This article discusses the causes, symptoms, diagnosis, treatment, and prevention of Aicardi-Goutières Syndrome (AGS), a rare genetic disorder that affects the brain, skin, and immune system.
The disease is caused by mutations in a number of genes involved in the immune response, particularly those related to nucleic acids, such as TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR. Due to these mutations, nucleic acids, including DNA and RNA, accumulate in the cells, causing inflammation that damages the brain and other tissues.
AGS usually manifests in infancy, but it can sometimes manifest later in childhood. Common symptoms include:
AGS is characterized by developmental delays, intellectual disabilities, seizures, and movement disorders.
Sun-exposed areas are more likely to experience skin abnormalities such as rash, lesions, and discoloration.
Symptoms of encephalopathy include irritability, poor feeding, and loss of previously acquired skills.
In some individuals with AGS, enlargement of the liver may occur.
AGS is associated with elevated levels of inflammatory markers such as interferon alpha in the blood and cerebrospinal fluid.
AGS is diagnosed through a combination of clinical evaluation, laboratory tests, and genetic testing. Diagnostic assessments may include:
The clinical evaluation consists of an assessment of symptoms, a medical history, and a physical examination in order to identify the characteristic features of AGS.
Inflammatory markers, such as interferon alpha, and abnormal liver function tests may be detected in blood tests.
MRI scans of the brain may reveal white matter changes, calcifications, and atrophy.
The diagnosis of AGS is confirmed by genetic testing to identify mutations in genes associated with the disease.
In the current state of research, there is no cure for AGS, and treatment consists of managing symptoms and providing supportive care. Treatment options may include:
Controlling seizures may be achieved with antiepileptic medications.
Individuals with AGS may benefit from physical and occupational therapy to improve motor skills, mobility, and adaptive functioning.
In order to address specific symptoms such as movement disorders, behavioral problems, and skin abnormalities, medications and therapies may be prescribed.
People with AGS and their families can benefit from multidisciplinary support from healthcare professionals such as neurologists, genetic counselors, and developmental specialists.
AGS is a genetic disorder, so there are no specific prevention measures. However, genetic counseling and testing can help identify those who are likely to pass on the mutated genes to their children. For families with a history of AGS or known genetic mutations, prenatal testing and preimplantation genetic diagnosis may be available.
