The role of genetics and ethnicity in epilepsy management.
Recent exciting developments in epilepsy genetics have led to significant insights into the mechanisms underlying seizure disorders. Success in epilepsy genetics research to date has resulted from identification of genes responsible for rare monogenic disorders, the majority encoding either voltage- or ligand-gated ion channels. For some conditions, such as benign familial neonatal seizures, an understanding of the underlying genetics is helpful in predicting prognosis. However, for other disorders, such as autosomal dominant nocturnal frontal lobe epilepsy, phenotypic severity is determined by factors other than the major dominant nicotinic subunit mutation found in some families. Further complexity arises when single-gene mutations give rise to heterogeneous phenotypes, as typically occur with generalized epilepsy with febrile seizures plus. Another area of increasing genetic endeavour, pharmacogenetics will allow tailoring of antiepileptic medication for each patient. Pharmacogenetics explores genetic polymorphisms in genes coding for drug-metabolizing enzymes, receptors and transporters. Polymorphisms have been identified that result in marked ethnic and interindividual differences in response to treatment. With further understanding of the impact of these differences, pharmacogenetic screening is likely to guide the management of epilepsy in the future.
Scheffer
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Department of Medicine and Paediatrics, The University of Melbourne, Epilepsy Research Centre, Melbourne, Vic., Australia. scheffer@unimelb.edu.au
D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000188:drug therapy / Q000208:ethnology* / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D030342:Genetic Diseases, Inborn / Q000235:genetics; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D008297:Male; D010375:Pedigree; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D013577:Syndrome
D000927:Anticonvulsants; D007473:Ion Channels; D003577:Cytochrome P-450 Enzyme System