GEFS+ Genetik Epilepsi Febril Nöbet Artı
Özet
Genetik Epilepsi Febril Nöbet artı (GEFS+), klasik febril nöbetler ile Dravet sendromu arasında değişen heterojen klinik fenotipler içeren bir ailevi epilepsi sendromudur. Aynı ailede en az biri febril olmak üzere aynı veya farklı GEFS+ fenotipinde nöbeti olan 2 veya daha fazla bireyin olduğu aileler GEFS+ ailesi olarak tanımlanmıştır. Sıklıkla otozomal dominant ve inkomplet penetrans ile kalıtım gösterir. Hem voltaj kapılı hem de ligand kapılı iyon kanallarını kodlayan genler, GEFS+ etiyolojisinde rol oynamaktadır. SCN1A, SCN1B, GABRG2, GABRD2, STX1B, HCN1, HCN2 gibi çeşitli mutasyonlar bildirilmiştir. Prognoz ve EEG bulguları klinik fenotipe göre değişkenlik göstermekle birlikte nadir görülen epileptik ensefalopatiler haricinde genel olarak kendini sınırlayan ve iyi prognozlu bir sendromdur.
Genetic Epilepsy Febrile Seizure plus (GEFS+) is a familial epilepsy syndrome with heterogeneous clinical phenotypes, ranging from classic febrile seizures to Dravet syndrome. A family is defined as a GEFS+ family if two or more individuals in the same family have seizures with the same or different GEFS+ phenotypes, at least one of which is febrile. GEFS+ is frequently inherited as autosomal dominant with incomplete penetrance. Genes encoding both voltage-gated and ligand-gated ion channels have been implicated in the aetiology of GEFS+. Various mutations, including those in SCN1A, SCN1B, GABRG2, GABRD2, STX1B, HCN1 and HCN2, have been reported. Although the prognosis and EEG findings vary according to the clinical phenotype, it is generally a self-limiting syndrome with a good prognosis, with the exception of rare epileptic encephalopathies.
Referanslar
Ling Y, Wang Y, Jiang X, Yuan C. Mechanism of the promotion of GEFS+ by the STAT3-mediated expression of interleukin-6. Transl Pediatr. 2022 Sep;11(9):1491-1501. doi: 10.21037/tp-22-333. PMID: 36247897; PMCID: PMC9561518.
Camfield P, Camfield C. Febrile seizures and genetic epilepsy with febrile seizures plus (GEFS+). Epileptic Disord. 2015;17(2):124-133. doi:10.1684/epd.2015.0737
Scheffer IE, Berkovic SF. Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes. Brain. 1997;120 ( Pt 3):479-490. doi:10.1093/brain/120.3.479
Engel J Jr; International League Against Epilepsy (ILAE). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia. 2001;42(6):796-803. doi:10.1046/j.1528-1157.2001.10401.x
Myers KA, Scheffer IE, Berkovic SF; ILAE Genetics Commission. Genetic literacy series: genetic epilepsy with febrile seizures plus. Epileptic Disord. 2018;20(4):232-238. doi:10.1684/epd.2018.0985
Zhang YH, Burgess R, Malone JP, et al. Genetic epilepsy with febrile seizures plus: Refining the spectrum. Neurology. 2017;89(12):1210-1219. doi:10.1212/WNL.0000000000004384
Scheffer IE, Zhang YH, Jansen FE, Dibbens L. Dravet syndrome or genetic (generalized) epilepsy with febrile seizures plus?. Brain Dev. 2009;31(5):394-400. doi:10.1016/j.braindev.2009.01.001
Bonanni P, Malcarne M, Moro F, et al. Generalized epilepsy with febrile seizures plus (GEFS+): clinical spectrum in seven Italian families unrelated to SCN1A, SCN1B, and GABRG2 gene mutations. Epilepsia. 2004;45(2):149-158. doi:10.1111/j.0013-9580.2004.04303.x
Singh R, Scheffer IE, Crossland K, Berkovic SF. Generalized epilepsy with febrile seizures plus: a common childhood-onset genetic epilepsy syndrome. Ann Neurol. 1999;45(1):75-81. doi:10.1002/1531-8249(199901)45:1<75::aid-art13>3.0.co;2-w
Baulac S, Gourfinkel-An I, Picard F, et al. A second locus for familial generalized epilepsy with febrile seizures plus maps to chromosome 2q21-q33. Am J Hum Genet. 1999;65(4):1078-1085. doi:10.1086/302593
Wallace RH, Wang DW, Singh R, et al. Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet. 1998;19(4):366-370. doi:10.1038/1252
Herini ES, Gunadi, Harahap IS, et al. Generalized epilepsy with febrile seizures plus (GEFS+) spectrum: clinical manifestations and SCN1A mutations in Indonesian patients. Epilepsy Res. 2010;90(1-2):132-139. doi:10.1016/j.eplepsyres.2010.04.003
Brunklaus A, Ellis R, Stewart H, et al. Homozygous mutations in the SCN1A gene associated with genetic epilepsy with febrile seizures plus and Dravet syndrome in 2 families. Eur J Paediatr Neurol. 2015;19(4):484-488. doi:10.1016/j.ejpn.2015.02.001
Nordli DR, Pellock JM. Generaized Epilepsy Febril Seizure Plus (GEFS+). In: Pellock JM, Nordli DR, Sankar R, Whelles JE, editors. Pellock’s Pediatric Epilepsy Diagnosis and Theraphy. 4. ed. 2017. P.265-7.
