Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry.

Autor:	Levy R; Paediatric Rheumatology, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France., Gérard L; Department of Clinical Immunology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France., Kuemmerle-Deschner J; Division of Pediatric Rheumatology, University Hospital Tübingen, Tuebingen, Germany., Lachmann HJ; National Amyloidosis Centre, University College London Medical School, Royal Free Campus, London, UK., Koné-Paut I; Paediatric Rheumatology, CEREMAI, CHU de Bicêtre, Assistance Publique-Hôpitaux de Paris, Paris, France., Cantarini L; Rheumatology Unit, Policlinico le Scotte, University of Siena, Siena, Italy., Woo P; Centre of Paediatric and Adolescent Rheumatology-UCL, London, UK., Naselli A; Pediatria II, Reumatologia, Istituto Giannina Gaslini, Genoa, Italy., Bader-Meunier B; Paediatric Rheumatology, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France., Insalaco A; Division of Rheumatology, Department of Pediatric Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Al-Mayouf SM; Department of Pediatric, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Ozen S; Department of Paediatric Nephrology and Rheumatology, Hacettepe University, Ankara, Turkey., Hofer M; Paediatric Rheumatology Unit of Western Switzerland, CHUV, University Hospital of Lausanne, Lausanne, Switzerland., Frenkel J; Department of Paediatrics, University Medical Center Utrecht, Utrecht, Netherlands., Modesto C; Reumatologia, Hospital Valle de Hebron, Barcelona, Spain., Nikishina I; Children's Department, Institute of Rheumatology RAMS, Moscow, Russian Federation., Schwarz T; Section of Paediatric Rheumatology and Osteology, University School of Medicine Children's Hospital, Würzburg, Germany., Martino S; Dip.to di Scienze Pediatriche e dell'Adolescenza, Clinica Pediatrica Universita' di Torino, Turin, Italy., Meini A; Pediatric Immunology and Rheumatology Unit, Pediatric Clinic, Spedali Civili and University of Brescia, Brescia, Italy., Quartier P; Paediatric Rheumatology, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France., Martini A; Pediatria II, Reumatologia, Istituto Giannina Gaslini, Genoa, Italy Department of Paediatrics, University of Genoa, Italy., Ruperto N; Pediatria II, Reumatologia, Istituto Giannina Gaslini, Genoa, Italy., Neven B; Paediatric Rheumatology, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France., Gattorno M; Pediatria II, Reumatologia, Istituto Giannina Gaslini, Genoa, Italy.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2015 Nov; Vol. 74 (11), pp. 2043-9. Date of Electronic Publication: 2014 Jul 18.
DOI:	10.1136/annrheumdis-2013-204991
Abstrakt:	Objective: To evaluate genetic, demographic and clinical features in patients with cryopyrin-associated periodic syndrome (CAPS) from the Eurofever Registry, with a focus on genotype-phenotype correlations and predictive disease severity markers. Methods: A web-based registry retrospectively collected data on patients with CAPS. Experts in the disease independently validated all cases. Patients carrying NLRP3 variants and germline-mutation-negative patients were included. Results: 136 patients were analysed. The median age at disease onset was 9 months, and the median duration of follow-up was 15 years. Skin rash, musculoskeletal involvement and fever were the most prevalent features. Neurological involvement (including severe complications) was noted in 40% and 12% of the patients, respectively, with ophthalmological involvement in 71%, and neurosensory hearing loss in 42%. 133 patients carried a heterozygous, germline mutation, and 3 patients were mutation-negative (despite complete NLRP3 gene screening). Thirty-one different NLRP3 mutations were recorded; 7 accounted for 78% of the patients, whereas 24 rare variants were found in 27 cases. The latter were significantly associated with early disease onset, neurological complications (including severe complications) and severe musculoskeletal involvement. The T348M variant was associated with early disease onset, chronic course and hearing loss. Neurological involvement was less strongly associated with V198M, E311 K and A439 V alleles. Early onset was predictive of severe neurological complications and hearing loss. Conclusions: Patients carrying rare NLRP3 variants are at risk of severe CAPS; onset before the age of 6 months is associated with more severe neurological involvement and hearing loss. These findings may have an impact on treatment decisions. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
Databáze:	MEDLINE
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