ÖZET
İyon kanallarının oluşumunu kodlayan genlerde meydana gelen mutasyonlar epileptik sendromlara neden olabilir. Bu epileptik sendromlar genel olarak jeneralize ve parsiyel olarak ikiye ayrılmaktadır. Kendi içerisinde mendelyan ve non-mendelyan geçiş gösteren jeneralize epilepsilere neden olan etkenler arasında sodyum kanalı, kalsiyum kanalı, GABAA reseptör ve nikotinik reseptör mutasyonları gösterilebilir. Mendelyan geçiş gösteren jeneralize epilepileptik sendromlar; febril nöbetler ile karakterize, otozomal dominant formlu juvenil miyoklonik, CLCN2 gen mutasyonuyla ilişkili, kalsiyum kanalı alt birimlerindeki mutasyonlarla ilişkili epilepsiler şeklinde farklılaşmaktadır. Non-mendelyan geçiş gösteren jeneralize epileptik sendromları ise juvenil miyoklonik ve juvenil absans jeneralize tonik-klonik nöbetli epilepsilerdir. Parsiyel özellik gösteren tek gen kalıtımı ile gerçekleşen Yenidoğan ve Süt Çocuğu Epilepsileri, Selim Ailesel Neonatal, Selim Ailesel İnfantil Konvülzionlar ve Selim Ailesel Neonatal-İnfaltil Nöbetler başlıklarıyla 3 sınıfta toplanmaktadır. Otozomal dominant parsiyel epilepsiler ise Otozomal Dominant Noktürnal Frontal Lob, Ailesel Meziyal Temporal Lob, Ailesel Lateral Temporal Lob, Değişken Odaklı Ailesel Parsiyel Lob Epilepsisi başlıkları altında incelenmektedir. Farklı iyon kanallarında meydana gelen çeşitli mutasyonlar benzer fenotipler oluşturabilirken, aynı gen üzerinde meydana gelen belli bir mutasyon da farklı fenotiplere neden olabilir. Bu derleme epileptik sendromlara neden olan nöral kanalopatilerin genetik tabanı ve patofizyolojik etkileri üzerinden epilepsi sınıflandırmasına ait bir özet sunmaktadır.
References
1
World Health Organization. Epilepsy [Internet]. [cited 2019 Jan 28]. Available from: https://www.who.int/news-room/fact-sheets/detail/epilepsy
2
Inouye E. Observations on forty twin index cases with chronic epilepsy and their co-twins. J Nerv Ment Dis. 1960;130:401-16.
3
Corey LA, Berg K, Pellock JM, Solaas MH, Nance WE, DeLorenzo RJ. The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins. Neurology 1991;41:1433-6.
4
Marshall AG, Hutchinson EO, Honisett J. Heredity in common diseases: A retrospective survey of twins in a hospital population. Br Med J. 1962;5270:1-6.
5
Schiottz-Christensen. GENETIC FACTORS IN FEBRILE CONVULSIONS An Investigation of 64 Same-Sexed Twin Pairs. Acta Neurol Scand. 1972;48:538-46.
6
Sillanpää M, Koskenvuo M, Romanov K, Kaprio J. Genetic factors in epileptic seizures: evidence from a large twin population. Acta Neurol Scand 1991;84:523-6.
7
Lerche, H., Jurkat-Rott, K., Lehmann-Horn F. Ion channels and epilepsy. Am J Med Genet - Semin Med Genet. 2001;106:146-59.
8
Scheffer IE, Zhang YH, Jansen FE, Dibbens L. Dravet syndrome or genetic (generalized) epilepsy with febrile seizures plus? Brain Dev [Internet]. 2009;31:394-400.
9
Kurian M, Picard F. Inherited epilepsy syndromes and channelopathies. Epileptologie. 2006;23:75-85.
10
Scheffer IE, Berkovic SF. The genetics of human epilepsy. Trends in Pharmacological Sciences. 2003.
11
Dervent A, Gökyiğit A. Çocukluk ve ergenlikte başlayan idiyopatik jeneralize epilepsiler. Epilepsi 2014;20:13-22.
12
Gardiner M. Genetics of idiopathic generalized epilepsies. Epilepsia [Internet] 2005;46(Suppl 9):15-20.
13
Zhang, Y-H. ve Scheffer I (2010). Generalized epilepsy with febrile seizures plus and classical idiopathic generalized epilepsy. Neurol Asia 2010;15(Supplement 1):3-4.
14
Harkin LA, McMahon JM, Iona X, Dibbens L, Pelekanos JT, Zuberi SM, et al. The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain 2007;13:843-52.
15
Scheffer IE, Berkovic SF. Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes. Brain 1997;120:479-90.
16
Wallace RH, Scheffer IE, Barnett S, Richards M, Dibbens L, Desai RR, et al. Neuronal Sodium-Channel 2001;859-65.
17
Renganathan R, Delanty N. Juvenile myoclonic epilepsy: under-appreciated and under-diagnosed. Postgrad Med J [Internet] 2003;79:78-80.
18
Robyn Wallace. Identification of a New JME Gene Implicates Reduced Apoptotic Neuronal Death as a Mechanism of Epileptogenesis. Epilepsy Curr 2005;5:11-3.
19
Turan OD. Juvenil myoklonik epilepsi hastaları ve asemptomatik akrabalarında uyku deprivayonlu kısa dönemli uykuda EEG özellikleri ve kognitif fonksiyonların değerlendirilmesi. 2009.