Guerrini R, Aicardi J. Epileptic encephalopathies with myoclonic seizures in infants and children (severe myoclonic epilepsy and myoclonic-astatic epilepsy). J Clin Neurophysiol. 2003;20(6):449-461. doi:10.1097/00004691-200311000-00007
Dravet C, Bureau M, Oguni H, Fukuyama Y, Cokar O. Severe myoclonic epilepsy in infancy: Dravet syndrome. Adv Neurol. 2005;95:71-102.
Audenaert D, Claes L, Ceulemans B, Löfgren A, Van Broeckhoven C, De Jonghe P. A deletion in SCN1B is associated with febrile seizures and early-onset absence epilepsy. Neurology. 2003;61(6):854-856. doi:10.1212/01.wnl.0000080362.55784.1c
Schubert J, Siekierska A, Langlois M, et al. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes. Nat Genet. 2014;46(12):1327-1332. doi:10.1038/ng.3130
Wallace RH, Wang DW, Singh R, et al. Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet. 1998;19(4):366-370. doi:10.1038/1252
Baulac S, Gourfinkel-An I, Picard F, et al. A second locus for familial generalized epilepsy with febrile seizures plus maps to chromosome 2q21-q33. Am J Hum Genet. 1999;65(4):1078-1085. doi:10.1086/302593
Moulard, B., Guipponi, M., Chaigne, D., Mouthon, D., Buresi, C., Malafosse, A. Identification of a new locus for generalized epilepsy with febrile seizures plus (GEFS+) on chromosome 2q24-q33. Am. J. Hum. Genet. 65: 1396-1400, 1999.
Buoni S, Orrico A, Galli L, et al. SCN1A (2528delG) novel truncating mutation with benign outcome of severe myoclonic epilepsy of infancy. Neurology. 2006;66(4):606-607. doi:10.1212/01.WNL.0000198504.41315.B1
Marini C, Harkin LA, Wallace RH, Mulley JC, Scheffer IE, Berkovic SF. Childhood absence epilepsy and febrile seizures: a family with a GABA(A) receptor mutation. Brain. 2003;126(Pt 1):230-240. doi:10.1093/brain/awg018
Tan HO, Reid CA, Single FN, et al. Reduced cortical inhibition in a mouse model of familial childhood absence epilepsy. Proc Natl Acad Sci U S A. 2007;104(44):17536-17541. doi:10.1073/pnas.0708440104
Audenaert D, Claes L, Claeys KG, et al. A novel susceptibility locus at 2p24 for generalised epilepsy with febrile seizures plus. J Med Genet. 2005;42(12):947-952. doi:10.1136/jmg.2005.031393
Dibbens LM, Feng HJ, Richards MC, et al. GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies. Hum Mol Genet. 2004;13(13):1315-1319. doi:10.1093/hmg/ddh146
Baulac S, Gourfinkel-An I, Couarch P, et al. A novel locus for generalized epilepsy with febrile seizures plus in French families. Arch Neurol. 2008;65(7):943-951. doi:10.1001/archneur.65.7.943
Singh NA, Pappas C, Dahle EJ, et al. A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome. PLoS Genet. 2009;5(9):e1000649. doi:10.1371/journal.pgen.1000649
Poduri A, Wang Y, Gordon D, et al. Novel susceptibility locus at chromosome 6q16.3-22.31 in a family with GEFS+. Neurology. 2009;73(16):1264-1272. doi:10.1212/WNL.0b013e3181bd10d3
Weber YG, Jacob M, Weber G, Lerche H. A BFIS-like syndrome with late onset and febrile seizures: suggestive linkage to chromosome 16p11.2-16q12.1. Epilepsia. 2008;49(11):1959-1964. doi:10.1111/j.1528-1167.2008.01646.x
Marini C, Porro A, Rastetter A, et al. HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond. Brain. 2018;141(11):3160-3178. doi:10.1093/brain/awy263 Marini C, Porro A, Rastetter A, et al. HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond. Brain. 2018;141(11):3160-3178. doi:10.1093/brain/awy263Marini C, Porro A, Rastetter A, et al. HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond. Brain. 2018;141(11):3160-3178. doi:10.1093/brain/awy263
Li M, Maljevic S, Phillips AM, et al. Gain-of-function HCN2 variants in genetic epilepsy. Hum Mutat. 2018;39(2):202-209. doi:10.1002/humu.23357
Referanslar
Ling Y, Wang Y, Jiang X, Yuan C. Mechanism of the promotion of GEFS+ by the STAT3-mediated expression of interleukin-6. Transl Pediatr. 2022 Sep;11(9):1491-1501. doi: 10.21037/tp-22-333. PMID: 36247897; PMCID: PMC9561518.
