Syndrome
Genetic test
Inheritance
Comment
(a) Syndromes beginning in the 1st year of life
Benign familial neonatal seizures
KCNQ2
KCNQ3
AD
M-channel subunit of voltage-gated potassium channel
Seizure onset often day of life 2–3
Diagnosis often clear without testing
Benign outcome
Benign familial neonatal-infantile seizures
SCN2A
AD
Sodium channel subunit
Seizures from 2 days to 6 months, normal development
Ohtahara syndrome
STXBP1
ARX
Various
Onset <6 months of age, tonic spasms, suppression burst on EEG
Early-onset spasms
CDKL5
(consider aCGH, TSC1/2, etc.)
X-linked
In girls (possibly lethal in males)
Hypermotor-tonic-spasms
X-linked infantile spasms
ARX
X-linked
In boys
(b) Syndromes with prominent Febrile seizures
Generalized Epilepsy with Febrile Seizures plus (GEFS+)
SCN1A
SCN1B
GABRG2
Can be AD or oligogenic
Sodium channel and GABAA receptor subunits
Early-onset febrile seizures and/or variable afebrile seizure types including absence
Dravet syndrome (or severe myoclonic epilepsy of infancy—SMEI)
SCN1A
AD
Sodium channel subunit
Early febrile and then various afebrile seizure types; psychomotor delay usually apparent during 2nd year of life
Childhood absence epilepsy with febrile seizures
GABRG2
AD
GABAA receptor subunit
Epilepsy and mental retardation limited to females
PCDH19
X-linked
(present only in heterozygous females)
Protocadherin
Early-onset seizures, autism, developmental delay
Affects only heterozygous females
(c) Idiopathic generalized epilepsies
Early-onset absence epilepsy
SLC2A1
AD
GLUT1 (glucose transporter type 1)
Can also see mutation in early-onset refractory seizures, movement disorders
Treat with ketogenic diet
Juvenile myoclonic epilepsy
GABRA1
EFHC1
AD
GABAA receptor
EF hand motif protein
(d) Focal epilepsies
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)
CHRNA4
CHRNA2
CHRNB2
AD
Nicotinic acetylcholine receptor subunits
Nocturnal clusters of brief motor seizures
Autosomal dominant partial epilepsy with auditory features (ADPEAF)
LGI1
AD
Also called autosomal dominant lateral temporal lobe epilepsy (ADLTLE)
Simple partial seizures with mainly acoustic hallucinations
Table 13.2
Genes identified in symptomatic epilepsy syndromes
