Disease phenotype and outcome depending on the age at disease onset in patients carrying the R92Q low-penetrance variant in TNFRSF1A gene

Estíbaliz Ruiz-Ortiz, Estíbaliz Iglesias, Alessandra Soriano, Segundo Buján-Rivas, Marta Español-Rego, Raul Castellanos-Moreira, Adrià Tomé, Jordi Yagüe, Jordi Antón, José Hernández-Rodríguez

Research output: Contribution to journalArticlepeer-review


Background: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal-dominant autoinflammatory disease caused by mutations in the TNFRSF1A gene. R92Q, a low-penetrance variant, is usually associated with a milder TRAPS phenotype than structural or pathogenic mutations. No studies differentiating R92Q-related disease in patients with pediatric and adult onset have been performed to date. Objective: To analyze clinical features and disease outcomes in patients diagnosed with TRAPS associated with R92Q variant and to investigate differences between patients with pediatric and adult disease onset. Methods: A retrospective review of patients with R92Q-related disease from four reference centers for autoinflammatory diseases was performed. Clinical and laboratory features, family history of autoinflammatory diseases, treatments received, and outcomes during follow-up were recorded and separately analyzed in pediatric and adult patients. Our results were included in the analysis with other reported pediatric and adult R92Q-related disease series. Results: Our series encompassed 18 patients (9 females and 9 males) with R92Q variant. In 61% of patients, disease onset occurred during infancy and in 39%, during adulthood, with a median diagnostic delay of 5 years and a follow-up of 5.4 years. A positive family history of autoinflammatory disease was detected in 28% of patients. All patients presented with febrile recurrent episodes. Other common symptoms included arthralgia/arthritis (61%), myalgia (39%), asthenia/fatigue (44%), abdominal pain (39%), headache (33%), odynophagia (33%), skin rash (28%), and chest pain (22%). During attacks, 80% of patients increased acute phase reactants levels. No patient had developed amyloidosis during the study period. At the end of follow-up, 28% of patients were asymptomatic and treatment free, 50% were receiving non-steroidal anti-inflammatory drugs or glucocorticoids on demand, and 22% were being treated with biologic agents. When differences between pediatric and adult patients were globally analyzed, adults tended to have longer attacks duration and presented more frequently with chest pain and headache, while abdominal pain, vomiting, cervical adenitis, and pharyngitis predominated in pediatric patients. No differences in outcomes and treatment requirements were observed in both age groups. Conclusion: This study has contributed to characterize R92Q-related disease by identifying trends in disease phenotypes depending on the age at disease onset.

Original languageEnglish
Article number299
JournalFrontiers in Immunology
Issue numberMAR
Publication statusPublished - Mar 27 2017
Externally publishedYes


  • Adult onset
  • Autoinflammatory diseases
  • Low-penetrance variants
  • Pediatric onset
  • R92Q
  • Tumor necrosis factor receptor-associated periodic syndrome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Disease phenotype and outcome depending on the age at disease onset in patients carrying the R92Q low-penetrance variant in TNFRSF1A gene'. Together they form a unique fingerprint.

Cite this