Epilepsy, Idiopathic Generalized, Susceptibility To, 13
A number sign (#) is used with this entry because of evidence that susceptibility to idiopathic generalized epilepsy-13 (EIG13), including juvenile myoclonic epilepsy-5 (EJM5) and childhood absence epilepsy-4 (ECA4), can be conferred by heterozygous mutation in the GABRA1 gene (137160) on chromosome 5q34.
DescriptionChildhood absence epilepsy and juvenile myoclonic epilepsy are both subtypes of what has classically been called idiopathic generalized epilepsy (IGE, EIG; see 600669).
For a phenotypic description and a discussion of genetic heterogeneity of idiopathic generalized epilepsy, see 600669.
For a phenotypic description and a discussion of genetic heterogeneity of juvenile myoclonic epilepsy and childhood absence epilepsy, see ECA1 (600131) and JME (254770), respectively.
Clinical FeaturesCossette et al. (2002) reported a French Canadian family in which 14 members over 4 generations had juvenile myoclonic epilepsy. All affected members had a similar phenotype, with no history of febrile seizures.
Lachance-Touchette et al. (2011) reported 2 unrelated French Canadian families with idiopathic generalized epilepsy. In 1 family, 3 affected individuals had late-onset afebrile, generalized tonic-clonic seizures as well as photosensitivity. In the other family, 4 affected individuals had mainly febrile seizures, with or without generalized tonic-clonic and absence seizures.
InheritanceThe transmission pattern of EJM5 in the family reported by Cossette et al. (2002) was consistent with autosomal dominant inheritance.
The transmission pattern of EIG13 in the families reported by Lachance-Touchette et al. (2011) was consistent with autosomal dominant inheritance and incomplete penetrance.
Molecular GeneticsIn 14 members of a French Canadian family with juvenile myoclonic epilepsy, Cossette et al. (2002) identified a heterozygous mutation in the GABRA1 gene (A322D; 137160.0001).
Among 98 German individuals with IGE, Maljevic et al. (2006) identified 1 boy with a heterozygous mutation in the GABRA1 gene (137160.0002). He had childhood absence epilepsy with onset of short episodes of loss of consciousness in daily clusters between 3 and 5 years of age. There were no febrile seizures and no family history of the disorder.
In affected members of 2 unrelated French Canadian families with EIG, Lachance-Touchette et al. (2011) identified 2 different heterozygous mutations in the GABRA1 gene (137160.0006 and 137160.0007, respectively). In vitro studies showed that the mutations reduced surface expression of the proteins and altered neurotransmitter effectiveness, resulting in a detrimental effect on inhibitory control of neuronal circuits.