Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations

Area of Science:

• Genetics
• Neurology
• Epilepsy Research

Background:

• SCN1B, encoding the sodium channel beta 1 subunit, is the first identified gene for generalized epilepsy with febrile seizures plus (GEFS+).
• Previously, SCN1B mutations were reported in only three families.
• This study expands the known genetic basis of epilepsy syndromes.

Purpose of the Study:

• To identify and characterize new SCN1B mutations associated with epilepsy syndromes.
• To define the phenotypic spectrum associated with SCN1B mutations, including temporal lobe epilepsy (TLE).
• To evaluate the efficacy of epilepsy surgery in patients with SCN1B-related TLE.

Main Methods:

• Genetic analysis of the SCN1B gene in 402 individuals with various epilepsy syndromes.
• Detailed electroclinical phenotyping of affected family members.
• Quantitative MRI in patients with temporal lobe epilepsy (TLE).

Main Results:

• Four new families with SCN1B missense mutations were identified, including two with the C121W mutation and one each with novel R85C and R85H mutations.
• The identified phenotypes included febrile seizures, GEFS+, and temporal lobe epilepsy (TLE).
• All individuals with SCN1B-related TLE carried the C121W mutation; two underwent successful temporal lobectomy.

Conclusions:

• SCN1B mutations are confirmed to play a role in GEFS+.
• The phenotypic spectrum of SCN1B mutations extends to include TLE as a sole manifestation.
• Epilepsy surgery is a viable option for TLE associated with SCN1B mutations.