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Muckle-Wells syndrome

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.

Related Gene(s)

Changes in this gene are associated with Muckle-Wells syndrome.

  • NLRP3

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.

  • Genetic Testing Registry: Familial amyloid nephropathy with urticaria AND deafness (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268390)

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.

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?

  • familial amyloid nephropathy with urticaria and deafness
  • MWS
  • UDA syndrome
  • urticaria-deafness-amyloidosis syndrome

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.

What if I still have specific questions about Muckle-Wells syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

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 ; 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).

References

  • Aksentijevich I, D Putnam C, Remmers EF, Mueller JL, Le J, Kolodner RD, Moak Z, Chuang M, Austin F, Goldbach-Mansky R, Hoffman HM, Kastner DL. The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum. 2007 Apr;56(4):1273-85. (http://www.ncbi.nlm.nih.gov/pubmed/17393462?dopt=Abstract)
  • Church LD, Cook GP, McDermott MF. Primer: inflammasomes and interleukin 1beta in inflammatory disorders. Nat Clin Pract Rheumatol. 2008 Jan;4(1):34-42. doi: 10.1038/ncprheum0681. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18172447?dopt=Abstract)
  • Cuisset L, Drenth JP, Berthelot JM, Meyrier A, Vaudour G, Watts RA, Scott DG, Nicholls A, Pavek S, Vasseur C, Beckmann JS, Delpech M, Grateau G. Genetic linkage of the Muckle-Wells syndrome to chromosome 1q44. Am J Hum Genet. 1999 Oct;65(4):1054-9. (http://www.ncbi.nlm.nih.gov/pubmed/10486324?dopt=Abstract)
  • Dodé C, Le Dû N, Cuisset L, Letourneur F, Berthelot JM, Vaudour G, Meyrier A, Watts RA, Scott DG, Nicholls A, Granel B, Frances C, Garcier F, Edery P, Boulinguez S, Domergues JP, Delpech M, Grateau G. New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes. Am J Hum Genet. 2002 Jun;70(6):1498-506. Epub 2002 Apr 25. (http://www.ncbi.nlm.nih.gov/pubmed/11992256?dopt=Abstract)
  • El-Darouti MA, Marzouk SA, Abdel-Halim MR. Muckle-Wells syndrome: report of six cases with hyperpigmented sclerodermoid skin lesions. Int J Dermatol. 2006 Mar;45(3):239-44. (http://www.ncbi.nlm.nih.gov/pubmed/16533222?dopt=Abstract)
  • Farasat S, Aksentijevich I, Toro JR. Autoinflammatory diseases: clinical and genetic advances. Arch Dermatol. 2008 Mar;144(3):392-402. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18347298?dopt=Abstract)
  • Gerbig AW, Dahinden CA, Mullis P, Hunziker T. Circadian elevation of IL-6 levels in Muckle-Wells syndrome: a disorder of the neuro-immune axis? QJM. 1998 Jul;91(7):489-92. (http://www.ncbi.nlm.nih.gov/pubmed/9797932?dopt=Abstract)
  • Haas N, Küster W, Zuberbier T, Henz BM. Muckle-Wells syndrome: clinical and histological skin findings compatible with cold air urticaria in a large kindred. Br J Dermatol. 2004 Jul;151(1):99-104. (http://www.ncbi.nlm.nih.gov/pubmed/15270877?dopt=Abstract)
  • Hawkins PN, Lachmann HJ, McDermott MF. Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med. 2003 Jun 19;348(25):2583-4. (http://www.ncbi.nlm.nih.gov/pubmed/12815153?dopt=Abstract)
  • Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet. 2001 Nov;29(3):301-5. (http://www.ncbi.nlm.nih.gov/pubmed/11687797?dopt=Abstract)
  • Kanazawa N, Furukawa F. Autoinflammatory syndromes with a dermatological perspective. J Dermatol. 2007 Sep;34(9):601-18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17727363?dopt=Abstract)
  • OMIM: MUCKLE-WELLS SYNDROME (http://omim.org/entry/191900)
  • Stankovic K, Grateau G. Auto inflammatory syndromes: Diagnosis and treatment. Joint Bone Spine. 2007 Dec;74(6):544-50. Epub 2007 Sep 20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17950649?dopt=Abstract)
  • Tunca M, Ozdogan H. Molecular and genetic characteristics of hereditary autoinflammatory diseases. Curr Drug Targets Inflamm Allergy. 2005 Feb;4(1):77-80. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15720239?dopt=Abstract)
  • Watts RA, Nicholls A, Scott DG. The arthropathy of the Muckle-Wells syndrome. Br J Rheumatol. 1994 Dec;33(12):1184-7. (http://www.ncbi.nlm.nih.gov/pubmed/8000753?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 healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2008
Published: July 7, 2014