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Performance of the new Eurofever/PRINTO classification criteria in Familial Mediterranean fever patients with a single exon 10 mutation in childhood

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Abstract

The diagnosis of Familial Mediterranean fever (FMF) based on clinical findings supported by genetic mutation. Recently, the new Eurofever/PRINTO classification criteria including genetic analysis were established. The aim of this study is to evaluate the performance of the new criteria in FMF patients with a single exon 10 mutation in childhood. The study group consisted of FMF patients who had a single exon 10 mutation in a referral center in Turkey. Patients with periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome were included as a control group. The medical charts of all patients were reviewed retrospectively. A total of 106 FMF patients (59 boys) were enrolled in the study group. The median age at first symptom was 5; the median age at diagnosis was 7 years. The mean follow-up was 33 ± 35.4 months. Majority of the patients (n = 58, 54.7%) had heterozygous M694V, 16 (15%) patients had M694V/E148Q and 13 (13.8%) patients had heterozygous M680I mutation. The sensitivity of the Yalcinkaya-Ozen criteria was 98.1% and it was 97.1% for the Eurofever/PRINTO classification criteria. The specificity of the new Eurofever/PRINTO classification criteria was 96.7% and it was 74.1% for the Yalcinkaya-Ozen criteria. The new Eurofever/PRINTO classification criteria have a good sensitivity as the Yalcinkaya-Ozen criteria in patients with a single exon 10 mutation. Additionaly, the new criteria have better specificity. It should be useful to apply the clinical only criteria where the carrier rate is high.

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References

  1. Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcınkaya F, Turkish FMF study group et al (2005) Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore) 84(1):1–11

    Article  Google Scholar 

  2. French FMF Consortium (1997) A candidate gene for familial Mediterranean fever. Nat Genet 17:25–31

    Article  Google Scholar 

  3. The International FMF Consortium (1997) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 90:797–807

    Article  Google Scholar 

  4. Pras M (1998) Familial Mediterranean fever: from the clinical syndrome to the cloning of the pyrin gene. Scand J Rheumatol 27(2):92–97

    Article  CAS  Google Scholar 

  5. Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T et al (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40(10):1879–1885

    Article  CAS  Google Scholar 

  6. Yalçinkaya F, Ozen S, Ozçakar ZB, Aktay N, Cakar N, Düzova A et al (2009) A new set of criteria for the diagnosis of Clin Rheumatol familial Mediterranean fever in childhood. Rheumatology (Oxford) 48:395–398

    Article  Google Scholar 

  7. Booty MG, Chae JJ, Masters SL, Remmers EF, Barham B, Lee JM et al (2009) Familial Mediterranean fever with a single MEFV mutation: where is the second hit? Arthritis Rheum 60:1851–1861

    Article  CAS  Google Scholar 

  8. Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I et al (2019) Classification criteria for autoinflammatory recurrent fevers. Ann Rheum Dis 78:1025–1032

    Article  CAS  Google Scholar 

  9. Marshall GS, Edwards KM, Butler J, Lawton AR (1987) Syndrome of periodic fever, pharyngitis, and aphthous stomatitis. J Pediatr 110(1):43–46

    Article  CAS  Google Scholar 

  10. Soylemezoglu O, Kandur Y, Gonen S, Düzova A, Ozcakar ZB, Fidan K et al (2016) Familial Mediterranean fever gene mutation frequencies in a sample Turkish population. Clin Exp Rheumatol 102(6):97–100

    Google Scholar 

  11. Hernández-Rodríguez J, Ruíz-Ortiz E, Tomé A, Espinosa G, Gonzalez-Roca E, Mensa-Vilaro A et al (2016) Clinical and genetic characterization of the autoinflammatory diseases diagnosed in an adult reference center. Autoimmun Rev 15(1):9–15

    Article  Google Scholar 

  12. Ozçakar ZB, Yalçınkaya F, Cakar N, Acar B, Bilgiç AE, Uncu N et al (2011) Application of the new pediatric criteria and Tel Hashomer criteria in heterozygous patients with clinical features of FMF. Eur J Pediatr 170(8):1055–1057

    Article  Google Scholar 

  13. Tanatar A, Sönmez HE, Karadağ ŞG, Çakmak F, Çakan M, Demir F et al (2020) Performance of Tel-Hashomer, Livneh, pediatric and new Eurofever/PRINTO classification criteria for familial Mediterranean fever in a referral center. Rheumatol Int 40(1):21–27

    Article  CAS  Google Scholar 

  14. Sag E, Demirel D, Demir S, Atalay E, Akca U, Bilginer Y et al (2020) Performance of the new 'Eurofever/PRINTO classification criteria' in FMF patients. Semin Arthritis Rheum 50(1):172–175

    Article  CAS  Google Scholar 

  15. Adrovic A, Yıldız M, Kanber M, Ulkersoy I, Gucuyener N, Koker O et al (2020) Performance of recently proposed periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome criteria in a region endemic for familial Mediterranean fever. Rheumatol Int 40(1):91–96

