Analysis of Cryopyrin-Associated Periodic Syndromes (CAPS) in German Children: Epidemiological, Clinical and Genetic Characteristics

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 degrees 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 10(7) 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.