |
The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature |
| title_fullStr |
The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature |
| title_full_unstemmed |
The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature |
| title_sort |
role of kras mutations in cortical malformation and epilepsy surgery: a novel report of nevus sebaceous syndrome and review of the literature |
| publisher |
MDPI AG |
| series |
Brain Sciences |
| issn |
2076-3425 |
| publishDate |
2021-06-01 |
| description |
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. |
| topic |
KRAS genetic variants nevus sebaceous syndrome pediatric epilepsy surgery hippocampal sclerosis focal cortical dysplasia RAS pathway |
| url |
https://www.mdpi.com/2076-3425/11/6/793 |
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doaj-3eae12bda15a49e4b738bcf6b97dd3892021-07-01T00:20:40ZengMDPI AGBrain Sciences2076-34252021-06-011179379310.3390/brainsci11060793The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the LiteratureChiara Pepi0Luca de Palma1Marina Trivisano2Nicola Pietrafusa3Francesca Romana Lepri4Andrea Diociaiuti5Francesca Diomedi Camassei6Giusy Carfi-Pavia7Alessandro De Benedictis8Camilla Rossi-Espagnet9Federico Vigevano10Carlo Efisio Marras11Antonio Novelli12Ingmar Bluemcke13Nicola Specchio14Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children’s Hospital IRCCS, Member of European Reference Network EpiCARE, 00165 Rome, ItalyRare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children’s Hospital IRCCS, Member of European Reference Network EpiCARE, 00165 Rome, ItalyRare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children’s Hospital IRCCS, Member of European Reference Network EpiCARE, 00165 Rome, ItalyRare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children’s Hospital IRCCS, Member of European Reference Network EpiCARE, 00165 Rome, ItalyTranslational Cytogenomics Research Unit, Laboratory of Medical Genetics, Bambino Gesù Children Hospital, IRCCS, 00165 Rome, ItalyGenodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, IRCCS, Member of European Reference Network SKIN, 00165 Rome, ItalyDepartment of Laboratories—Pathology Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyRare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children’s Hospital IRCCS, Member of European Reference Network EpiCARE, 00165 Rome, ItalyNeurosurgery Unit, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Member of European Reference Network EpiCARE, 00165 Rome, ItalyNeuroradiology Unit, Imaging Department, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyDepartment of Neuroscience, Bambino Gesù Children’s Hospital IRCCS, Member of European Reference Network EpiCARE, 00165 Rome, ItalyNeurosurgery Unit, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Member of European Reference Network EpiCARE, 00165 Rome, ItalyTranslational Cytogenomics Research Unit, Laboratory of Medical Genetics, Bambino Gesù Children Hospital, IRCCS, 00165 Rome, ItalyInstitute of Neuropathology, Member of European Reference Network EpiCARE, University Hospitals Erlangen, 91054 Erlangen, GermanyRare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children’s Hospital IRCCS, Member of European Reference Network EpiCARE, 00165 Rome, ItalyThe 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.https://www.mdpi.com/2076-3425/11/6/793KRAS genetic variantsnevus sebaceous syndromepediatric epilepsy surgeryhippocampal sclerosisfocal cortical dysplasiaRAS pathway |