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 Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

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 writte ...

and recurrent

hives Hives, also known as urticaria, is a kind of skin rash with red or flesh-colored, 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 typically ...

, 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, weigh ...

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

joint pain Arthralgia () literally means 'joint pain'. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication Medication (also called medicament, medicine, pharmaceutic ...

. As a result, MWS is considered a type of periodic fever syndrome. MWS is caused by a defect in the CIAS1 gene which creates the protein cryopyrin. 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 syndromes (CAPS).

Sign and symptoms

* Sensorineural

* Recurrent

urticaria Hives, also known as urticaria, is a kind of skin rash with red or flesh-colored, 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 typically ...

(hives) * Fevers * Chills *

Arthralgia Arthralgia () literally means ' joint pain'. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication Medication (also called medicament, medicine, pharmaceuti ...

(painful joints)

Causes

Muckle-Wells syndrome occurs when a mutation in the ''

NLRP3 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. NLRP ...

'' gene leads to increased activity of the protein NLRP3 (cryopyrin). 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 Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

. This cytokine interacts with a

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

on the surface of other immune cells to produce symptoms of

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

such as fever,

arthritis Arthritis is a general medical term used to describe a disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, Joint effusion, swelling, and decreased range of motion of ...

, and malaise. Increased activity of cryopyrin leads to an increase in interleukin 1β, which in turn leads to inflammation all throughout the body with the associated symptoms.

Diagnosis

Treatment

* Treatment with anakinra, 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 t ...

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

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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

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 o ...

program, '' White Coat, Black Art'', 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 works with a girl with this condition through Make-A-Wish Foundation.

References

External links

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