Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Study Design
2.3. Structural Analysis
2.4. Statistical Analysis
3. Results
3.1. Neurological Data
3.2. Electroclinical Data
3.2.1. Clinical Epilepsy Data
3.2.2. Electrophysiological Assessment
3.3. Other Paroxysmal Phenomena
3.4. MRI Data
3.5. Structural Analyses and Genotype–Phenotype Correlations
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Ethical Publication Statement
References
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Patient (Age; Sex) | Follow-Up (y) | BRAF Amino Acid Substitution | Mutation Class | Age of Seizure Onset | Epilepsy Type | Neurological Features | ID/Behavioral Disorders | PNE | SD | Brain MRI |
---|---|---|---|---|---|---|---|---|---|---|
Group 1 | ||||||||||
#1 (23 y; M †) | 23 | Lys601Gnl | II | 2 m | Combined focal and generalized | Tetraparesis, nystagmus | Profound Regression | Hpx | Yes | CA, HS |
# 2 (17 y; M) | 15 | Asp638Glu | III | 2 y | Combined focal and generalized | Tetraparesis, dystonia, nystagmus | Profound/AT | Hpx | Yes | CA, bilateral HS, gliosis |
# 3 (15 y; M) | 15 | Asp638Glu | III | 5 m | Combined focal and generalized | Tetraparesis | Profound/AT | Hpx | Yes | CA, HS, cortical dysplasia |
#4 (14 y; F) | 12 | Phe595Leu | II | 1.5 y | Focal | Tetraparesis | Profound/AT | Hpx | Yes | CA, gliosis |
#5 (13 y; M) | 11 | Lys 601Gnl | II | 1.5 y | Combined focal and generalized | Tetraparesis, strabismus | Severe | Hpx | Yes | CA |
#6 (12 y; F) | 7 | Asp638Glu | III | 1.5 y | Combined focal and generalized | Tetraparesis, strabismus | Severe Regression | Hpx | Yes | CA, HS |
#7 (7 y; F †) | 6 | Phe595Leu | II | 7 m | Combined focal and generalized | Tetraparesis, strabismus | Profound Regression | Hpx | Yes | CA, HS, hippocampal hypoplasia |
#8 (6 y; F) | 6 | Val487Gly | II | 8 day | Focal | Tetraparesis | Profound/AT | Hpx | Yes | CA, hippocampal hypoplasia |
#9 (5 y; M †) | NA | Asp565Glu | I | 4 y | Combined focal and generalized | Tetraparesis, strabismus | Profound | Hpx | NA | CA, thin CC |
#10 (3 y; M) | 3 | Pro468Ser | II | 1 m | Focal | Tetraparesis | Profound/AT | NA | Yes | CA + bilateral HS |
Group 2 | ||||||||||
#11 (27 y; F) | 25 | Trp531Cys | II | 2 y | Focal | Ataxia, strabismus | Severe | NA | NA | Normal |
#12 (23 y; M) | 10 | Thr241Pro | I | 17 y | Focal | Hypotonia | Mild | NA | NA | Normal |
#13 (22 y; F) | 20 | Lys499Asn | II | 1.6 y | Focal | Ataxia | Moderate | Hpx | Yes | Removal results of cerebellar astrocytoma |
#14 (20 y; M) | 5 | Lys483Asn | II | 18 y | Focal | Hypotonia | Moderate | No | No | Normal |
#15 (19 y; F) | 15 | Leu485Phe | II | 14 y | Focal | Tetraparesis, strabismus | Severe/AT | Blinking | Yes | CA |
#16 (15 y; F) | 10 | Trp531Cys | II | 9 y | Combined focal and generalized | Tetraparesis, strabismus | Severe | Hpx | Yes | Thin CC |
#17 (15 y; F) | 8 | Leu525Pro | II | 11 y | Focal | Tetraparesis, strabismus | Moderate | Hpx | Yes | CA, gliosis |
#18 (12 y; F) | 2 | Gln257Arg | I | 10 y | Focal | Ataxia | Severe/AT | No | Yes | Gliosis |
#19 (12 y; F) | 4 | Gln257Arg | I | 10 y | Focal | Ataxia | Severe | Blinking | Yes | CA, HS |
# 20 (8 y; F) | 7 | Gln257Arg | I | 6 y | Combined focal and generalized | Tetraparesis, strabismus | Severe/AT | No | No | Normal |
#21 (8 y; F) | 5 | Thr599Arg | II | 6 y | Combined focal and generalized | Tetraparesis, strabismus | Severe/AT | Hpx | Yes | Gliosis |
#22 (4 y; F) | 3 | Gln257Arg | I | 4 y | Generalized | Ataxia, strabismus | Severe | No | Yes | Ventriculomegaly |
Group 3 | ||||||||||
#23 (53 y; F) | 7 | Ala246Pro | I | - | - | Normal | NA | No | NA | NA |
#24 (43 y; F) | 10 | Thr241Met | I | - | - | Normal | NA | No | NA | NA |
#25 (27 y; F) | 6 | Thr241Arg | I | - | - | Normal | Mild | NA | NA | NA |
#26 (24 y; F) | 17 | Gln709Arg | I | - | - | Normal | Mild | No | Yes | Normal |
#27 (19 y; M) | 14 | Glu501Lys | II | - | - | Normal | Severe | NA | NA | NA |
#28 (15 y; M) | 6 | Leu245Phe | I | - | - | Normal | Mild | NA | NA | NA |
#29 (14 y; F) | 8 | Gly469Glu | II | - | - | Normal | Moderate | No | NA | Thin CC |
#30 (12 y; M) | 2 | Thr470Pro | II | - | - | Normal | Moderate | No | No | Gliosis |
#31 (11 y; F) | 7 | Gln257Arg | I | - | - | Normal | Moderate | NA | NA | Thin CC |
#32 (7 y; F) | 5 | Gln257Arg | I | - | - | Normal | Moderate | No | Yes | Thin CC, cerebellar malrotation |
#33 (7 y; F) | 5 | Trp531Arg | II | - | - | Normal | Moderate | No | Yes | Normal |
#34 (3 y; F) | 2 | Asn581Asp | II | - | - | Normal | Mild | No | NA | NA |
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Battaglia, D.I.; Gambardella, M.L.; Veltri, S.; Contaldo, I.; Chillemi, G.; Veredice, C.; Quintiliani, M.; Leoni, C.; Onesimo, R.; Verdolotti, T.; et al. Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations. Genes 2021, 12, 1316. https://doi.org/10.3390/genes12091316
Battaglia DI, Gambardella ML, Veltri S, Contaldo I, Chillemi G, Veredice C, Quintiliani M, Leoni C, Onesimo R, Verdolotti T, et al. Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations. Genes. 2021; 12(9):1316. https://doi.org/10.3390/genes12091316
Chicago/Turabian StyleBattaglia, Domenica I., Maria Luigia Gambardella, Stefania Veltri, Ilaria Contaldo, Giovanni Chillemi, Chiara Veredice, Michela Quintiliani, Chiara Leoni, Roberta Onesimo, Tommaso Verdolotti, and et al. 2021. "Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations" Genes 12, no. 9: 1316. https://doi.org/10.3390/genes12091316