Autoinflammatory disorders

Genetic testing is clinically relevant for the following indications, including but not limited to:

• Suspected monogenic autoinflammatory disease with unexplained recurrent or periodic fever and systemic inflammation, such as serositis, rash or arthralgia
• Patients meeting the for an autoinflammatory recurrent fever
• Differential diagnosis among overlapping recurrent fever phenotypes, such as FMF, TRAPS, CAPS or mevalonate kinase deficiency
• Organ-specific features such as uveitis suggestive of an underlying monogenic autoinflammatory syndrome

Testing is typically requested by paediatric and adult rheumatologists, clinical immunologists and paediatricians.

When recurrent fever and systemic inflammation suggest a monogenic autoinflammatory disorder, panel testing can help distinguish between overlapping phenotypes and support the diagnosis of a specific condition. A molecular diagnosis may inform prognosis, including the risk of AA amyloidosis in selected disorders, and support clinical decision-making, including the use of targeted anti-inflammatory therapies.

• A pathogenic or likely pathogenic variant supports the specific molecular diagnosis, identifying the causative gene and condition.
• A variant of uncertain significance (VUS) cannot currently be classified as likely benign or likely pathogenic, and reanalysis can be offered as evidence accumulates.
• In other cases, no pathogenic variant is detected in the analysed genes. A pathogenic variant cannot, however, be entirely excluded, as the causative change may lie in a gene not yet linked to the condition or in a regulatory region that current methods cannot reliably capture.
• Each variant is classified according to .

When a pathogenic variant is identified, it supports the diagnosis of a specific autoinflammatory syndrome and may inform prognosis, including the risk of AA amyloidosis in selected disorders. The molecular diagnosis may support treatment decisions, including consideration of interleukin-1-targeted therapies. Because most of these disorders are inherited, a confirmed diagnosis carries familial implications, and cascade or predictive testing of at-risk relatives can be considered.

is an important part of the testing process. It helps patients and families understand the test, interpret results, and make well-informed medical decisions, and it supports physicians in delivering informed care. Availability of genetic counselling services may vary by country. Please to check out access in your region.

Testing is performed using based multi-gene panels. For selected indications, additional long-read sequencing technologies are used.