The familial occurrence of several rare forms of epilepsy have provided geneticists using linkage analysis the opportunity to assign a chromosomal locus to the defective gene, and, in a few instances, the gene itself has been cloned and mutations identified.7,8 Examples of these are shown in Table: Genetic Forms of Epilepsy.

In the syndrome of benign familial neonatal convulsions, the seizures remit spontaneously by 6 weeks without treatment. Two loci for this autosomal dominant disorder have been found, each of which contains a potassium channel gene (KCNQ2, KCNQ3) in which mutations have been identified.

Another familial disorder, termed generalized epilepsy with febrile seizures plus, has been described with mutations in a sodium channel gene (SCN1B). This gene, coded on chromosome 19, was considered a likely candidate because of the existence of ion channel defects in other paroxysmal disorders and the recognition that the anticonvulsants phenytoin and carbamazepine block sodium channels. The existence of rodent models of epilepsy involving other ion channel genes suggests that additional human epilepsies caused by channelopathies are likely to be discovered.

Ryan9 has suggested that children with Angelman’s syndrome who have a deletion in chromosome 15q11-13 may have more severe epilepsy than those with other causes of Angelman’s syndrome because the deleted region includes the gene GABRB3, which codes for a GABA receptor–chloride ionophore â subunit.

Adapted from: Kolodny, EH. Metabolic and genetic disorders. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;17–22. 
With permission from Elsevier (www.elsevier.com).

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