The role of genetic mutations in epilepsy

Multiple disease mechanisms underpinned by genetic mutations have been implicated in the development of epilepsy.^1,2

Genetic mutations can be passed down from a parent, or they can arise spontaneously in the individual.¹ They result in an alteration – loss or gain – of the function of the affected gene or of the protein encoded by the gene, and subsequently in a disruption of one or more of the biological processes underpinning normal neuronal and brain function, associated with epilepsy.¹ Loss-of-function mutations in sodium channel gene SCN1A have been detected in most patients with Dravet syndrome and gain-of-function mutations in the sodium-activated potassium channel gene KCNT1 have been detected in around half of infancy epilepsy cases with migrating focal seizures.¹

Genetic causes of epilepsy can also affect the function of neurons through mechanisms unrelated to seizures, e.g., aberrant neuronal migration or the formation of abnormal neuronal networks.¹

Variation in phenotype of genetic epilepsy can be driven by changes at the gene level, within the neuron, or across networks of neurons.²

DNA=deoxyribonucleic acid; mTOR=mammalian target of rapamycin