ReviewFamilial Mediterranean fever: New phenotypes
Section snippets
Familial Mediterranean fever (FMF): definition and diagnostic criteria
Familial Mediterranean fever (FMF, OMIM ID: 249100) is an autosomal recessive disease characterized by recurring self-limited short episodes of fever and serositis resulting in pain in the abdomen, chest, joints and muscles; it is the most common of the periodic hereditary fevers.
FMF mainly affects Middle Eastern populations and other ethnic groups living around the Mediterranean basin, such as Jews, Armenians, Turks, Arabs, with high prevalence (1/200–1/1000); also, it is not considered rare
The FMF phenotypes
Clinically, FMF can be distinguished into three phenotypes: type 1, which is commonly associated with recurrent short episodes of inflammation and serositis, including fever, peritonitis, synovitis, pleuritis, but also pericarditis, orchitis or meningitis episodes; type 2, characterized by the evidence of amyloidosis as the first clinical manifestation of the disease in an otherwise asymptomatic individual; type 3, referred to the ‘silent’ homozygous or compound heterozygote state, in which two
Our experience
Since 1990s the Periodic Fevers Research Centre of Catholic University of Sacred Heart of Rome had dedicated its attention to the diagnosis and treatment of patients with periodic autoinflammatory syndromes, accruing a patients experience of more than 1100 individuals and providing us an extensive clinical familiarity with these conditions.
Since 1998 to 2011, among all patients evaluated in our Centre for fever of unknown origin (FUO), 311 (163 M: 148 F) received certain diagnosis of FMF,
Conclusions
As diagnosis of FMF is clinical, an accurate clinical history, together with the monitoring of disease activity through the parameters of inflammation (CRP, SAA, ESR, fibrinogen, white blood cell count), is pivotal for the clinician to determine a correct diagnosis in suspected cases of FMF.
The awareness of FMF prevalence in the population as well as the presence of referee Centers with expert-field clinicians, have a major role to achieve an early diagnosis and thus, to shorten the diagnostic
Take-home messages
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FMF is an autosomal recessive disease caused by MEFV gene mutations on chromosome 16
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The identification of MEFV mutations contribute to the different FMF phenotype diagnosis.
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MEFV mutation may aggravate the autoimmune disease course and influence the therapy.
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There are variable penetrance and expression of FMF, also in heterozygous subjects.
Conflict of interest statement
The authors deny any financial and personal relationships with other people or organizations that could inappropriately influence the content of this article.
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Isolated parenchymal pulmonary presentation of familial Mediterranean fever
2019, Annals of Allergy, Asthma and ImmunologyHow to prescribe a genetic test for the diagnosis of autoinflammatory diseases?
2019, Presse MedicaleCitation Excerpt :Problems encountered during molecular diagnosis of the FMF, the most common SAID, are well characterised. In 20–25% of the patients with the clinical diagnosis of FMF and a positive response to colchicine therapy, the second variant in the MEFV gene has not been identified [84]. Moreover, some MEFV variants have been reported to cause dominant FMF, namely p.M694del, p.T577N, p.T577S and p.T577A [13].
Screening of the most common MEFV mutations in a large cohort of Egyptian patients with Familial Mediterranean fever
2018, Gene ReportsCitation Excerpt :Furthermore, other genes could be responsible for causing FMF (Jéru et al., 2013). Moreover; several possibilities including the presence of mutations in another autoinflammatory gene, epigenetic or post-translational modifications, environmental factors as well as having hidden biomarkers might play a role in heterozygosity as a casualty of FMF in our patients (Booty et al., 2009, Moradian et al., 2010, Soriano and Manna, 2012; Erdem et al., 2017). The term “missing heritability”, usually used to describe the gap between predictive transmission models of complex traits and statistical explanatory power of susceptibility genes identified by genome-wide association studies (GWAS), could also apply to this particular situation (Manolio et al., 2009).
Familial Mediterranean Fever: Diagnostic Difficulties in an Atypical Case
2017, Actas Dermo-SifiliograficasAn Update on Familial Mediterranean Fever
2023, International Journal of Molecular Sciences