Administration Of SCN1A Genetic Testing As A Pre-Prognostic Indicator in Early Onset Recurrent Febrile Seizures

Hatice Mutlu Albayrak; Peren Perk Yücel; Emre Kırat

doi:10.12956/tchd.809273

Öz

Amaç: 1 yaş ve altı tekrarlayan ateşli nöbeti olan çocukların epileptik yatkınlıklarının SCN1A gen dizi analizi kullanılarak daha erken tahmin edilip edilemeyeceğini belirlemek.

Gereç ve Yöntemler: Çalışmaya çocuk acil servisine ateşli nöbet ile başvuran 0-18 yaş arası 55 hasta dahil edildi. Hastalar, bir yaş ve altında tekrarlayan (iki veya daha fazla) ateşli nöbetleri olma, normal kraniyal görüntülemeye sahip olma ve merkezi sinir sistemi enfeksiyonları ekarte edilme kriterlerine göre seçildi. SCN1A gen dizi analizi, yeni nesil dizileme yöntemi kullanılarak gerçekleştirildi.

Bulgular: c.1738C> T ve c.4181C> T daha önce bildirilmişken, c.2914-1G> A ve c.473A>G, yeni heterozigot hastalığa neden olan SCN1A varyantlarıydı. 55 akraba olmayan aileden 5 çocuk için (% 9.09) c.1738C> T, c.2914-1G> A ve c.4181C> T varyanta sahip olan hastalar olası Dravet sendromu veya Dravet sendromu, ancak c.473A> G olan diğer ikisi ateşli nöbet artı genetik epilepsi fenotipi gösterdi.

Sonuç: Erken başlangıçlı ateşli nöbetlerde SCN1A genetik testinin önceden uygulanması, prognozu belirlemek ve uzun dönem takibi tasarlamak için klinik risk faktörlerinden daha önemli bir gösterge olabilir.

