TY - JOUR
T1 - Epilepsy and BRAF mutations: Phenotypes, natural history and genotype-phenotype correlations
AU - Battaglia, Domenica Immacolata
AU - Gambardella, Maria Luigia
AU - Veltri, Stefania
AU - Contaldo, Ilaria
AU - Chillemi, Giovanni
AU - Veredice, Chiara
AU - Quintiliani, Michela
AU - Leoni, Chiara
AU - Onesimo, Roberta
AU - Verdolotti, Tommaso
AU - Radio, Francesca Clementina
AU - Martinelli, Diego
AU - Martinelli, Daniela
AU - Trivisano, Marina
AU - Specchio, Nicola
AU - Dravet, Charlotte
AU - Tartaglia, Marco
AU - Zampino, Giuseppe
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - BRAF
KW - Cardiofaciocutaneous syndrome
KW - Epilepsy
KW - Genotype–phenotype correlations
KW - Hyperekplexia
KW - Phenotype
KW - Status epilepticus
KW - BRAF
KW - Cardiofaciocutaneous syndrome
KW - Epilepsy
KW - Genotype–phenotype correlations
KW - Hyperekplexia
KW - Phenotype
KW - Status epilepticus
UR - http://hdl.handle.net/10807/197177
U2 - 10.3390/genes12091316
DO - 10.3390/genes12091316
M3 - Article
SN - 2073-4425
VL - 12
SP - 1
EP - 15
JO - Genes
JF - Genes
ER -