Camfield P, Camfield C. Febrile seizures and genetic epilepsy with febrile seizures plus (GEFS+). Epileptic Disord. 2015;17(2):124-133. doi:10.1684/epd.2015.0737
Scheffer IE, Berkovic SF. Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes. Brain. 1997;120 ( Pt 3):479-490. doi:10.1093/brain/120.3.479
Engel J Jr; International League Against Epilepsy (ILAE). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia. 2001;42(6):796-803. doi:10.1046/j.1528-1157.2001.10401.x
Myers KA, Scheffer IE, Berkovic SF; ILAE Genetics Commission. Genetic literacy series: genetic epilepsy with febrile seizures plus. Epileptic Disord. 2018;20(4):232-238. doi:10.1684/epd.2018.0985
Zhang YH, Burgess R, Malone JP, et al. Genetic epilepsy with febrile seizures plus: Refining the spectrum. Neurology. 2017;89(12):1210-1219. doi:10.1212/WNL.0000000000004384
Scheffer IE, Zhang YH, Jansen FE, Dibbens L. Dravet syndrome or genetic (generalized) epilepsy with febrile seizures plus?. Brain Dev. 2009;31(5):394-400. doi:10.1016/j.braindev.2009.01.001
Bonanni P, Malcarne M, Moro F, et al. Generalized epilepsy with febrile seizures plus (GEFS+): clinical spectrum in seven Italian families unrelated to SCN1A, SCN1B, and GABRG2 gene mutations. Epilepsia. 2004;45(2):149-158. doi:10.1111/j.0013-9580.2004.04303.x
Singh R, Scheffer IE, Crossland K, Berkovic SF. Generalized epilepsy with febrile seizures plus: a common childhood-onset genetic epilepsy syndrome. Ann Neurol. 1999;45(1):75-81. doi:10.1002/1531-8249(199901)45:1<75::aid-art13>3.0.co;2-w
Baulac S, Gourfinkel-An I, Picard F, et al. A second locus for familial generalized epilepsy with febrile seizures plus maps to chromosome 2q21-q33. Am J Hum Genet. 1999;65(4):1078-1085. doi:10.1086/302593
Wallace RH, Wang DW, Singh R, et al. Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet. 1998;19(4):366-370. doi:10.1038/1252
Herini ES, Gunadi, Harahap IS, et al. Generalized epilepsy with febrile seizures plus (GEFS+) spectrum: clinical manifestations and SCN1A mutations in Indonesian patients. Epilepsy Res. 2010;90(1-2):132-139. doi:10.1016/j.eplepsyres.2010.04.003
Brunklaus A, Ellis R, Stewart H, et al. Homozygous mutations in the SCN1A gene associated with genetic epilepsy with febrile seizures plus and Dravet syndrome in 2 families. Eur J Paediatr Neurol. 2015;19(4):484-488. doi:10.1016/j.ejpn.2015.02.001
Nordli DR, Pellock JM. Generaized Epilepsy Febril Seizure Plus (GEFS+). In: Pellock JM, Nordli DR, Sankar R, Whelles JE, editors. Pellock’s Pediatric Epilepsy Diagnosis and Theraphy. 4. ed. 2017. P.265-7.
