Exploring the Role of MEFV Gene Mutations in Pediatric Drug-Resistant Epilepsy
Iranian Journal of Child Neurology,
Vol. 19 No. 4 (2025),
15 Shahrivar 2025
,
Page 81-85
https://doi.org/10.22037/ijcn.v19i4.47439
Abstract
Objectives:
Despite the advancements in antiepileptic drugs over the past decades, drug-resistant epilepsy (DRE) remains a significant challenge, particularly in children. Familial Mediterranean fever (FMF), attributed to mutations in the Mediterranean fever (MEFV) gene, has been linked to various neurological disorders, including seizures. This study investigates the potential association between MEFV gene mutations and DRE and evaluates their impact on the disease course.
Materials & Methods:
A case-control study was conducted involving 22 children under 18 years of age with DRE, referred to the Pediatric Neurology Clinic of Children’s Medical Center, Tehran, Iran, between March 2021 and March 2022. The control group comprised 30 healthy individuals randomly selected from the FMF database of Ardabil University, Iran. Relevant information, including age, demographics, disease characteristics, and treatment details, was collected using a structured form. Blood samples were analyzed for 12 common MEFV gene mutations
Results:
Out of 52 subjects, the case group consisted of 22 children diagnosed with DRE, compared to 30 patients without FMF in the control group. The mean age of the case group was 9.2 ± 4.5 years, with a mean age at seizure onset of 38.13 ± 32.21 months. MEFV mutations were identified in eight patients (15.4%), with seven in the control group and one (4.5%) in the case group. However, the difference in MEFV gene mutations between the case and control groups did not reach statistical significance (P=0.13).
Conclusion:
The prevalence of MEFV gene mutations in children with DRE was 4.5%, suggesting that these mutations may not significantly influence the occurrence of DRE in this population.
- Familial Mediterranean fever
- Drug Resistant Epilepsy
- Epilepsy
- Gene mutation
How to Cite
References
Devinsky O, Vezzani A, O'Brien TJ, Jette N, Scheffer IE, de Curtis M, Perucca P. Epilepsy. Nat Rev Dis Primers. 2018 May 3;4:18024. doi: 10.1038/nrdp.2018.24. PMID: 29722352.
Mesraoua B, Brigo F, Lattanzi S, Abou-Khalil B, Al Hail H, Asadi-Pooya AA. Drug-resistant epilepsy: Definition, pathophysiology, and management. J Neurol Sci. 2023 Sep 15;452:120766. doi: 10.1016/j.jns.2023.120766. Epub 2023 Aug 14. PMID: 37597343.
Kharod P, Mishra D, Juneja M. Drug-resistant epilepsy in Indian children at a tertiary-care public hospital. Childs Nerv Syst. 2019;35(5):775-8.
Kalilani L, Sun X, Pelgrims B, Noack-Rink M, Villanueva V. The epidemiology of drug-resistant epilepsy: A systematic review and meta-analysis. Epilepsia. 2018;59(12):2179-93.
Myers KA. Genetic Epilepsy Syndromes. Continuum (Minneap Minn). 2022 Apr 1;28(2):339-362. doi: 10.1212/CON.0000000000001077. PMID: 35393962.
Parrini E, Marini C, Mei D, Galuppi A, Cellini E, Pucatti D, Chiti L, Rutigliano D, Bianchini C, Virdò S, De Vita D, Bigoni S, Barba C, Mari F, Montomoli M, Pisano T, Rosati A; Clinical Study Group; Guerrini R. Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes. Hum Mutat. 2017 Feb;38(2):216-225. doi: 10.1002/humu.23149. Epub 2016 Dec 9. PMID: 27864847.
Auvin S, Specchio N. Pharmacotherapeutic strategies for drug-resistant epilepsy in children. Epilepsy Behav. 2024 Dec;161:110139. doi: 10.1016/j.yebeh.2024.110139. Epub 2024 Nov 7. PMID: 39515006.
Weber YG, Lerche H. Genetic mechanisms in idiopathic epilepsies. Dev Med Child Neurol. 2008 Sep;50(9):648-54. doi: 10.1111/j.1469-8749.2008.03058.x. PMID: 18754913.
