EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 11
General Information (adopted from Orphanet):
Synonyms, Signs:
EJM8, INCLUDED
EJA2, INCLUDED
EIG11 EPILEPSY, JUVENILE MYOCLONIC, SUSCEPTIBILITY TO, 8, INCLUDED
EPILEPSY, JUVENILE ABSENCE, SUSCEPTIBILITY TO, 2, INCLUDED
Both juvenile myoclonic epilepsy and juvenile absence epilepsy are subtypes of idiopathic generalized epilepsy (EIG).
For a general phenotypic description and a discussion of genetic heterogeneity of these disorders, see EIG (600669), EJM (254770), and EJA ... Both juvenile myoclonic epilepsy and juvenile absence epilepsy are subtypes of idiopathic generalized epilepsy (EIG). For a general phenotypic description and a discussion of genetic heterogeneity of these disorders, see EIG (600669), EJM (254770), and EJA (607631).
In 2 sibs with juvenile absence epilepsy found by Sander et al. (2000) to be linked to chromosome 3q26,Haug et al. (2003) identified a heterozygous mutation in the CLCN2 gene (G715E; 600570.0003). Another sib with generalized spike-wave discharges ... In 2 sibs with juvenile absence epilepsy found by Sander et al. (2000) to be linked to chromosome 3q26,Haug et al. (2003) identified a heterozygous mutation in the CLCN2 gene (G715E; 600570.0003). Another sib with generalized spike-wave discharges on EEG also carried the mutation. The father, who also carried the mutation, reportedly had unclassified seizures in childhood, but his severe alcoholism as an adult rendered his disease status uncertain. Functional studies of the mutant channel showed normal current amplitudes, but altered voltage-dependent gating, potentially leading to hyperexcitability. The family structure, diagnosis, and mutation status were confirmed by Kleefuss-Lie et al. (2009). The mutation was not observed in 4,700 German control individuals. In 3 of 46 unrelated families with IGE localized to 3q26 (including some of the families reported by Sander et al. (2000)), Haug et al. (2003) identified 3 mutations in the CLCN2 gene (600570.0001-600570.0003). In a reevaluation of 2 of the families, 1 with juvenile myoclonic epilepsy and 1 with childhood absence epilepsy Haug et al. (2003), Kleefuss-Lie et al. (2009) found discrepancies in the family structure, phenotype, and genetic analysis. On this basis, all but one of the original authors retracted the paper. Niemeyer et al. (2010) disagreed with the conclusion by Kleefuss-Lie et al. (2009) that some of the work by Haug et al. (2003) had merit. Based on lack of functional consequences of the variants reported by Haug et al. (2003) (600570.0001-600570.0003), Niemeyer et al. (2010) asserted that there is no evidence for a role of CLCN2 variants in idiopathic generalized epilepsy. In 2 sibs of Tunisian origin with juvenile myoclonic epilepsy, Saint-Martin et al. (2009) identified a heterozygous mutation in the CLCN2 gene (R235Q; 600570.0004). Another sib with JME was not available for genetic analysis. The mutation was not observed in 263 control individuals from North Africa or 183 French controls. Saint-Martin et al. (2009) identified a different heterozygous mutation in the CLCN2 gene (R577Q; 600570.0005) in 2 German sibs with idiopathic generalized epilepsy. The mutation was not observed in 203 German controls or 183 French controls. In both families, the unaffected father also had the mutation, suggesting either reduced penetrance or that additional unidentified factors are necessary for full phenotypic expression.