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

• Human RIPK1 Deficiency with Combined Immunodeficiency and Inflammatory Bowel Disease
• RIPK1 Autoinflammatory Disease (RIPK1-AID)
• RIPK1-AID (RIPK1 Autoinflammatory Disease)

What is RIPK1-Induced Autoinflammatory Syndrome? (Definition/Background Information)

• RIPK1-Induced Autoinflammatory Syndrome/Disease (RIPK1-AID) is a rare genetic disorder that is characterized by recurrent episodes of fever, skin rashes, joint pain, and chronic inflammation that can affect multiple organs and systems in the body
• The disorder is caused by mutations in the RIPK1 gene (that encodes the RIPK1 protein) and is inherited in an autosomal recessive manner. Thus, the risk factor for RIPK1-Induced Autoinflammatory Syndrome includes a positive family history of the disorder
• The onset of signs and symptoms of RIPK1-Induced Autoinflammatory Syndrome occurs in early childhood. It is typically diagnosed based on a combination of clinical examination, blood tests, imaging scans, as needed, and genetic testing of the RIPK1 gene
• Treatment is typically symptomatic and supportive and may include medications, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and newer medications to decrease inflammation in a more specific manner
• The prognosis of RIPK1-Induced Autoinflammatory Syndrome is normally guarded. All individuals are observed to have severe immunodeficiency with recurrent severe infection. The mortality rates are high; most of the affected individuals succumb to the disorder before reaching adulthood

Who gets RIPK1-Induced Autoinflammatory Syndrome? (Age and Sex Distribution)

• RIPK1-Induced Autoinflammatory Syndrome is a rare disorder with congenital manifestation
• The onset of symptoms occurs in young children; before they reach 5 years of age
• It affects both males and females
• Because of the recent discovery of this disease, the frequency and extent of this disease are not currently known

What are the Risk Factors for RIPK1-Induced Autoinflammatory Syndrome? (Predisposing Factors)

The risk factors for RIPK1-Induced Autoinflammatory Syndrome include:

• Having a family history of the disorder
• Inheriting two copies of the mutated RIPK1 gene, one from each parent, to develop the disorder
• The risk is the highest in consanguineous pairings (closely related to each other), where the mother and father share significant genetic similarity

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 RIPK1-Induced Autoinflammatory Syndrome? (Etiology)

RIPK1-Induced Autoinflammatory Syndrome is a genetic disorder caused by mutations in the RIPK1 gene

• The RIPK1 gene encodes a protein called the receptor-interacting serine/threonine-protein kinase 1 (RIPK1), which plays a role in regulating inflammation
• These mutations lead to abnormal functioning of the RIPK1 protein, which can cause recurrent inflammation
• The disorder has an autosomal recessive pattern of transmission

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of RIPK1-Induced Autoinflammatory Syndrome?

The common signs and symptoms of RIPK1-Induced Autoinflammatory Syndrome include:

• Continuous fever is a major sign
• Swollen lymph nodes (lymphadenopathy)
• Joint pain; inflammatory arthritis
• Frequent severe infections
• Oral ulcers
• Skin rash
• Inflammatory bowel disease with abdominal pain and diarrhea is present in all cases
• Central nervous system (CNS) symptoms

How is RIPK1-Induced Autoinflammatory Syndrome Diagnosed?

RIPK1-Induced Autoinflammatory Syndrome is 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
• Imaging studies, as needed
• Testing for bacteria and other organisms during frequent infections
• Lymph node biopsy, if possible
• Genetic testing for mutations in the RIPK1 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 RIPK1-Induced Autoinflammatory Syndrome?

Complications of RIPK1-Induced Autoinflammatory Syndrome may include:

• Failure to thrive
• Slow developmental progress
• Chronic joint disease
• Swollen spleen or splenomegaly (frequently seen)
• Thrombocytopenia from splenomegaly
• Chronic lung disease (frequently seen)

Early mortality is observed in many cases.

How is RIPK1-Induced Autoinflammatory Syndrome Treated?

Treatment for RIPK1-Induced Autoinflammatory Syndrome is typically symptomatic and supportive and may include medications to reduce inflammation and prevent recurrent episodes such as:

• Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids
• Anti-inflammatory drugs directed against Interleukin-6 (tocilizumab)
• Anti-inflammatory drugs directed against Interleukin-1 (canakinumab)
• Specific RIPK1 inhibitors are available on a research basis

How can RIPK1-Induced Autoinflammatory Syndrome be Prevented?

Presently, it is not possible to prevent RIPK1-Induced Autoinflammatory Syndrome as the cause is a genetic mutation.

• 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 RIPK1-Induced Autoinflammatory Syndrome? (Outcomes/Resolutions)

• The prognosis of RIPK1-Induced Autoinflammatory Syndrome is generally poor despite adequate treatment
• The published early mortality rate is 46%, and most cases of mortality occur before adulthood

Additional and Relevant Useful Information for RIPK1-Induced Autoinflammatory Syndrome:

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

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