Table 2.
Clinical Features of Subjects with SLC1A2 and YWHAG Mutations
|
SLC1A2 |
YWHAG |
|||||
|---|---|---|---|---|---|---|
| Subject A | Subject C | Subject B | Subject D | Subject E | Subject F | |
| Genetic findings | c.244G>A (p.Gly82Arg) | c.866C>G (p.Pro289Arg) | c.394C>T (p.Arg132Cys) | c.44A>C (p.Glu15Ala) | c.394C>T (p.Arg132Cys) | c.394C>T (p.Arg132Cys) |
| Sex | male | male | female | female | female | female |
| Seizure onset | 6 weeks | 5 days | 12 months | 6 months | <6 months | <6 years (unknown) |
| Age | 6 years | 10 years | 18 years | 10 years | 22 years | 15 years |
| Diagnosis | developmental and EE (treatment resistant) | developmental and EE (treatment resistant) | developmental and EE | unclassified epilepsy | unclassified or genetic generalized epilepsy | unclassified or genetic generalized epilepsy |
| Seizure type at onset | focal motor (left leg, right arm) initially without impaired awareness | focal motor (face, eyes, and right foot) | generalized myoclonic | prolonged focal motor seizure with fever | myoclonic | absence, eyelid myoclonia, myoclonic |
| Course of seizures | focal motor ± impaired awareness evolving to bilateral tonic-clonic | multiple seizure types | generalized myoclonic, atypical absence, GTC, no febrile seizure |
second prolonged seizure with fever and then two episodes of status epilepticus associated with regression and hemiparesis | prolonged GTC with fever, generalized myoclonic, absence, GTC | persistence of absence seizures |
| Ictal EEG | not available, but capture of right arm jerks and chin twitching showed no EEG correlate | spike-and-wave discharges (age 7 weeks) | myoclonic jerks, generalized spike-and-wave discharge | not available | spike-and-slow wave, polyspike, and slow-wave discharges | not available |
| Interictal EEG | 2 months: paroxysmal delta and frequent bilateral mid-central parietal spikes and sharp waves, occasional right temporal spikes; 4 years: slow dysrhythmic background, multifocal epileptiform discharges | very high amplitude (>500 μV), 0.7–3.3 Hz delta and very slow waves with intermixed generalized sharp waves (age 8 months) | 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 |
| Timing of seizure occurrence | diurnal or nocturnal | not provided | diurnal | not provided | frequently early morning | not provided |
| Head circumference | 45.1 cm at 8 months (50%), 52 cm at 5 years (50th percentile) | 44 cm at 4 months (91st percentile) | normal | ∼+1 SD (mother has macrocephaly) |
53.7 cm at 15 years (20th percentile) | normal (50th percentile) |
| Neurologic findings | visually inattentive with sluggish pupils, axial hypotonia, mild limb spasticity, dyskinetic movements of arms | hypotonia with up-going plantars and severe thoraco-lumbar kyphoscoliosis | action tremor in upper extremities and mild coordination difficulties | hypotonia, joint hyperlaxity | ataxia, thoracolumbar scoliosis | thoracolumbar kyphoscoliosis |
| Response to treatment | partial response to phenobarbital, levetiracetam, and clobazam; longest seizure-free period was 16 months |
partial response to ketogenic diet and phenytoin, no response to other antiseizure medications | responded to clonazepam, which was stopped at 8 years; lamotrigine at 10 years was ineffective for atypical absence and GTC seizure; seizure free since 11 years on divalproex sodium and ethosuximide; ethosuximide was weaned off by 17 years | epilepsy under control with divalproex sodium | partial response to divalproex sodium and stiripentol | epilepsy under control with divalproex sodium and lamotrigine |
| ID | yes (profound) | yes (severe) | mild to moderate ID | yes (IQ ca. 55) | yes (moderate to severe) | WPPSI III (6 years), VIQ 73, PIQ 58 |
| Development | delayed (severe), nonverbal, unable to sit unsupported | yes (severe) | early language delay, fine motor difficulties with tremor, ADHD | delayed | delayed | mildly delayed |
| Brain MRI | 6 weeks: normal; 2 years: incomplete myelination, generalized atrophy, thin corpus callosum, abnormal signal in thalami, putamen, and caudate, and abnormal peritrigonal white-matter signal; 4 years: progressive generalized atrophy, persistent abnormal signal in basal ganglia and thalami, and periventricular white-matter signal abnormalities | 2 months: normal; 2.5 years: severely delayed myelination, cerebral atrophy, and bilateral T2 prolongation in caudate heads and putamina | 3 years: asymmetric brainstem not thought to be significant | generalized atrophy with diffuse loss of white matter | 10 years: normal | normal |
Abbreviations are as follows: ADHG, attention-deficit hyperactivity disorder; EE, epileptic encephalopathy; EEG, electroencephalography; GTC, generalized tonic-clonic; ID, intellectual disability; PIQ, performance IQ; VIQ, verbal IQ; WPPSI, Wechsler Preschool and Primary Scale of Intelligence.