Aicardi-Goutieres syndrome 1

Aicardi-Goutieres syndrome 1 is a severe neuroinflammatory disorder that primarily affects the brain and other organ systems. It is caused by mutations in the TREX1 gene, which disrupts the normal clearance of nucleic acids and triggers an immune response. The condition typically presents in early infancy with signs of developmental delay and neurological impairment. Prevalence data are not well established, and not all individuals experience all features, with severity varying considerably.

Individuals with Aicardi-Goutieres syndrome 1 commonly exhibit a range of characteristic features that reflect both central nervous system involvement and systemic inflammation. Neurologically, almost all affected children have global developmental delay, absent speech, spasticity, and CNS demyelination, along with basal ganglia and intracerebral periventricular calcifications. Other consistent findings include dystonia, microcephaly, and chronic cerebrospinal fluid lymphocytosis, which underscore the profound impact on brain function. Less common but notable features such as hepatomegaly, chilblains, and thrombocytopenia occur in a subset of individuals. Not all individuals experience every feature, and severity varies considerably.

Aicardi-Goutieres syndrome 1 is caused by mutations in the TREX1 gene, which plays an important role in DNA repair and immune regulation. Disruption of TREX1 function leads to an abnormal accumulation of nucleic acids that subsequently triggers an inflammatory response affecting the central nervous system and other organs. Multiple inheritance patterns have been reported for this condition, as it can be inherited in both autosomal recessive and autosomal dominant manners. This mixed pattern means that in some families a single mutated copy may cause the condition, while in others two copies are required; genetic counseling is recommended to help families understand these implications.

Currently, management focuses on supportive care and symptom management, with treatment tailored to the specific needs of each individual. Care is typically provided by a multidisciplinary team that may include neurologists, developmental specialists, and other healthcare providers. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Families are encouraged to discuss treatment options with their healthcare team and pursue genetic counseling to better understand recurrence risks and available supportive services. Although investigational therapies are under development, none have yet received regulatory approval.

Aicardi-Goutieres syndrome 1 is a lifelong condition characterized by significant neurodevelopmental challenges and systemic complications. The clinical course is highly variable; some individuals may experience a period of stabilization after initial symptoms, while others continue to face progressive motor and cognitive difficulties. With current standards of care, outcomes have improved and regular monitoring helps address emerging issues. Outcomes described in medical literature continue to evolve as standards of care improve, and families often find it helpful to connect with specialists familiar with this condition as well as seek genetic counseling for ongoing management and future planning.