Diagnosis of cryopyrin-associated periodic syndrome: challenges, recommendations and emerging concepts

Expert Rev Clin Immunol. 2015;11(7):827-35. doi: 10.1586/1744666X.2015.1047765. Epub 2015 May 15.


Cryopyrin-associated periodic syndrome are rare autosomal dominantly inherited diseases. They include three overlapping phenotypes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem autoinflammatory syndrome (NOMID/CINCA). Recurrent fevers, joint pain, and urticarial skin rash are the main clinical features of these conditions. Renal amyloidosis and sensorineural complications may occur. Gain-of-function mutations in NLRP3 gene are responsible for the overactivation of the NLRP3 inflammasome, a multimolecular complex involved in the inflammatory process. Missense mutations are almost always encountered, particularly in exon 3, which encodes the nucleotide-binding domain. Mosaicism is not rare, especially in CINCA/NOMID. Next-generation sequencing will grant access to new insights about NLRP3 implication in oligogenic and multifactorial diseases.

Keywords: CAPS; CINCA; FCAS; MWS; NLRP3; autoinflammatory syndrome; cryopyrin; inflammasome; mosaicism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carrier Proteins* / genetics
  • Carrier Proteins* / immunology
  • Cryopyrin-Associated Periodic Syndromes* / diagnosis
  • Cryopyrin-Associated Periodic Syndromes* / genetics
  • Cryopyrin-Associated Periodic Syndromes* / immunology
  • Humans
  • Inflammasomes* / genetics
  • Inflammasomes* / immunology
  • Mosaicism*
  • Mutation*
  • NLR Family, Pyrin Domain-Containing 3 Protein


  • Carrier Proteins
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human