Talk: Demographic and Genetic Results From the EUROFEVERS/EUROTRAPS Consortia in the Largest Series of Patients with TRAPS Yet Reported (2011 ACR/ARHP Annual Scientific Meeting)

Monday, November 7, 2011: 9:00 AM-6:00 PM

Hall F2 - Poster Hall (McCormick Place West)

Helen J. Lachmann¹, Antonella Meini², Isabelle Touitou³, Laura Obici⁴, Martina Finetti⁵, Kirsten Minden⁶, Luca Cantarini⁷, Marine Desjonqueres⁸, Joost Frenkel⁹, Isabelle Kone-Paut¹⁰, Olga Vougiouka¹¹, Maria Jesus Rua Elorduy¹², Nicola Ruperto¹³, Patricia Woo¹ and Marco Gattorno¹⁴, ¹University College London Medical School, London, United Kingdom, ²Dipartimento di Pediatria, University of Brescia, Brescia, Italy, ³CHU Montpellier - Hôpital Arnaud de Villeneuve, Montpellier, France, ⁴IRCCS Policlinico S. Matteo, Pavia, Italy, ⁵IRCCS Istituto G. Gaslini, Genova, Italy, ⁶Charite, Berlin, Germany, ⁷Policlinico le Scotte, Sienna, Italy, ⁸Hopital Femme Mere Enfant, Groupement Hospitalier Est, Lyon, France, ⁹University Medical Center Utrecht, Utrecht, Netherlands, ¹⁰CHU Le Kremlin Bicetre, Paris, France, ¹¹P. A. Kyriakou Childrens Hospital of Athens University, Athens, Greece, ¹²Hospital de Cruces, Barakaldo, Spain, ¹³Paediatric Rheumatology International Trials Organisation – IRCCS [PRINTO], Genova, Italy, ¹⁴G Gaslini Institute, Genoa, Italy

Presentation Number: 988

Background/Purpose: The TNF receptor associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory syndrome due to mutations in the TNFRSF1A gene. It is associated with severe morbidity and increased mortality due a high risk of AA amyloidosis. The estimated prevalence is 1 per million and experience has previously been limited to small series.

Method: The Eurofever/Eurotraps consortia (funded by the European Union) have developed a common web-based registry for all autoinflammatory diseases . The registry is accessed from the member area of the PRINTO web-site (www.printo.it/eurofever) and is available to all interested specialists physicians.

Result: 178 patients with clinical disease and a TNFRSF1A mutation were identified from 11 countries. The series included cases with 66 different mutations and 2 low penetrance mutations/polymorphisms, R92Q and P46L. Of the 66 mutations 8 (12%) were reported in more than 1 unrelated individual or kindred; 19 (29%) mutations affected a cysteine residue and of these 5 (26%) were seen in at least 2 unrelated patients. The T50M mutation was the most widespread and was found in 5 families originating from 5 different European countries. More than 1 disease associated mutation was identified at 7 sites, including 5 cysteine residues. In total of the 122 patients with a TNFRSF1A mutation: 68 (60.7%) reported a family history of similar symptoms; 58 (51.8%) were male; 105 (93.8%) were of Caucasian ethnicity and the mean age at symptom onset was 7.6 yrs (range: neonatal to 49 yrs). Of note in 10 patients (9%) the first symptoms developed after the age of 30 yrs. The 59 patients with R92Q polymorphism were 98% Caucasian, 45.8% male and 17% gave a family history of similar inflammatory disease. They presented at an average age of 10 yrs (range: neonatal to 52.6 yrs). The 7 patients with the P46L polymorphism included 2 patients of African ancestry, 1 Turk and a Gulf Arab, they presented at an average age of 16.6 yrs (range: 2.5 to 66.3 yrs) and 2 of them reported that other family members had similar disease.

Conclusion: The EUROFEVERS/EUROTRAPS consortia have collected data on 178 mutation positive TRAPS patients from 11 countries constituting the most extensive clinical series to date. The patients were largely contributed by European centres which may explain the dominance of Caucasian ethnicity. It confirms that TRAPS usually presents in childhood with a median age at presentation of less than 5 yrs but 9% of patients present well into adult life. 60% of patients report a family history of disease and most reported kindreds are small and mutations are family specific. Mutations affecting cysteine residues in extracellular domains are over represented but the most widespread disease causing mutation is T50M. Symptomatic patients with the well recognised polymorphism of R92Q and P46L make up 38% of the patients and appear to have a later onset of disease symptoms with lower penetrance. The availability of a large patient cohort will facilitates interpretation of the significance of TNFRSF1A mutations/polymorphism and understanding of genotype phenotype correlations.

Keywords: inflammation

Disclosure: H. J. Lachmann, None; A. Meini, None; I. Touitou, None; L. Obici, None; M. Finetti, None; K. Minden, Abbott Immunology Pharmaceuticals, 6 ; L. Cantarini, None; M. Desjonqueres, None; J. Frenkel, None; I. Kone-Paut, None; O. Vougiouka, None; M. J. Rua Elorduy, None; N. Ruperto, None; P. Woo, None; M. Gattorno, None.

988 - Demographic and Genetic Results From the EUROFEVERS/EUROTRAPS Consortia in the Largest Series of Patients with TRAPS Yet Reported