*This information is compiled from resources with the most current data. Sources sited below.
Aicardi-Goutieres syndrome is a disorder that mainly affects the brain, the immune system and the skin.
Most newborns with Aicardi-Goutieres syndrome do not show any signs or symptoms of the disorder at birth. However, about 20 percent are born with a combination of features that include an enlarged liver and spleen (hepatosplenomegaly), elevated blood levels of liver enzymes, a decrease in blood platelets (thrombocytopenia), and abnormal neurological responses. While this combination of signs and symptoms is typically associated with the immune system's response to congenital viral infection, no actual infection is found in these infants. For this reason, Aicardi-Goutieres syndrome is sometimes referred to as a "mimic of congenital infection."
Most people with Aicardi-Goutieres syndrome have profound intellectual disability. They also have significant neuromuscular problems including muscle stiffness (spasticity); involuntary tensing of various muscles (dystonia), especially those in the arms; and weak muscle tone (hypotonia) in the trunk.
About 40 percent of people with Aicardi-Goutieres syndrome have painful, itchy skin lesions, usually on the fingers, toes, and ears. These puffy, red lesions, which are called chilblains, are caused by inflammation of small blood vessels. They may be brought on or made worse by exposure to cold. Vision problems, like cortical visual impairment (CVI), joint stiffness, and mouth ulcers may also occur in this disorder.
As a result of the severe neurological problems usually associated with Aicardi-Goutieres syndrome, some people with this disorder do not survive past childhood. However, some affected individuals who have later onset and milder neurological problems may live into adulthood.
There are currently seven identified mutations and they are labeled as such: AGS 1-7. The mutations for AGS 1-5 are inherited while the mutations for AGS 6-7 are spontaneous events. Regarding prenatal testing, there are parents who, once they've tested positive as a carrier for a genetic mutation of AGS 1-5, have undergone extensive preimplantation genetic diagnostic testing through IVF to determine whether there are affected embryos.
The First Year
Within the first year of life most individuals with Aicardi-Goutieres syndrome experience an episode of severe brain dysfunction (encephalopathy), typically lasting for several months. During this phase of the disorder, affected babies are usually extremely irritable and do not feed well. They may develop intermittent fevers in the absence of infection (sterile pyrexias) and may have seizures. They stop developing new skills and begin losing skills they had already acquired (developmental regression). Growth of the brain and skull slows down, resulting in an abnormally small head size (microcephaly). In this phase of the disorder, white blood cells and molecules associated with inflammation can be detected in the cerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system). These abnormal findings are consistent with inflammation and tissue damage in the central nervous system.
The encephalopathic phase
The encephalopathic phase of Aicardi-Goutieres syndrome leaves behind permanent neurological damage that is usually severe. Medical imaging reveals deterioration of white matter in the brain (leukodystrophy). White matter consists of nerve fibers covered by myelin, which is a substance that insulates and protects nerves. Affected individuals also have abnormal deposits of calcium (calcification) in the brain.