Muckle-Wells Syndrome (MWS)

Muckle-Wells Syndrome (MWS) is another CAPS disorder that has been found to be caused by genetic mutations on the CIAS1 gene that encodes the cryopyrin protein. MWS gene mutations have been found to be transmitted as an autosomal DOMINANT disorder (meaning if one parent has the mutation, it can be given to the children, and DOES NOT require two parents to have the mutation to pass the syndrome genetically to their offspring, like other syndromes that are caused by recessive mutations). There can be a variable level of expression of symptoms and number of cases of MWS within families, and even from one family to another. Most people with MWS do not have the same degree of inflammatory damage to their bodies NOMID, and do not have mental or cognitive affects like NOMID, so many more people with MWS have been able to get married and have children over generations. This has led to the syndrome being present in some families. However, the mutation can occur randomly and spontaneously during early cell divisions at conception as well. The common characteristics of MWS include:

Rashes During Infancy
	1. Chronic, recurrent, generally non-pruritic (not itchy) urticaria, that is usually present during early infancy, or occasionally starts in early childhood. This can be very debilitating, because the rash is ever-present, all over the body. The rash looks similar to the rashes seen in NOMID and FCAS.

Periodic Fevers

2. Moderate, low-grade fevers that are often present add to the suffering, and start in early infancy in conjunction with the rash. The fever is periodic, and is associated with flare ups of symptoms, including: rashes, joint pain, headaches and eye inflammation. Symptoms of fever with the other symptoms usually last 1-2 days, and can be triggered at random, or sometimes by cold temperatures, stress or exercise. FCAS is generally triggered by cold temperatures, but MWS does not always have this component, and can be more unpredictable and variant. NOMID flare ups are the most unpredictable, debilitating and frequent-sometimes occuring almost daily, with longer periods of flare ups of symptoms. Cold temperatures are not much of a factor in bringing on flares with NOMID.

Joint pains
	3. There are often joint pains (arthralgias or arthritides), but generally NO tissue and cartilage changes can be seen on X rays. This is one characteristic that sets MWS apart from NOMID/CINCA, since bony changes, especially at the knees, can be seen in some NOMID patients, but are NOT commonly found in MWS or FCAS.

Eyes

4. Conjunctivitis (inflammation of the white part of the eye, but in this case,not from infection) in the eyes is a recurrent problem with MWS, especially during flare ups of symptoms. Many MWS patients have also been found to have a haze on their corneas, which does not affect vision nearly as much as one would expect for the degree of haze. MWS generally does NOT cause the other eye changes seen in NOMID/CINCA, that can be serious, since CNS (brain and spinal cord fluid) pressure is NOT generally present in MWS. Some NOMID/CINCA patients can have conjunctivitis, especially with flare ups of symptoms, but usually also suffer from inflammation inside the eye, and swelling (papilledema) at the optic disc.

Adolescent Hearing Loss

5. Neurosensory hearing loss occurs in most MWS patients during early adolescence, and can be very severe. It can often be improved with hearing aids. NOMID/CINCA patients often have neurosensory hearing loss, or progressive losses, but this begins in infancy or early childhood. It is too soon to tell if early treatment for MWS or NOMID/CINCA will prevent, or decrease the development of hearing loss, but there is great hope that it will make a difference.

Amyloidosis & Treatment

6. MWS can have severe consequences due to a life of high inflammation in the body. This can be life-threatening if Genralized Amyloidosis of the AA type develops, due to long-term buildup of amyloid protein products from the chronic inflammation in MWS. Over 25% of MWS patients have elevated Serum Amysloid, and at least 25% have amyloidosis. Serum AA testing is essential to follow, along with C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR) and other lab tests. Amyloidosis is also a risk to some FCASand NOMID/CINCA patients, but is not seen at the same level as in MWS. Generalized Amyloidosis is due to a permanent buildup of amyloid in the kidneys, liver and elsewhere, and can be fatal. The current studies with various interleukin-1 blocking drugs are being found to help sufferers of Muckle-Wells greatly, but more clinical trials are still being preformed (see the Links page under Clinical trials for more information). Hopefully these drugs can improve the lives of sufferers. The hope is that these drugs could possibly reduce the chances for amyloid deposits building up in the body, and deafness, if started at a young age in these patients. References include an article on Orphanet by Professor Gille Grateau. See Links section on this site for the article, and also Amyloidosis