Genetic liability to epilepsy in Kerala State, India.
BACKGROUND
Familial clustering is common in epilepsies, but pedigree patterns suggest a multi-factorial inheritance. Genetic liability for multi-factorial inheritance is population specific and such data are not available for the population of Kerala or other states in south India.


OBJECTIVE
In this study, we have attempted to determine the genetic liability to epilepsy based on an adult population of this state.


METHODS
Pedigrees were recorded for probands who reported to the Kerala Registry of Epilepsy and Pregnancy. In order to obtain a genetically matched sample for comparison and estimation of empiric risks, we have used the family history of the spouse except when the spouse was proband's relative. The ILAE criteria were followed for diagnosis and classification of epilepsy.


RESULTS
Data were collected on 18,419 family members of 505 probands with epilepsy (82 men and 423 women) and 10,231 family members of spouses (control). The frequency of epilepsy in first and second-degree relatives of the spouses was comparable to the population frequency (0.5%), justifying the use of this sample as control. Positive family history was observed in 22.2% of probands and 8.24% of controls (Odd's Ratio 3.2, 95% Confidence Interval 2.12-4.73). An affected first-degree relative was observed in 7.5% of probands. The corresponding figure for GE, LRE and other epileptic syndromes were 10.2%, 5.8% and 5.12%, respectively. The segregation ratio for Juvenile Myoclonic Epilepsy (JME) (1:19) was higher than that for other types of Generalized Epilepsy (GE) (1:24) and Localization Related Epilepsy (LRE) (1:52). Prevalence of epilepsy among the first-degree relatives (1.96%) was greater than the square root of the population frequency (0.51%) and was higher than that for second-degree (1.24%) and third-degree (0.64%) relatives for the probands. Probands had higher parental consanguinity (13.07%) compared to controls (6.64%). The above factors support a complex inheritance. Genetic liability to epilepsy (heritability) is greater for GE (0.6) and significantly higher for JME (0.7) compared to LRE (0.4). A limitation of this study is that the inferences are based on a predominantly adult female proband sample but no gender specific differences were identified.


CONCLUSIONS
The observations of this study indicate complex inheritance and the liability values are useful for genetic counseling in the local population. Further studies involving more individuals from younger age group and male gender are envisaged.
Nair
R Renuka
RR
Kerala Registry of Epilepsy and Pregnancy, Departments of Neurology and Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695011, India.
Thomas
Sanjeev V
SV
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004827:Epilepsy / Q000145:classification / Q000453:epidemiology* / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D016017:Odds Ratio; D010375:Pedigree; D015995:Prevalence; D012042:Registries / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D035781:Siblings