Tumor necrosis factor receptor associated periodic syndrome
A periodic fever syndrome from TNF receptor mutations.
Tumor necrosis factor receptor associated periodic syndrome, or TRAPS, is a condition that causes recurring fevers and is passed down in an autosomal dominant pattern. It stems from mutations in a receptor for the molecule tumor necrosis factor (TNF). People with TRAPS experience episodes that include high fevers, a rash, abdominal pain, joint and muscle aches, and puffy eyes. The responsible gene is TNFRSF1A, located at 12p13.31.
Symptoms and signs of TRAPS include episodic fever, an elevated erythrocyte sedimentation rate, pericarditis, an enlarged spleen (splenomegaly), uveitis, vertigo, and AA amyloidosis. The condition is linked to around 70 known mutations in the TNFRSF1A gene.
TNF is mainly produced by immune cells called macrophages in response to infection or other triggers. It helps activate other immune cells and is key to starting inflammation. In TRAPS, mutations affect the tumor necrosis factor receptor-1 (TNFR1), though exactly how these mutations lead to the syndrome is not yet understood. One possible defect is impaired shedding of the TNF receptor; most mutations affect the receptor's extracellular domain, and some affect the cleavage site.
Diagnosis may involve a blood test showing increased IgD levels, along with a clinical evaluation and genetic testing. For treatment, corticosteroids can help reduce the severity of symptoms, and NSAIDs may be used to manage fever. Research into medications for TRAPS has included etanercept, infliximab, and anakinra.
Quick Facts
- Field
- Immunology
- Symptoms
- Vertigo, pericarditis
- Causes
- Mutations in the TNFRSF1A gene
- Diagnosis
- Blood test, Genetic test
- Treatment
- Corticosteroids, NSAIDS
Facts from the source article.
Lore & Background
TNF receptor associated periodic syndrome (TRAPS) is a genetic disorder characterized by recurrent episodes of fever and systemic inflammation. The condition is caused by mutations in the TNFRSF1A gene, which encodes the tumor necrosis factor receptor-1 (TNFR1). Approximately 70 mutations have been linked to TRAPS, and the inheritance pattern is autosomal dominant. The cytogenetic location of the gene is 12p13.31.
The main source of TNF is macrophages, which produce it in response to infection and other stimuli. TNF helps activate other immune cells and plays a major role in initiating inflammation. The mechanisms by which mutations in TNFR1 lead to the TRAPS phenotype are still unknown, though impaired shedding of the TNF receptor is one possible defect. Most mutations affect the extracellular domain of the receptor, and some affect the cleavage site.
Diagnosis of TRAPS may show an increased IgD level in a possibly affected individual. Definite diagnosis can be made through blood tests, genetic testing, and clinical evaluation. Treatment includes corticosteroids to reduce severity and NSAIDs for fever. Several medications have been studied for treatment, including etanercept, infliximab, and anakinra.
Reader's Guide
Tumor necrosis factor receptor associated periodic syndrome (TRAPS) is significant as a model of autoinflammatory disease linked to a specific genetic mutation in the TNF receptor pathway. Its autosomal dominant inheritance and the identification of about 70 mutations in the TNFRSF1A gene highlight the role of genetic factors in periodic fever syndromes. The condition's episodic symptoms—including fever, rash, abdominal pain, joint/muscle aches, and puffy eyes—along with complications such as pericarditis, splenomegaly, uveitis, vertigo, and AA amyloidosis, underscore its systemic impact. The uncertainty regarding the exact mechanism by which TNFR1 mutations cause the phenotype, with impaired receptor shedding as a possible defect, reflects ongoing research challenges. Diagnosis relies on clinical evaluation, blood tests, and genetic testing, while treatment options include corticosteroids and NSAIDs, with investigational biologics like etanercept, infliximab, and anakinra. TRAPS thus contributes to understanding inflammation and targeted therapies in autoinflammatory disorders.
Did You Know?
- TRAPS is associated with mutations in the TNFRSF1A gene at cytogenetic location 12p13.31.
- About 70 mutations of the TNFRSF1A gene have been linked to TRAPS.
- Impaired shedding of the TNF receptor is one possible defect, but the exact mechanism is still unknown.
More in Autoinflammatory syndromes 1-24
Spotted an error? Know more?
Reader corrections go straight into our review queue. Suggest an edit · How this site is sourced