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Reviewed September 2008
What is Muckle-Wells syndrome?
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.
How common is Muckle-Wells syndrome?
Muckle-Wells syndrome is a rare disorder. It has been reported in many regions of the world, but its prevalence is unknown.
What genes are related to Muckle-Wells syndrome?
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.
Read more about the NLRP3 gene.
How do people inherit 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.
Where can I find information about diagnosis or management of Muckle-Wells syndrome?
These resources address the diagnosis or management of Muckle-Wells syndrome and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about Muckle-Wells syndrome?
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.
What other names do people use for Muckle-Wells syndrome?
What if I still have specific questions about Muckle-Wells syndrome?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding Muckle-Wells syndrome?
amyloid ; amyloidosis ; autosomal ; autosomal dominant ; cell ; domain ; familial ; fever ; gene ; immune system ; inflammation ; inheritance ; inheritance pattern ; inherited ; 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.
See also Understanding Medical Terminology.
References (15 links)
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? in the Handbook.