Familial Mediterranean Fever Genetics and Management

Familial Mediterranean fever (FMF) is an autosomal autoinflammatory disorder characterised by recurrent episodes of fever and serosal inflammation. The condition arises primarily from mutations in the MEFV gene, which encodes the pyrin protein, a critical regulator of the inflammasome and interleukin-1β production. Although classically inherited in an autosomal recessive manner, a proportion of heterozygous carriers manifest disease, reflecting complex genotype–phenotype interactions and modifier effects. Mutations clustering in exon 10, such as M694V and V726A, are associated with more severe disease and higher risk of renal amyloidosis, whereas variants in other regions often produce milder phenotypes. Clinically, FMF attacks present with serositis, arthritis or pericarditis, accompanied by elevated acute-phase reactants. The most feared long-term complication is amyloid A amyloidosis, leading to progressive renal impairment. Management hinges on lifelong colchicine prophylaxis, which prevents attacks and reduces amyloid risk. In cases of colchicine intolerance or resistance, anti-interleukin-1 therapies such as anakinra and canakinumab have demonstrated efficacy. Regular monitoring of inflammatory markers and renal function guides therapy adjustment. Advances in genetic testing have improved diagnostic accuracy, enabling earlier intervention across diverse populations, including those outside traditional Mediterranean ethnicities. Emerging data on biomarker profiles, immune cell phenotypes and long-term outcomes are refining the approach to personalised risk stratification and targeted treatment.

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Familial Mediterranean Fever Genetics and Management publication trend

The graph below shows the total number of articles in familial mediterranean fever genetics and management across all publications each year (not limited to Nature Index journals).

Technical terms

MEFV gene: The gene encoding pyrin, mutations of which cause familial Mediterranean fever.

Pyrin: A protein that regulates inflammasome assembly and interleukin-1β secretion in innate immune cells.

Inflammasome: A cytosolic multiprotein complex that activates inflammatory caspases, leading to interleukin-1β maturation.

Amyloidosis: Deposition of serum amyloid A protein fibrils in tissues, most critically the kidney, as a complication of chronic inflammation.

Colchicine: An anti-microtubule agent used as first-line prophylaxis to prevent FMF attacks and amyloidosis.

References

1. Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries. Frontiers in Immunology (2024).
2. Peripheral T Cell Populations are Differentially Affected in Familial Mediterranean Fever, Chronic Granulomatous Disease, and Gout. Journal of Clinical Immunology (2023).
3. Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management. Frontiers in Immunology (2017).
4. Efficacy and safety of canakinumab in adolescents and adults with colchicine-resistant familial Mediterranean fever. Arthritis Research & Therapy (2015).
5. Familial Mediterranean fever is no longer a rare disease in Japan. Arthritis Research & Therapy (2016).
6. An Update on Familial Mediterranean Fever. International Journal of Molecular Sciences (2023).