Genetic analysis as a valuable key to diagnosis and treatment of periodic fever

We describe 2 Dutch patients with recurrent fever attacks undiagnosed for m ore than 40 years. The diagnosis of periodic fever was made when molecular analysis revealed novel mutations in the tumor necrosis factor (TNF) recept or gene (TNFRSF1A), establishing the diagnosis of TNF receptor-associated p eriodic syndrome. This syndrome is an autosomal dominant disorder character ized by recurring episodes of fever, arthralgia, and skin lesions that is c aused by mutations in the 55-kd TNFRSF1A gene. This finding has facilitated treatment for TNF receptor-associated periodic syndrome because blocking o f TNF signaling seems to alleviate the symptoms. Use of a short course of r ecombinant p75TNFR:Fc fusion protein (etanercept) induced prolonged remissi on in one patient.