Phenotypes and genotypes in epilepsy with febrile seizures plus

Area of Science:

• Genetics
• Neurology
• Epilepsy Research

Background:

• Mutations in sodium channel genes (SCN1A, SCN2A, SCN1B) and GABA(A) receptor gene (GABRG2) are known causes of certain epilepsies associated with febrile seizures.
• Febrile seizures plus (FS+) and subsequent epilepsies represent a spectrum of seizure disorders with complex genetic underpinnings.

Purpose of the Study:

• To investigate the genetic basis of febrile seizures plus (FS+) and related epilepsies in Japanese families.
• To identify specific gene mutations responsible for seizure phenotypes in affected individuals.

Main Methods:

• Genetic analysis of 19 unrelated Japanese families with probands exhibiting FS+ or epilepsy following FS+.
• Identification and characterization of mutations in sodium channel genes (SCN1A, SCN2A) and potentially other related genes.

Main Results:

• Two missense mutations in SCN1A were identified in two FS+ families, and one mutation in SCN2A was found in another family.
• The combined frequency of mutations in SCN1A, SCN2A, SCN1B, SCN2B, and GABRG2 was 15.8% in Japanese patients with FS+.
• One family exhibited digenic inheritance with an SCN2A mutation, suggesting the involvement of modifier genes.

Conclusions:

• The study identified SCN1A and SCN2A mutations contributing to FS+ and related epilepsies in the Japanese population.
• A new term, epilepsy with febrile seizures plus (EFS+), is proposed due to the complex and often non-autosomal-dominant inheritance patterns observed.
• Simultaneous involvement of multiple genes is a potential factor in the complex seizure phenotypes of EFS+.