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Muckle-Wells syndrome is a disorder characterized by periodic episodes of skin rash, fever, and joint pain. Progressive hearing loss and kidney damage also occur in this disorder.
People with Muckle-Wells syndrome have recurrent "flare-ups" that begin during infancy or early childhood. These episodes may appear to arise spontaneously or be triggered by cold, heat, fatigue, or other stresses. Affected individuals typically develop a non-itchy rash, mild to moderate fever, painful and swollen joints, and in some cases redness in the whites of the eyes (conjunctivitis).
Hearing loss caused by progressive nerve damage (sensorineural deafness) typically becomes apparent during the teenage years. Abnormal deposits of a protein called amyloid (amyloidosis) cause progressive kidney damage in about one-third of people with Muckle-Wells syndrome; these deposits may also damage other organs. In addition, pigmented skin lesions may occur in affected individuals.
Muckle-Wells syndrome is a rare disorder. It has been reported in many regions of the world, but its prevalence is unknown.
Mutations in the NLRP3 gene (also known as CIAS1) cause Muckle-Wells syndrome. The NLRP3 gene provides instructions for making a protein called cryopyrin.
Cryopyrin belongs to a family of proteins called nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins. These proteins are 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 (inhibits) the inflammatory response to prevent damage to its own cells and tissues.
Cryopyrin is involved in the assembly of a molecular complex called an inflammasome, which helps trigger the inflammatory process. Researchers believe that NLRP3 gene mutations that cause Muckle-Wells syndrome result in a hyperactive cryopyrin protein and an inappropriate inflammatory response. Impairment of the body's mechanisms for controlling inflammation results in the episodes of fever and damage to the body's cells and tissues seen in Muckle-Wells syndrome.
Changes in this gene are associated with Muckle-Wells syndrome.
This condition is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, the inheritance pattern is unknown.
These resources address the diagnosis or management of Muckle-Wells syndrome and may include treatment providers.
You might also find information on the diagnosis or management of Muckle-Wells syndrome in Educational resources (http://ghr.nlm.nih.gov/condition/muckle-wells-syndrome/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/muckle-wells-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.
You may find the following resources about Muckle-Wells syndrome 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.
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.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
amyloid ; amyloidosis ; autosomal ; autosomal dominant ; cell ; domain ; familial ; fever ; gene ; immune system ; inflammation ; inheritance ; inheritance pattern ; injury ; joint ; kidney ; leucine ; nephropathy ; nucleotide ; prevalence ; protein ; sensorineural ; syndrome ; teenage ; tissue ; white blood cells
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
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.