Aicardi-Goutières syndrome

Aicardi-Goutières syndrome (AGS) is a rare, genetically determined inflammatory disorder that primarily affects the brain, immune system, and skin. It belongs to a group of conditions known as type I interferonopathies, characterized by inappropriate activation of the innate immune system, specifically the type I interferon signaling pathway. The disease mimics congenital viral infection and was first described by Jean Aicardi and Françoise Goutières in 1984. AGS is caused by mutations in genes involved in nucleic acid metabolism, including TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, and IFIH1, corresponding to AGS subtypes 1 through 7. The condition typically presents in early infancy with progressive encephalopathy characterized by irritability, feeding difficulties, intermittent sterile fevers, and psychomotor regression or developmental delay. Key neurological features include intracranial calcifications (particularly in the basal ganglia), white matter abnormalities (leukodystrophy), and cerebral atrophy. Chronic cerebrospinal fluid (CSF) lymphocytosis and elevated interferon-alpha levels in the CSF are hallmark laboratory findings. Many affected children develop spasticity, dystonia, and profound intellectual disability. Skin manifestations, particularly chilblain-like lesions on the fingers, toes, and ears, are common and can be an important diagnostic clue. Some patients also develop features overlapping with systemic lupus erythematosus, including thrombocytopenia, hepatosplenomegaly, and elevated liver enzymes. There is currently no cure for Aicardi-Goutières syndrome, and management remains largely supportive, focusing on seizure control, nutritional support, physical therapy, and management of complications. Emerging therapeutic strategies targeting the interferon pathway, including Janus kinase (JAK) inhibitors such as baricitinib and ruxolitinib, have shown promise in clinical studies and are being investigated as potential disease-modifying treatments. Genetic counseling is recommended for affected families. The prognosis varies depending on the genetic subtype, with some forms presenting more severely in the neonatal period and others having a later onset with relatively milder progression.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Aicardi-Goutières syndrome