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The exact prevalence of FCAS is unknown. Most cases have been published in the USA, and this CAPS phenotype could be less frequent in Europe in comparison with MWS and CINCA.

FCAS generally starts in childhood (<10 years, often at birth), but may occasionally start later, and is characterized by recurrent episodes of non-pruritic urticaria-like rash triggered by exposure to cold (5 minutes to 3 hours and not necessarily by touch). Lesions last about 12 hours (range 30 minutes to 72 hours) and are typically associated with a burning sensation. Low-grade, daylong episodes of fever, malaise, conjunctivitis, and abdominal discomfort are also observed. Polyarthralgias involving hands, knees, and ankles are very common and incapacitating. Other joints involved are feet, wrists, and elbows. Profuse sweating, drowsiness, headache, extreme thirst, and nausea are also noticed after cold exposure. Amyloidosis, arthritis are uncommon while deafness, lymphadenopathy, and serositis are absent

FCAS is caused by gain-of-function point mutations in the NLRP3 gene (1q44), which encodes cryopyrin. Mutations in NLRP3 gene ultimately lead to the increased secretion of the proinflammatory cytokine interleukin (IL)-1 beta and dysregulated inflammation. Mutations in this gene may also cause two additional forms of CAPS which are Muckle-Wells syndrome (MWS) and CINCA syndrome (see these terms), demonstrating that all three disorders are allelic. Some patients with a classical phenotype of FCAS, MWS or CINCA syndrome may not have mutations in NLRP3, suggesting involvement of additional genes. In addition, somatic NLRP3 mosaicism could explain 30-60% of patients with negative conventional genetic testing. Patients carrying identical amino acid substitution may present with distinctly different clinical subtypes, suggesting that additional genetic and/or environmental modifying factors are required to define the clinical phenotype.

Transmission is autosomal dominant. Genetic counseling may be proposed and the recurrence risk is 50%.