Familial cold autoinflammatory syndrome

What causes familial cold autoinflammatory syndrome?

Familial cold autoinflammatory syndrome is caused by changes (mutations) in either one of two genes: NLRP3 or NLRP12. These genes normally provide instructions for making proteins involved in the immune system, helping to regulate the process of inflammation. Changes in these genes impair the body's mechanisms for controlling inflammation, resulting in the signs and symptoms of this condition. It remains unclear why episodes are triggered by cold exposure.

Last updated on 05-01-20

How is familial cold autoinflammatory syndrome diagnosed?

Familial cold autoinflammatory syndrome (FCAS) is primarily a clinical diagnosis, meaning that it is mostly based on the presence or absence of specific of signs and symptoms as well as family history. Diagnostic criteria have been proposed in order to distinguish FCAS from acquired cold urticaria and other periodic fever disorders. The criteria include: recurring episodes of fever and rash that primarily follow cold exposures; autosomal dominant pattern of disease inheritance in a family; age of onset younger than 6 months; duration of most attacks less than 24 hours; conjunctivitis in association with attacks; and absence of deafness, swelling around the eyes, enlarged lymph nodes, and serositis. Having four of six of the criteria strongly suggests a diagnosis of FCAS. A diagnosis of FCAS may also be confirmed in some affected individuals by genetic testing.

Last updated on 05-01-20

How is familial cold autoinflammatory syndrome inherited?

Familial cold autoinflammatory syndrome is inherited in an autosomal dominant manner. This means that a mutation in only one of the two copies of the responsible gene is sufficient to cause signs and symptoms of the condition. When an individual with an autosomal dominant condition has children, each child has a 50% (1 in 2) risk to inherit the mutated copy of the gene. This also means that each child has a 50% risk to not inherit the mutated copy of the gene and therefore be unaffected.

There have been reported cases of this condition occurring in individuals with no history of the condition in the family; in these cases, the condition was not inherited from a parent, but occurred for the first time in the affected individual.

Last updated on 05-01-20

Is it common for several individuals in a family to have familial cold autoinflammatory syndrome? Can it skip a generation?

Familial cold autoinflammatory syndrome (FCAS) is a rare condition, but because it is genetic and is inherited in an autosomal dominant manner, it can affect many individuals within a family. Each child of an individual with FCAS has a 50% (1 in 2) risk to inherit the mutated (changed) copy of the responsible gene from the affected parent. This also means that each sibling of an individual with an affected parent has a 50% risk to inherit the mutated copy of the gene.

There have been reports of individuals inheriting the disease-causing mutation from an affected parent and not having any symptoms of FCAS. This is called reduced penetrance. In autosomal dominant conditions with reduced penetrance, the condition may appear to "skip a generation." Genetic testing may help determine whether an unaffected individual did not inherit he mutation, or did inherit the mutation but does not have any symptoms. An individual with a mutation who does not have symptoms still has a 50% risk to pass the mutation on to each child.

Last updated on 05-01-20

What is the long-term outlook for familial cold autoinflammatory syndrome?

Symptoms of familial cold autoinflammatory syndrome continue throughout one's lifetime, but may improve with treatment. Rare complications that have been reported in individuals with this disorder include amyloidosis and kidney failure.

Last updated on 05-01-20

How might familial cold autoinflammatory syndrome be treated?

Individuals with familial cold autoinflammatory syndrome (FCAS) are generally advised to avoid exposure to cold temperatures. Bed rest, warmth and corticosteroids can be used to treat an acute attack. Treatment may include the use of biologic agents (drugs derived from living material) which can control the symptoms of FCAS by blocking interleukin-1; they are called selective recombinant interleukin-1 receptor agonists. Examples of these agents are rilonacept, anakinra, and canakinumab. These agents reportedly have a significant beneficial effect on quality of life for individuals with FCAS.

Last updated on 05-01-20

Clinical Research Resources

NIH study familial cold autoinflammatory syndrome

The National Institute of Allergy and Infectious Diseases (NIAID) study, Pathogenesis of Physical Induced Urticarial Syndromes is currently recruiting participants. The study aims to investigate mechanisms that may cause physical hives or urticaria and to reproduce urticaria through challenge testing (procedures to test the skin for a reaction to a stimulus), followed by mast cell studies, measurement of IL-1, genetic studies, and other molecular studies to lead to a better understanding of urticaria and to design safe and more effective treatments.

Last updated on 04-27-20

Name: American Autoimmune Related Diseases Association (AARDA) 22100 Gratiot Avenue
Eastpointe, MI, 48021, United States
Phone: 586-776-3900 Toll Free: 800-598-4668 Fax : 586-776-3903 Email: aarda@aarda.org Url: https://www.aarda.org/
Name: FMF & AID Global Association Schüracherstrasse 25a 8306 Brüttisellen
Phone: +41 76 415 4010 Email: info@fmfandaid.org Url: https://www.fmfandaid.org/

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