From: Effective treatment of NR2F1-related epilepsy with perampanel
Patient (age/sex) | NR2F1 variant | Age at onset | Seizure type | Brain MRI | EEG | ASMs used | Effective ASMs | Epilepsy outcome | References |
---|---|---|---|---|---|---|---|---|---|
7 years/M | 5q15 [88,945,075–134-105,929,496–555; 17 Mb] | 6 years | GTCS | Bilateral PH, involving the temporal and occipital horns | Normal background activity with no epileptic-form discharges | NA | NA | Seizure-free | [9] |
5 years/F | 5q15 [87,086,298–35-95,538,640–699;8.4 Mb] | 9 months | IES | Bilateral PH, involving the temporal and occipital horns | Poorly organized background activity and multifocal epileptic-form discharges | Resistant to anti-epileptic medication | NA | Not controlled | [9] |
5 years/M | 5q15 [88,659,488–547-94,986,541–600; 6.3 Mb] | 8 months | Episodes of unresponsiveness, myoclonus | Bilateral PH, involving the temporal and occipital horns. Rotated hippocampi, more severely on the right, and irregular thickening and folding of the cortex in the posterior perisylvian regions, consistent with polymicrogyria | Bursts of multifocal and bilaterally synchronous epileptic-form activity | VPA | VPA | Seizure-free at 3 years | [9] |
F | c.403C > T; p.Arg135Cys | 4 months | IES, secondary generalized seizures | Normal | Hypsarrhythmia | NA | NA | NA | [2] |
4 years/F | c.403C > A; p.Arg135Ser | 4 months | IES | Thin corpus callosum | NA | Prednisone and OXC | NA | NA | [3] |
6 years/M | c.328_330del; p.Phe110del | 4 months | IES | Thin corpus callosum | Hypsarrhythmia | NA | NA | NA | [3] |
21 years/M | c.1103G > A; p.Gly368Asp | 18 years | Generalized seizure | Normal | Spike discharges in the paracentral and central areas | NA | NA | NA | [3] |
43 years/M | C.2_4del; p.Met1? | 13 years and 18 years | Two GTCS attacks | Normal | NA | VPA | VPA | Seizure-free at 18 years | [3] |
7 years/M | c.328_330del; p.Phe110del | 3 months | IES | Mild asymmetry of the lateral ventricle | Hypsarrhythmia and electroclinical spams | NA | NG | NA | [10] |
23 years/F | c.403C > T; p.Arg135Cys | 4 months | IES, GTS, GTCS, focal seizure | Normal | Pyridoxine, VPA, nitrazepam, steroid, and CZP | CZP,VPA | Seizure-free at around 20 years | [11] | |
14 years/M | c.257G > T; p.Cys86Phe | 6 months | One-episode IES | Unremarkable and limited ophthalmologic evaluation disclosed bilateral mild optic nerve hypoplasia | Left-occipital-onset seizure with secondary generalization, hypsarrhythmia grade 3, generalized and multifocal spikes and sharp waves, and right temporal intermittent rhythmic delta activity | ACTH | ACTH | Seizure-free at 6 months | [12] |
32 years/M | c.253 G > T; p.Glu85X | 5 years | Episodes of behavioral arrest and non-responsiveness that lasted for 4 to 6 min | Unremarkable | Unremarkable | Phenobarbital, phenytoin, TPM, LEV, and LTG | TPM,LTG | Still on CZP | [5] |
9 years/M | c.1080del; p.Asn362fs*33 | 2.5 years | Myoclonus, astatic seizure | Hypoplasia of the optic nerve and chiasma opticum as well as a hypoplastic corpus callosum | NA | Triple therapy | NA | Still having subcIinical epileptiform discharges at the last follow-up at age of 9 years and 10 months | [6] |
20 years/F | c.2 T > C; p.Met1? | 6 years | Episodic jerking movements | Markedly slender anterior visual pathways, almost complete absence of the septum pellucidum and possible truncation of the rostrum of the corpus callosum, highly suggestive of septooptic dysplasia | EEG at 12 years of age showed possible occipital seizures with repetitive high-amplitude spikes and slow waves bilaterally, with maximal activities in the posterior and occipital regions with a frequency of 2–4 per second | Clobazam | Clobazam (started on clobazam at age of 12) | NA | [13] |
3 years and 10 months/Ma | c.365G > T; p.Cys122Phe | 6 months | IES, GTS | Thin corpus callosum | Bursts of high-amplitude spikes, multiple spikes and spike-and-slow waves, and multiple clinical attacks (with a spasm of the whole body trunk) (5 months); low-amplitude fast waves, spikes and spike-and-slow waves in the right middle and posterior temporal areas during sleep (2 years and 5 months); | ACTH, TPM, vitamin B6, and Perampanel | Perampanel | seizures-free | |
3 years and 5 months/Ma | c.383G > T; P.Cys128Tyr | 0.5 month | IES | DM | High-amplitude arrhythmia, bilateral discharges mainly in the posterior area (4 months); slow, spikes and spike-and-slow waves in the bilateral parietal, occipital and posterior temporal areas; a series of focal spasms were detected (6.5 months); no high-amplitude arrhythmia, spikes-slow, sharp-slow wave in the bilateral posterior areas (10 months) | ACTH, Magnesium sulphate, Sabril, TPM, vitamin B6, KD, and Perampanel | Perampanel | seizures-free | |
8 years and 8 months/Ma | c.382 T > C; p.Cys128Arg | 2 months | IES, GTS, myoclonus | Normal | Spike-and-slow/shar-slow waves, multiple spike-and-slow/slow waves mainly in the posterior and midline areas; isolated and series of spasms or mild tonic attacks (7 years and 6 months); spike-and-slow/sharp-slow, slow, sharp, and spike wave rhythm mainly in the posterior and midline area (8 years) | ACTH, Sabril, TPM, VPA, CZP, LEV, LTG, and Perampanel | Perampanel | seizures-free | |
1 year and 8 month/Ma | c.449G > T; p.Gly150Val | 4 months | IES | Normal | Hypsarrhythmia during awake time and sleep, with intermittent phenomenon; 3 episodes of isolated spasm (7.5 months) | LEV, ACTH, Sabril, TPM, vitamin B6, VPA, and Perampanel | Perampanel | seizures-free | |
3 years and 5 months/Ma | c.449G > T; p.Gly150Val | 4 months | IES, focal seizure | Thin corpus callosum | Multifocal slow waves, spikes and sharp waves, and one attack of focal origin (8 months); 6–7 Hz rhythm with medium-to-high wave amplitude and a 15–20 Hz fast wave rhythm with a large number of continuous discharges in the bilateral occipitotemporal regions (2 years and 7 months) | VPA, TPM, LTG, and Perampanel | Perampanel | seizures-free | |
2 years and 3 months/Fa | c.328_330; p.Phe110del | 2 months | IES, AS, myoclonus | Wider outer frontotemporal space | Multifocal spike-and-slow/ sharp-slow waves, spikes, sharp waves marked in the bilateral posterior areas. Several spasms were detected, and atonic seizure followed myoclonic seizures (1 year and 6 months) | Perampanel | Perampanel | seizures-free |