Epilepsy, Idiopathic Generalized, Susceptibility To, 9
A number sign (#) is used with this entry because of evidence that susceptibility to idiopathic generalized epilepsy-9 (EIG9) and juvenile myoclonic epilepsy-6 (EJM6) is conferred by mutation in the CACNB4 gene (601949) on chromosome 2q23.
DescriptionFor a general phenotypic description and a discussion of genetic heterogeneity of idiopathic generalized epilepsy, see 600669. Juvenile myoclonic epilepsy is a subtype of idiopathic generalized epilepsy; see 254770 for a general phenotypic description and a discussion of genetic heterogeneity of JME.
Clinical FeaturesEscayg et al. (2000) reported a woman with a history of sporadic typical absence seizures (brief spells of loss of consciousness) and repetitive bilateral myoclonic jerks in the shoulders and arms after awakening, since age 9 years. She never had loss of consciousness. Her epilepsy syndrome was classified as juvenile myoclonic epilepsy. She later experienced several generalized tonic-clonic seizures, usually within 1 hour of awakening. EEGs of the proband's daughter showed generalized 3/s spike-wave discharges without epileptic seizures.
Escayg et al. (2000) also reported a German father and son with an atypical but similar clinical syndrome of idiopathic generalized epilepsy with rare juvenile atypical prolonged absences and occasional generalized tonic-clonic seizures (GTCS). The father had normal intellectual and psychomotor development. One febrile convulsion occurred at age 3 years. After age 6, he had occasional GTCS, predominantly on awakening, and, after age 12, occasional episodes of absence were described. A prolonged atypical absence occurred in his eldest son at age 14 years while he was playing cards. At age 17, he experienced GTCS shortly after awakening. Two years later, he experienced a generalized tonic seizure while playing a complex strategic game after sleep withdrawal. He also experienced occasional prolonged staring spells when lacking sleep. Both affected individuals reported that seizures were precipitated by playing complex strategic games (praxis induction), suggesting an unusual cognitive trigger of seizure initiation (Inoue et al., 1992).
Molecular GeneticsIn a woman with juvenile myoclonic epilepsy, Escayg et al. (2000) identified a heterozygous mutation in the CACNB4 gene (R482X; 601949.0001). A German father and son with EIG had a heterozygous mutation in the CACNB4 gene (C104F; 601949.0002).