Table 1.
Demographic, genetic and clinical characterization of the study cohort.
| 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 |
y: year; †: patient dead; ID: intellectual disability; PNE: paroxysmal non-epileptic events; SD: sleep disorder; M: male; Hpx: hyperekplexia; ID: intellectual disability; CA: cortical atrophy; HS: hippocampal sclerosis; AT: autistic traits; NA: not available; m: months; F: female; CC: corpus callosum.