Familial Mediterranean fever is no longer a rare disease in Italy

Abstract

Familial Mediterranean fever (FMF) is an autosomal recessive disorder, characterised by short, recurrent attacks of fever with abdominal, chest or joint pain and erysipelas-like erythema. It is an ethnically restricted genetic disease, found commonly among Mediterranean populations, as well as Armenians, Turks, Arabs and Jews. Traditionally, Italians have been considered little affected by FMF, despite the geographical position of Italy (northern Mediterranean basin) and the migratory changes in its population. The objective was to characterise the demographic, clinical and genetic features of FMF in Italy. Patients of Italian origin were recruited from those referred to Italian-French medical centres for FUO (Fever of Unknown Origin) or 'surgical' emergencies; clinical history, genealogy and physical examination were recorded; all other possible infectious, neoplastic, auto-immune and metabolic diseases were excluded. Mutational analysis of the gene responsible for FMF (MEFV on 16p13.3) was performed, after which geno-phenotypical correlations were established. Italian FMF patients, 40 women and 31 men, aged from 3 to 75 years, have shown all the clinical manifestations indicative of FMF described in the literature, but with a lower incidence of amyloidosis. The genetic tests have been contributive in 42% of cases. The frequency of each different mutation has been similar to that found in a series of 'endemic' countries. The geno-phenotypical correlations have suggested the existence of genetic and/or environmental modifier-factors. Among Italians FMF seems to be more frequent than was believed in the past. The data presented are consistent with their geographical location and their history.

A population genetics study of the Familial Mediterranean Fever gene: evidence of balancing selection under an overdominance regime

“…It is worth noting that no heterozygote excess was observed among ITs, a population with a reportedly 59 high frequency of FMF (not confirmed in this survey). Yet, it should be pointed out that none of the most common FMF mutations was identified in our subjects (either IT or of different geographic origin), suggesting that the maintenance of disease-associated mutations in Mediterranean populations and the persistence of the two major lineages we observe here are accounted for by different evolutionary processes.…”

Familial Mediterranean Fever in the World

“…In addition to the above countries, FMF is found in significant numbers in North African countries, Greece, Crete, France, Germany, Italy, and the US (11)(12)(13)(14). In recent years, approximately 100 cases have been reported in Japan (15,16, and Tsuchiya-Suzuki A, et al: unpublished observations).…”

“…Most FMF patients in Italy are located in the central and southern parts of the peninsula. Their origin is probably composed of Greeks, Turks, and Phoenicians who came by way of the sea (14). FMF migrated from the Middle East (to Europe) in ancient times and reached the "new world" (the US) in modern times.…”

Clinical and molecular analysis of common MEFV gene mutations in familial Mediterranean fever in Sivas population

“…FMF is also reported in other countries of the Mediterranean, including Cyprus, Italy and Spain (Deltas et al 2002;La Regina et al 2003;Aldea et al 2004). It is characterized by recurrent, self-limited attacks of fever accompanied by peritonitis, arthritis or pleuritis and insidious development of systemic amyloidosis (Sohar et al 1967;Ben-Chetrit & Levy 1998).…”