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Genetics Home Reference: your guide to understanding genetic conditions
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Tumor necrosis factor receptor-associated periodic syndrome

(often shortened to TRAPS)
Reviewed August 2011

What is TRAPS?

Tumor necrosis factor receptor-associated periodic syndrome (commonly known as TRAPS) is a condition characterized by recurrent episodes of fever. These fevers typically last about 3 weeks but can last from a few days to a few months. The frequency of the episodes varies greatly among affected individuals; fevers can occur anywhere between every 6 weeks to every few years. Some individuals can go many years without having a fever episode. Fever episodes usually occur spontaneously, but sometimes they can be brought on by a variety of triggers, such as minor injury, infection, stress, exercise, or hormonal changes.

During episodes of fever, people with TRAPS can have additional signs and symptoms. These include abdominal and muscle pain and a spreading skin rash, typically found on the limbs. Affected individuals may also experience puffiness or swelling in the skin around the eyes (periorbital edema); joint pain; and inflammation in various areas of the body including the eyes, heart muscle, certain joints, throat, or mucous membranes such as the moist lining of the mouth and digestive tract. Occasionally, people with TRAPS develop amyloidosis, an abnormal buildup of a protein called amyloid in the kidneys that can lead to kidney failure. It is estimated that 15 to 20 percent of people with TRAPS develop amyloidosis.

The fever episodes characteristic of TRAPS can begin at any age, from infancy to late adulthood, but most people have their first episode in early childhood.

How common is TRAPS?

TRAPS is the second most common inherited recurrent fever syndrome, following a similar condition called familial Mediterranean fever. More than 1,000 people have been diagnosed with TRAPS worldwide.

What genes are related to TRAPS?

Mutations in the TNFRSF1A gene cause TRAPS. This gene provides instructions for making a protein called tumor necrosis factor receptor 1 (TNFR1). This protein is found within the membrane of cells, where it attaches (binds) to another protein called tumor necrosis factor (TNF). This binding sends signals that can trigger the cell either to initiate inflammation or to self-destruct. Signaling within the cell initiates a pathway that turns on a protein called nuclear factor kappa B that triggers inflammation and leads to the production of immune system proteins called cytokines. The self-destruction of the cell (apoptosis) is initiated when the TNFR1 protein, bound to the TNF protein, is brought into the cell and triggers a process known as the caspase cascade.

Most TNFRSF1A gene mutations that cause TRAPS result in a TNFR1 protein that is folded into an incorrect 3-dimensional shape. These misfolded proteins are trapped within the cell and are not able to get to the cell surface to interact with TNF. Inside the cell, these proteins clump together and are thought to trigger alternative pathways that initiate inflammation. The clumps of protein constantly activate these alternative inflammation pathways, leading to excess inflammation in people with TRAPS. Additionally, because only one copy of the TNFRSF1A gene has a mutation, some normal TNFR1 proteins are produced and can bind to the TNF protein, leading to additional inflammation. It is unclear if disruption of the apoptosis pathway plays a role in the signs and symptoms of TRAPS.

Related Gene(s)

Changes in this gene are associated with tumor necrosis factor receptor-associated periodic syndrome.

  • TNFRSF1A

How do people inherit TRAPS?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, some people who inherit the altered gene never develop features of TRAPS. (This situation is known as reduced penetrance.) It is unclear why some people with a mutated gene develop the disease and other people with the mutated gene do not.

In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of TRAPS?

These resources address the diagnosis or management of TRAPS and may include treatment providers.

  • Genetic Testing Registry: TNF receptor-associated periodic fever syndrome (TRAPS) (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1275126)

You might also find information on the diagnosis or management of TRAPS in Educational resources (http://www.ghr.nlm.nih.gov/condition/tumor-necrosis-factor-receptor-associated-periodic-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/tumor-necrosis-factor-receptor-associated-periodic-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about TRAPS?

You may find the following resources about TRAPS helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for TRAPS?

  • autosomal dominant familial periodic fever
  • FPF
  • Hibernian familial fever
  • TNF receptor-associated periodic fever syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about TRAPS?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding TRAPS?

amyloid ; amyloidosis ; apoptosis ; autosomal ; autosomal dominant ; caspase ; cell ; digestive ; edema ; familial ; fever ; gene ; immune system ; infection ; inflammation ; inherit ; inherited ; injury ; joint ; kidney ; mucous ; mutation ; necrosis ; penetrance ; protein ; receptor ; stress ; syndrome ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Aganna E, Hammond L, Hawkins PN, Aldea A, McKee SA, van Amstel HK, Mischung C, Kusuhara K, Saulsbury FT, Lachmann HJ, Bybee A, McDermott EM, La Regina M, Arostegui JI, Campistol JM, Worthington S, High KP, Molloy MG, Baker N, Bidwell JL, Castañer JL, Whiteford ML, Janssens-Korpola PL, Manna R, Powell RJ, Woo P, Solis P, Minden K, Frenkel J, Yagüe J, Mirakian RM, Hitman GA, McDermott MF. Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes. Arthritis Rheum. 2003 Sep;48(9):2632-44. (http://www.ncbi.nlm.nih.gov/pubmed/13130484?dopt=Abstract)
  • Kimberley FC, Lobito AA, Siegel RM, Screaton GR. Falling into TRAPS--receptor misfolding in the TNF receptor 1-associated periodic fever syndrome. Arthritis Res Ther. 2007;9(4):217. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17666110?dopt=Abstract)
  • Masson C, Simon V, Hoppé E, Insalaco P, Cissé I, Audran M. Tumor necrosis factor receptor-associated periodic syndrome (TRAPS): definition, semiology, prognosis, pathogenesis, treatment, and place relative to other periodic joint diseases. Joint Bone Spine. 2004 Jul;71(4):284-90. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15288852?dopt=Abstract)
  • McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M, Mansfield E, Gadina M, Karenko L, Pettersson T, McCarthy J, Frucht DM, Aringer M, Torosyan Y, Teppo AM, Wilson M, Karaarslan HM, Wan Y, Todd I, Wood G, Schlimgen R, Kumarajeewa TR, Cooper SM, Vella JP, Amos CI, Mulley J, Quane KA, Molloy MG, Ranki A, Powell RJ, Hitman GA, O'Shea JJ, Kastner DL. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell. 1999 Apr 2;97(1):133-44. (http://www.ncbi.nlm.nih.gov/pubmed/10199409?dopt=Abstract)
  • Pettersson T, Kantonen J, Matikainen S, Repo H. Setting up TRAPS. Ann Med. 2012 Mar;44(2):109-18. doi: 10.3109/07853890.2010.548399. Epub 2011 Feb 1. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21284532?dopt=Abstract)
  • Rebelo SL, Bainbridge SE, Amel-Kashipaz MR, Radford PM, Powell RJ, Todd I, Tighe PJ. Modeling of tumor necrosis factor receptor superfamily 1A mutants associated with tumor necrosis factor receptor-associated periodic syndrome indicates misfolding consistent with abnormal function. Arthritis Rheum. 2006 Aug;54(8):2674-87. (http://www.ncbi.nlm.nih.gov/pubmed/16871532?dopt=Abstract)
  • Rezaei N. TNF-receptor-associated periodic syndrome (TRAPS): an autosomal dominant multisystem disorder. Clin Rheumatol. 2006 Nov;25(6):773-7. Epub 2006 Jan 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16447098?dopt=Abstract)
  • Stojanov S, McDermott MF. The tumour necrosis factor receptor-associated periodic syndrome: current concepts. Expert Rev Mol Med. 2005 Oct 10;7(22):1-18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16216134?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2011
Published: July 28, 2014