Genetics of Epilepsy

ABSTRACT

Epilepsy is a common and very heterogeneous neurologic disorder. Genetic factors are likely to play a role in most cases, either because the underlying cause of epilepsy is primarily genetic or because genes modulate susceptibility to an epileptogenic insult. Primarily genetic epilepsies include conditions in which altered brain development or neurodegeneration are at the basis of seizures, but also conditions in which the brain is grossly normal, and the main, if not only, clinical feature is epilepsy. These are called idiopathic epilepsies, though this definition may change in the future. A few idiopathic epilepsies are monogenic disorders due to mutations in a variety of genes affecting neuronal excitability, synaptic transmission, or network development. Most cases have a complex etiology that combines predisposing genetic variants with nongenetic factors. Few of these have been identified so far and only in very few affected individuals, consisting mostly of deletions of critical chromosomal regions. Genetic factors also play a role in the response to antiepileptic drugs, affecting both their efficacy and their tolerability. There have been recent advances in discovering such factors, in particular those underlying risk to medication toxicity.

KEYWORDS

Epilepsy - Mendelian genetics - complex genetics - gene mapping - mutation analysis - genetic association studies - copy number variation - single nucleotide polymorphism - ion channel - neurotransmitter - brain development - brain metabolism - pharmacogenetics - drug response - drug toxicity

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Truncating mutations involving the gene PRRT2 have been identified in the vast majority of well-characterized families with Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the synaptic proteins.[139]