Learn About Muckle-Wells Syndrome

What is the definition of Muckle-Wells Syndrome?

Cryopyrin-associated periodic syndromes (CAPS) are a group of conditions that have overlapping signs and symptoms and the same genetic cause. The group includes three conditions known as familial cold autoinflammatory syndrome type 1 (FCAS1), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disorder (NOMID). These conditions were once thought to be distinct disorders but are now considered to be part of the same condition spectrum. FCAS1 is the least severe form of CAPS, MWS is intermediate in severity, and NOMID is the most severe form.

The signs and symptoms of CAPS affect multiple body systems. Generally, CAPS are characterized by periodic episodes of skin rash, fever, and joint pain. These episodes can be triggered by exposure to cold temperatures, fatigue, other stressors, or they may arise spontaneously. Episodes can last from a few hours to several days. These episodes typically begin in infancy or early childhood and persist throughout life.

While the CAPS spectrum shares similar signs and symptoms, the individual conditions tend to have distinct patterns of features. People with FCAS1 are particularly sensitive to the cold, and exposure to cold temperatures can trigger a painful or burning rash. The rash usually affects the torso and limbs but may spread to the rest of the body. In addition to fever and joint pain, other possible symptoms include muscle aches, chills, drowsiness, eye redness, headache, and nausea.

Individuals with MWS develop the typical periodic episodes of skin rash, fever, and joint pain after cold exposure, although episodes may occur spontaneously or all the time. Additionally, they can develop progressive hearing loss in their teenage years. Other features of MWS include skin lesions or kidney damage from abnormal deposits of a protein called amyloid (amyloidosis).

In people with NOMID, the signs and symptoms of the condition are usually present from birth and persists throughout life. In addition to skin rash and fever, affected individuals may have joint inflammation, swelling, and joint deformities called contractures that may restrict movement. People with NOMID typically have headaches, seizures, and cognitive impairment resulting from chronic meningitis, which is inflammation of the tissue that covers and protects the brain and spinal cord (meninges). Other features of NOMID include eye problems, short stature, distinctive facial features, and kidney damage caused by amyloidosis.

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What are the causes of Muckle-Wells Syndrome?

CAPS are caused by variants (also known as mutations) in the NLRP3 gene. The NLRP3 gene provides instructions for making a protein called cryopyrin. Cryopyrin is a member of a family of proteins called intracellular "NOD-like" receptor (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 foreign invaders and help repair damaged tissues. After 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 variants that cause CAPS result in an overactive cryopyrin protein, which leads to inappropriate inflammatory responses. 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 CAPS.

How prevalent is Muckle-Wells Syndrome?

CAPS are rare, with an estimated prevalence of 2 to 5 per million individuals, collectively. However, it is thought that the conditions are underdiagnosed since the features of CAPS are similar to other more common conditions.

Is Muckle-Wells Syndrome an inherited disorder?

CAPS are usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. People with the condition are born with one altered copy of the NLRP3 gene in each cell. In most cases, the altered gene is inherited from an affected parent. The remaining cases are a result of new variants in the NLRP3 gene and occur in people with no history of the disorder in their family.

Rarely, the genetic change that causes CAPS is not inherited but occurs at some point during embryonic development or later in life. As cells continue to grow and divide, some of these cells will have the genetic change, and others will not (a situation known as mosaicism).

Who are the top Muckle-Wells Syndrome Local Doctors?
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Rheumatology

National Institutes Of Health

Bethesda, MD 

Raphaela Goldbach-Mansky is a Rheumatologist in Bethesda, Maryland. Dr. Goldbach-Mansky is rated as an Elite doctor by MediFind in the treatment of Muckle-Wells Syndrome. She is also highly rated in 24 other conditions, according to our data. Her top areas of expertise are Familial Cold Autoinflammatory Syndrome, Neonatal Onset Multisystem Inflammatory Disease, Muckle-Wells Syndrome, and Griscelli Syndrome. She is licensed to treat patients in Maryland.

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University Of Tübingen

Tuebingen, BW, DE 

Jasmin Deschner-Kuemmerle is in Tuebingen, Germany. Deschner-Kuemmerle is rated as an Elite expert by MediFind in the treatment of Muckle-Wells Syndrome. She is also highly rated in 25 other conditions, according to our data. Her top areas of expertise are Familial Cold Autoinflammatory Syndrome, Neonatal Onset Multisystem Inflammatory Disease, Muckle-Wells Syndrome, and Familial Mediterranean Fever.

 
 
 
 
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Charite

Berlin, BE, DE 

Tilmann Kallinich is in Berlin, Germany. Kallinich is rated as an Elite expert by MediFind in the treatment of Muckle-Wells Syndrome. They are also highly rated in 18 other conditions, according to our data. Their top areas of expertise are Neonatal Onset Multisystem Inflammatory Disease, Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, and Familial Mediterranean Fever.

What are the latest Muckle-Wells Syndrome Clinical Trials?
An Open-label, Single Arm Phase II Study of DFV890 to Assess the Safety, Tolerability and Efficacy in Participants With Familial Cold Auto-inflammatory Syndrome (FCAS)
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Efficacy and Safety of Tranilast in Patients With Cryopyrin-Associated Periodic Syndrome (CAPS): A Single-Arm Prospective Cohort Study
What are the Latest Advances for Muckle-Wells Syndrome?
Reasons for canakinumab initiation among patients with periodic fever syndromes: a retrospective medical chart review from the United States.
A Novel Mutation in the NBD Domain of NLRC4 Causes Mild Autoinflammation With Recurrent Urticaria.
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CT-guided Chemical Lumbar Sympathectomy in the Treatment of Cold Hypersensitivity in the Hands and Feet.