Aicardi-Goutières Syndrome

Aicardi-Goutières syndrome is an inherited disease that mainly affects the brain, immune system, and the skin. Loss of white matter in the brain (leukodystrophy) and abnormal deposits of calcium (calcification) in the brain leads to an early-onset severe brain dysfunction (encephalopathy) that usually results in severe intellectual and physical disability. Additional symptoms may include epilepsy, painful, itchy skin lesion (chilblains), vision problems, and joint and muscle stiffness (spasticity), involuntary muscle twisting and contractions (dystonia), and weak muscle tone (hypotonia) in the torso. Other signs and symptoms may include a very small head (microcephaly), presence of white blood cells and other sign of inflammation in the cerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system). There are several types of Aicardi-Goutières syndrome, depending on the gene that causes the condition: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR and IFIH1, genes. Most cases are inherited in an autosomal recessive pattern, although rare autosomal dominant cases have been reported.

Genetic Mutations: Aicardi-Goutières syndrome is caused by genetic mutations, also known as pathogenic variants. Genetic mutations can be hereditary, when parents pass them down to their children, or they may occur randomly when cells are dividing. Genetic mutations may also result from contracted viruses, environmental factors, such as UV radiation from sunlight exposure, or a combination of any of these.

If you suspect you may have this disease, you may want to start collecting your family health history. Information such as other family members who have had similar symptoms, when their/your symptoms first appeared, or exposures to any potential disease-causing environmental factors should be discussed with your medical team.

Known Genetic Mutations: Aicardi-Goutières syndrome is caused by genetic mutations in the following known gene(s):

RNASEH2B, SAMHD1, RNASEH2A, IFIH1, RNASEH2C, ADAR, TREX1

Given these known genetic mutation(s), you may want to ask your health care team if genetic testing is right for you. Genetic tests are laboratory tests that use samples of blood, saliva, or other tissues to help identify changes in genes, chromosomes, or proteins. Genetic testing can help confirm or rule out a suspected genetic disease, or can provide other useful information to your health care team.

Damaged White Matter in CNS: Aicardi-Goutières syndrome is caused by damaged white matter in the central nervous system (CNS). The brain and spinal cord make up the CNS. The white matter portions of the CNS get its color from a tissue called myelin. Myelin is made up of proteins and fatty materials called lipids. Myelin wraps around nerves, protecting them and helping to speed up the signals between nerves in the CNS. Genetic changes can affect the growth or function of myelin, which can slow or block the communication between nerves.

Yes. It is possible for a biological parent to pass down genetic mutations that cause or increase the chances of getting this disease to their child. This is known as inheritance. Knowing whether other family members have previously had this disease, also known as family health history, can be very important information for your medical team.

There are multiple ways, or patterns, a disease can be inherited depending on the gene(s) involved. Based on GARD’s current data, this disease can be inherited in the following pattern(s):

Autosomal Dominant: Autosomal means the gene involved is located on one of the numbered chromosomes. Dominant means that a child only needs to inherit one copy of the mutated gene, from either biological parent, to be affected by the disease.

People affected by an autosomal dominant disease have a 50% chance of passing on the mutated gene to their biological child.

Autosomal Recessive: Autosomal means the gene involved is located on one of the numbered chromosomes. Recessive means that a child must inherit two copies of the mutated gene, one from each biological parent, to be affected by the disease. A carrier is a person who only has one copy of the genetic mutation. A carrier usually doesn’t show any symptoms of the disease.

If both biological parents are carriers, there is a 25% chance their child inherits both copies of the mutated gene and is affected by the disease. Additionally, there is a 50% chance their child inherits only one copy of the mutated gene and is a carrier.