Familial Mediterranean fever (FMF) phenotype in patients homozygous to the MEFV M694V mutation.

The clinical presentation of familial Mediterranean fever (FMF) is remarkably variable, ranging from a quiescent to a severe and disabling disease. The M694V mutation is one of approximately 300 published genetic variations in the FMF gene. While some studies have reported a more severe phenotype for the homozygous M694V mutation, studies dedicated solely to featuring the phenotype of homozygous M694V genotype are meager. The objective of the study was to present a comprehensive characterization of the homozygous M694V mutation associated phenotype, compared to the phenotypes of other FMF genotypes. For that aim, we compared between the demographic and clinical characteristics of 57 FMF patients, homozygous for the M694V MEFV mutation, and 56 patients with other MEFV genotypes. A questionnaire, detailing demographic and clinical features was completed for each patient based on an interview, physical examination and medical file data. Compared with the control group, the double M694V MEFV mutation group comprised more patients with severe disease (89.4 vs. 32.1%, p < 0.0001) and affected with FMF-related comorbidities (29.8 vs. 12.5%, p = 0.0373). The mean frequency of attacks per year was higher for patients with the double M694V MEFV mutation, before and during colchicine treatment (23.6 ± 9.3 vs.15.6 ± 11.7, p = 0.0001 and 7.2 ± 7.8 vs. 3.5 ± 5.5, p = 0.0007, respectively); and the mean dose of colchicine used was higher (1.9 ± 0.48 vs.1.48 ± 0.54 mg/day, p = 0.0001). Among the genotypes tested, homozygosity to the M694V MEFV mutation was found to be associated with the most grievous phenotype in the clinical spectrum of FMF.