INDEPENDENT CONFIRMATION OF DISTINCT GENETIC EFFECTS ON MYOCLONIC AND ABSENCE SEIZURES
Abstract number :
1.204
Submission category :
Year :
2003
Submission ID :
3714
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Melodie R. Winawer, Carla Marini, Daniel Rabinowitz, Samuel F. Berkovic, Ingrid E. Scheffer, Ruth Ottman Department of Neurology, Columbia University, New York, NY; G.H. Sergievsky Center, Columbia University, New York, NY; Department of Epidemiology, Col
Using a novel approach we have recently shown that some of the genetic effects on myoclonic and absence seizures are distinct, while the shared versus distinct genetic effects on existing idiopathic generalized epilepsy syndromes (IGEs) are less clear. Here we apply this novel method to examine genetic contributions to myoclonic and absence seizures in an independent set of families, in order to confirm our original findings.
We examined evidence for distinct genetic contributions to myoclonic and absence seizures in families containing [ge]2 individuals with idiopathic generalized epilepsy. For this purpose we used a permutation test to evaluate whether different seizure types co-occur within families to a degree greater than expected by chance. We performed a similar analysis to examine evidence for distinct genetic contributions to juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and childhood absence epilepsy (CAE).
The analysis included 41 families containing 103 individuals with either myoclonic seizures alone, absence seizures alone, or both seizure types. Overall, 30 of the families (73%) were concordant for seizure type. The observed number of concordant families was significantly greater than that expected (30 vs. 18.02, Z=4.90, p[lt]0.0001).
36 of the families had 2 or more individuals with CAE, JAE, or JME. The observed number of families concordant for syndrome was significantly greater than expected when JME was compared to absence epilepsies (JAE+CAE) (27 vs 16.36, Z=4.34, p[lt]0.0001), but not when JAE was compared with CAE (13 vs 11.40, Z=0.85, p=0.3953).
These results confirm previous evidence for distinct genetic effects on absence and myoclonic seizures in an independent set of families. They also suggest that genetic differences among IGE syndromes may be driven by the seizure types that define them. The approach used here can direct the selection of subgroups of families more likely to be genetically homogenous for linkage analysis. In future linkage studies of IGEs, a focus on seizure type in addition to syndrome type may be useful.
[Supported by: NIH Grants R01 NS20656 , R01 NS43472, R01 NS36319, K23 NS02211
NIH/NIGMS R01 GM055978-06
National Health and Medical Research Council of Australia
Bionomics Ltd.]