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Familial Mediterranean fever: Epidemiology, genetics, and pathogenesis

Author
Eldad Ben-Chetrit, MD
Section Editors
David S Pisetsky, MD, PhD
J Thomas Lamont, MD
Deputy Editors
Monica Ramirez Curtis, MD, MPH
Shilpa Grover, MD, MPH, AGAF

INTRODUCTION

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder characterized by recurrent attacks of fever and serosal inflammation. This topic will review the epidemiology, genetics, and pathogenesis of FMF. The clinical manifestations, diagnosis, and management of FMF are discussed in detail separately. (See "Clinical manifestations and diagnosis of familial Mediterranean fever" and "Management of familial Mediterranean fever".)

EPIDEMIOLOGY

Familial Mediterranean fever (FMF) is most prevalent in individuals of Turkish, Armenian, North African, Jewish, and Arab descent. Among Armenians, the carrier rate for FMF is approximately one in seven, with an observed disease rate of roughly 1 in 500 [1]   Among the Jewish population in Israel, the carrier rate varies from one in eight in those of Ashkenazi origin, to one in six in those of North African origin, to one in four in those of Iraqi origin [2].

However, FMF is not restricted to these ethnic groups. It has also been reported at a lower prevalence in many other populations such as in Greece, Italy, and even Japan [2,3]. In the United States, FMF is frequently encountered in Ashkenazi Jews and immigrants from the Middle East and Armenia. In Germany, most FMF patients are of Turkish origin. In France, there is a relatively large FMF population that originated in North Africa. In the Balkans, the number of FMF patients and the rate of MEFV mutations carriage is decreasing as the country is farther from Turkey [3]. Similarly, the prevalence of FMF is highest in southern Italy and decreases gradually toward the northern area. It is hypothesized that the origin of FMF was more than 3000 years ago in Mesopotamia [4]. From there, the disease was spread to Armenia and Turkey in the Ancient World. In the modern world, the spread of the disease to countries far from the Mediterranean basin can be explained by easy transportation overseas and later by the air.

FMF shows considerable variability in severity and type of clinical manifestations by region. This variability is probably due to differences in MEFV mutations, additional genetic modifiers, and associated environmental factors. (See "Clinical manifestations and diagnosis of familial Mediterranean fever" and 'Genotype-phenotype correlation' below.)

GENETICS

MEFV gene mutations — Familial Mediterranean fever (FMF) is usually considered an autosomal recessive disease, and affected individuals have biallelic pathogenic mutations in the MEFV gene located on the short arm of chromosome 16 (16 pm 13.3) [3-5]. Five founder mutations, V726A, M694V, M694I, M680I, and E148Q, account for approximately 75 percent of FMF chromosomes from typical cases in Armenians, Arabs, Jews, and Turks [6]. Among them, M694V is the most frequent mutation in all four populations, with a prevalence ranging from 20 to 65 percent. However, approximately 10 to 20 percent of individuals who meet diagnostic criteria for FMF have no MEFV mutations [7,8].

     
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Literature review current through: Nov 2017. | This topic last updated: Apr 26, 2017.
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