Table 2 Clinical and genetic characteristics of RAS/MAPK-associated epileptic encephalopathies
Clinical manifestation | RAS/MAPK-associated genes | |||
|---|---|---|---|---|
BRAF | MEK1 | KRAS | PPP1CB | |
Associated syndrome | CFC | CFC3 | Noonan syndrome 3 | NSLH2 |
Reported mutations | L485F; L485S; F468S; Q257R; del E11; F595 L; T599R; G534R; D638E; K499 N | F53F; Y130N | D153V | E183A |
Age of onset of epileptic encephalopathies | Birth to 11y | 2 reported patients (1y and15y) | 3 m with Myo/11 m with IS | 4 m |
Seizure type | CPS, GTCS or sGTCS, Abs, IS, Tonic spasms, SE | GTCS, Abs, CPS | IS, Myo | IS, Myo |
Interictal EEG | Hypsarrhythmia (some patients) | Focal epileptiform discharges to hypsarrhythmia. | Hypsarrhythmia (11 m); asynchronous slow waves with irregular spike-wave or polyspikes with and without waves (6 y). | Chaotic, high voltage, polymorphic delta and theta rhythms with superimposed multifocal spikes and wave discharges. |
Development delay | Severe | Severe | Severe | Moderate to severe |
Seizures refractory to AEDs or required multiple AEDs use | Yes | Yes | Yes | Yes |
Seizure prognosis | Difficult to control | Difficult to control | Controlled with ACTH | Favorable to KD |
Brain MRI | Cortical atrophy, hypoplastic CC | Hydrocephalus, cortical atrophy | Cortical atrophy, agenesis of the CC | Unremarkable |
References | [15] | [18] | The present study | |