Clinical and genetic heterogeneity in a large cohort of Armenian patients with late-onset familial Mediterranean fever.

PurposeThis work aimed at investigating demographic, clinical, and genetic characteristics of individuals experiencing their first familial Mediterranean fever (FMF) attack at age ≥40 years in a very large cohort of Armenian FMF patients.MethodsIn total, 10,370 Armenian patients diagnosed with FMF based on the Tel Hashomer criteria and carrying at least one MEFV mutant allele were included in this study.ResultsA total of 354 (3.40%) patients had late-onset FMF. Of these, 194 (54.80%) were female and 160 (45.20%) were male. The following genotypes were significantly associated with the late-onset variant: M680I/E148Q (P = 0.004), M694V/E148Q (P < 0.001), and V726A/V726A (P< 0.001). Of note, 12/354 (3.40%) patients were found to be homozygous for the M694V mutation. Individuals with late-onset FMF had a milder disease phenotype presenting significantly less frequent fever, skin manifestation, and chest pain compared to individuals with a disease onset before 40 years of age. Abdominal pain was found more often in the late-onset FMF group, whereas arthritis, proteinuria, and amyloidosis did not differ significantly between the two groups.ConclusionOur data suggest that late-onset FMF is more prevalent in women and is of greater clinical as well as genetic heterogeneity than previously reported.GENETICS in MEDICINE advance online publication, 15 March 2018; doi:10.1038/gim.2018.46.