Aicardi-Goutieres Syndrome (AGS) is a progressive, early onset encephalopathy, which is transmitted in an autosomal recessive manner. AGS is characterized by mental and physical deformations due to calcifications of the basal ganglia, which sometimes extends to the white matter, cerebral atrophy, chronic CSF leukocytosis, and elevated levels of alpha-interferon in the spinal fluid and blood. Other symptoms include microcephaly, feeding difficulties, vomiting, irritability, spasticity, dystonia, cortical blindness, ocular jerks, poor or no eye contact, and lack of progress of motor and social skills. A quarter of the affected patients may show tonic-clonic or focal tonic seizures, while another quarter may present with chilblain-like swellings at the extremities. The condition is a severe one, with 25% of the patients dying before the age of 17-years. Surviving patients generally persist in a vegetative state, with very little contact with their surroundings.
AGS is a genetically heterogeneous disorder. AGS1 (Aicardi-Goutieres Syndrome 1, Autosomal Dominant) is associated with mutations in TREX1 (3-Prime @Repair Exonuclease 1) gene, which encodes an exonuclease that plays a major role in DNA repair. It is postulated that defects in mismatch repair lead to development of AGS.