Clinical Indicators of Genetic Susceptibility to Epilepsy

Abstract

We evaluated clinical indicators of genetic susceptibility to epilepsy in the families of 1,957 adults with epilepsy (probands) ascertained from voluntary organizations. Very few of the probands in this series had idiopathic epilepsy syndromes. Among relatives of probands with postnatal CNS insults, risks of epilepsy were no higher than in the general population. Risk was increased in relatives of probands without identified CNS insults (i.e., those with idiopathic/cryptogenic epilepsy) or with neurological deficit presumed present at birth, compared with relatives of probands with postnatal CNS insults. Among relatives of probands with idiopathic/cryptogenic epilepsy, risks were higher in parents and siblings, but not in offspring, of probands with generalized onset as compared with partial onset seizures. Risks in offspring were higher if the probands had onset of idiopathic/cryptogenic epilepsy before age 10 as compared with age > or = 10 years, but risks in parents and siblings were not associated with the probands's age at onset. These results suggest that genetic susceptibility increases risk of some forms of cryptogenic epilepsy and of epilepsy associated with neurological deficit presumed present at birth, but not of postnatal symptomatic epilepsy. The influences on risk in offspring may differ from those in parents and siblings.

Relations of genetic and environmental factors in the etiology of epilepsy

“…In addition, risk was significantly increased for epilepsy associated with neurodeficits among relatives of probands with idiopathic/cryptogenic epilepsy (2.1-fold, see Table 2). The consistency of these findings provides support for the possibility of a shared genetic susceptibility to epilepsy and cerebral palsy, as we and others have suggested [8,[19][20][21].Risk of epilepsy was not increased among relatives of probands with postnatal symptomatic epilepsy. Schaumann and associates [22] also reported that risk was not increased in relatives of probands with post-traumatic epilepsy.…”

“…In this study, we extended our previous investigations of epilepsy in the families of probands from the EFSCU [8,17], by evaluating the relations between genetic and environmental factors in their effects on risk. For this purpose, we computed SMRs for specific etiologies of epilepsy in the relatives of probands with specific etiologies, using age-and decade-specific incidence of epilepsy from the Rochester-Olmsted County Record Linkage Project as the reference.…”

“…Data from Rochester [15] indicate that incidence of epilepsy has not increased in individuals younger than age 40 during the time periods we investigated; thus, we concluded that the apparent cohort effect is likely to be due to underreporting of epilepsy that was present at young ages in older relatives. In previous analyses, we have controlled for this underreporting by adding birth year of the relatives as a covariate [8]. Analysis restricted to the period after 1955 allows a more refined control for underreporting, because regardless of the birth year of the relatives, we expect less underreporting of epilepsy for recent time periods than for those in the past.…”

“…In the classic twin study of epilepsy by Lennox [3], the difference in concordance rates between monozygotic and dizygotic twins was smaller when the index twin's epilepsy was symptomatic than when it was idiopathic or cryptogenic. In our recent study [8], risk of epilepsy was higher in relatives of probands with idiopathic/cryptogenic epilepsy than in relatives of probands with symptomatic epilepsy. An exception to this pattern, however, was the subgroup of symptomatic epilepsy associated with neurodeficit from birth.…”

Epilepsias parciais familiares

“…A influência de fatores genéticos nas epilepsias sempre foi suspeitada, sendo que a recorrência familiar foi inicialmente demostrada nas epilepsias generalizadas [1][2][3][4][5] e mais recentemente também nas epilepsias parciais [6][7][8][9][10][11] . Clinicamente, muitas destas síndromes se apresentam de forma heterogênea, o que pode dificultar o reconhecimento da recorrência familiar.…”