Aicardi-Goutieres syndrome

Aicardi-Goutieres syndrome (AGS) is an inherited subacute encephalopathy that primarily affects the brain, characterized by basal ganglia calcifications, leukodystrophy, and cerebrospinal fluid lymphocytosis. The condition is caused by pathogenic variants in several genes—RNU7-1, TREX1, RNASEH2C, RNASEH2A, RNASEH2B, SAMHD1, LSM11, ADAR, and IFIH1—that play essential roles in nucleic acid metabolism and the regulation of the immune response. AGS typically presents in infancy with early neurodevelopmental delays that evolve over time. Although precise prevalence data are not available, it is recognized as a rare condition.

The clinical picture of AGS involves significant central nervous system involvement. Affected individuals often exhibit multifocal cerebral white matter abnormalities, global developmental delay, and profound intellectual disability. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, and later may develop spasticity, hypertonia, seizures, and loss of speech. Additional features can include porencephalic cysts, cerebral calcifications on imaging, as well as systemic findings such as dry skin, hepatosplenomegaly, and signs of autoimmunity. Not all individuals experience all features, and severity varies considerably.

Aicardi-Goutieres syndrome is linked to pathogenic variants in several genes, including RNU7-1, TREX1, RNASEH2C, RNASEH2A, RNASEH2B, SAMHD1, LSM11, ADAR, and IFIH1. These genes are integral to proper nucleic acid processing and the regulation of the innate immune response, and disruptions in their function lead to abnormal inflammatory processes in the brain. The exact inheritance pattern is not clearly defined in the available data, and families are encouraged to seek genetic counseling to understand the implications of these genetic findings.

Currently, management of Aicardi-Goutieres syndrome focuses on supportive care and symptom management, with treatment plans tailored to the individual’s needs. A multidisciplinary approach is essential, with regular surveillance to detect complications early and interventions that may include physical therapy, speech therapy, and other supportive strategies. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended to help families understand and manage the condition.

Aicardi-Goutieres syndrome is a lifelong neurodevelopmental condition characterized by an initial phase of developmental regression followed by a period of relative stabilization and, in some individuals, later motor decline. Severity and symptoms vary widely between individuals, and outcomes depend on factors such as age at diagnosis and access to comprehensive, multidisciplinary care. With current standards of care, many individuals benefit from regular surveillance and supportive therapies, and outcomes described in medical literature continue to evolve as care practices improve. Families are encouraged to connect with specialists and genetic counselors for ongoing guidance and support.

Clinical trials are underway exploring new treatment approaches for Aicardi-Goutieres syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.