Skip to main content

Epidemiology of FMF Worldwide

  • Chapter
Familial Mediterranean Fever

Part of the book series: Rare Diseases of the Immune System ((RDIS,volume 3))

Abstract

The familial Mediterranean fever (FMF) is the primarily described and most prevalent autoinflammatory disease known in the world. FMF was so named by Heller, because of its high prevalence in the Mediterranean population [1]. Indeed, it was previously denominated as benign paroxysmal peritonitis by Siegal, a New York allergist of Jewish origin [2], whereas it has been described as Maladie periodique by French authors [3].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 119.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Heller H, Sohar E, Kariv I, Sherf L. Familial Mediterranean fever. Harefuah. 1955;48:91.

    CAS  PubMed  Google Scholar 

  2. Siegal S. Benign paroxysmal peritonitis. Ann Intern Med. 1945;23:1–21.

    Article  Google Scholar 

  3. Mamou H, Cattan R. La maladie périodique (sur 14 cas personnels dont 8 compliqués de néphropathies). Semaine hôp. Paris. 1952;28:1062.

    Google Scholar 

  4. Tunca M, Akar S, Onen F, et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore). 2005;84(1):1–11.

    Article  Google Scholar 

  5. Zaks N, Shinar Y, Padeh S, et al. Analysis of the three most common MEFV mutations in 412 patients with familial Mediterranean fever. Isr Med Assoc J. 2003;5(8):585–8.

    CAS  PubMed  Google Scholar 

  6. Tchernitchko D, Legendre M, Cazeneuve C, Delahaye A, Niel F, Amselem S. The E148Q MEFV allele is not implicated in the development of familial Mediterranean fever. Hum Mutat. 2003;22(4):339–40.

    Article  PubMed  Google Scholar 

  7. Chaabouni HB, Ksantini M, M’Rad R, et al. MEFV mutations in Tunisian patients suffering from familial Mediterranean fever. Semin Arthritis Rheum. 2007;36(6):397–401.

    Article  CAS  PubMed  Google Scholar 

  8. Ippocrate, Aforismi e Giuramento, Tascabili Economici Newton, Roma, 1994.

    Google Scholar 

  9. Ben-Chetrit E, Levy M. Familial Mediterranean fever. Lancet. 1998;351:659–64.

    Article  CAS  PubMed  Google Scholar 

  10. Eliakim M, Levy M, Ehrenfeld M. Recurrent polyserositis (familial Mediterranean fever, periodic disease). New York: Elsevier North-Holland; 1981. p. 5–14.

    Google Scholar 

  11. Touitou I. The spectrum of familial Mediterranean fever (FMF) mutations. Eur J Hum Genet. 2001;9:473–83.

    Article  CAS  PubMed  Google Scholar 

  12. Cobankara V, Fidan G, Turk T, Zencir M, Colakoglu M, Ozen S. The prevalence of familial Mediterranean fever in the Turkish province of Denizli: a field study with a zero patient design. Clin Exp Rheumatol. 2004;22 Suppl 34:S27–30.

    CAS  PubMed  Google Scholar 

  13. Sarkisian T, Ajrapetian H, Beglarian A, Shahsuvarian G, Egiazarian A. Familial Mediterranean fever in Armenian population. Georgian Med News. 2008;156:105–11.

    PubMed  Google Scholar 

  14. Nucera G, La Regina G, Diaco ML, Neri G, Gasbarrini G, Manna R. La febbre mediterranea familiare: un’antica eredità. Ann Ital Med Int Vol 18, N 3 Luglio-Settembre 2003.

    Google Scholar 

  15. Daniels M, Shohat T, Brenner-Ullman A, Shohat M. Familial Mediterranean fever: high gene frequency among the non-Ashkenazic and Ashkenazic Jewish populations in Israel. Am J Med Genet. 2005;55:311–4.

    Article  Google Scholar 

  16. Medlej-Hashim M, Serre JL, Corbani S, Saab O, Jalkh N, Delague V, et al. Familial Mediterranean fever (FMF) in Lebanon and Jordan: a population genetics study and report of three novel mutations. Eur J Med Genet. 2005;48:412–20.

