Table 1 The variants and clinical manifestation of reported patients (only those patients with detailed clinical descriptions)
Literature [3] | Literature [5] | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
Subject B | Subject D | Subject E* | Subject F | Patient 1 | Patient 2 | Patient 3 | Patient 4* | Patient 5 | Patient 6 | Patient 7 | |
Variant | c.394C > T (p.R132C) | c.44A > C (p.E15A) | c.394C > T (p.R132C) | c.394C > T (p.R132C) | c.169C > G (p.R57G) | c.398A > C (p.Y133S) | c.532A > G (p.N178D) | c.394C > T (p.R132C) | c.394C > T (p.R132C) | c.169C > T (p.R57C) | c.529C > A (p.L177I) |
Inheritance | De novo | De novo | De novo | De novo | De novo | De novo | De novo | De novo | De novo | De novo | De novo |
Sex | Female | Female | Female | Female | Female | Male | Male | Female | Male | Female | Female |
Age | 18 years | 10 years | 22 years | 15 years | 15 years | 16 years | 7 years | 23 years | 4 years | 10 years | 7.5 years |
ID | Mild-moderate | yes (IQ ca.55) | yes (moderate to severe) | WPPSI III (6 years), VIQ 73, PIQ 58 | Mild–moderate | Mild–moderate | Moderate | Moderate | Mild | Moderate | Mild–moderate |
Speech | Early language delay | Delayed | Delayed | Mildly delayed | Normal | Normal | Speech delay, echolalia | Delayed | Mild delay | Requires support. Unclear speech. Short simple sentences | Delayed |
Walking | Unknown | Unknown | Unknown | Unknown | 15 m | 23 m | 24–30 m | 16 m | 21 m | 22 m | 18 m |
ASD | ADHD | – | – | – | present | – | present | present | – | – | – |
Age of seizure onset | 12 months | 6 months | < 6 months | < 6 years (unknown) | 10 months | 16 years | 2 years | < 6 months | 2 years | < 5 years | – |
Seizure type | Generalized myoclonic, atypical absence, generalized tonic–clonic | Prolonged seizure with fever and then two episodes of status epilepticus associated with regression and hemiparesis | Myoclonic, prolonged generalized tonic–clonic with fever, generalized myoclonic, absence, generalized tonic–clonic | Absence, eyelid myoclonia, myoclonic, persistence of absence seizures | Absence, focal and generalized tonic–clonic | Isolated generalized tonic–clonic | Absence | Generalized tonic–clonic, generalized myoclonic, absence | Generalized tonic–clonic | Frontal lobe epilepsy | Absence |
Anti-epileptic drugs | Clonazepam, lamotrigine, divalproex sodium, ethosuximide | Divalproex sodium | Divalproex sodium, stiripentol | Divalproex sodium, lamotrigine | Levetiracetam, ethosuximide | None | Ethosuximide | Stiripentol, divalproex sodium | Sodium valproate | Sodium valproate, carbamazepine | None |
Treatment resistant? | No | No | Partial response | No | No | N/a | No response to LTG | Partial response | No | No | N/a |
Ictal EEG | Myoclonic jerks, generalized spike-and wave discharge | Not available | Spike-and-slow wave, poly-spike, and slow-wave discharges | Not available | – | Not performed | – | – | – | – | |
Interictal EEG | 2 years: dysrhythmic background, generalized atypical spike wave, frequent bifrontal spikes; 14 years: dysrhythmic background, rare sharp waves in bianterior quadrants | Not available | 21 months: generalized 3 Hz spike wave with absence seizures; 10 years: generalized polyspike wave with myoclonic seizures; 14 years: occasional spike wave | 8 years: bilateral frontotemporal spikes, generalized spike waves | – | Not performed | Prolonged burst of generalized 2.5 Hz spike and wave activity noted | Generalized polyspike wave and slow wave discharges | – | – | Normal |
Cranial MRI | 3 years: asymmetric brainstem not thought to be significant | Generalized atrophy with diffuse loss of white matter | 10 years: normal | Normal | Normal | Normal | Normal | Normal | Focus of hyperintensity frontal lobe | Subtle signal changes in frontal subcortical white matter | Normal |
Literature [9] | Literature [19] | Our patients | ||
|---|---|---|---|---|
Proband | Mother | |||
Variant | c.619G > A (p.E207K) | c.170G > A (p.R57H) | c.170G > A (p.R57H) | c.170G > A (p.R57H) |
Inheritance | De novo | De novo | Inherited | De novo |
Sex | Male | Male | Male | Female |
Age | 4 years 9 months | 8 years | 3 years 10 months | 34 years |
ID | Normal | Mild | Moderate | Mild–moderate |
Speech | Normal | Delayed | Delayed | Delayed |
Walking | 16 m | 15 m | 18 m | Unknown |
ASD | – | ADHD | – | – |
Age of seizure onset | 9 months | 1 years 6 months | 1 years 11 months | 2 years |
Seizure type | Myoclonic jerks with extension of the hands with no clusters of spasms(9 months). Short events of staring with eye blinking. Head and eye deviation to the left and staring (3 years10 months) | Absence seizures, febrile and afebrile generalized tonic–clonic seizures | Generalized tonic–clonic | Generalized tonic–clonic |
Anti-epileptic drugs | Valproic acid, levetiracetam | valproic acid | Sodium valproate | Phenytoin sodium, carbamazepine, sodium valproate |
Treatment resistant? | Partial response to valproic acid, seizure free with levetiracetam | No | No | Partial response |
Ictal EEG | Generalized spike waves with bilateral frontal predominance(9 months) | – | – | – |
Interictal EEG | Generalized discharges of spikes with no decrement and no hypsarrhythmia pattern(9 months) Spikes at the right posterior frontal region and independent on the left posterior frontal region(3 years 10 months) | Used to be normal or mildly abnormal to background slowing. Only some EEG recordings showed generalized or bifrontal spikes and SW complexes | Normal | Normal |
Cranial MRI | Some nonspecific hyperintensity signals on fluid-attenuated inversion recovery (FLAIR) sequence | Normal | Normal | – |