Aicardi-Goutières Syndrome

What is Aicardi-Goutières syndrome?

Aicardi-Goutières syndrome (AGS) is a rare inherited disease that affects the brain, immune system, and the skin. Variants (also called mutations) in a small group of specific genes cause AGS. These variants cause an increase in the production of a chemical called interferon. 

In AGS, the body’s immune system mistakenly turns on itself and targets white matter in the brain. White matter is made up of nerve fibers coated in myelin, which protects the nerves and allows them to rapidly send and receive information. This loss of white matter causes permanent brain damage that can lead to intellectual or physical disabilities. 

There are two forms of AGS: an early-onset form and a later-onset form. Early-onset AGS happens at birth and is the more serious form, often leading to permanent damage to brain function and severe lifelong disabilities. 

Children with later-onset AGS develop and behave normally for the first few weeks or months of life. Symptoms of later-onset AGS are not as severe as early-onset AGS. They may last for several months and then usually lessen and stabilize. But later-onset AGS may still leave neurological problems that never go away completely.

AGS is also known as pseudotoxoplasmosis syndrome, encephalopathy with basal ganglia calcification, or Cree encephalitis. AGS is different from Aicardi syndrome, where the structure that connects the two sides of the brain (called the corpus callosum) is partly or completely missing.

Symptoms of AGS

Early-onset AGS signs and symptoms include:

Later-onset AGS signs and symptoms include:

Who is more likely to get Aicardi-Goutières syndrome?

AGS is autosomal, which means the gene variants that cause it are on non-sex chromosomes. It can pass down in families in different ways. 

In most cases, AGS is inherited in an autosomal recessive pattern. This means a person must inherit two copies of the affected gene, one from each parent, to have the disease. The parents of a person with an autosomal recessive condition each carry one copy of the altered gene, but they typically don’t show signs and symptoms of the condition. 

In rarer cases, AGS can be inherited in an autosomal dominant pattern. In these cases, a different set of gene variants causes the condition, and a person only needs to inherit one copy of the affected gene from either parent to have the disease. 

If you think someone in your family may have AGS or that you might be a carrier, let your medical team know and they may refer you for genetic testing. 

How is Aicardi-Goutières syndrome diagnosed and treated?

Diagnosing AGS

To diagnose AGS, a doctor will do a physical exam and review the person’s medical history, including any symptoms they are experiencing. Diagnostic tests for AGS may include the following: 

• MRI (magnetic resonance imaging) is key to diagnosing AGS, as it can detect shrinking or small areas of the brain and calcium buildup (calcification) in the brain. 
• Cerebrospinal fluid (CSF) testing can show an increase in immune system activity that appears in AGS. This test is not used alone to diagnose AGS, but if results are positive, a doctor can look for other signs of the disease.
• Genetic testing from a blood sample can show changes in one of the genes associated with AGS. Results from this test along with others can help diagnose a specific type of AGS. 

Find out more about neurological diagnostic tests and procedures.

Treating AGS 

There’s no known cure for AGS. Treatment is available to manage symptoms and to help keep people comfortable. Some people may need treatment for breathing problems, including physical therapy and devices to help clear their lungs. People who need support with feeding may require a special diet. For people who experience seizures with AGS, antiseizure medications can help. Many people with AGS benefit from speech and physical therapy.

The immune system problems in AGS can affect many organs of the body including the lungs, liver, heart, skin, blood cells, and kidneys. As a result, people with AGS should be monitored for these conditions related to the disease and treated if detected:

• Signs of glaucoma 
• Scoliosis and dislocated joints
• Diabetes
• Underactive thyroid
• Problems with the heart, lungs, and blood vessels and platelets

For any learning disabilities associated with AGS, a formal assessment can help teachers understand the child's academic and intellectual potential. This can help uncover any additional supports that children with AGS may need in school or other learning environments. 

What are the latest updates on Aicardi-Goutières syndrome?

NINDS, a part of the National Institutes of Health (NIH), is the leading federal funder of research on the brain and nervous system. NINDS and other NIH institutes have supported research to better understand, diagnose, and treat AGS and related disorders. 

ADAR1 is an RNA editing enzyme that, when mutated, causes AGS. Researchers have developed novel mouse models to study how the disease develops and the relationship between RNA editing and natural immunity. 

Researchers don’t clearly understand how the widespread inflammation seen in AGS leads to such significant problems in the central nervous system. This limits researchers’ ability to develop effective and targeted therapies and is an area of active exploration. In one study, NINDS-funded researchers are using animal models of AGS that replicate the brain changes seen in the disorder—paired with new gene and cell targeting approaches—to test which cells cause the problems in the brain seen in AGS. This may help advance treatment development.

Recent medical advances have shown that a class of medications used to reduce inflammation (called Janus kinase inhibitors) can help ease symptoms of AGS. Specifically, baricitinib—a drug used to prevent inflammation in rheumatoid arthritis and other conditions—has been shown to help people with AGS achieve new milestones and develop new skills. 

For more information on research about AGS, check NIH RePORTER, a searchable database of current and past research projects funded by NIH and other federal agencies. RePORTER also has links to publications and resources from these projects. 

For research articles and summaries on AGS, search PubMed, which contains citations from medical journals and other sites.

How can I or my loved one help improve care for people with Aicardi-Goutières syndrome?

Consider participating in a clinical trial so clinicians and scientists can learn more about AGS and related disorders. Clinical research with human study participants helps researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of participants are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with AGS at ClinicalTrials.gov, a searchable database of current and past clinical studies and research results.