    Article  PubMed  Google Scholar 

  17. Mattit H, Joma M, Al-Cheikh S, El-Khateeb M, Medlej-Hashim M, Salem N, et al. Familial Mediterranean fever in the Syrian population: gene mutation frequencies, carrier rates and phenotype-genotype correlation. Eur J Med Genet. 2006;49:481–6.

    Article  PubMed  Google Scholar 

  18. Medlej-Hashim M, Chouery E, Salem N, Delague V, Lefranc G, Loiselet J, Mégarbané A. Familial Mediterranean fever in a large Lebanese family: multiple MEFV mutations and evidence for a Founder effect of the p.[M694I] mutation. Eur J Med Genet. 2011;54:50–e 54.

    Article  PubMed  Google Scholar 

  19. Medlej-Hashim M, Loiselet J, Lefranc G, Mégarbané A. La fièvre méditerranéenne familiale (FMF): du diagnostic au traitment. Cah Santé. 2004;14:261–6.

    Google Scholar 

  20. Gershoni-Baruch R, Shinawi M, Kasinetz L, Badarnah K, Riva B. Familial Mediterranean fever: prevalence, penetrance and genetic drift. Eur J Med Genet. 2001;9:634–7.

    CAS  Google Scholar 

  21. Cattan D. MEFV mutation carriers and diseases other than familial Mediterranean fever: proved and non-proved associations; putative biological advantage. Curr Drug Targets Inflamm Allergy. 2005;4:105–12.

    Article  CAS  PubMed  Google Scholar 

  22. Chae JJ, Komarow HD, Cheng J, Wood G, Raben N, Liu P, Kastner D. Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis. Mol Cell. 2003;11:591–604.

    Article  CAS  PubMed  Google Scholar 

  23. Wang J, Wakeham J, Harknass R, Xing ZJ. Macrophages are a significant source of type 1 cytokines during mycobacterial infection. Clin Invest. 1999;103:1023–9.

    Article  CAS  Google Scholar 

  24. Lipsitch M, Sousa A. Historical intensity of natural selection for resistance to tuberculosis. Genetics. 2002;161:1599–607.

    PubMed Central  PubMed  Google Scholar 

  25. Ozen S. What advantage did the heterozygotes for MEFV mutations have – if any. Clin Exp Rheumatol. 2002;20 Suppl 26:69.

    Google Scholar 

  26. The International Familial Mediterranean Fever Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell. 1997;90:797–807.

    Article  Google Scholar 

  27. Bernot A, da Silva C, Petit JL, Cruaud C, Caloustian C, Castet V, et al. Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF). Hum Mol Genet. 1998;7:1317–25.

    Article  CAS  PubMed  Google Scholar 

  28. Milhavet F, Cuisset L, Hoffman HM, Slim R, El-Shanti H, Aksentijevich I, et al. The Infevers autoinflammatory mutation online registry: update with new genes and functions. Hum Mutat. 2008;29:803–8.

    Article  PubMed  Google Scholar 

  29. Anna Aldea A, Calafell F, Aróstegui JI, Lao O, Rius J, Plaza S, Masó M, Vives J, Buades J, Yagüe J. The west side story: MEFV haplotype in Spanish FMF patients and controls, and evidence of high LD and a recombination “hot-spot” at the MEFV locuS. Hum Mutat. 2004;23(4):399.

    Article  PubMed  Google Scholar 

  30. Ben-Chetrit E, Touitou I. Familial Mediterranean fever in the World. Arthritis Rheum (Arthritis Care Res). 2009;61(10):1447–53.

    Article  CAS  Google Scholar 

  31. Aksentijevich I, Torosyan Y, Samuels J, Centola M, Pras E, Chae JJ, et al. Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population. Am J Hum Genet. 1999;64:949–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Tomiyama N, Higashiuesato Y, Oda T, Baba E, Harada M, Azuma M, Yamashita T, Uehara K, Miyazato A, Hatta K, Ohya Y, Iseki K, Jinno Y, Takishita S. MEFV mutation analysis of familial Mediterranean fever in Japan. Clin Exp Rheumatol. 2008;26(1):13–7.

    CAS  PubMed  Google Scholar 

  33. La Regina M, Nucera G, Diaco M, Procopio A, Gasbarrini G, Notarnicola C, Kone-Paut I, Touitou I, Manna R. Familial Mediterranean fever is no longer a rare disease in Italy. Eur J Hum Genet. 2003;11(1):50–6.

