Epilepsy

Epilepsy is characterized by recurrent seizures, resulting from abnormal neuronal excitability or circuits. To date, more than 10 genes have been found to be associated with epilepsy. Most of them encode ion channels, which are known to play essential roles in nerve excitation.

There are many different epilepsy syndromes, which may be divided into two broad categories: generalized and partial.  Generalized epilepsy begins simultaneously in both cerebral hemispheres whereas partial epilepsy begins in a localized area. Genes associated with the following syndromes have been identified.

Generalized epilepsies

Benign familial neonatal convulsion (BFNC)

This syndrome begins in a few days after birth, and usually remits within a few weeks even without treatment. Genes associated: KCNQ2, KCNQ3 (voltage-gated potassium channel).

Childhood absence epilepsy (CAE)

This syndrome begins at the ages of 4 to 8 years. During absence seizures, patients stare and lose consciousness for a few seconds and then return immediately to normal. The syndrome is due to alteration in the circuitry between the thalamus and the cerebral cortex. Genes associated: CACNA1H (T-type calcium channel) and GABRG2 (GABA receptor channel).

Juvenile myoclonic epilepsy (JME)

This syndrome is characterized by myoclonic jerks and generalized tonic-clonic seizures. Gene associated: GABRA1 (GABA receptor channel).

Generalized epilepsy with febrile seizures plus (GEFS⁺)

This syndrome encompasses a spectrum of childhood-onset phenotypes including febrile seizures (with fever), febrile seizures plus (without fever), partial epilepsies, myoclonic astatic epilepsy, and severe myoclonic epilepsy of infancy. Genes associated: GABRG2 (GABA receptor channel), SCN1A, SCN1B, SCN2A (voltage-gated sodium channel).

Severe myoclonic epilepsy of infancy (SMEI)

This syndrome begins in infancy with prolonged clonic febrile and afebrile seizures. Genes associated: SCN1A (voltage-gated sodium channel).

X-linked epilepsy

This type of epilepsy is caused by mutation of one or more genes in X chromosome. It is often associated with mental retardation. Genes associated: ARX, STK9, SLC6A8, PHF6.

Partial epilepsies

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)

This syndrome is characterized by clusters of nocturnal motor seizures, lasting from a few seconds to five minutes. Genes associated: CHRNA4, CHRNB2 (nicotinic acetylcholine receptor channel)

Autosomal dominant partial epilepsy with auditory features (ADPEAF)

This syndrome is characterized by infrequent partial seizures with or without auditory disturbances. Genes associated: LGI1. The cellular function of LGI1 is not known, but it shares some sequence homology with MASS1 gene, which is associated with an audiogenic epilepsy in a mouse model (reference).

Review Article:

Molecular background of progressive myoclonus epilepsy - EMBO J., 2003.