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Genetic epilepsy with febrile seizures plus (GEFS+)

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Febrile seizures (FS) occur in about 2–3% of children aged 3 months to 5 years. Atypical febrile seizures are those with a focal component. Each subsequent febrile attack increases the risk of transformation into epilepsy. After the third febrile seizure, the risk of additional episodes of febrile seizures is already approaching 50%, and the risk of formation of epilepsy is 15.8%. Recent studies show the great contribution of genetic causes to the development of genetic epilepsy with febrile seizures plus (GEFS+). GEFS+ includes a combination of some febrile seizures with subsequent afebrile attack, or recurring febrile seizures after 6 years. The genetic causes of GEFS+ are both monogenic (in particular, disorders in the SCN1B, SCN1A, GABRG2, GABRD, SCN9A, STX1B, HCN1 genes, etc.) and copy number variations. Twin methods suggest that different genetic factors play a role in the case of FS, FS+ and FS with subsequent epilepsy. Genetic cause can be found in about 30% of cases, that affects not only the final diagnosis and prognosis for the patient, but also the prevention of disease in the family. In GEFS+ seizures are usually generalized tonic-clonic, less often myoclonic, myoclonic-atonic seizures, absences and status epilepticus, but sometimes they also describe focal seizures. The clinical picture of patients with GEFS+ varies from family febrile seizures (the least severe cases) to Drave-like syndrome (the most severe cases), although all of them have a predominantly normal level of intellect.

About the Author

A. A. Sharkov
Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University
Russian Federation

Artem A. Sharkov – MD, Research Associate, neurologist

WoS ResearcherID: AAO-7543-2020; SPIN-code: 8727-5997

2 Taldomskaya Str., Moscow 125412


1. Nelson K. B., Ellenberg J. H. Predictors of epilepsy in children who have experienced febrile seizures. New England Journal of Medicine. 1976; 295 (19): 1029–1033.

2. Arzimanoglou A., Guerrini R. Neonatal seizures: Aicardi’s epilepsy in children. 2004.

3. Bertelsen E. N. et al. Childhood epilepsy, febrile seizures, and subsequent risk of ADHD. Pediatrics. 2016; 138 (2): e20154654.

4. Aicardi J. Epilepsies with generalized tonic-clonic seizures. Epilepsy in children, 2nd edn. New York: Raven Press. 1994; 118–129.

5. Scheffer I. E., Berkovic S. F. Generalized epilepsy with febrile seizures plus: a genetic disorder with heterogeneous clinical phenotypes. Brain. 1997; 120: 479–490.

6. Wallace R. H., Wang D. W., Singh R., Scheffer I. E., George A. L., Jr., Phillips H. A., Saar K., Reis A., Johnson E. W., Sutherland G. R., Berkovic S. F., Mulley J. C. Febrile seizures and generalized epilepsy associated with a mutation in the Na(+)-channel beta-1 subunit gene SCN1B. Nature Genet. 1998; 19: 366–370.

7. Lopes-Cendes I. et al. A new locus for generalized epilepsy with febrile seizures plus maps to chromosome 2. The American Journal of Human Genetics. 2000; 66 (2): 698–701.

8. Depienne C. et al. Mutations and deletions in PCDH19 account for various familial or isolated epilepsies in females. Human mutation. 2011; 32 (1): E1959–E1975.

9. Goldberg-Stern H., Aharoni S., Afawi Z., Bennett O., Appenzeller S., Pendziwiat M., Helbig I. Broad Phenotypic Heterogeneity due to a Novel SCN1A Mutation in a Family With Genetic Epilepsy With Febrile Seizures Plus. Journal of Child Neurology. 2014; 29 (2): 221–226. DOI: 10.1177/0883073813509016.

10. Zhang Y. H. et al. Genetic epilepsy with febrile seizures plus: Refining the spectrum. Neurology. 2017; 89 (12): 1210–1219.

11. Dadali E.L., Sharkov A.A., Sharkova I.V., Kanivets I.V., Konovalov F.A., Akimova I.A. Hereditary diseases and syndromes accompanied by febrile convulsions: clinical and genetic characteristics and diagnostic procedures. Russian Journal of Child Neurology. 2016; 11 (2): 33-41. (In Russ.) DOI:

12. Abou-Khalil B., Auce P., Avbersek A., Bahlo M., Balding D.J., Bast T., et al. Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies. Nature Communications. 2018; 9 (1): 5269. DOI: 10.1038/s41467-018-07524-z.

13. Makinson C.D., Dutt K., Lin F., et al. An Scn1a epilepsy mutation in Scn8a alters seizure susceptibility and behavior. Exp Neurol. 2016; 275 (1): 46–58. DOI:10.1016/j.expneurol.2015.09.008.

14. Eckhaus J. et al. Genetics of febrile seizure subtypes and syndromes: a twin study. Epilepsy research. 2013; 105 (1-2): 103–109.

15. Scheffer I. E., Berkovic S., Capovilla G., Connolly M. B., French J., Guilhoto L., Hirsch E., Jain S., Mathern G. W., Moshé S. L., Nordli D. R., Perucca E., Tomson T., Wiebe S., Zhang Y.-H., Zuberi S. M. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017; DOI:10.1111/epi.13709 1-3.

16. Avakyan G.N., Blinov D.V., Lebedeva A.V., Burd S.G., Avakyan G.G. ILAE classification of the epilepsies: the 2017 revision and update. Epilepsia i paroksizmal`nye sostoania / Epilepsy and Paroxysmal Conditions. 2017; 9 (1): 6–25. (In Russ.) DOI:

17. Belousova E.D., Zavadenko N.N., Kholin A.A., Sharkov A.A. New classifications of epilepsies and seizure types created by the International League against Epilepsy (2017). S.S. Korsakov Journal of Neurology and Psychiatry / Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2017; 117 (7): 99-106 (In Russ.). DOI:


For citations:

Sharkov A.A. Genetic epilepsy with febrile seizures plus (GEFS+). Epilepsy and paroxysmal conditions. 2020;12(1S):S50-S56. (In Russ.)

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ISSN 2077-8333 (Print)
ISSN 2311-4088 (Online)