Authors' recommendations: Febrile seizures (seizures triggered by fever) occur in 2% to 5% of children in the general population, generally occurring between the ages of 6 months and 6 years, with spontaneous remission by the age of 6. The persistence of febrile seizures beyond 6 years of age, or febrile seizures in conjunction with afebrile convulsions, is referred to as febrile seizures plus (FS+). A heritable disorder characterized by febrile seizures is known as generalized epilepsy with febrile seizures plus (GEFS+). GEFS+ is a spectrum disorder typified by febrile seizures or FS+ in multiple family members, some of whom progress to epilepsy. The range of seizure types that may occur in families with GEFS+ is broad and may include generalized (involving both cerebral hemispheres) tonic-clonic seizures, myoclonic seizures, and absence seizures. The most severe form of seizures seen in GEFS+ families is severe myoclonic epilepsy of infancy (SMEI), which is typically accompanied by ataxia and intellectual deterioration. Focal seizures (involving part of a single hemisphere; also known as partial seizures) are less common, but may be seen in some GEFS+ families. The clinical manifestations of GEFS+ are highly variable and often include multiple seizure types of varying severity in a single family. GEFS+ is inherited in an autosomal dominant manner, although the condition is characterized by incomplete penetrance, with only 60% to 80% of patients known to carry a pathogenic gene variant developing febrile and/or afebrile seizures. Sequence variants in three genes have been identified in multiple GEFS+ families: SCN1A (2q24), SCN1B (19q13.1), and GABRG2 (5q34). SCN1A and SCN1B encode the alpha ()1 and beta ()1 subunits of the voltage-gated sodium channel Nav1.1, a channel responsible for initiating and propagating neuronal action potentials. GABRG2 encodes the gamma ()2 subunit of the type A -aminobutyric acid (GABAA) receptor, a ligand-gated chloride channel that mediates fast synaptic inhibition in the central nervous system. While GEFS+ is generally considered a familial condition, sporadic GEFS+ cases (i.e., FS+ in the absence of a family history of seizures) have been reported. In addition, de novo SCN1A gene variants, particularly, variants leading to protein truncation and large deletions involving the SCN1A locus, are found in the majority of sporadic SMEI cases. This report focuses on GEFS+, with no in-depth analysis of related disorders, such as SMEI.

Project Status: Completed

Year Published: 2011

URL for published report: http://www.hayesinc.com/hayes/crd/?crd=12993

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

Contact Name: saleinfo@hayesinc.com

Contact Email: saleinfo@hayesinc.com

Copyright: 2011 Winifred S. Hayes, Inc