Reviewed September 2008
What is familial Mediterranean fever?
Familial Mediterranean fever is an inherited condition characterized by recurrent episodes of painful inflammation in the abdomen, chest, or joints. These episodes are often accompanied by fever and sometimes a rash. The first episode usually occurs in childhood or the teenage years, but in some cases, the initial attack occurs much later in life. Typically, episodes last 12 to 72 hours and can vary in severity. The length of time between attacks is also variable. Without treatment to help prevent attacks and complications, a buildup of certain protein deposits (amyloidosis) in the body's organs and tissues may occur, which can lead to kidney failure.
How common is familial Mediterranean fever?
Familial Mediterranean fever primarily affects populations originating in the Mediterranean region, particularly people of Armenian, Arab, Turkish, and Jewish ancestry. The disorder affects from 1 in 250 people to 1 in 1,000 people in these populations. It is less common in other populations.
What genes are related to familial Mediterranean fever?
Mutations in the MEFV gene cause familial Mediterranean fever. The MEFV gene provides instructions for making a protein called pyrin (also known as marenostrin), which is found in white blood cells. This protein is involved in the immune system, helping to regulate the process of inflammation. Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has been accomplished, the body stops the inflammatory response to prevent damage to its own cells and tissues.
Mutations in the MEFV gene reduce the activity of the pyrin protein, which disrupts control of the inflammation process. An inappropriate or prolonged inflammatory response can result, usually accompanied by fever and pain in the abdomen, chest, or joints.
Normal variations in the SAA1 gene may modify the course of familial Mediterranean fever. Some evidence suggests that a particular version of the SAA1 gene (called the alpha variant) may increase the risk of amyloidosis among people with familial Mediterranean fever.
Changes in these genes are associated with familial Mediterranean fever.
How do people inherit familial Mediterranean fever?
Familial Mediterranean fever is almost always inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
In rare cases, this condition appears to be inherited in an autosomal dominant pattern, in which one copy of the altered gene in each cell is sufficient to cause the disorder and affected individuals often inherit the mutation from one affected parent. However, there are other possible explanations of this apparent pattern. A gene mutation that occurs frequently in a population may result in a disorder with autosomal recessive inheritance appearing in multiple generations in a family, a pattern that mimics autosomal dominant inheritance. If one parent has familial Mediterranean fever (with two mutations in the MEFV gene) and the other parent is an unaffected carrier (with one mutation in the MEFV gene), it may appear as if the affected child inherited the disorder only from the affected parent. This appearance of autosomal dominant inheritance when the pattern is actually autosomal recessive is called pseudodominance.
Where can I find information about diagnosis or management of familial Mediterranean fever?
These resources address the diagnosis or management of familial Mediterranean fever and may include treatment providers.
- Gene Review: Familial Mediterranean Fever (http://www.ncbi.nlm.nih.gov/books/NBK1227/)
- Genetic Testing Registry: Familial Mediterranean fever (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0031069)
- MedlinePlus Encyclopedia: Familial Mediterranean fever (http://www.nlm.nih.gov/medlineplus/ency/article/000363.htm)
- MedlinePlus Encyclopedia: Secondary systemic amyloidosis (http://www.nlm.nih.gov/medlineplus/ency/article/000585.htm)
You might also find information on the diagnosis or management of familial Mediterranean fever in
Educational resources (http://www.ghr.nlm.nih.gov/condition/familial-mediterranean-fever/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/familial-mediterranean-fever/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 familial Mediterranean fever?
You may find the following resources about familial Mediterranean fever helpful. These materials are written for the general public.
MedlinePlus - Health information
- Encyclopedia: Familial Mediterranean fever (http://www.nlm.nih.gov/medlineplus/ency/article/000363.htm)
- Encyclopedia: Secondary systemic amyloidosis (http://www.nlm.nih.gov/medlineplus/ency/article/000585.htm)
- Health Topic: Fever (http://www.nlm.nih.gov/medlineplus/fever.html)
- Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/6421/resources/resources/1)
Additional NIH Resources - National Institutes of Health
- National Human Genome Research Institute (http://www.genome.gov/12510679)
- National Institute of Diabetes and Digestive and Kidney Diseases: Amyloidosis and Kidney Disease (http://kidney.niddk.nih.gov/kudiseases/pubs/amyloidosis/)
Educational resources - Information pages
- Madisons Foundation (http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=130)
- Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=342)
- The Merck Manual Home Edition for Patients and Caregivers (http://www.merckmanuals.com/home/childrens_health_issues/hereditary_periodic_fever_syndromes/familial_mediterranean_fever.html)
Patient support - For patients and families
- Chicago Center for Jewish Genetic Disorders (http://www.jewishgenetics.org/?q=content/familial-mediterranean-fever)
- National Organization for Rare Disorders (NORD) (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/127/viewAbstract)
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1227/)
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Familial Mediterranean fever (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0031069)
- ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22familial%20mediterranean%20fever%22)
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Familial%20Mediterranean%20Fever%5BMAJR%5D)%20AND%20(Mediterranean%20fever%5BTIAB%5D)%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20360%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/249100)
What other names do people use for familial Mediterranean fever?
