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Genetic and Rare Diseases Information Center (GARD)

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Periodic fever, familial, autosomal dominant

Other Names for this Disease
  • Familial Hibernian fever
  • FHF
  • FPF
  • Hibernian fever, familial
  • TNF receptor-associated periodic syndrome
More Names
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Your Question

I am affected by familial autosomal dominant periodic fever, as are two of my three children. Can you provide us with information about this condition?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is familial autosomal dominant periodic fever?

Familial autosomal dominant periodic fever is an inherited condition characterized by episodes of fever, abdominal pain, diarrhea, painful red skin rashes, muscle pain and swelling around the eye. The former name of this syndrome was familial Hibernian fever and it is sometimes referred to as tumor necrosis factor receptor associated periodic syndrome or TRAPS.[1] Familial autosomal dominant periodic fever is caused by mutations in the Tumor Necrosis Factor Receptor gene (TNFRSF1A), which are inherited in an autosomal dominant fashion.[1][2] Although there is no proven definitive treatment to prevent or cure this condition, various anti-inflammatory agents may help to relieve symptoms. Nonetheless, most patients will experience episodes of symptoms throughout their life.[1] 
Last updated: 1/9/2009

What are the main symptoms of familial autosomal dominant periodic fever?

The main symptoms of familial autosomal dominant periodic fever include recurrent episodes of fever typically lasting two or three weeks, associated with chills and intense muscle pain involving the trunk and the upper limbs. A characteristic red and painful rash, representing an underlying inflammation of the skin and muscle, moves from one place to another on the body, usually from the arms and legs to the trunk. Most patients feel a cramp-like muscle pain at the onset of attacks that gradually increases in strength and also moves from one part of the body to another. Abdominal pain with nausea and vomiting are common, as are inflammation of the membrane covering the front of the eye (conjunctiva), and/or swelling around the eye.[1]

Other less common features include chest pain, as a result of inflammation of the pleura (the membrane surrounding the lungs) or the pericardium (the membrane surrounding the heart), and amyloidosis, a severe late complication which may result in large amounts of proteins in the urine and kidney failure. The disease symptoms vary from person to person, as do the length of episodes and the time between episodes. The reasons for these differences are based in part on differences in the specific gene defect.[1] 

Last updated: 1/9/2009

What causes familial autosomal dominant periodic fever?

Familial autosomal dominant periodic fever is caused by mutations in TNFRSF1A, the gene that encodes the receptor for tumor necrosis factor (TNF).[2] This mutation leads to an increase of the patient’s normal inflammatory response when tumor necrosis factor, the protein that causes inflammation, overacts, since the receptor that usually binds to it is not present to control its activity. Infection, trauma or psychological stress may trigger episodes.[1] 
Last updated: 1/9/2009

How is familial autosomal dominant periodic fever inherited?

Familial autosomal dominant periodic fever is inherited in an autosomal dominant manner, which means that one gene defect is enough to cause the disease. In many cases, an individual inherits familial autosomal dominant periodic fever from a parent. In other cases, the gene defect is newly formed (de novo) and there is no known family history.[1]
Last updated: 1/9/2009

How might familial autosomal dominant periodic fever be treated?

There is no proven definitive treatment to prevent or cure familial autosomal dominant periodic fever.[1] However, nonsteroidal anti-inflammatory drugs (NSAIDs) may relieve symptoms of fever and glucocorticoids may decrease the severity of musculoskeletal and abdominal symptoms in most patients. Unfortunately, neither of these treatments alters the frequency of attacks.[2] Recent studies have shown that giving a medicine that is similar to the TNF receptor called Enbrel (a medicine used to treat juvenile idiopathic arthritis) can control acute symptoms of familial autosomal dominant periodic fever, as well as reverse or slow the progression of amyloidosis in some patients.[2] This treatment appears to be most effective when given at the beginning or an attack and may even decrease the frequency, duration, and severity of attacks.[1][2] 
Last updated: 1/9/2009

What is the long-term outcome and course of familial autosomal dominant periodic fever?

It is hard to predict the prognosis in any one patient since outcome depends so much on the presence of amyloidosis which appears in only a minority of patients.[1][2] The risk to develop amyloidosis is dependent in part on the genetic defect and on other unclear environmental factors. Patients with familial autosomal dominant periodic fever typically have episodes of symptoms throughout their life.[1] 
Last updated: 1/9/2009