Complex inheritance and parent-of-origin effect in juvenile myoclonic epilepsy.
BACKGROUND
Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epilepsy (IGE) with complex inheritance. Previous studies have suggested maternal inheritance and female excess in IGEs but have not been specific for JME. We investigated evidence for maternal inheritance, female excess and patterns of familial seizure risk in a well-characterized sample of JME families.


METHODS
We ascertained 89 families through a JME proband and 50 families through a non-JME IGE proband. JME families were divided into those with and without evidence of linkage to the EJM1 susceptibility locus on chromosome 6. We analyzed transmission in 43 multigenerational families, calculated the adjusted sex ratio for JME, and looked for evidence of seizure specific risk in 806 family members.


RESULTS
We found evidence for preferential maternal transmission in both EJM1-linked and unlinked families (2.7:1), evidence even more marked when potential selection factors were excluded. The adjusted female: male risk ratio was very high in JME (RR=12.5; 95% CI: 1.9-83.7). Absence seizures in JME probands increased the overall risk of seizures in first degree relatives (15.8% vs. 7.0%, P=0.011), as well as first-degree relatives' specific risk of absence seizures (6% vs. 1.6%, P=0.01), but not myoclonic seizures.


CONCLUSIONS
We have confirmed the finding of maternal inheritance in JME, which is not restricted to JME families linked to the EJM1 locus. The striking female excess in JME may relate to anatomical and/or endocrine sexual dimorphism in the brain. Evidence for independent inheritance of absence and myoclonic seizures in JME families reinforces a model in which combinations of loci confer susceptibility to the component seizure types of IGE.
Pal
Deb K
DK
Clinical and Genetic Epidemiology Unit, Department of Psychiatry, Columbia University, NY 10032, USA. dkp28@columbia.edu
Durner
Martina
M
Klotz
Irene
I
Dicker
Elisa
E
Shinnar
Shlomo
S
Resor
Stanley
S
Cohen
Jeffrey
J
Harden
Cynthia
C
Moshé
Solomon L
SL
Ballaban-Gill
Karen
K
Bromfield
Edward B
EB
Greenberg
David A
DA
D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004569:Electroencephalography / Q000379:methods; D004829:Epilepsy, Generalized; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020190:Myoclonic Epilepsy, Juvenile / Q000453:epidemiology / Q000235:genetics*; D012306:Risk; D012737:Sex Factors