Guerrini R, Aicardi J. Epileptic encephalopathies with myoclonic seizures in infants and children (severe myoclonic epilepsy and myoclonic-astatic epilepsy). J Clin Neurophysiol. 2003;20(6):449-461. doi:10.1097/00004691-200311000-00007
Dravet C, Bureau M, Oguni H, Fukuyama Y, Cokar O. Severe myoclonic epilepsy in infancy: Dravet syndrome. Adv Neurol. 2005;95:71-102.
Audenaert D, Claes L, Ceulemans B, Löfgren A, Van Broeckhoven C, De Jonghe P. A deletion in SCN1B is associated with febrile seizures and early-onset absence epilepsy. Neurology. 2003;61(6):854-856. doi:10.1212/01.wnl.0000080362.55784.1c
Schubert J, Siekierska A, Langlois M, et al. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes. Nat Genet. 2014;46(12):1327-1332. doi:10.1038/ng.3130
Wallace RH, Wang DW, Singh R, et al. Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet. 1998;19(4):366-370. doi:10.1038/1252
Baulac S, Gourfinkel-An I, Picard F, et al. A second locus for familial generalized epilepsy with febrile seizures plus maps to chromosome 2q21-q33. Am J Hum Genet. 1999;65(4):1078-1085. doi:10.1086/302593
Moulard, B., Guipponi, M., Chaigne, D., Mouthon, D., Buresi, C., Malafosse, A. Identification of a new locus for generalized epilepsy with febrile seizures plus (GEFS+) on chromosome 2q24-q33. Am. J. Hum. Genet. 65: 1396-1400, 1999.
Buoni S, Orrico A, Galli L, et al. SCN1A (2528delG) novel truncating mutation with benign outcome of severe myoclonic epilepsy of infancy. Neurology. 2006;66(4):606-607. doi:10.1212/01.WNL.0000198504.41315.B1
Marini C, Harkin LA, Wallace RH, Mulley JC, Scheffer IE, Berkovic SF. Childhood absence epilepsy and febrile seizures: a family with a GABA(A) receptor mutation. Brain. 2003;126(Pt 1):230-240. doi:10.1093/brain/awg018
Tan HO, Reid CA, Single FN, et al. Reduced cortical inhibition in a mouse model of familial childhood absence epilepsy. Proc Natl Acad Sci U S A. 2007;104(44):17536-17541. doi:10.1073/pnas.0708440104
Audenaert D, Claes L, Claeys KG, et al. A novel susceptibility locus at 2p24 for generalised epilepsy with febrile seizures plus. J Med Genet. 2005;42(12):947-952. doi:10.1136/jmg.2005.031393
Dibbens LM, Feng HJ, Richards MC, et al. GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies. Hum Mol Genet. 2004;13(13):1315-1319. doi:10.1093/hmg/ddh146
Baulac S, Gourfinkel-An I, Couarch P, et al. A novel locus for generalized epilepsy with febrile seizures plus in French families. Arch Neurol. 2008;65(7):943-951. doi:10.1001/archneur.65.7.943
Singh NA, Pappas C, Dahle EJ, et al. A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome. PLoS Genet. 2009;5(9):e1000649. doi:10.1371/journal.pgen.1000649
Poduri A, Wang Y, Gordon D, et al. Novel susceptibility locus at chromosome 6q16.3-22.31 in a family with GEFS+. Neurology. 2009;73(16):1264-1272. doi:10.1212/WNL.0b013e3181bd10d3
Weber YG, Jacob M, Weber G, Lerche H. A BFIS-like syndrome with late onset and febrile seizures: suggestive linkage to chromosome 16p11.2-16q12.1. Epilepsia. 2008;49(11):1959-1964. doi:10.1111/j.1528-1167.2008.01646.x
Marini C, Porro A, Rastetter A, et al. HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond. Brain. 2018;141(11):3160-3178. doi:10.1093/brain/awy263 Marini C, Porro A, Rastetter A, et al. HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond. Brain. 2018;141(11):3160-3178. doi:10.1093/brain/awy263Marini C, Porro A, Rastetter A, et al. HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond. Brain. 2018;141(11):3160-3178. doi:10.1093/brain/awy263
Li M, Maljevic S, Phillips AM, et al. Gain-of-function HCN2 variants in genetic epilepsy. Hum Mutat. 2018;39(2):202-209. doi:10.1002/humu.23357
