Severe FMF Presentation with Rare Association of MEFV Variants (p.Pro369Ser/p.Glu148Gln)

We report the case of a 28-year-old man who presented with recurring episodes of high fever, pleural and pericardial effusions and bilateral hydrocele. He was diagnosed with familial Mediterranean fever (FMF) and responded well to colchicine therapy. Genetic testing showed variants of the MEFV gene (p.Pro369Ser and p.Glu148Gln) previously independently described as having a more benign course of the disease. Their association is very rarely reported. Our patient and our review of the literature suggest that these genetic variants are associated with indolent courses but might also trigger the classic symptoms seen in severe FMF, probably in a compound heterozygous fashion. The combination of these variants should be taken into consideration in the diagnosis and management of patients. LEARNING POINTS: Familial Mediterranean fever is characterized by recurring episodes of fever with serositis, arthritis or abdominal pain. Many mutations of the MEFV gene are responsible for the syndrome, but some variants are still of uncertain clinical significance. The p.Pro369Ser and p.Glu148Gln variants are rarely described together and can be pathogenic.