    Article  PubMed  Google Scholar 

  34. Data acquired by courtesy of Professor Raffaele Manna – Periodic Fever Research Center- UCSC- Rome (2013).

    Google Scholar 

  35. Nucera G, La Regina M, Diaco ML, Neri G, Gasbarrini GB, Manna R. La Febbre Mediterranea Familiare: un’antica eredità.

    Google Scholar 

  36. La Regina M, Nucera G, Diaco M, Federico G, Manna R, Gasbarrini G. Why Europeans should study hereditary inflammatory disorders. Clin Exp Rheumatol. 2002;20 Suppl 26:S92–3.

    Google Scholar 

  37. Manna R, La Regina M, Nucera G, Touitou I, Gasbarrini G. Episodic febrile auto-inflammatory diseases (EFAIDs) in the Mediterranean area. Eur J Intern Med. 2001;12:147.

    Google Scholar 

  38. Piazza A, Cappello N, Olivetti E, Rendine S. A genetic history of Italy. Ann Hum Genet 1988; 52 (Part 3): 203–13. French Familial Mediterranean Fever Consortium. A candidate gene for familial Mediterranean fever. Nat Genet. 1997;17:25–31.

    Google Scholar 

  39. Konstantopoulos K, Kanta A, Deltas C, Atamian V, Mavrogianni D, Tzioufas AG, Kollainis I, Ritis K, Moutsopoulos H. Familial Mediterranean fever associated pyrin mutations in Greece. Ann Rheum Dis. 2003;62:479–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Giaglis S, Papadopoulos V, Kambas K, et al. MEFV alterations and population genetics analysis in a large cohort of Greek patients with familial Mediterranean fever. Clin Genet. 2007;71:458–67.

    Article  CAS  PubMed  Google Scholar 

  41. Papadopoulos VP, Giaglis S, Mitroulis I, Ritis K. The population genetics of familial Mediterranean fever: a meta-analysis study. Ann Hum Genet. 2008;72:752–61.

    Article  CAS  PubMed  Google Scholar 

  42. Fragouli E, Eliopoulos E, Petraki E, Sidiropoulos P, Aksentijevich I, Galanakis E, Kritikos H, Repa A, Fragiadakis G, Boumpas DT, Goulielmos GN. Familial Mediterranean fever in Crete: a genetic and structural biological approach in a population of intermediate risk. Clin Genet. 2008;73:152–9.

    Article  CAS  PubMed  Google Scholar 

  43. Cornelius N, Duno M. Molecular evaluation of 458 patients referred with a clinical diagnosis of familial Mediterranean fever in Scandinavia. Rheumatol Int. 2011;31:1531–3.

    Article  PubMed  Google Scholar 

  44. Lainka E, Bielak M, Lohse P, Timmann C, Stojanov S, von Kries R, Niehues T, Neudorf U. Familial Mediterranean fever in Germany: epidemiological, clinical, and genetic characteristics of a pediatric population. Eur J Pediatr. 2012;171:1775–85.

    Article  CAS  PubMed  Google Scholar 

  45. Kisacik B, Yildirim B, Tasliyurt T. Increased frequency of familial Mediterranean fever in northern Turkey: a population based study. Rheumatol Int. 2009;11:1307–9.

    Article  Google Scholar 

  46. Onen F, Sumer H, Turkay S, et al. Increased frequency of familial Mediterranean fever in central Anatolia, Turkey. Clin Exp Rheumatol. 2004;22(4 Suppl 34):S31–3.

    CAS  PubMed  Google Scholar 

  47. Ozen S, Frenkel J, Ruperto N, et al. The Eurofever project: towards better care for autoinflammatory diseases. Eur J Pediatr. 2011;170:445–52.

    Article  PubMed  Google Scholar 

  48. Ozen S, Aktay N, Lainka E, Duzova A, Bakkaloglu A, Kallinich T. Disease severity in children and adolescents with familial Mediterranean fever: a comparative study to explore environmental effects on a monogenic disease. Ann Rheum Dis. 2009;68:246–8.

