A GABRB3 mutation (c.5G>A, p.Trp2*) in twins with generalized epilepsy with febrile seizures: A case report

In children aged 3 months to 6 years, convulsions that occur when the body temperature reaches >38˚C are referred to as febrile seizures (FS), provided that central nervous system infections and other metabolic etiologies are excluded. Generalized epilepsy with FS plus (GEFS+) refers to children who continue to suffer from FS after the age of 6 years with or without generalized and partial epileptic seizures. It is characterized by incomplete penetrance and genetic heterogeneity. In recent years, genetic techniques have undergone advancements, such that multiple genes can now be identified in clinical screenings, providing assistance in the diagnosis and delineation of diseases. Evidence suggests that mutations in a protein coding gene, γ-aminobutyric acid type A receptor β3 subunit (GABRB3) may be associated with GEFS+. The present case reports female twins with febrile seizures that typically occurred after fever, with seizures still occurring after the age of 6. Their growth and development were uneventful, with their laboratory, imaging and electroencephalography results almost within normal limits. After inquiring their medical history, it was found that the father of the twins had similar seizures when he was young. Next, peripheral blood samples were collected from the twins and their parents for whole-exome sequencing. The gene sequencing results showed that the twins and their father had a GABRB3 nonsense mutation (c.5G>A, p.Trp2*), which causes translation to terminate prematurely at the second tryptophan position. After consulting the literature, it was considered that they may have GABRB3 mutation-associated GEFS+. After treatment with levetiracetam, the seizures in children have been effectively controlled and their growth and development have not been affected, which is within the normal range.