Analysis of cryopyrin-associated periodic syndromes (CAPS) in German children: epidemiological, clinical and genetic characteristics

Klin Padiatr. 2010 Nov;222(6):356-61. doi: 10.1055/s-0030-1265181. Epub 2010 Nov 5.


Background: Cryopyrin-associated periodic syndromes (CAPS) are rare disorders belonging to the group of hereditary periodic fever (HPF)syndromes. These auto-inflammatory diseases(AID) are characterized by recurrent episodes of inflammation with attacks of fever variably associated with serosal, synovial and / or cutaneous inflammation, usually in a self-limiting manner, and with a mostly monogenic origin. The aims were to determine the incidence of CAPS and the spectrum of mutations in the NLRP3 (formerly= CIAS1) gene and to describe the clinical manifestations.

Patients and methods: A prospective surveillance of children with CAPS was conducted in Germany during a time period of 3 years(2003-2006). Monthly inquiries were sent to 370 children's hospitals by the German Paediatric Surveillance Unit (Clinic-ESPED, n1) and to 2 laboratories (Laboratory-ESPED, n2). Inclusion criteria were children ≤ 16 years of age, disease-associated NLRP3 mutation, more than 3 self-limiting episodes of fever > 38.5 ° C, and increased inflammation markers. Clinical, epidemiological and genetic data were evaluated via questionnaires.

Findings: 6 out of 14 patients were identified in Clinic-ESPED (n1) and 13 / 14 in Laboratory-ESPED(n2). Clinical and laboratory surveys overlapped in 5 of 14 cases. The incidence of CAPS in German children was estimated to be 3.43 per 10⁷ person-years. The patients carried 11 different NLRP3 mutations and were classified as MWS(n = 6), CINCA (n = 4), FCAS (n = 1) and undefined CAPS (n = 3).

Interpretation: The incidence of CAPS in Germany is very low and corresponds to 2-7 newly diagnosed patients ≤ 16 years per year.

MeSH terms

  • Adolescent
  • Age of Onset
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Cryopyrin-Associated Periodic Syndromes / diagnosis
  • Cryopyrin-Associated Periodic Syndromes / epidemiology*
  • Cryopyrin-Associated Periodic Syndromes / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Carrier Screening
  • Germany
  • Humans
  • Incidence
  • Infant
  • Male
  • Population Surveillance
  • Prospective Studies