- Benign paroxysmal peritonitis
- Familial paroxysmal polyserositis
- Hereditary Periodic Fever Syndromes
- Mediterranean Fever, Familial
- Periodic Disease
- Periodic peritonitis
- Recurrent polyserositis
- Reimann periodic disease
- Siegal-Cattan-Mamou disease
- Wolff Periodic Disease
For more information about naming genetic conditions, see the Genetics Home Reference
Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide)
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 familial Mediterranean fever?
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
What glossary definitions help with understanding familial Mediterranean fever?
autosomal dominant ;
autosomal recessive ;
immune system ;
white blood cells
You may find definitions for these and many other terms in the Genetics Home Reference
- Aksentijevich I, Torosyan Y, Samuels J, Centola M, Pras E, Chae JJ, Oddoux C, Wood G, Azzaro MP, Palumbo G, Giustolisi R, Pras M, Ostrer H, Kastner DL. Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population. Am J Hum Genet. 1999 Apr;64(4):949-62. (http://www.ncbi.nlm.nih.gov/pubmed/10090880?dopt=Abstract)
- Bakkaloglu A. Familial Mediterranean fever. Pediatr Nephrol. 2003 Sep;18(9):853-9. Epub 2003 Jun 27. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12836090?dopt=Abstract)
- Bhat A, Naguwa SM, Gershwin ME. Genetics and new treatment modalities for familial Mediterranean fever. Ann N Y Acad Sci. 2007 Sep;1110:201-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17911435?dopt=Abstract)
- Booth DR, Gillmore JD, Lachmann HJ, Booth SE, Bybee A, Soytürk M, Akar S, Pepys MB, Tunca M, Hawkins PN. The genetic basis of autosomal dominant familial Mediterranean fever. QJM. 2000 Apr;93(4):217-21. (http://www.ncbi.nlm.nih.gov/pubmed/10787449?dopt=Abstract)
- Lidar M, Livneh A. Familial Mediterranean fever: clinical, molecular and management advancements. Neth J Med. 2007 Oct;65(9):318-24. (http://www.ncbi.nlm.nih.gov/pubmed/17954950?dopt=Abstract)
- Mikula M, Buller A, Sun W, Strom CM. Prevalence of known mutations in the familial Mediterranean fever gene (MEFV) in various carrier screening populations. Genet Med. 2008 May;10(5):349-52. doi: 10.1097/GIM.0b013e3181723cc8. (http://www.ncbi.nlm.nih.gov/pubmed/18496034?dopt=Abstract)
- Ozen S. Familial mediterranean fever: revisiting an ancient disease. Eur J Pediatr. 2003 Jul;162(7-8):449-54. Epub 2003 May 16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12751000?dopt=Abstract)
- Rabinovitch E, Harats D, Yaron P, Luvish T, Lidar M, Kedem R, Shaish A, Ben-Dov I, Livneh A. Familial Mediterranean fever gene and protection against asthma. Ann Allergy Asthma Immunol. 2007 Dec;99(6):517-21. doi: 10.1016/S1081-1206(10)60380-8. (http://www.ncbi.nlm.nih.gov/pubmed/18219832?dopt=Abstract)
- Ross JJ. Goats, germs, and fever: Are the pyrin mutations responsible for familial Mediterranean fever protective against Brucellosis? Med Hypotheses. 2007;68(3):499-501. Epub 2006 Sep 26. (http://www.ncbi.nlm.nih.gov/pubmed/17005326?dopt=Abstract)
- Stoffman N, Magal N, Shohat T, Lotan R, Koman S, Oron A, Danon Y, Halpern GJ, Lifshitz Y, Shohat M. Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups. Eur J Hum Genet. 2000 Apr;8(4):307-10. (http://www.ncbi.nlm.nih.gov/pubmed/10854115?dopt=Abstract)
- Stojanov S, Kastner DL. Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Curr Opin Rheumatol. 2005 Sep;17(5):586-99. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16093838?dopt=Abstract)
- Telatar M, Grody WW. Molecular genetic testing for familial Mediterranean fever. Mol Genet Metab. 2000 Sep-Oct;71(1-2):256-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11001819?dopt=Abstract)
- Yepiskoposyan L, Harutyunyan A. Population genetics of familial Mediterranean fever: a review. Eur J Hum Genet. 2007 Sep;15(9):911-6. Epub 2007 Jun 13. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17568393?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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.