Mutations in the GABRG2 gene cause a spectrum of seizure disorders, ranging from early-onset isolated febrile seizures to generalized epilepsy with febrile seizures plus, type 3, which represents a more severe phenotype. Patients with isolated febrile seizures usually ... Mutations in the GABRG2 gene cause a spectrum of seizure disorders, ranging from early-onset isolated febrile seizures to generalized epilepsy with febrile seizures plus, type 3, which represents a more severe phenotype. Patients with isolated febrile seizures usually have onset in the first year of life and show spontaneous remission by age 6 years, whereas patients with GEFS+ continue to have various types of febrile and afebrile seizures later in life (summary by Singh et al., 1999). Mutation in the GABRG2 gene can also cause childhood absence epilepsy (ECA2; 607681). Mutations in certain genes can cause a phenotypic spectrum of overlap between the isolated febrile phenotype and the GEFS+ phenotype. For a general phenotypic description and a discussion of genetic heterogeneity of GEFS+, see 604233. For a phenotypic description and a discussion of genetic heterogeneity of familial febrile seizures, see 121210.
Baulac et al. (2001) studied a family in which members in 3 successive generations had a phenotype consistent with GEFS+. Some had febrile seizures, others had afebrile epileptic seizures, and some had ... - GEFS+ Type 3 Baulac et al. (2001) studied a family in which members in 3 successive generations had a phenotype consistent with GEFS+. Some had febrile seizures, others had afebrile epileptic seizures, and some had both. Carvill et al. (2013) reported a 2.5-year-old boy with generalized epilepsy with febrile seizures plus. He had onset of febrile seizures at age 8 months, followed by absence seizures, atonic seizures, myoclonic jerks, and tonic-clonic seizures. EEG was normal and he had normal development. Genetic analysis identified a de novo heterozygous mutation in the GABRG2 gene (R323Q; 137164.0006). The patient was ascertained from a large cohort of 500 patients with epileptic encephalopathy who underwent candidate gene sequencing; this was the only patient found to carry a GABRG2 mutation. - Familial Febrile Seizures 8 Audenaert et al. (2006) reported a family in which 2 sibs and their father had isolated febrile seizures. Age at onset was between 13 and 18 months, and seizures resolved in all 3 patients by age 5 years. Mental development was normal, and epilepsy did not develop later in life. Molecular analysis identified a heterozygous mutation in the GABRG2 gene (R139G; 137164.0005) in all 3 patients. The paternal grandfather, who was reportedly unaffected, also carried the mutation, suggesting incomplete penetrance. - Clinical Variability Wallace et al. (2001) reported a 4-generation family in which febrile seizures and childhood absence epilepsy (ECA2; 607681) occurred alone or in combination. The authors noted that the 2 syndromes have different ages of onset, and that the physiology of each is distinct. However, all affected individuals were found to have the same mutation in the GABRG2 gene (R43Q; 137164.0002). The findings suggested that the mutation has age-dependent effects on different neuronal networks that influence the expression of these clinically distinct, but genetically related, epilepsy phenotypes. Kananura et al. (2002) reported a German family in which the father had isolated febrile convulsions as a child, but his 2 children had both febrile seizures and childhood absence epilepsy. All 3 had the same heterozygous truncation mutation in the GABRG2 gene (137164.0004). The findings indicated that in some families there is a phenotypic spectrum of childhood absence epilepsy and febrile convulsions with a similar underlying genetic defect.
In affected members of a family with GEFS+, Baulac et al. (2001) identified a heterozygous mutation in the GABRG2 gene (K289M; 137164.0001). The mutation affected a highly conserved residue located in the extracellular loop between transmembrane segments M2 ... In affected members of a family with GEFS+, Baulac et al. (2001) identified a heterozygous mutation in the GABRG2 gene (K289M; 137164.0001). The mutation affected a highly conserved residue located in the extracellular loop between transmembrane segments M2 and M3. Analysis of the mutated and wildtype alleles in Xenopus laevis oocytes confirmed the predicted effect of the mutation, a decrease in the amplitude of GABA-activated currents. In affected members of a family with febrile seizures and childhood absence epilepsy (ECA2; 607681), Wallace et al. (2001) identified a heterozygous mutation in the GABRG2 gene (R43Q; 137164.0002). In a German family in which the father had isolated febrile convulsions as a child, but his 2 children had both febrile seizures and childhood absence epilepsy, Kananura et al. (2002) identified a heterozygous truncation mutation in the GABRG2 gene (137164.0004).