    Article  CAS  PubMed  Google Scholar 

  49. Giese A, Örnek A, Kilic L, Kurucay M, Şendur SN, Lainka E, Henning BF. Disease severity in adult patients of Turkish ancestry with familial Mediterranean fever living in Germany or Turkey. Does the country of residence affect the course of the disease? J Clin Rheumatol. 2013;19(5):246–51.

    Article  PubMed  Google Scholar 

  50. Ben-Zvi I, Brandt B, Berkun Y, Lidar M, Livneh A. The relative contribution of environmental and genetic factors to phenotypic variation in familial Mediterranean fever (FMF) Gene. 2012;491(2):260–3.

    CAS  PubMed  Google Scholar 

  51. Mimouni A, Magal N, Stoffman N, Shohat T, Minasian A, Krasnov M, Halpern GJ, Rotter JI, Fischel-Ghodsian N, Danon YL, Shohat M. Familial Mediterranean fever: effects of genotype and ethnicity on inflammatory attacks and amyloidosis. Pediatrics. 2000;105(5):E70.

    Article  CAS  PubMed  Google Scholar 

  52. Touitou I, Sarkisian T, Medlej-Hashim M, et al. Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever. Arthritis Rheum. 2007;56:1706–12.

    Article  PubMed  Google Scholar 

  53. Schwabe AD, Peters RS. Familial Mediterranean fever in Armenians. Analysis of 100 cases. Med (Baltimore). 1974;53:453–62.

    Article  CAS  Google Scholar 

  54. Samuels J, Aksentijevich I, Torosyan Y, Centola M, Deng Z, Sood R, Kastner DL. Familial Mediterranean fever at the millennium. Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes o Health. Med (Baltimore). 1998;77(4):268–97.

    Article  CAS  Google Scholar 

  55. Ong FS, Vakil H, Xue Y, Kuo JZ, Shah KH, Lee RB, Bernstein KE, Rimoin DL, Getzug T, Das K, Deignan JL, Rotter JI, Grody WW. The M694V mutation in Armenian-Americans: a 10-year retrospective study of MEFV mutation testing for familial Mediterranean fever at UCLA. Clin Genet. 2013;84(1):55–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Booth DR, Gillmore JD, Booth MB, et al. Pyrin/Marenostrin mutations in familial Mediterranean fever. Q J Med. 1998;91:603–6.

    Article  CAS  Google Scholar 

  57. Rozenbaum M, Touitou I, Pertnoy E, Morkos S, Rosner I. A molecular basis for the absence of familial Mediterranean fever in Ethiopian Jews. Clin Exp Rheumatol. 2006;24(5 Suppl 42):S127.

    Google Scholar 

  58. Migita K, Uehara R, Nakamura Y, Yasunami M, et al. Familial Mediterranean fever in Japan. Medicine (Baltimore). 2012;91(6):337–43.

    Article  Google Scholar 

  59. Migita K, Agematsu K, Yazaki M, Nonaka F, Nakamura A, Toma T, Kishida D, Uehara R, Nakamura Y, Jiuchi Y, Masumoto J, Furukawa H, Ida H, Terai C, Nakashima Y, Kawakami A, Nakamura T, Eguchi K, Yasunami M, Yachie A. Familial Mediterranean fever: genotype-phenotype correlations in Japanese patients. Medicine (Baltimore). 2014;93(3):158–64.

    Article  CAS  Google Scholar 

  60. Casey P, Lane M, Ameratunga R. Familial Mediterranean fever: 36 years to diagnosis. N Z Med J. 2004;117(1194):U894.

    PubMed  Google Scholar 

  61. Kastner DL, Aksentijevich I. Intermittent and periodic arthritis syndromes, in Arthritis and Allied Conditions, 15th ed., WJ Koopman and LW Moreland, eds., (2005) pp. 1411–1461.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Raffaele Manna .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Cerrito, L., Sicignano, L.L., Verrecchia, E., Manna, R. (2015). Epidemiology of FMF Worldwide. In: Gattorno, M. (eds) Familial Mediterranean Fever. Rare Diseases of the Immune System, vol 3. Springer, Cham. https://doi.org/10.1007/978-3-319-14615-7_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-14615-7_5

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-14614-0

  • Online ISBN: 978-3-319-14615-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics