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Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations

Objective: Cardiofaciocutaneous syndrome (CFCS) is a rare developmental disorder caused by upregulated signaling through the RAS-mitogen-activated protein kinase (MAPK) pathway, mostly resulting from de novo activating BRAF mutations. Children with CFCS are prone to epilepsy, which is a major life-t...

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Autores principales: Battaglia, Domenica I., Gambardella, Maria Luigia, Veltri, Stefania, Contaldo, Ilaria, Chillemi, Giovanni, Veredice, Chiara, Quintiliani, Michela, Leoni, Chiara, Onesimo, Roberta, Verdolotti, Tommaso, Radio, Francesca Clementina, Martinelli, Diego, Trivisano, Marina, Specchio, Nicola, Dravet, Charlotte, Tartaglia, Marco, Zampino, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470450/
https://www.ncbi.nlm.nih.gov/pubmed/34573299
http://dx.doi.org/10.3390/genes12091316
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author Battaglia, Domenica I.
Gambardella, Maria Luigia
Veltri, Stefania
Contaldo, Ilaria
Chillemi, Giovanni
Veredice, Chiara
Quintiliani, Michela
Leoni, Chiara
Onesimo, Roberta
Verdolotti, Tommaso
Radio, Francesca Clementina
Martinelli, Diego
Trivisano, Marina
Specchio, Nicola
Dravet, Charlotte
Tartaglia, Marco
Zampino, Giuseppe
author_facet Battaglia, Domenica I.
Gambardella, Maria Luigia
Veltri, Stefania
Contaldo, Ilaria
Chillemi, Giovanni
Veredice, Chiara
Quintiliani, Michela
Leoni, Chiara
Onesimo, Roberta
Verdolotti, Tommaso
Radio, Francesca Clementina
Martinelli, Diego
Trivisano, Marina
Specchio, Nicola
Dravet, Charlotte
Tartaglia, Marco
Zampino, Giuseppe
author_sort Battaglia, Domenica I.
collection PubMed
description Objective: Cardiofaciocutaneous syndrome (CFCS) is a rare developmental disorder caused by upregulated signaling through the RAS-mitogen-activated protein kinase (MAPK) pathway, mostly resulting from de novo activating BRAF mutations. Children with CFCS are prone to epilepsy, which is a major life-threatening complication. The aim of our study was to define the natural history of epilepsy in this syndrome and exploring genotype–phenotype correlations. Methods: We performed an observational study, including 34 patients with molecularly confirmed diagnosis (11 males, mean age: 15.8 years). The mean follow-up period was 9.2 years. For all patients, we performed neurological examination, cognitive assessment when possible, neuroimaging, electrophysiological assessment and systematic assessment of epilepsy features. Correlation analyses were performed, taking into account gender, age of seizure onset, EEG features, degree of cognitive deficits, type of mutation, presence of non-epileptic paroxysmal events and neuroimaging features. Results: Epilepsy was documented in 64% of cases, a higher prevalence compared to previous reports. Patients were classified into three groups based on their electroclinical features, long-term outcome and response to therapy. A genotype–phenotype correlation linking the presence/severity of epilepsy to the nature of the structural/functional consequences of mutations was observed, providing a stratification based on genotype to improve the clinical management of these patients.
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spelling pubmed-84704502021-09-27 Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations Battaglia, Domenica I. Gambardella, Maria Luigia Veltri, Stefania Contaldo, Ilaria Chillemi, Giovanni Veredice, Chiara Quintiliani, Michela Leoni, Chiara Onesimo, Roberta Verdolotti, Tommaso Radio, Francesca Clementina Martinelli, Diego Trivisano, Marina Specchio, Nicola Dravet, Charlotte Tartaglia, Marco Zampino, Giuseppe Genes (Basel) Article Objective: Cardiofaciocutaneous syndrome (CFCS) is a rare developmental disorder caused by upregulated signaling through the RAS-mitogen-activated protein kinase (MAPK) pathway, mostly resulting from de novo activating BRAF mutations. Children with CFCS are prone to epilepsy, which is a major life-threatening complication. The aim of our study was to define the natural history of epilepsy in this syndrome and exploring genotype–phenotype correlations. Methods: We performed an observational study, including 34 patients with molecularly confirmed diagnosis (11 males, mean age: 15.8 years). The mean follow-up period was 9.2 years. For all patients, we performed neurological examination, cognitive assessment when possible, neuroimaging, electrophysiological assessment and systematic assessment of epilepsy features. Correlation analyses were performed, taking into account gender, age of seizure onset, EEG features, degree of cognitive deficits, type of mutation, presence of non-epileptic paroxysmal events and neuroimaging features. Results: Epilepsy was documented in 64% of cases, a higher prevalence compared to previous reports. Patients were classified into three groups based on their electroclinical features, long-term outcome and response to therapy. A genotype–phenotype correlation linking the presence/severity of epilepsy to the nature of the structural/functional consequences of mutations was observed, providing a stratification based on genotype to improve the clinical management of these patients. MDPI 2021-08-26 /pmc/articles/PMC8470450/ /pubmed/34573299 http://dx.doi.org/10.3390/genes12091316 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Battaglia, Domenica I.
Gambardella, Maria Luigia
Veltri, Stefania
Contaldo, Ilaria
Chillemi, Giovanni
Veredice, Chiara
Quintiliani, Michela
Leoni, Chiara
Onesimo, Roberta
Verdolotti, Tommaso
Radio, Francesca Clementina
Martinelli, Diego
Trivisano, Marina
Specchio, Nicola
Dravet, Charlotte
Tartaglia, Marco
Zampino, Giuseppe
Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations
title Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations
title_full Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations
title_fullStr Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations
title_full_unstemmed Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations
title_short Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations
title_sort epilepsy and braf mutations: phenotypes, natural history and genotype-phenotype correlations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470450/
https://www.ncbi.nlm.nih.gov/pubmed/34573299
http://dx.doi.org/10.3390/genes12091316
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