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Generalized epilepsy with febrile seizures plus 3(GEFSP3)

MedGen UID:
347692
Concept ID:
C1858674
Disease or Syndrome
Synonyms: GEFS+, TYPE 3; GEFSP3
 
OMIM®: 137164; 607681

Definition

Mutations in the GABRG2 gene cause a spectrum of seizure disorders, ranging from early-onset isolated febrile seizures to generalized epilepsy with febrile seizures plus, type 3, which represents a more severe phenotype. Patients with isolated febrile seizures usually have onset in the first year of life and show spontaneous remission by age 6 years, whereas patients with GEFS+ continue to have various types of febrile and afebrile seizures later in life (summary by Singh et al., 1999). Mutation in the GABRG2 gene can also cause childhood absence epilepsy (ECA2; 607681). Mutations in certain genes can cause a phenotypic spectrum of overlap between the isolated febrile phenotype and the GEFS+ phenotype. For a general phenotypic description and a discussion of genetic heterogeneity of GEFS+, see 604233. For a phenotypic description and a discussion of genetic heterogeneity of familial febrile seizures, see 121210. [from OMIM]

Additional description

From MedlinePlus Genetics
Genetic epilepsy with febrile seizures plus (GEFS+) is a spectrum of seizure disorders of varying severity. GEFS+ is usually diagnosed in families whose members have a combination of febrile seizures, which are triggered by a high fever, and recurrent seizures (epilepsy) of other types, including seizures that are not related to fevers (afebrile seizures). The additional seizure types usually involve both sides of the brain (generalized seizures); however, seizures that involve only one side of the brain (partial seizures) occur in some affected individuals. The most common types of seizure in people with GEFS+ include myoclonic seizures, which cause involuntary muscle twitches; atonic seizures, which involve sudden episodes of weak muscle tone; and absence seizures, which cause loss of consciousness for short periods that appear as staring spells.

The most common and mildest feature of the GEFS+ spectrum is simple febrile seizures, which begin in infancy and usually stop by age 5. When the febrile seizures continue after age 5 or other types of seizure develop, the condition is called febrile seizures plus (FS+). Seizures in FS+ usually end in early adolescence.

A condition called Dravet syndrome (also known as severe myoclonic epilepsy of infancy or SMEI) is often considered part of the GEFS+ spectrum and is the most severe disorder in this group. Affected infants typically have prolonged seizures lasting several minutes (status epilepticus), which are triggered by fever. Other seizure types, including afebrile seizures, begin in early childhood. These types can include myoclonic or absence seizures. In Dravet syndrome, these seizures are difficult to control with medication, and they can worsen over time. A decline in brain function is also common in Dravet syndrome. Affected individuals usually develop normally in the first year of life, but then development stalls, and some affected children lose already-acquired skills (developmental regression). Many people with Dravet syndrome have difficulty coordinating movements (ataxia) and intellectual disability.

Family members with GEFS+ may have different combinations of febrile seizures and epilepsy. For example, one affected family member may have only febrile seizures, while another also has myoclonic epilepsy. While GEFS+ is usually diagnosed in families, it can occur in individuals with no history of the condition in their family.

Some people with GEFS+ have seizure disorders of intermediate severity that may not fit into the classical diagnosis of simple febrile seizures, FS+, or Dravet syndrome.  https://medlineplus.gov/genetics/condition/genetic-epilepsy-with-febrile-seizures-plus

Professional guidelines

PubMed

Fendri-Kriaa N, Kammoun F, Rebai A, Kolsi D, Hadj Salem I, Fakhfakh F, Triki C
Eur J Neurol 2009 Jun;16(6):697-704. Epub 2009 Feb 19 doi: 10.1111/j.1468-1331.2009.02570.x. PMID: 19236456

Recent clinical studies

Etiology

Johannesen K, Marini C, Pfeffer S, Møller RS, Dorn T, Niturad CE, Gardella E, Weber Y, Søndergård M, Hjalgrim H, Nikanorova M, Becker F, Larsen LH, Dahl HA, Maier O, Mei D, Biskup S, Klein KM, Reif PS, Rosenow F, Elias AF, Hudson C, Helbig KL, Schubert-Bast S, Scordo MR, Craiu D, Djémié T, Hoffman-Zacharska D, Caglayan H, Helbig I, Serratosa J, Striano P, De Jonghe P, Weckhuysen S, Suls A, Muru K, Talvik I, Talvik T, Muhle H, Borggraefe I, Rost I, Guerrini R, Lerche H, Lemke JR, Rubboli G, Maljevic S
Neurology 2016 Sep 13;87(11):1140-51. Epub 2016 Aug 12 doi: 10.1212/WNL.0000000000003087. PMID: 27521439
Camfield P, Camfield C
Epileptic Disord 2015 Jun;17(2):124-33. doi: 10.1684/epd.2015.0737. PMID: 25917466
Terczyńska I, Szczepanik E, Duszyc K, Górka P, Tataj R, Hoffman-Zacharska D
Dev Period Med 2014 Oct-Dec;18(4):426-31. PMID: 25874779
Tan EH, Razak SA, Abdullah JM, Mohamed Yusoff AA
Epilepsy Res 2012 Dec;102(3):210-5. Epub 2012 Sep 1 doi: 10.1016/j.eplepsyres.2012.08.004. PMID: 22944210
Veggiotti P, Cardinali S, Montalenti E, Gatti A, Lanzi G
Epileptic Disord 2001 Jan-Mar;3(1):29-32. PMID: 11313220

