Table 2. Typical childhood epilepsy syndromes of genetic origin.

Syndrome	Gene	Key diagnostic marker or outcome	Comment
Epilepsy and mental retardation157	PCDH19	Female epilepsy syndrome—transmitted by unaffected fathers to daughters Onset in infancy, often provoked by fever Seizures occur in clusters Rigid personalities (possible autistic spectrum disorder) Seizures remit in adolescence Intellectual disability and behavioural disturbances are common	Previously, patients with this mutation were diagnosed with Dravet syndrome—now regarded as a separate entity
Infantile spasms (X-linked)	CDKL5158,159	Female epilepsy syndrome—transmitted by unaffected fathers to daughters Early-onset epileptic encephalopathy before 5 months of age (10 days to 3 weeks of age) Infantile spasms, including multiple seizure types Rett syndrome-like features include hand stereotypies* and deceleration in head growth during early childhood Severe mental retardation (absence of speech)	Severely affected males reported in some cohorts Phenotype with dysmorphology Mutation type relates to severity of disease58,158 Patients have residual hand function, poor eye fixation with avoidance of eye contact, and feeding difficulties159
	STXBP1160	Short periods of control with AEDs but frequent relapses EESB Rare 10% of patients of patients with EESB Infantile spasms described without preceding EESB Seizure types include tonic seizures, focal and generalized seizures Most patients are refractory to treatment Age of onset 1 day to 6 months of age Severe developmental delay	Clinical spectrum can be diverse; overlap with Ohtahara syndrome Few cases reported with frontal hypoplasia and thin and dysmorphic corpus callosum Some patients become seizure-free in the first year of life160
	ARX161,162	Occurs in boys Early infantile epileptic encephalopathy Ohtahara syndrome Seizure onset in the neonatal period Predominantly tonic spasms Patients eventually develop West syndrome EEG—burst suppression Severe mental retardation and dystonia AED-resistant	ARX mutations with polyalanine expansion associated with risk of mental retardation, dystonia and epilepsy Severity depends on length of polyalanine tract Brain malformations not detectable on neuroimaging Some males have a micropenis with evidence of delayed puberty
Malignant migrating partial seizures of infancy163	KCNT1 (in up to 50% of patients);164 SCN1A, PLCB1, TBC1D24, SLC25A22163	Infantile epileptic encephalopathy syndrome Treatment-resistant Developmental delay Polymorphous epilepsy with symptom onset before 6 months of age Seizure migrates across from different regions of the brain Estimated prevalence 0.11 per 100,000 children	Expanded criteria includes gut dysmotility Seizure phenotype can include hypsarryhthmia and burst suppression165 KCNT1 genotyping first is recommended; the other mutations should be considered if this result is negative

Awareness of the typical phenotypes could support targeted genetic analyses in patients with atypical presentation.

^*Symmetrical movements at the midline.

Abbreviations: AED, antiepileptic drug; EESB, epileptic encephalopathy with suppression bursts.