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

• T8AAD Syndrome
• TAAD Syndrome
• Trisomy 8 Associated Behçet's-like Disease

What is Trisomy 8 Associated Autoinflammatory Disease? (Definition/Background Information)

• Trisomy 8 Associated Autoinflammatory Disease (T8AAD) is a rare genetic disorder caused by the presence of an extra copy of chromosome 8. The condition is characterized by recurrent oral and genital aphthous ulcers, uveitis, and gastrointestinal lesions, joint pain, and other inflammatory symptoms
• The primary cause of Trisomy 8 Associated Autoinflammatory Disease is a chromosomal disorder known as trisomy 8, which results in the presence of three copies of chromosome 8 in some cells of the body. This extra copy leads to overactivity of certain genes and an overproduction of inflammatory molecules in the body, resulting in the symptoms of T8AAD Syndrome
• Trisomy 8 Associated Autoinflammatory Disease can affect individuals of all ages. The syndrome can be seen as the only manifestation, or it can be seen along-with myelodysplastic syndrome (MDS). MDS form a group of conditions characterized by the disordered development of all non-lymphocyte blood cells (called myeloid cells). MDS is caused by various abnormalities of the bone marrow, and is relatively common in trisomy 8
• Trisomy 8 Associated Autoinflammatory Disease is diagnosed through a combination of genetic testing and clinical examination. Genetic testing is used to confirm the presence of trisomy 8, while a physical examination is used to evaluate symptoms and rule out other conditions. Blood tests and bone marrow studies are needed when MDS symptoms are present
• Treatment is focused on managing symptoms and preventing complications. Medications, such as non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, are often used to reduce inflammation and alleviate symptoms. The prognosis for individuals varies depending on the severity of symptoms and the presence of any complications

Who gets Trisomy 8 Associated Autoinflammatory Disease? (Age and Sex Distribution)

• Trisomy 8 Associated Autoinflammatory Disease is a rare disorder that affects individuals of all ages
• Males are more frequently diagnosed with trisomy 8
• The frequency of trisomy 8 with/without associated anti-inflammatory disease is presently unknown

What are the Risk Factors for Trisomy 8 Associated Autoinflammatory Disease? (Predisposing Factors)

• Trisomy 8 Associated Autoinflammatory Disease is caused by a genetic mutation. The risk factor for the condition is having a third chromosome 8, instead of the usual two copies. The chromosome pattern would be expressed as 47 XY in males or 47 XX in females

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 Trisomy 8 Associated Autoinflammatory Disease? (Etiology)

The primary cause of Trisomy 8 Associated Autoinflammatory Disease (T8AAD) is a chromosomal disorder known as trisomy 8, which results in the presence of an extra copy of chromosome 8. This extra copy leads to overactivity of certain genes and an overproduction of inflammatory molecules in the body, resulting in the symptoms.

• Trisomy 8 in all cells of the body is not considered compatible with life. Trisomy 8 is seen always in its mosaic form. That means some cells have the normal two copies of chromosome 8, some have three copies. Hence, trisomy 8 is also referred to as chromosome 8 mosaicism
• It is noted that many trisomy 8 affected individuals have the associated autoinflammatory disease as well as myelodysplastic syndrome (MDS)
• T8AAD is caused by a random genetic mutation, and therefore there are no known risk factors for the condition, apart from trisomy 8 (the condition can occur in any individual with an extra copy of chromosome 8)

A February 2023 case report from Japan noted mutations in the MEFV gene. These were not in the same location as the MEFV mutations seen in familial Mediterranean fever (FMF). With further cases, this might be confirmed as the genetic cause of T8AAD. Also, a mutation in NLRP3 of uncertain significance has been reported.

What are the Signs and Symptoms of Trisomy 8 Associated Autoinflammatory Disease?

The signs and symptoms of Trisomy 8 Associated Autoinflammatory Disease vary, but typically include:

• Recurrent fevers
• Recurrent oral and genital ulcers
• Joint pain (arthralgias)
• Ulcers of the colon (large intestine)
• Perianal abscesses and fistulas
• Sjögren’s syndrome
• Autoimmune hemolytic anemia
• Periarteritis nodosa
• Sweet syndrome
• Mesenteric panniculitis
• Thromboses (blood clots)
• Other inflammatory symptoms

Some individuals may also experience the signs and symptoms of myelodysplastic syndrome that include:

• Anemia (low red blood cell count)
• Low platelet count
• Low white blood cell count

How is Trisomy 8 Associated Autoinflammatory Disease Diagnosed?

Trisomy 8 Associated Autoinflammatory Disease (T8AAD) is diagnosed through a combination of genetic testing and clinical examination.

• All individuals with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) are typically tested for trisomy 8 mosaicism, which would assist in a prompt diagnosis
• Bone marrow examination may be undertaken in those with MDS and AML
• Genetic testing is used to confirm the presence of trisomy 8, while a physical examination is used to evaluate symptoms and rule out other conditions
• Detailed genetic testing of the MEFV gene can help further define the ultimate genetic defect in T8AAD

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 Trisomy 8 Associated Autoinflammatory Disease?

Complications of Trisomy 8 Associated Autoinflammatory Disease can include:

• Joint damage
• Severe perianal abscesses and deep intestinal ulcerations
• Myelodysplastic syndrome (MDS) with associated anemia, thrombocytopenia, and low white blood cell count
• Frequent infections
• Acute myelogenous leukemia (AML); between 10% and 20% of MDS develop AML

How is Trisomy 8 Associated Autoinflammatory Disease Treated?

Treatment for Trisomy 8 Associated Autoinflammatory Disease is focused on managing symptoms and preventing complications.

• Medications, such as non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, are often used to reduce inflammation and alleviate the symptoms
• The JAK inhibitor tofacitinib has been helpful in several cases
• Methotrexate and cyclophosphamide have been used

In a French series of 21 patients, of the seven treated with azacytidine for myelodysplastic syndrome, the autoinflammatory disease component resolved in five and improved in the other two.

How can Trisomy 8 Associated Autoinflammatory Disease be Prevented?

• Presently, it is not possible to prevent Trisomy 8 Associated Autoinflammatory Disease as the cause is due to genetic factors
• However, early diagnosis and treatment can help to manage symptoms and prevent complications

What is the Prognosis of Trisomy 8 Associated Autoinflammatory Disease? (Outcomes/Resolutions)

• The prognosis for individuals with Trisomy 8 Associated Autoinflammatory Disease varies depending on the severity of symptoms and the presence of any complications
• With appropriate treatment, most individuals are able to manage their symptoms and lead an improved quality of life

Additional and Relevant Useful Information for Trisomy 8 Associated Autoinflammatory Disease:

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

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