Muckle–Wells syndrome (MWS) is a rare

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...

disease which causes sensorineural

deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is written ...

and recurrent

hives Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

, and can lead to

amyloidosis Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weig ...

. Individuals with MWS often have episodic fever, chills, and

joint pain Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...

. As a result, MWS is considered a type of

periodic fever syndrome Periodic fever syndromes are a set of disorders characterized by recurrent episodes of systemic and organ-specific inflammation. Unlike autoimmune disorders such as systemic lupus erythematosus, in which the disease is caused by abnormalities of ...

. MWS is caused by a defect in the

CIAS1 NLR family pyrin domain containing 3 (NLRP3) (previously known as NACHT, LRR and PYD domains-containing protein 3 ALP3and cryopyrin), is a protein that in humans is encoded by the ''NLRP3'' gene located on the long arm of chromosome 1. NLRP3 ...

gene which creates the protein

cryopyrin NLR family pyrin domain containing 3 (NLRP3) (previously known as NACHT, LRR and PYD domains-containing protein 3 ALP3and cryopyrin), is a protein that in humans is encoded by the ''NLRP3'' gene located on the long arm of chromosome 1. NLRP3 is ...

. MWS is closely related to two other syndromes, familial cold urticaria and neonatal onset multisystem inflammatory disease—in fact, all three are related to mutations in the same gene and subsumed under the term

cryopyrin-associated periodic syndrome Cryopyrin-associated periodic syndrome (CAPS) is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin 1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. ...

s (CAPS).

Sign and symptoms

* Sensorineural

* Recurrent

urticaria Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

(hives) * Fevers * Chills *

Arthralgia Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...

(painful joints)

Causes

MWS occurs when a mutation in the ''

'' gene, encoding for NLRP3, leads to increased activity of the protein

. This protein is partly responsible for the body's response to damage or infection. During these states, a cytokine called interleukin 1β is produced by an innate immune cell known as a macrophage. This cytokine interacts with a receptor on the surface of other immune cells to produce symptoms of

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

such as fever,

arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some ...

, and malaise. In MWS, the increased activity of cryopyrin leads to an increase in interleukin 1β. This leads to inflammation all throughout the body with the associated symptoms.

Diagnosis

Treatment

* Treatment with

anakinra Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a recombinant and slightly modif ...

, an

interleukin 1 The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults. Discovery Discovery of these cytokines began with studies on ...

receptor antagonist, can lead to an improvement in the hearing loss. * Rilonacept (Arcalyst) a dimeric fusion protein for the treatment of CAPS. *

Canakinumab Canakinumab (INN), sold under the brand name Ilaris, is a medication for the treatment of systemic juvenile idiopathic arthritis (SJIA) and active Still's disease, including adult-onset Still's disease (AOSD). It is a human monoclonal antibody ...

, a

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...

against interleukin-1β

Prognosis

The chronic inflammation present in MWS over time can lead to sensorineural hearing loss. In addition, the prolonged inflammation can lead to deposition of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

s in the kidney, a condition known as

History

MWS was first described in 1962 by Thomas James Muckle (1938-2014) and Michael Vernon Wells (born 1932).

Society and culture

The

CBC Radio One CBC Radio One is the English-language news and information radio network of the publicly owned Canadian Broadcasting Corporation. It is commercial-free and offers local and national programming. It is available on AM and FM to 98 percent of ...

program, ''

White Coat, Black Art ''White Coat, Black Art'' is a Canadian radio documentary series on CBC Radio One, hosted by physician Brian Goldman that examines the business and culture of medicine from an insider's perspective. Its name is a reference to the white coats that ...

'', hosted by Dr. Brian Goldman, presents a real-life study of the self-diagnosis by and successful treatment of a father and daughter with Muckle–Wells syndrome In the episode of popular '' TV series House'', the main patient of the Season 7 episode Recession Proof is ultimately diagnosed with this condition.In an episode of TV series '' Cake Boss'',

Buddy Valastro Bartolo "Buddy" Valastro Jr. (born March 3, 1977) is an American baker and reality television personality of Italian heritage. He is the owner of Carlo's Bakery, as well as the face of Buddy V's Ristorante. Valastro is best known as the star of ...

works with a girl with this condition through

Make-A-Wish Foundation The Make-A-Wish Foundation is a 501(c)(3) nonprofit organization founded in the United States that helps fulfill the wishes of children with a critical illness between the ages of and 18 years old. Make-A-Wish was founded in 1980 and headquar ...

References

External links

{{DEFAULTSORT:Muckle-Wells syndrome Rheumatology Autoinflammatory syndromes Rare genetic syndromes Syndromes with sensorineural hearing loss Syndromes affecting the skin