Only about 1% of all epilepsy cases are caused by the presence of a single "epilepsy gene". However many more cases than this show some sort of family inheritance pattern. A study of four generations
of a French family, reported last month in the journal Neurology, describes an interesting example where two genes interact.

Dr Rima Nabbout and colleagues from the Institute for Medical Research in Paris studied a single extended family of 51 people. Thirteen people in this family had experienced febrile seizures by the age of seven years. Six of them went on to develop epilepsy, five having childhood absence epilepsy and one having temporal lobe epilepsy.

The researchers carried out a genetic analysis of the 13 family members who had had seizures and another 13 members who had not, to see if there were any genes or sequences of genes that were associated with having seizures. They were particularly interested in genes that had previously been identified (in other research studies) as being associated with febrile seizure syndromes.

Dr Nabbout and colleagues found a sequence of genes on chromosome 3p that occurred in all family members who had experienced febrile seizures. Another section of genes on chromosome 18p showed an interesting pattern: a particular sequence was common to all family members who went on to develop epilepsy after febrile seizures, but did not occur in those who only had febrile seizures, or in those who had never had seizures.

This study is a very neat example of what's called an "oligogenic" epilepsy, that is an epilepsy caused by a handful of genes interacting. Here, one gene (on 3p) appears to make members of this family susceptible to febrile seizures, but it's the presence of an additional mutation (a "modifier gene" on 18p) that decides whether they go on to develop epilepsy afterwards.

The other important point here is that the genes associated with epilepsy in this family have not been associated with epilepsy in other studies in other families, even though the outward appearance of the seizures was the same. These results may therefore not be applicable to other families.

Febrile seizures happen to some children when they have a high body temperature. For most, they don't cause any permanent injury to the brain, but some children do go on to develop epilepsy afterwards. Epilepsy Research UK is currently funding a study in Manchester to find out how the body's immune response may be involved in
how febrile seizures damage the brain, leading to epilepsy.

Dr Nabbout attended the Expert International Workshop on the genetics of epilepsy organised by the Epilepsy Research
Foundation (now Epilepsy Research UK) in March 2006. The proceedings of the workshop will shortly be published in the journal Epileptic Disorders.

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