20
D’Agostino D, Bertelli M, Gallo S, Cecchin S, Albiero E, Garofalo PG, et al. Mutations and polymorphisms of the CLCN2 gene in idiopathic epilepsy. Neurology 2004;63:1500-2.
21
Saint-Martin C, Gauvain G, Teodorescu G, Gourfinkel-An I, Fedirko E, Weber YG, et al. Two novel CLCN2 mutations accelerating chloride channel deactivation are associated with idiopathic generalized epilepsy. Hum Mutat 2009;30:397-405.
22
Heyes S, Pratt WS, Rees E, Dahimene S, Ferron L, Owen MJ, et al. Genetic disruption of voltage-gated calcium channels in psychiatric and neurological disorders. Prog Neurobiol [Internet] 2015;134:36-54.
23
Zhang YH, Burgess R, Malone JP, Glubb GC, Helbig KL, Vadlamudi L, et al. Genetic epilepsy with febrile seizures plus. Refining the spectrum. Neurology 2017;89:1210-9.
24
Rogawski MA. Rogawski00 2000;1-6. Available from: papers3://publication/uuid/CAF83C20-944B-4128-B979-5B120146CE99
25
Schroeder, B.C., Kubisch, C., Stein, V. Ve Jentsch TJ. Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Macmillian Publ Ltd Nature 1998;396.
26
Bebek N. ve Baykan B. Epilepsilerin genetik yönü ve idyopatik epilepsi genetiğinde son gelişmeler. J Neurol Sci [Turkish] 2006;23:70-83.
27
Callenvach, P.MC., De Coo, R.FM., Vein, A.A., Arts, W.F.M., Oosterwijk, J.C., Hageman, G., Houten, R.T., Terwindt, G.M., Lindhout, D., Frants, R.R. ve Brouwer OF. Benign familial infantile convulsions: a clinical study of seven Duch families. Eur J Paediatr Neurol 2002;6:269-83.
28
Herlenius, E., Heron, S.E., Grington, B.E., Keay, D., Scheffer, I.E., Mulley, J.C. ve Berkovic SF. SCN2A mutations and benign familial neonatal-infantile seizures: the phenotypic spectrum. Epilepsia 2007;48:1138-42.
29
Engel J. Mesial Temporal Lobe Epilepsy: What Have We Learned? Neurosci [Internet] 2001;7:340-52.
30
Cersósimo R, Flesler S, Bartuluchi M, Soprano AM, Pomata H, Caraballo R. Mesial temporal lobe epilepsy with hippocampal sclerosis: Study of 42 children. Seizure 2011;20:131-7.
31
De Marco E V., Gambardella A, Annesi F, Labate A, Carrideo S, Forabosco P, et al. Further evidence of genetic heterogeneity in families with autosomal dominant nocturnal frontal lobe epilepsy. Epilepsy Res 2007;74:70-3.
32
Trivisano M, Terracciano A, Milano T, Cappelletti S, Pietrafusa N, Bertini ES, et al. Mutation of CHRNA2 in a family with benign familial infantile seizures: Potential role of nicotinic acetylcholine receptor in various phenotypes of epilepsy. Epilepsia. 2015;56:e53-7.
33
Rochette J, Roll P, Fu YH, Lemoing AG, Royer B, Roubertie A, et al. Novel familial cases of ICCA (infantile convulsions with paroxysmal choreoathetosis) syndrome. Epileptic Disord 2010;12:199-204.
34
Guerrini R, Sanchez-Carpintero R, Deonna T, Santucci M, Bhatia KP, Moreno T, et al. Early-onset absence epilepsy and paroxysmal dyskinesia. Epilepsia 2002;43:1224-9.
35
Akay, A., Turanlıgil-Sümer, N.C., Uyanıkgil Y. İyon kanalları ve epilepsi patojenezindeki rolleri. Arşiv Kaynak Tarama Derg 2010;19:72.
36
Escayg, A., De Waard, M., Lee, D.D., Bichet, D., Wolf, P., Mayer, T., Johnston, J., Baloh, R., Sander, T., ve Meisler MH. Coding and noncoding variation of the human calcium-channel ß4-Subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet 2000;66:1531-9.
37
Reid CA, Berkovic SF, Petrou S. Mechanisms of human inherited epilepsies. Prog Neurobiol 2009;87:41-57.
38
Dedek K, Kunath B, Kananura C, Reuner U, Jentsch TJ, Steinlein OK. Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channel. Proc Natl Acad Sci U S A [Internet] 2001;98:12272-7.
39
Weckhuysen S, Mandelstam S, Suls A, Audenaert D, Deconinck T, Claes LRF, et al. KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol [Internet] 2012;71:15-25.
40
Browne, T.R. ve Holmes GR. Epilepsi El Kitabı. İstanbul: İstanbul: Güneş Tıp Kitabevleri; 2013.
41
Deprez L, Weckhuysen S, Peeters K, Deconinck T, Claeys KG, Claes LRF, et al. Epilepsy as part of the phenotype associated with ATP1A2 mutations. Epilepsia 2008;49:500-8.
42
Fujiwara T, Sugawara T, Mazaki-Miyazaki E, Takahashi Y, Fukushima K, Watanabe M, et al. Mutations of sodium channel α subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures. Brain 2003;126:531-46.
