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Familial Mediterranean fever: new phenotypes
Alessandra Soriano1, Raffaele Manna
1Periodic Fever Research Centre, National Reference Centre for FMF, Catholic University of the Sacred Heart, Rome, Italy.
Autoimmunity Reviews
|August 11, 2012
Summary
Familial Mediterranean fever (FMF) is an inherited autoinflammatory disorder caused by MEFV gene mutations. Understanding its diverse phenotypes and genetic factors is key to comprehending this complex disease.
Area of Science:
- Genetics
- Immunology
- Rheumatology
Background:
- Familial Mediterranean fever (FMF) is an inherited autosomal recessive autoinflammatory syndrome.
- It is primarily observed in individuals of Mediterranean descent and is caused by mutations in the Mediterranean Fever (MEFV) gene.
- FMF represents the most common periodic febrile syndrome within the spectrum of autoinflammatory diseases.
Purpose of the Study:
- To delineate the distinct clinical phenotypes of FMF.
- To explore the genetic underpinnings, including MEFV mutations and their inheritance patterns.
- To investigate the factors contributing to phenotypic variability and incomplete penetrance in FMF.
Main Methods:
- Clinical classification into three distinct FMF phenotypes.
- Genetic analysis focusing on MEFV gene mutations (homozygous, compound heterozygous, and heterozygous states).
- Consideration of modifier genes and environmental factors influencing disease presentation.
Main Results:
- Phenotype 1: Recurrent inflammatory episodes with serositis (peritonitis, pleuritis, synovitis).
- Phenotype 2: AA amyloidosis as the initial manifestation in asymptomatic individuals.
- Phenotype 3: 'Silent' carrier state with MEFV mutations but no disease symptoms.
- Identification of 'FMF-like' disease in heterozygous carriers, indicating incomplete or mild forms.
Conclusions:
- FMF presents with diverse clinical phenotypes, ranging from acute inflammation to amyloidosis and asymptomatic carrier states.
- MEFV gene mutations are central to FMF pathogenesis, with varying clinical outcomes based on genotype.
- Genetic modifiers and environmental factors significantly influence FMF penetrance and phenotypic expression, highlighting the disease's complexity.
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