    Article  CAS  Google Scholar 

  16. ButbulAviel Y, Harel L, Abu Rumi M, Brik R, Hezkelo N, Ohana O et al (2019) Familial Mediterranean fever is commonly diagnosed in children in Israel with periodic fever aphthous stomatitis, pharyngitis, and adenitis syndrome. J Pediatr 204:270–274

    Article  Google Scholar 

  17. Pehlivan E, Adrovic A, Sahin S, Barut K, KulCınar O, Kasapcopur O (2018) PFAPA Syndrome in a population with endemic Familial Mediterranean fever. J Pediatr 192:253–255

    Article  Google Scholar 

  18. Gunes M, Cekic S, Kilic SS (2017) Is colchicine more effective to prevent periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis episodes in Mediterranean fever gene variants? Pediatr Int 59(6):655–660

    Article  CAS  Google Scholar 

  19. Batu ED, Kara Eroğlu F, Tsoukas P, Hausmann JS, Bilginer Y, Kenna MA et al (2016) Periodic fever, aphthosis, pharyngitis, and adenitis syndrome: analysis of patients from two geographic areas. Arthritis Care Res (Hoboken) 68(12):1859–1865

    Article  Google Scholar 

  20. Adrovic A, Sahin S, Barut K, Kasapcopur O (2019) Familial Mediterranean fever and periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: shared features and main differences. Rheumatol Int 39(1):29–36

    Article  Google Scholar 

  21. Demirkaya E, Saglam C, Turker T, Koné-Paut I, Woo P, Doglio M et al (2016) Performance of different diagnostic criteria for Familial Mediterranean fever in children with periodic fevers: results from a multicenter international registry. J Rheumatol 43(1):154–160

    Article  CAS  Google Scholar 

  22. Kondi A, Hentgen V, Piram M, Letierce A, Guillaume-Czitrom S, Koné-Paut I (2010) Validation of the new paediatric criteria for the diagnosis of familial Mediterranean fever: data from a mixed population of 100 children from the French reference centre for auto-inflammatory disorders. Rheumatology (Oxford) 49(11):2200–2203

    Article  Google Scholar 

  23. Ben-Chetrit E, Touitou I (2009) Familial Mediterranean fever in the world. Arthritis Rheum 61:1447–1453

    Article  CAS  Google Scholar 

  24. Yilmaz E, Ozen S, Balcı B, Duzova A, Topaloglu R, Besbas N (2001) Mutation frequency of Familial Mediterranean fever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet 9:553–555

    Article  CAS  Google Scholar 

  25. Ben-Chetrit E, Lerer I, Malamud E, Domingo C, Abeliovich D (2000) The E148Q mutation in the MEFV gene: ıs ıt a disease-causing mutation or a sequence variant? Hum Mutat 15(4):385–386

    Article  CAS  Google Scholar 

  26. Aydın F, Çakar N, Özçakar ZB, Uncu N, Başaran Ö, Özdel S et al (2019) Clinical features and disease severity of Turkish FMF children carrying E148Q mutation. J Clin Lab Anal 33(4):e22852

    Article  Google Scholar 

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Authors and Affiliations

  1. Division of Pediatric Rheumatology, Department of Pediatrics, Ministry of Health, Ankara City Hospital, Ankara, Turkey

    Fatma Aydın, Tuba Kurt, Müge Sezer, Nilüfer Tekgöz, Zahide Ekici Tekin, Cüneyt Karagöl, Serkan Coşkun & Banu Çelikel Acar

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  1. Fatma Aydın
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  2. Tuba Kurt
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  3. Müge Sezer
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  4. Nilüfer Tekgöz
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  5. Zahide Ekici Tekin
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  6. Cüneyt Karagöl
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  7. Serkan Coşkun
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  8. Banu Çelikel Acar
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Contributions

All authors contributed to the study conception and design. FA designed the study, drafted the initial manuscript, and had full access to all the data in the study; TK, MS, NT designed the study, conducted the data analyses, drafted the initial manuscript; ZET, CK and SC drafted the initial manuscript; BÇA conceptualized and designed the study, drafted the final manuscript, and all authors read and approved the final and revised manuscript.

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Correspondence to Fatma Aydın.

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The authors declare that they don’t have any conflict of interest.

Ethical approval

The study was reviewed and approved by the local ethical review committee of Ministry of Health, Ankara City Hospital, Department of Pediatrics (Ethics approval number: 31.12.2019-03).

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All participants and parents provided written informed consent.

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Aydın, F., Kurt, T., Sezer, M. et al. Performance of the new Eurofever/PRINTO classification criteria in Familial Mediterranean fever patients with a single exon 10 mutation in childhood. Rheumatol Int 41, 95–101 (2021). https://doi.org/10.1007/s00296-020-04709-y

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  • DOI: https://doi.org/10.1007/s00296-020-04709-y

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