Anahtar Kelimeler: Ateşli nöbet, SCN1A, Dravet sendrom

Referanslar

1. Duffner PK, Baumann RJ, Berman P, Green JL, Schneider S, Hodgson ES, et al. Febrile Seizures: Clinical Practice Guideline for the Long-term Management of the Child With Simple Febrile Seizures. Pediatrics 2008;121:1281-6.
2. Miller IO, Sotero de Menezes MA. SCN1A Seizure Disorders. In: Genereviews. [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2020. 2007 Nov 29 [updated 2019 Apr 18]. Available from: https://pubmed.ncbi.nlm.nih.gov/20301494/
3. Zuberi SM, Brunklaus A, Birch R, Reavey E, Duncan J, Forbes GH. Genotype–phenotype associations in SCN1A-related epilepsies. Neurology 2011;76:594-600.
4. Offringa M, Newton R, Cozijnsen AM, Nevitt SJ. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev. 2017;2:CD003031.
5. Richards S, Aziz N2, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-24.
6. Meng H, Xu HQ, Yu L, Lin GW, He N, Su T, et al. The SCN1A mutation database: updating information and analysis of the relationships among genotype, functional alteration, and phenotype. Hum Mutat. 2015;36:573-80.
7. Shi YW, Yu MJ, Long YS, Qin B, He N, Meng H, et al. Mosaic SCN1A mutations in familial partial epilepsy with antecedent febrile seizures. Genes Brain Behav. 2012;11:170-6.
8. Arlier Z, Bayri Y, Kolb LE, Erturk O, Ozturk AK, Bayrakli F, et al. Four novel SCN1A mutations in Turkish patients with severe myoclonic epilepsy of infancy (SMEI). J Child Neurol. 2010;25:1265-8.
9. Depienne C, Trouillard O, Saint-Martin C, Gourfinkel-An I, Bouteiller D,Carpentier Wet al. Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. J Med Genet. 2009;46:183-91.
10. da Silva LFM, Turolla GS,Ortega MM,de Aguiar PHP. Dravet Syndrome and SCN1A gene mutations: a review. J Neurol Stroke. 2020;10:61‒65.
11. Global Variome shared LOVD [Internet]. Cited 2020 Jul 12. Available from: www. https://databases.lovd.nl/shared/genes/SCN1A.
12. American Academy of Pediatrics. Steering Committee on Quality Improvement and Management, Subcommitee on Febrile Seizures. Febrile Seizures: clinical practice guideline for long term management of child with simple febrile seizures. Pediatrics 2008;121:1281-6
13. Capovilla G, Mastrangelo M, Romeo A, Vigevano F. Recommendations for the management of "febrile seizures": Ad Hoc Task Force of LICE Guidelines Commission. Epilepsia. 2009;50:2-6.
14. Woods NT, Baskin R, Golubeva V, Jhuraney A, De-Gregoriis G, Vaclova T. Functional Assays Provide a Robust Tool for the Clinical Annotation of Genetic Variants of Uncertain Significance. NPJ Genom Med 2016;1:16001.
15. Ishii A, Watkins JC, Chen D, Hirose S, Hammer MF. Clinical Implications of SCN1A Missense and Truncation Variants in a Large Japanese Cohort With Dravet Syndrome. Epilepsia 2017;58:282-290.
16. Xu X, Yang X, Wu Q, Liu A, Yang X, Ye AY,et al. Amplicon Resequencing Identified Parental Mosaicism for Approximately 10% of "De Novo" SCN1A Mutations in Children With Dravet Syndrome. Hum Mutat 2015;36:861-72.
17. Claes LR, Deprez L, Suls A, Baets J, Smets K, Van Dyck T,et al. The SCN1A variant database: a novel research and diagnostic tool. Hum Mutat. 2009;30:E904-20.
18. Kanai K, Hirose S, Oguni H, Fukuma G, Shirasaka Y, Miyajima T, et al. Effect of localization of missense mutations in SCN1A on epilepsy phenotype severity. Neurology. 2004;63:329-34.
19. Herini ES, Gunadi, Harahap IS, Yusoff S, Morikawa S, Patria SY,et al. Generalized Epilepsy With Febrile Seizures Plus (GEFS+) Spectrum: Clinical Manifestations and SCN1A Mutations in Indonesian Patients. Epilepsy Res. 2010;90:132-9.
20. Hirose S, Scheffer IE, Marini C, De Jonghe P, Andermann E, Goldman AM,et al. SCN1A testing for epilepsy: application in clinical practice. Epilepsia. 2013;54:946-52.
21. Villeneuve N, Laguitton V,Viellard M, Lépine A, Chabrol B, Dravet C, et al. Cognitive and adaptive evaluation of 21 consecutive patients with Dravet syndrome. Epilepsy Behav 2014;31:143-8.
22. Knupp KG, Wirrell EC. Treatment Strategies for Dravet Syndrome. CNS Drugs. 2018;32:335-350.
23. Thanh TN, Chiron C, Dellatolas G, Rey E, Pons G, Vincent J, et al. Long-term efﬁcacy and tolerance of stiripentaol in severe myoclonic epilepsy of infancy (Dravet’s syndrome). Arch Pediatr. 2002;9:1120-7.
24. Mueller A, Boor R, Coppola G, Striano P, Dahlin M, von Stuelpnagel C, Lotte J, Staudt M, Kluger G. Low long-term efﬁcacy and tolerability of add-on ruﬁnamide in patients with Dravet syndrome. Epilepsy Behav. 2011;21:282–4.
25. Ceulemans B. Overall management of patients with Dravet syndrome. Dev Med Child Neurol. 2011;53:19-23.

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Nasıl atıf yapılır

Mutlu Albayrak H, Perk Yücel P, Kırat E. Erken Başlangıçlı Tekrarlayan Ateşli Nöbetlerde Pre-Prognostik Bir Gösterge Olarak SCN1A Genetik Testinin Uygulanması. Turk J Pediatr Dis [Internet]. 2021 Nov. 26 [cited 2025 May 24];15(6):476-81. Available from: https://turkjpediatrdis.org/article/view/737

Atıf indir

[ref1] 1. Duffner PK, Baumann RJ, Berman P, Green JL, Schneider S, Hodgson ES, et al. Febrile Seizures: Clinical Practice Guideline for the Long-term Management of the Child With Simple Febrile Seizures. Pediatrics 2008;121:1281-6.

[ref2] 2. Miller IO, Sotero de Menezes MA. SCN1A Seizure Disorders. In: Genereviews. [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2020. 2007 Nov 29 [updated 2019 Apr 18]. Available from: https://pubmed.ncbi.nlm.nih.gov/20301494/

[ref3] 3. Zuberi SM, Brunklaus A, Birch R, Reavey E, Duncan J, Forbes GH. Genotype–phenotype associations in SCN1A-related epilepsies. Neurology 2011;76:594-600.

[ref4] 4. Offringa M, Newton R, Cozijnsen AM, Nevitt SJ. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev. 2017;2:CD003031.

[ref5] 5. Richards S, Aziz N2, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-24.

[ref6] 6. Meng H, Xu HQ, Yu L, Lin GW, He N, Su T, et al. The SCN1A mutation database: updating information and analysis of the relationships among genotype, functional alteration, and phenotype. Hum Mutat. 2015;36:573-80.

[ref7] 7. Shi YW, Yu MJ, Long YS, Qin B, He N, Meng H, et al. Mosaic SCN1A mutations in familial partial epilepsy with antecedent febrile seizures. Genes Brain Behav. 2012;11:170-6.

