|Down syndrome||Infantile spasms common (2%) and easily overlooked||Interictal EEG slow general spike wave or hypsarrhythmia (chromosomes of course)|
|1p36 deletion||Dysmorphism with straight eyebrows and deep-set eyes, the most common seizure type is infantile spasms||Karyotype, fluorescent in situ hybridization, multiplex ligation-dependent probe amplification|
|Ring chromosome 14||Very mild dysmorphism, early infantile serial tonic||Count sufficient metaphases|
|Lesional epilepsy||Vast range of lesions especially focal cortical dysplasia; partial epilepsies of any kind with onset at any age||Brain MRI but may need ictal SPECT, PET and high-resolution MRI especially if surgical intervention likely|
|Epilepsia partialis continua||Unilateral with atrophy may suggest Rasmussen encephalitis||Anti-brain antibodies not helpful in diagnosing Rasmussen|
|Unilateral onset in infancy||High-resolution brain MRI for cortical dysplasia|
|Variable sites may suggest mitochondrial, especially Alpers, with RHADS (rhythmic high-amplitude delta with superimposed spikes) on EEG||P0LG1 and other mitochondrial investigations|
|Video game epileptic seizures||Situational photic or pattern-sensitive epileptic seizures||EEG/EC6 with photic and pattern stimulation including monocular|
|Progressive myoclonus epilepsies||Various|
|Common metabolic problems (sodium, calcium, glucose, etc.)||Convulsive seizures most likely clonic, perhaps tonic-clonic, depends on age||'Routine' electrolytes, calcium, phosphorus, glucose|
|Pyridoxine dependency||Neonatal especially with suppression-burst, neonatal tonic-clonic epilepsy with status until age 3y, might be Dravet-like||Pyridoxine trial, plasma and urine alpha-aminoadipic semialdehyde (α-AASA), pipecolic acid|
|Pyridoxal phosphate-responsive seizures||Neonatal encephalopathy with suppression-burst, not known if occurs later in infancy||Pyridoxal phosphate trial. CSF amino acids. PNPO gene analysis|
|Folinic acid-responsive seizures||As for pyridoxine dependency||Folinic acid trial but also pyridoxine|
|Adenylosuccinate lyase (ADSL) deficiency||Delay with hypotonia usually precedes epilepsy, autism, self-mutilation, postconvulsive hemiplegia reported, various seizures may be intractable with EEG S/W; MRI may show 'hypomyelination'||Urine succinylpurines, possible ADSL mutation|
|Serine synthesis deficiency||Early (first month) intractable seizures ('cyanotic episode') jerking, tonic posturing. Microcephaly. MRI ± hypomyelination||CSF serine and glycine, gene analysis especially P5AT1|
|Menkes disease, mild forms possible||Kinky hair detectable on microscopy, bone changes and subdural haemorrhage may simulate child abuse, various seizures including spasms||Copper, copper oxidase|
|Untreated phenylketonuria (PKU) missed||Missed PKU may be seen in countries without neonatal screening tests; autism, stereotypies, developmental delay, infantile spasms||Plasma and urine amino acids|
|Mitochondrial disorder||Seizures especially epilepsia partialis continua; may have basal ganglia signal change or cerebellar atrophy or lesions in cortical grey matter especially in occipital regions; multiorgan involvement||Lactates:. Genes: especially P0LG1|
|Guanidinoacetate methyl transferase deficiency||Developmental delay; epileptic seizures ± early absences and myoclonus; brain H-MRS: absent creatine peak||↑ urine guanidinoacetate, ↓ creatine on brain H-MRS|
|Glucose transporter 1 deficiency||Acquired microcephaly, spasticity and delayed development may be absent; early absences and myoclonic seizures may be feed- or meal-related, worse when hungry; epileptic seizures are ketogenic diet-responsive, as may be paroxysmal movements and ataxia||Fasting blood and CSF glucose|
- a pathogenic mutation is not necessary for the diagnosis of GEFS+ (SCN1A mutations are found in <10%)
- although most children with Dravet syndrome have SCN1A mutations the detection of such mutations is not necessary for that diagnosis to be established
- the diagnosis of Dravet syndrome in infancy is possible with some combination of onset of (1) febrile seizures aged 7 months or earlier; (2) five or more seizures with hemiconvulsions; and/or (3) seizures lasting more than 30 minutes].
- Recently mutations in PCDH19 have been found in SCNlA-negative patients, mainly female, with a Dravet-like syndrome.
- The most useful neurological investigation is a EEG (with sleep activation if need be), which usually shows multifocal high-amplitude sharp and slow wave complexes on a normal background. SCN1A mutations may be sought.
The epileptic seizures of early school-age onset are most typically hemifacial with unilateral tonic contraction of the lower lip and numbness of the lip and perhaps tingling inside the mouth. Inability to speak (anarthria) is accompanied by a gurgly sound and excess saliva that dribbles down the chin.
EEG spike complexes that are seen interictally are more sylvian than temporal. These rolandic spikes are much more common in children without epilepsy, so it is essential to have the clinical diagnosis before making inferences from the EEG investigation.
If diagnosis is confirmed unlike focal epilepsies in general - brain MRI is not indicated.
Eventually the seizures remit spontaneously but language and behavioural difficulties are quite common, and sometimes CSWS may develop, such that all-night EEG is indicated if there is a suggestion of regression.
BRE/BECTS has been reported in fragile X syndrome but testing for FMR1 is indicated only when other clinical features of the fragile X syndrome are present.
Other chromosomal abnormalities are associated with epilepsies, in particular infantile spasms but also Lennox-Gastaut syndrome (inv-dup chromosome 15). Either an unusual epilepsy or an unusual EEG appearance should prompt at least standard chromosome karyotype examination.
Mary D. King, 2009. A Handbook of Neurological Investigations in Children. 1 Edition. Mac Keith Press.