Feld O, Yahalom G, Livneh A. Neurologic and other systemic manifestations in FMF: published and own experience. Best Pract Res Clin Rheumatol. 2012 Feb;26(1):119-33. doi: 10.1016/j.berh.2012.01.004. PMID: 22424198.
Canpolat M, Gumus H, Gunduz Z, Dusunsel R, Kumandas S, Bayram AK, Yel S, Poyrazoglu HG, Yilmaz K, Doganay S, Yikilmaz A, Dundar M, Per H. Neurological Manifestations in Familial Mediterranean Fever: Results of 22 Children from a Reference Center in Kayseri, an Urban Area in Central Anatolia, Turkey. Neuropediatrics. 2017 Apr;48(2):79-85. doi: 10.1055/s-0036-1593374. Epub 2016 Sep 22. Erratum in: Neuropediatrics. 2017 Oct;48(5):402. doi: 10.1055/s-0037-1599783. PMID: 27656843.
Salehzadeh F, Azami A, Motezarre M, Nematdoust Haghi R, Ahmadabadi F. Neurological Manifestations in Familial Mediterranean Fever: a Genotype-Phenotype Correlation Study. Open Access Rheumatol. 2020 Jan 15;12:15-19. doi: 10.2147/OARRR.S238649. PMID: 32021503; PMCID: PMC6970254.
Ozen F, Kocak N, Kelekci S, Yildirim IH, Hacimuto G, Ozdemir O. The prevalence of Familial Mediterranean Fever common gene mutations in patients with simple febrile seizures. Eur Rev Med Pharmacol Sci. 2014;18(5):657-60. PMID: 24668705.
Ertekin V, Selimoğlu MA, Pirim I. Familial Mediterranean fever in a childhood population in eastern Turkey. Pediatr Int. 2005 Dec;47(6):640-4. doi: 10.1111/j.1442-200x.2005.02140.x. PMID: 16354216.
Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*). Annu Rev Immunol. 2009;27:621-68. doi: 10.1146/annurev.immunol.25.022106.141627. PMID: 19302049; PMCID: PMC2996236.
Kanemoto K, Kawasaki J, Miyamoto T, Obayashi H, Nishimura M. Interleukin (IL)1beta, IL-1alpha, and IL-1 receptor antagonist gene polymorphisms in patients with temporal lobe epilepsy. Ann Neurol. 2000 May;47(5):571-4. PMID: 10805326.
Çomak E, Tüfekçi Ö, Kılıçbay F, Isıyel E, Sever AH, Aslanger A, Ekici B. Febrile seizures in children with familial Mediterranean fever: Coincidence or association? Eur J Paediatr Neurol. 2015 Sep;19(5):572-6. doi: 10.1016/j.ejpn.2015.05.004. Epub 2015 May 16. PMID: 26028444.
Biro O, Gileles-Hillel A, Dor-Wollman T, Eisenstein EM, Berkun Y. Neurological and neurodevelopmental symptoms in children with familial Mediterranean fever and their siblings. Eur J Pediatr. 2022 Mar;181(3):973-978. doi: 10.1007/s00431-021-04286-7. Epub 2021 Oct 15. PMID: 34652509.
Heida JG, Moshé SL, Pittman QJ. The role of interleukin-1beta in febrile seizures. Brain Dev. 2009 May;31(5):388-93. doi: 10.1016/j.braindev.2008.11.013. Epub 2009 Feb 13. PMID: 19217733; PMCID: PMC2699664.
Asadi-Pooya AA. Epilepsy and consanguinity in Shiraz, Iran. Eur J Paediatr Neurol. 2005;9(6):383-6. doi: 10.1016/j.ejpn.2005.06.002. Epub 2005 Aug 2. PMID: 16061410.
Khan H, Mohamed A, Al-Sakini Z, Zulfiquar K, Sohail A. Consanguinity, family history, and risk of epilepsy: A case control study. Gulf Medical Journal. 2012; 1 (1): 32-36.
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