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

• Autoinflammation, Panniculitis, and Dermatosis Syndrome (AIPDS)
• ORAS (OTULIN-Related Autoinflammatory Syndrome)
• OTULIPENIA

What is OTULIN-Related Autoinflammatory Syndrome? (Definition/Background Information)

• OTULIN-Related Autoinflammatory Syndrome (ORAS) is a rare genetic disorder characterized by recurrent episodes of inflammation and fever, inflammation of the subcutaneous fat, diarrhea, and arthritis. The onset of ORAS takes place following the birth of the child (congenital disorder)
• The disorder is caused by mutations in the OTULIN gene (that encodes a protein called OTULIN) and is inherited in an autosomal recessive manner. Thus, the risk factor for OTULIN-Related Autoinflammatory Syndrome includes a positive family history of the disorder
• OTULIN-Related Autoinflammatory Syndrome is typically diagnosed based on a combination of clinical examination, blood tests for inflammatory markers, and genetic tests to measure defects in the OTULIN gene
• The treatment is typically symptomatic and supportive and may include using medications, such as non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, to reduce inflammation and prevent recurrent episodes. However, such treatments are not known to be very effective
• Currently, there are no available measures to prevent OTULIN-Related Autoinflammatory Syndrome as it is a genetic condition. Genetic counseling and testing may be recommended for individuals with a family history of ORAS and couples planning to have children
• The prognosis of OTULIN-Related Autoinflammatory Syndrome is typically guarded. The affected individuals are known to have life-threatening episodes of inflammation. Bone marrow transplantation has been effective in some cases

Who gets OTULIN-Related Autoinflammatory Syndrome? (Age and Sex Distribution)

• OTULIN-Related Autoinflammatory Syndrome (ORAS) is an extremely rare disorder with congenital manifestation (onset of symptoms occur in the neonatal period, during the first month of life)
• It affects both males and females
• No information about the frequency or world distribution of this syndrome can be made because of its recent discovery and rarity. As of early 2019, only six patients have been described with ORAS

What are the Risk Factors for OTULIN-Related Autoinflammatory Syndrome? (Predisposing Factors)

The risk factors for OTULIN-Related Autoinflammatory Syndrome (ORAS) include:

• Having a family history of the disorder
• Inheriting two copies of the mutated OTULIN gene, one from each parent, to develop the disorder
• ORAS tends to be found more frequently in consanguineous pairings (closely related to each other), where the mother and father share significant genetic similarity
• A single patient was reported with a different inheritance

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 OTULIN-Related Autoinflammatory Syndrome? (Etiology)

OTULIN-Related Autoinflammatory Syndrome (ORAS) is a genetic disorder caused by mutations in the OTULIN gene

• The OTULIN gene encodes the protein OTULIN, which regulates the activity of the innate inflammatory system
• The mutation leads to abnormal regulation of TNF, an important up-regulatory component of the inflammatory system
• These mutations lead to abnormal functioning of the OTULIN protein, causing 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 OTULIN-Related Autoinflammatory Syndrome?

The most common signs and symptoms of OTULIN-Related Autoinflammatory Syndrome (ORAS) include:

• Recurrent episodes of fever
• Panniculitis (fat inflammation)
• Joint pain and swelling
• Diarrhea
• Cataract

How is OTULIN-Related Autoinflammatory Syndrome Diagnosed?

OTULIN-Related 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
• Blood tests to measure the levels of inflammatory mediators, and routine blood testing
• Skin and subcutaneous fat biopsy to determine the cell type and pattern of panniculitis
• Genetic testing for alterations in the OTULIN 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 OTULIN-Related Autoinflammatory Syndrome?

Complications of OTULIN-Related Autoinflammatory Syndrome (ORAS) may include the following:

• Recurrent episodes of signs and symptoms
• Arthritis
• Failure to thrive

Severe cases of ORAS can result in fatalities.

How is OTULIN-Related Autoinflammatory Syndrome Treated?

Treating OTULIN-Related Autoinflammatory Syndrome symptomatically and using routine medications is not found to be very helpful.

• Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, to reduce inflammation and prevent recurrent episodes, may be beneficial in some cases
• Bone marrow transplantation has been shown to be promising and effective

How can OTULIN-Related Autoinflammatory Syndrome be Prevented?

Presently, it is not possible to prevent OTULIN-Related 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 OTULIN-Related Autoinflammatory Syndrome? (Outcomes/Resolutions)

• The prognosis of OTULIN-Related Autoinflammatory Syndrome is generally unfavorable and poor
• Bone marrow transplantation brings in a functioning version of the OTULIN gene and can be effective. However, bone marrow transplantation is a major procedure with inherent risks

Additional and Relevant Useful Information for OTULIN-Related Autoinflammatory Syndrome:

A recent report described a patient with onset at age 7, with OTULIN Syndrome, but with a different ORAS gene defect. An autosomal recessive pattern of inheritance was not noted.