of Genetic Terms
Definitions for the genetic terms used on this page
NIH Researchers Lead International Group in Identifying Gene for Familial Mediterranean Fever
Researchers identify key to molecular signals in disease affecting Mediterranean populations
May 31, 2011
Learning About Familial Mediterranean Fever
What is Familial Mediterranean Fever?
Familial Mediterranean Fever (FMF) is an inherited disease, characterized by recurrent attacks of fever, inflammation of the abdominal lining (peritonitis), inflammation of the lining surrounding the lungs (pleurisy), painful, swollen joints (arthralgia and occasionally arthritis), and a characteristic ankle rash. This condition is also sometimes referred to as recurrent polyserositis or familial paroxysmal polyserositis.
FMF is considered a rare disease worldwide. However, it is very common in people of Sephardic (non-Ashkenazi) Jewish, Armenian, Arab and Turkish heritage. Among people with these backgrounds, about 1 in 200 has FMF. The availability of genetic testing has helped identify numerous cases among several additional populations with Mediterranean roots, including: Ashkenazi Jews, Italians, Greeks, Spaniards, and Cypriots, and occasional cases in a broad range of other ethnicities (Northern Europeans and Japanese).
FMF is characterized by relatively short, usually 1- to 3-day, episodes of fever accompanied with serositis, synovitis or skin rash. In some patients, attacks begin in infancy or very early childhood, but 80 to 90 percent of patients experience their first episode by age 20. Young children sometimes present with recurrent fevers alone. The frequency of FMF attacks is highly variable, both among groups of patients or for any individual patient, with the interval between attacks ranging from days to years. Moreover, the type of attack - whether abdominal, pleural or arthritic - may also vary over time. Between attacks, people commonly are symptom-free.
Other symptoms that may occur include inflammation of the lining surrounding the heart (pericarditis), inflammation of the testis (orchitis), benign, recurrent inflammation of the membrane that surrounds the brain and spinal chord (meningitis), headaches and amyloidosis. Amyloidosis occurs when a particular protein, called amyloid, builds up in various tissues of the body, primarily the kidney. Potentially, it is the most serious complication of FMF, causing kidney failure. In some cases the amyloidosis can develop even without overt attacks of FMF.
What do we know about heredity and Familial Mediterranean Fever?
Familial Mediterranean Fever (FMF) is an autosomal recessive inherited disease, which means it appears only in individuals who received two copies of the mutant (altered) gene that causes FMF, one from each parent. As many as 1 in 5 people of Sephardic (non-Ashkenazi) Jewish, Armenian, Arab and Turkish heritage have one mutant copy of the gene and are therefore carriers of FMF, which means they carry the mutant gene but do not suffer from FMF themselves.
Located on the short (p) arm of chromosome 16, MEFV (MEditerranean FeVer) is the gene that, when mutated, causes FMF. This gene provides the instructions (codes) for creating a protein, called pyrin (also known as marenostrin), which is found in the white blood cells (granulocytes), which are important in the immune response, and myeloid bone marrow precursors. Although the precise function of pyrin is as yet unknown, researchers believe it most likely plays a role in keeping inflammation under control, possibly by inhibiting the immune inflammatory response. There are more than 30 mutations in the MEFV gene known to cause FMF, but four of them are very common in the patients of Middle Eastern ancestry.
How is Familial Mediterranean Fever diagnosed?
In making a diagnosis of Familial Mediterranean Fever (FMF), doctors take all of these factors into account:
- Whether or not the patient has the clinical symptoms common for the disease and whether the symptoms are recurrent.
- How he or she responds to colchicine treatment (see "How is Familial Mediterranean Fever treated?" below).
- Usually a positive family history in people of Middle Eastern ancestry.
- The results of genetic testing.
Also helpful in establishing a correct diagnosis of FMF is the patient's ancestry. Testing for the following can also be helpful:
- Elevated white blood cell count, which is an indication of an immune response.
- Elevated erythrocyte sedimentation rate (ESR), which is an indication of an inflammatory response.
- Elevated plasma fibrinogen, which helps stop bleeding. An elevated amount would indicate that something might be wrong with this mechanism.
- Elevated serum haptoglobin, which would indicate that red blood cells are being destroyed, a common occurrence in rheumatic diseases, such as FMF.
- Elevated C-reactive protein, which is a special type of protein, produced by the liver, that is only present during episodes of acute inflammation.
- Elevated albumin in the urine, which is demonstrated by urinalysis. The presence of the protein albumin in the urine can be a symptom of kidney disease, along with microscopic hematuria (very small - microscopic - amounts of blood or blood cells in the urine), during attacks.
Is there a test for Familial Mediterranean Fever?
Since the gene mutations responsible for this condition have been identified, there are a few labs in the United States and Canada and a few more in Europe and the Middle East that are offering molecular or DNA testing for Familial Mediterranean Fever (FMF). Most centers, however, only test for a subset of the mutations that cause FMF, particularly those common in FMF patients.
How is Familial Mediterranean Fever treated?
At present, there is no known cure for Familial Mediterranean Fever (FMF). Physicians can only treat the symptoms of the disease.
A common therapy for FMF is daily use of the drug colchicine, a medicine that reduces inflammation. This therapy has been successful in preventing attacks of fever in 75 percent of patients who take the drug regularly, and over 90 percent of patients demonstrate a marked improvement. Even if colchicine does not prevent the fever attacks, it does prevent the amyloidosis. However, compliance in taking colchicine every day is very important. If a patient stops taking the drug, an attack can occur within a couple of days.
Since the gene that causes FMF codes for the protein pyrin, researchers hope that by studying how this protein works they will ultimately develop improved treatments for FMF, and possibly for other conditions involving excess inflammation.
Clinical Research on Familial Mediterranean Fever
Currently, NHGRI is not conducting research on Familial Mediterranean Fever
Additional Resources for Familial Mediterranean Fever
- Familial Mediterranean Fever [nlm.nih.gov]
An article in MEDLINEplus, the National Library of Medicine Web encyclopedia of health information.
- Familial Mediterranean Fever [ghr.nlm.nih.gov]
Summary FAQ from the Genetics Home Reference at the National Library of Medicine.
- Familial Mediterranean Fever from GENEReviews [ncbi.nlm.nih.gov]
GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management and genetic counseling of patients with specific inherited conditions.
- Genes and Disease: Familial Mediterranean Fever [ncbi.nlm.nih.gov]
Information from the National Center for Biotechnology Information (NCBI), a division of the National Library of Medicine at the National Institutes of Health.
- Mediterranean Fever, Familial [emedicine.medscape.com]
An overview of Familial Mediterranean Fever provided by eMedicine, a clinical knowledge database for physicians and health professionals.
- MUMS National Parent-to-Parent Network [netnet.net]
Based in Wisconsin, MUMS is a national organization that puts parents of children with various conditions in touch with other parents of children with the same condition. Familial Mediterranean Fever is listed in their "List of Disorders."
- NIH Leads International Group that Identifies Gene for Familial Mediterranean Fever [niams.nih.gov]
A press release regarding the identification of the gene that causes Familial Mediterranean Fever (FMF). Includes general information about the genetics of FMF.
- Familial Mediterranean Fever [rarediseases.info.nih.gov]
Information from the Genetics and Rare Diseases Information Center.
- Finding Reliable Health Information Online
A listing of information and links for finding comprehensive genetics health information online.
Last Updated: November 17, 2011