Autoinflammatory diseases [87 genes]

Autoinflammatory diseases (AID) are disorders of the immune system that primarily affect innate immunity and are characterized by recurrent episodes of inflammation. There are monogenic forms with high penetrance and multifactorial forms with high environmental influence that predispose to the development of the disease and make its diagnosis difficult. Both gain-of-function variants in genes that induce the pro-inflammatory response and loss-of-function variants in genes that intervene in the control of inhibition of inflammation can cause this type of disease.

• Inflammation
• Fever
• Arthralgia
• Skin lesions
• Multisystemic manifestations

• Monogenic forms: ~1/5,000 – 1/100,000 individuals

• Diagnosis and genetic counseling
• Anti-inflammatories
• Monoclonal antibodies
• Immunosuppressants

Identification of a disease-causing variant allows an accurate disease diagnosis and provides genetic counseling to the family. Regarding management and according to clinical guidelines such as the “ISSAID/EMQN Best Practice Guidelines for the Genetic Diagnosis of Monogenic Autoinflammatory Diseases”, the genetic study is a recommended test in suspected cases of autoinflammatory syndromes, which can identify the origin of the disease, help to target treatment options and avoid other lines of not recommended therapies.

Autoinflammatory diseases comprise a very heterogeneous set of pathologies whose spectrum of clinical manifestations and severity is very variable, from periodic fevers to multisystem disorders that endanger the patient’s life. According to the diagnostic criteria, there are several groups of autoinflammatory syndromes depending on the biochemical pathway affected including inflammasomopathies, interferonopathies, and “NFkBopathies”, among others. There are more than 50 different entities based on molecular diagnosis, among which there is a high clinical overlap. Even within the same gene, phenotypes of varying severity may exist depending on the variant nature.

Despite numerous studies carried out over the last two decades, the diagnostic yield of the study of autoinflammatory diseases is estimated between 15%-20%.