What are the other Names for this Condition? (Also known as/Synonyms)

• Familial Cold Autoinflammatory Syndrome 2 (FCAS2)
• Guadeloupe Periodic Fever
• NLRP12-AID (NLRP12-Associated Autoinflammatory Disorder)

What is NLRP12-Associated Autoinflammatory Disorders (Definition/Background Information)

• NLRP12-Associated Autoinflammatory Disorders (NLRP12-AID) are a group of rare genetic disorders caused by mutations in the NLRP12 gene. This gene plays a role in the body’s inflammatory response, and the mutations result in an overactive immune response, leading to chronic inflammation
• The main risk factor for NLRP12-Associated Autoinflammatory Disorders is having a family history of the disorder. Most of the cases are manifested in childhood, and these disorders can cause widely varying signs and symptoms including recurrent fever, abdominal pain, skin rashes, joint pain, and recurrent infections
• A diagnosis is made based on the clinical presentation, blood tests, and genetic testing of the NLRP12 gene. The treatment of NLRP12-Associated Autoinflammatory Disorders mainly focuses on managing the symptoms and reducing inflammation, and the options include corticosteroids, nonsteroidal anti-inflammatory drugs, and immunosuppressive medications
• There is no known prevention for NLRP12-Associated Autoinflammatory Disorders as they are caused by a genetic mutation. The prognosis depends on the severity of the disorder, and individuals are at a significant risk for chronic symptoms and lifelong disability

Who gets NLRP12-Associated Autoinflammatory Disorders? (Age and Sex Distribution)

• NLRP12-Associated Autoinflammatory Disorders (NLRP12-AID) are rare genetic disorders that can affect individuals of all ages. However, the onset of symptoms typically occurs in early childhood
• Both males and females may be susceptible to NLRP12-AID
• The frequency of these disorders is unknown. A few cases have been reported from the islands of Guadeloupe and Martinique, including from the nations of USA, France, Italy, and Armenia

What are the Risk Factors for NLRP12-Associated Autoinflammatory Disorders? (Predisposing Factors)

• The main risk factor for NLRP12-Associated Autoinflammatory Disorders is having a family history of the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of NLRP12-Associated Autoinflammatory Disorders? (Etiology)

NLRP12-Associated Autoinflammatory Disorders (NLRP12-AID) are caused by mutations in the NLRP12 gene.

• These mutations result in an overactive immune response leading to chronic inflammation.
• Some cases have no family history, and spontaneous mutations in NLRP12 have been observed
• When a positive family history is noted, the inheritance pattern is autosomal dominant

Autosomal dominant mode of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly functioning gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of NLRP12-Associated Autoinflammatory Disorders?

The signs and symptoms of NLRP12-Associated Autoinflammatory Disorders (NOMID) can vary widely from individual to individual. Some of the common presentations include:

• Recurrent fever
• Abdominal pain
• Skin rashes
• Joint pain and swelling
• Recurrent infections
• Headaches and myalgia with flares

How is NLRP12-Associated Autoinflammatory Disorders Diagnosed?

NLRP12-Associated Autoinflammatory Disorders are typically diagnosed based on a combination of the following:

• Clinical examination and assessment of presenting signs and symptoms
• Evaluation of family history of the condition
• Blood tests
• Genetic testing of the NLRP12 gene

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of NLRP12-Associated Autoinflammatory Disorders?

NLRP12-Associated Autoinflammatory Disorders can lead to the following complications:

• Chronic recurrent fever
• Mobility issues from bone joint injury
• Some patients rarely develop sensorineural hearing loss

How is NLRP12-Associated Autoinflammatory Disorders Treated?

• Treatment for NLRP12-Associated Autoinflammatory Disorders mainly focuses on managing the symptoms and reducing inflammation.
• Treatment options include corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), other immunosuppressive medications, and biologic agents

How can NLRP12-Associated Autoinflammatory Disorders be Prevented?

Presently, it is not possible to prevent NLRP12-Associated Autoinflammatory Disorders as the cause is due to genetic factors.

• Genetic counseling and testing may be recommended for individuals with a family history of the disorder and couples planning to have children
• However, early diagnosis and appropriate treatment can help manage the symptoms and prevent complications

What is the Prognosis of NLRP12-Associated Autoinflammatory Disorders? (Outcomes/Resolutions)

The prognosis for NLRP12-Associated Autoinflammatory Disorders (NLRP12-AID) depends on the severity of the disorder

• NLRP12-AID carry a significant risk of chronic symptoms; also, permanent bone and joint damage have been reported
• Long term organ damage besides hearing loss is seldom observed

Additional and Relevant Useful Information for NLRP12-Associated Autoinflammatory Disorders:

The following link is a useful resource for information on other rare conditions on DoveMed:

https://www.dovemed.com/diseases-conditions/rare-disorders/