Aicardi-Goutières syndrome [8 genes]

Aicardi-Goutières syndrome (AGS) is a hereditary encephalopathy of early onset that presents both dominant and recessive inheritance. This disease presents typical characteristics of inflammatory pathologies (inflammation and tissue damage of the central nervous system) and autoimmune (about 40% of patients with AGS show lupus perniosis in the phalanges and ears typical of the lupus-like syndrome (SLE-like) and recurrent fevers in the absence of infection). The genes included in this panel are involved in processes of DNA repair, dysregulation of the innate immune response, and mRNA processing.

Unknown. Few families described.

• The identification of the defective gene causing SAG allows for establishing a precise molecular diagnosis, which is useful for understanding the pathological mechanisms of the disease and defining the inheritance pattern. There are different manifestations of the disease depending on the causative gene.
• AGS occurs in most cases with a recessive inheritance pattern (ADAR, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, TREX1), although the genes TREX1, ADAR, and IFIH1 present dominant forms.
• The management of patients with AGS is based on symptomatic treatment and monitoring of the disease. Immunosuppressive therapy is under investigation.

Genetic testing is indicated in patients in whom there is clinical suspicion of AGS. Clinical features suggestive of AGS include:

• Encephalopathy and/or intellectual disability
• Microcephaly acquired during the first year of life
• Dystonia
• Relapsing fever
• Hepatosplenomegaly
• Perniosis in exposed areas, but it can also be generalized

The diagnosis of SAG is established when there are clinical findings compatible with the disease such as, calcification of the basal ganglia and white matter and leukodystrophic alterations, as well as the identification of pathogenic or probably pathogenic variants in the genes that cause the disease.