Diagnosis

Heron SE, Regan BM, Harris RV, Gardner AE, Coleman MJ, Bennett MF, Grinton BE, Helbig KL, Sperling MR, Haut S, Geller EB, Widdess-Walsh P, Pelekanos JT, Bahlo M, Petrovski S, Heinzen EL, Hildebrand MS, Corbett MA, Scheffer IE, Gécz J, Berkovic SF
Neurology 2021 May 4;96(18):e2251-e2260. Epub 2021 Mar 23 doi: 10.1212/WNL.0000000000011855. PMID: 34038384Free PMC Article
Bisulli F, Licchetta L, Baldassari S, Muccioli L, Marconi C, Cantalupo G, Myers C, Menghi V, Minardi R, Caporali L, Marini C, Guerrini R, Mefford HC, Tinuper P, Pippucci T
Epileptic Disord 2019 Apr 1;21(2):185-191. doi: 10.1684/epd.2019.1046. PMID: 30977726
Gataullina S, Bienvenu T, Nabbout R, Huberfeld G, Dulac O
Dev Med Child Neurol 2019 Aug;61(8):891-898. Epub 2019 Jan 25 doi: 10.1111/dmcn.14152. PMID: 30680721
Iwasaki N, Nakayama J, Hamano K, Matsui A, Arinami T
Epilepsia 2002;43 Suppl 9:32-5. doi: 10.1046/j.1528-1157.43.s.9.8.x. PMID: 12383277
Veggiotti P, Cardinali S, Montalenti E, Gatti A, Lanzi G
Epileptic Disord 2001 Jan-Mar;3(1):29-32. PMID: 11313220

Therapy

Selmer KK, Lund C, Brandal K, Undlien DE, Brodtkorb E
Epilepsy Behav 2009 Nov;16(3):555-7. Epub 2009 Sep 24 doi: 10.1016/j.yebeh.2009.08.021. PMID: 19782004
Lucas PT, Meadows LS, Nicholls J, Ragsdale DS
Epilepsy Res 2005 May;64(3):77-84. doi: 10.1016/j.eplepsyres.2005.03.003. PMID: 15922564

Prognosis

Heron SE, Regan BM, Harris RV, Gardner AE, Coleman MJ, Bennett MF, Grinton BE, Helbig KL, Sperling MR, Haut S, Geller EB, Widdess-Walsh P, Pelekanos JT, Bahlo M, Petrovski S, Heinzen EL, Hildebrand MS, Corbett MA, Scheffer IE, Gécz J, Berkovic SF
Neurology 2021 May 4;96(18):e2251-e2260. Epub 2021 Mar 23 doi: 10.1212/WNL.0000000000011855. PMID: 34038384Free PMC Article
Surovy M, Soltysova A, Kolnikova M, Sykora P, Ilencikova D, Ficek A, Radvanszky J, Kadasi L
Gen Physiol Biophys 2016 Jul;35(3):333-42. Epub 2016 Apr 5 doi: 10.4149/gpb_2016002. PMID: 27045673
Camfield P, Camfield C
Epileptic Disord 2015 Jun;17(2):124-33. doi: 10.1684/epd.2015.0737. PMID: 25917466
Weber YG, Jacob M, Weber G, Lerche H
Epilepsia 2008 Nov;49(11):1959-64. Epub 2008 May 8 doi: 10.1111/j.1528-1167.2008.01646.x. PMID: 18479394
Alekov A, Rahman MM, Mitrovic N, Lehmann-Horn F, Lerche H
J Physiol 2000 Dec 15;529 Pt 3(Pt 3):533-9. doi: 10.1111/j.1469-7793.2000.00533.x. PMID: 11118488Free PMC Article

Clinical prediction guides

Heron SE, Regan BM, Harris RV, Gardner AE, Coleman MJ, Bennett MF, Grinton BE, Helbig KL, Sperling MR, Haut S, Geller EB, Widdess-Walsh P, Pelekanos JT, Bahlo M, Petrovski S, Heinzen EL, Hildebrand MS, Corbett MA, Scheffer IE, Gécz J, Berkovic SF
Neurology 2021 May 4;96(18):e2251-e2260. Epub 2021 Mar 23 doi: 10.1212/WNL.0000000000011855. PMID: 34038384Free PMC Article
Kang JQ, Macdonald RL
JAMA Neurol 2016 Aug 1;73(8):1009-16. doi: 10.1001/jamaneurol.2016.0449. PMID: 27367160Free PMC Article
Camfield P, Camfield C
Epileptic Disord 2015 Jun;17(2):124-33. doi: 10.1684/epd.2015.0737. PMID: 25917466
Veggiotti P, Cardinali S, Montalenti E, Gatti A, Lanzi G
Epileptic Disord 2001 Jan-Mar;3(1):29-32. PMID: 11313220
Baulac S, Gourfinkel-An I, Picard F, Rosenberg-Bourgin M, Prud'homme JF, Baulac M, Brice A, LeGuern E
Am J Hum Genet 1999 Oct;65(4):1078-85. doi: 10.1086/302593. PMID: 10486327Free PMC Article

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