Table 1.
Clinical features in three individuals with the recurrent variant p.R1636Q of NaV1.1.
| Individual 1 | Individual 2 | Individual 3 | Individual 4 | Individual 5 | Individual 6 | Individual 7 | Individual 8 | Individual 9 | Individual 10 | Individual 11 | Individual 12 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Source | This study | This study | This study | This study | Butler (2017) | Nair (2018) | Alame (2019) | Harkin (2007); Brunklaus (2022) | Brunklaus (2022) | Brunklaus (2022) | Brunklaus (2022) | Brunklaus (2022) |
| Age (sex) | 13m (male) | 4y (male) | 19y (female) | 35m (male) | N/A | N/A | N/A | 20y* (male) | 8y* (female) | 11y (male) | 23y (female) | 5y (male) |
| Variant | c.4907G>A, p.R1636Q de novo | c.4907G>A, p.R1636Q de novo | c.4907G>A, p.R1636Q, not paternally inherited | c.4907G>A, p.R1636Q de novo | c.4907G>A, p.R1636Q unknown | c.4907G>A, p.R1636Q unknown | c.4097G>A, p.R1636Q de novo | c.4907G>A, p.R1636Q de novo | c.4907G>A, p.R1636Q unknown | c.4907G>A, p.R1636Q de novo | c.4907G>A, p.R1636Q de novo | c.4907G>A, p.R1636Q de novo |
| Seizure types (onset of first seizure) | T (2w) | GTC (DOL3), T (infancy) | T (infancy) | T (neonatally), F (2 months), SE (4 months), A (12 months) | M, otherwise unknown | “early seizures” “Dravet syndrome” | “Dravet syndrome” | TC (3w), Ab, AtA, T, F, IS, M, HC | T (3m), F, TC | TC (2m), C, F, T, M, SE | TC (10w), M, HC, T, SE, At | TC (2m), F, SE, T, HC |
| EEG | FD | MF discharges, ESES | N/A | MF spikes | N/A | N/A | N/A | MF discharges, FD, ESES | GSW, PSW, NCSE | GSW, FD, EPC | MF discharges, ESES, NCSE | MF discharges, FD |
| Brain MRI | Normal 8w | Normal 1m and 1.5y | Normal 2.5y and 4y | Normal 4m | N/A | N/A | N/A | Normal 5y and 18y | Normal 5m, mild atrophy 1.5y | Normal 2y and 5y | Normal 3y and 6y | Normal 1.5y |
| Neurological/physical exam | Normal | Axial hypotonia, NA, NV, bilateral chorea, profound DD | NV, broad-based gait, severe ID | Axial hypotonia, brisk reflexes unilaterally (left) | Dystonia, spasticity | N/A | N/A | Hypotonia, right UL weakness & posturing (18 m), ataxic (2.5 y), crouch gait (6 y), wheelchair bound (20 y) | Hypotonia, chorea of UL, myoclonus (1 y), Profound ID, NV, NA (2.5y ➔ regression), acquired microcephaly, bone fractures, eyelid myoclonia | Dystonia, dyskinesia (7y), delay (1y) and regression (7y), profound ID, NA, NV, acquired microcephaly, eyelid myoclonia | Dyskinesia of right UL (2y), delay (1–2y) and regression (5y), severe ID, hypotonia | Head tremor (2y), intermittent ataxia, delay (1–2y), severe ID, single words, ambulant, autism-like features |
A: Atonic, Ab: Absence, AtA: atypical absence, DD: developmental delay, EPC: epilepsia partialis continua , ESES: electrical status epilepticus in sleep, F: focal, FD: focal discharges, GSW: Generalized spike-wave, HC: hemiclonic, ID: intellectual disability, IS: infantile spasms, LTG: lamotrigine, M: myoclonic, MF: multifocal, NA: non-ambulatory, NCSE: non-convulsive status epilepticus, NV: non-verbal, OXC: oxcarbazepine, PHT: phenytoin, PSW: polyspike wave, SE: status epilepticus, T: tonic, TC: tonic-clonic, UL: upper limb
*
: deceased