Mutations in the SCN9A gene cause a spectrum of seizure disorders, ranging from early-onset isolated febrile seizures to generalized epilepsy with febrile seizures plus, type 7, which represents a more severe phenotype. Patients with isolated febrile seizures usually ... Mutations in the SCN9A gene cause a spectrum of seizure disorders, ranging from early-onset isolated febrile seizures to generalized epilepsy with febrile seizures plus, type 7, which represents a more severe phenotype. Patients with isolated febrile seizures usually have onset between ages 5 months to 4 years and show spontaneous remission by age 6 years (summary by Singh et al., 2009), whereas patients with GEFS+ continue to have various types of febrile and afebrile seizures later in life (summary by Singh et al., 1999). 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.
Singh et al. (2009) studied a large Utah family with autosomal dominant GEFS+. The family was originally reported by Peiffer et al. (1999) as having predominantly febrile seizures, which was mapped to a locus on chromosome 2q24 designated ... Singh et al. (2009) studied a large Utah family with autosomal dominant GEFS+. The family was originally reported by Peiffer et al. (1999) as having predominantly febrile seizures, which was mapped to a locus on chromosome 2q24 designated 'FEB3.' However, Moulard et al. (2000) and Scheffer et al. (2000) both concluded that the phenotype reported in the family by Peiffer et al. (1999) was most consistent with GEFS+, since afebrile seizures continued beyond childhood in several affected individuals. The follow-up report by Singh et al. (2009) stated that this family showed a broad spectrum of seizure manifestations. Eleven individuals experienced only febrile seizures before age 6 years, whereas 10 additional individuals developed later afebrile seizures. In 8 of the 10, seizures remitted by age 16 years. The remaining 2 affected individuals developed intractable epilepsy: 1 had complex-partial seizures associated with left mesial temporal sclerosis, and the other had afebrile generalized convulsive seizures requiring the placement of a vagal nerve stimulator. This phenotype is designated GEFS+, type 7. Singh et al. (2009) also reported 2 unrelated patients with simple febrile seizures and 2 different heterozygous mutations in the SCN9A gene (I62V; 603415.0020 and P149Q; 603415.0021, respectively). This phenotype is designated FEB3B.
In affected members of a large Utah family with generalized epilepsy with febrile seizures plus, type 7, originally reported by (Peiffer et al., 1999), Singh et al. (2009) identified a heterozygous mutation in the SCN9A gene (N641Y; 603415.0018) ... In affected members of a large Utah family with generalized epilepsy with febrile seizures plus, type 7, originally reported by (Peiffer et al., 1999), Singh et al. (2009) identified a heterozygous mutation in the SCN9A gene (N641Y; 603415.0018) on 2q24. In 2 unrelated probands with isolated febrile seizures (FEB3B), Singh et al. (2009) identified 2 different heterozygous mutations in the SCN9A gene (I62V, 603415.0020 and P149Q, 603415.0021, respectively).