Generalized Epilepsy With Febrile Seizures Plus, Type 8

Description

Generalized epilepsy with febrile seizures-plus (GEFS+) is a familial epilepsy syndrome with extremely variable expressivity. Seizure phenotypes include classic infantile febrile seizures, febrile seizures persisting beyond age 6 years or accompanied by afebrile generalized tonic-clonic seizures (GTCS), generalized or localization-related epilepsy, and more rarely, severe seizures with encephalopathy (summary by Poduri et al., 2009).

For a discussion of genetic heterogeneity of GEFS+, see 604233.

Clinical Features

Poduri et al. (2009) reported a 4-generation family from Central America with a range of seizure phenotypes consistent with the GEFS+ spectrum. Six had onset of febrile seizures between ages 8 and 12 months and resolution before age 4 years. Two had early febrile seizures and later epilepsy, including localization-related epilepsy and GTCS. Two had febrile seizures-plus, 1 with persistence of febrile seizures until age 7 and both with GTCS. Finally, 4 patients did not have febrile seizures in infancy, but developed afebrile GTCS later in life. One patient had a severe form of epilepsy associated with recurrent febrile and afebrile seizures and developmental delay after the first year of life.

Inheritance

The transmission pattern of GEFS+ in the 4-generation family reported by Poduri et al. (2009) was consistent with autosomal dominant inheritance.

Mapping

By genomewide analysis of a large 4-generation family from Central America with GEFS+, Poduri et al. (2009) found linkage to an 18.1-Mb (12.4-cM) region on chromosome 6q16.3-q22.31 between markers D6S962 and D6S287 (maximum multipoint lod score of 4.68). Sequencing of 16 candidate genes did not reveal a causative mutation, and there were no deletions or duplications within the region. Poduri et al. (2009) noted that no genes encoding ion channels map to this region.