The spectrum of MEFV clinical presentations--is it familial Mediterranean fever only?

FMF is an autosomal recessive hereditary disease, associated with a single gene named MEFV. This gene is considered to be responsible only for FMF. In the present study, we tried to find out whether the MEFV gene is associated with or responsible for clinical conditions other than FMF.

We looked for patients who presented with signs and symptoms not typical for FMF but carried MEFV mutations. We also searched for reports about similar conditions in the English medical literature, and we surveyed the website 'Infevers' for MEFV mutations defined as associated with 'atypical FMF'.

We encountered three patients carrying MEFV mutations who presented with distinct clinical presentations not typical of FMF. We identified additional reports about MEFV-related non-FMF disease entities such as palindromic rheumatism. By screening the 'Infevers' website, we further disclosed 13 cases with MEFV mutations that were defined as 'atypical FMF' and 4 cases categorized as 'recurrent arthritis'.

These findings suggest that the MEFV gene is associated with clinical conditions other than FMF. Changing our concept regarding the MEFV gene and its link to such clinical phenotypes may call for a higher awareness of the existence of additional autoinflammatory diseases. Furthermore, a correct diagnosis of these MEFV gene mutation-associated syndromes will justify a therapeutic trial with colchicine, thereby relieving suffering of many patients who up to now have been misdiagnosed.