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A Twin Study of Genetic Influences on Epilepsy Outcome

  • Michael R. Johnson (a1), Roger L. Milne (a2), Yvonne Torn-Broers (a3), John L. Hopper (a4), Ingrid E. Scheffer (a5) and Samuel F. Berkovic (a6)...

Abstract

The identification of genetic factors that confer susceptibility to the epilepsies has to date been the focus of genetic efforts in this field. Few studies have assessed the genetic contribution to disease course in epilepsy, yet an understanding of the genetic influences on epilepsy outcome is key to developing new therapeutic strategies. The aim of this study was to assess the genetic contributions to epilepsy outcome in twin pairs concordant for epilepsy. We studied 37 epilepsy concordant twin pairs (27 monozygotic, 10 dizygotic) in whom there were no recognized environmental contributions (e.g., acquired brain injury) to epilepsy, and in whom the most likely cause for epilepsy was a shared genetic susceptibility. Clinical outcome was determined using the binary measure of Seizure Status (seizure remission or recurrence) and on a six-category ordinal Outcome Scale. Epilepsy outcome was independent of age of seizure onset, age at assessment and major epilepsy syndrome diagnosis. The proportion of twin pairs concordant for Seizure Status was 0.81 (22/27) for monozygous and 1.0 (10/10) for dizygous pairs, p = 0.3. Within-pair correlation in outcome (Outcome Scale) was 0.60 (95% CI: 0.32, 0.78) in monozygous and 0.78 (0.48, 0.92) in dizygous pairs. These data provide no evidence for genetic influences on epilepsy outcome independent of those that contribute to disease susceptibility. The observed high correlations for outcome suggest that, for epilepsy, susceptibility genes also have a major influence on outcome.

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Copyright

Corresponding author

*Address for correspondence: Michael R. Johnson, Division of Neurosciences and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London W6 8RF, UK.

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