[ref8] 8. Arlier Z, Bayri Y, Kolb LE, Erturk O, Ozturk AK, Bayrakli F, et al. Four novel SCN1A mutations in Turkish patients with severe myoclonic epilepsy of infancy (SMEI). J Child Neurol. 2010;25:1265-8.

[ref9] 9. Depienne C, Trouillard O, Saint-Martin C, Gourfinkel-An I, Bouteiller D,Carpentier Wet al. Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. J Med Genet. 2009;46:183-91.

[ref10] 10. da Silva LFM, Turolla GS,Ortega MM,de Aguiar PHP. Dravet Syndrome and SCN1A gene mutations: a review. J Neurol Stroke. 2020;10:61‒65.

[ref11] 11. Global Variome shared LOVD [Internet]. Cited 2020 Jul 12. Available from: www. https://databases.lovd.nl/shared/genes/SCN1A.

[ref12] 12. American Academy of Pediatrics. Steering Committee on Quality Improvement and Management, Subcommitee on Febrile Seizures. Febrile Seizures: clinical practice guideline for long term management of child with simple febrile seizures. Pediatrics 2008;121:1281-6

[ref13] 13. Capovilla G, Mastrangelo M, Romeo A, Vigevano F. Recommendations for the management of "febrile seizures": Ad Hoc Task Force of LICE Guidelines Commission. Epilepsia. 2009;50:2-6.

[ref14] 14. Woods NT, Baskin R, Golubeva V, Jhuraney A, De-Gregoriis G, Vaclova T. Functional Assays Provide a Robust Tool for the Clinical Annotation of Genetic Variants of Uncertain Significance. NPJ Genom Med 2016;1:16001.

[ref15] 15. Ishii A, Watkins JC, Chen D, Hirose S, Hammer MF. Clinical Implications of SCN1A Missense and Truncation Variants in a Large Japanese Cohort With Dravet Syndrome. Epilepsia 2017;58:282-290.

[ref16] 16. Xu X, Yang X, Wu Q, Liu A, Yang X, Ye AY,et al. Amplicon Resequencing Identified Parental Mosaicism for Approximately 10% of "De Novo" SCN1A Mutations in Children With Dravet Syndrome. Hum Mutat 2015;36:861-72.

[ref17] 17. Claes LR, Deprez L, Suls A, Baets J, Smets K, Van Dyck T,et al. The SCN1A variant database: a novel research and diagnostic tool. Hum Mutat. 2009;30:E904-20.

[ref18] 18. Kanai K, Hirose S, Oguni H, Fukuma G, Shirasaka Y, Miyajima T, et al. Effect of localization of missense mutations in SCN1A on epilepsy phenotype severity. Neurology. 2004;63:329-34.

[ref19] 19. Herini ES, Gunadi, Harahap IS, Yusoff S, Morikawa S, Patria SY,et al. Generalized Epilepsy With Febrile Seizures Plus (GEFS+) Spectrum: Clinical Manifestations and SCN1A Mutations in Indonesian Patients. Epilepsy Res. 2010;90:132-9.

[ref20] 20. Hirose S, Scheffer IE, Marini C, De Jonghe P, Andermann E, Goldman AM,et al. SCN1A testing for epilepsy: application in clinical practice. Epilepsia. 2013;54:946-52.

[ref21] 21. Villeneuve N, Laguitton V,Viellard M, Lépine A, Chabrol B, Dravet C, et al. Cognitive and adaptive evaluation of 21 consecutive patients with Dravet syndrome. Epilepsy Behav 2014;31:143-8.

[ref22] 22. Knupp KG, Wirrell EC. Treatment Strategies for Dravet Syndrome. CNS Drugs. 2018;32:335-350.

[ref23] 23. Thanh TN, Chiron C, Dellatolas G, Rey E, Pons G, Vincent J, et al. Long-term efﬁcacy and tolerance of stiripentaol in severe myoclonic epilepsy of infancy (Dravet’s syndrome). Arch Pediatr. 2002;9:1120-7.

[ref24] 24. Mueller A, Boor R, Coppola G, Striano P, Dahlin M, von Stuelpnagel C, Lotte J, Staudt M, Kluger G. Low long-term efﬁcacy and tolerability of add-on ruﬁnamide in patients with Dravet syndrome. Epilepsy Behav. 2011;21:282–4.

[ref25] 25. Ceulemans B. Overall management of patients with Dravet syndrome. Dev Med Child Neurol. 2011;53:19-23.

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Erken Başlangıçlı Tekrarlayan Ateşli Nöbetlerde Pre-Prognostik Bir Gösterge Olarak SCN1A Genetik Testinin Uygulanması

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