Aicardi-Goutières syndrome is a rare neurological condition that causes intellectual and physical disability. While there’s no cure, symptom management can improve quality of life.

Aicardi-Goutières syndrome (AGS) is a progressive genetic brain disorder caused by gene mutations passed through families. It goes by several other names, such as:

  • pseudotoxoplasmosis syndrome
  • Cree encephalitis
  • encephalopathy with basal ganglia calcification

Children with AGS have excess production of molecules called interferons. Interferons are normally produced when a healthy cell is infected with a virus. These interferons “interfere” and keep a virus from reproducing. However, excess interferons can lead to brain damage that often causes severe intellectual and physical impairment.

AGS is a particularly rare condition. Actual incidence rates in the United States and worldwide are unknown, but in a 2022 study, researchers estimated that it occurs in less than 1 in 100,000 newborns in Denmark.

AGS develops from mutations in one of several genes. These genetic mutations lead to the buildup of calcium in the brain. It’s thought that this buildup triggers an autoimmune response caused by the increased production of alpha-interferons.

These interferon molecules normally tell your immune system that there are viruses that need to be destroyed. In people with AGS, the immune system becomes active to attack a virus that doesn’t exist and damages healthy brain tissue.

AGS falls into a group of disorders called interferonopathies all characterized by interferon dysregulation.

AGS is divided into early-onset and later-onset forms:

  • Early-onset: The early-onset form occurs at birth and generally causes more serious symptoms. It often leads to severe mental and physical disability. It makes up about 20% of cases.
  • Later-onset: The later-onset form develops within weeks to months of birth. Symptoms are generally milder, but it can still cause debilitating neurological problems.

The symptoms of AGS tend to be more severe in people with early-onset AGS. It can lead to severe intellectual and physical disability.

Early-onset AGS can cause signs and symptoms such as:

  • jittery behavior
  • poor feeding ability in infants
  • neurological and liver abnormalities from birth
  • liver inflammation
  • smaller-than-normal head (microcephaly)
  • seizures
  • rashes

Later-onset AGS can lead to signs and symptoms such as:

  • weak and stiff muscles (spasticity)
  • irritability and inconsolable crying
  • delayed head growth
  • unexplained fever that comes and goes
  • seizures
  • chilblains, rashes or swelling of the fingers, toes, and ears that get worse in cold

AGS can lead to additional complications such as:

AGS is caused by mutations in one of several genes. Researchers have identified at least nine genes associated with AGS, which include:

  • TREX1
  • SAMHD1
  • ADAR
  • IFIH
  • LSM11
  • RNU7-1

Gene mutations associated with AGS are normally passed through families in a recessive pattern of inheritance. You require one associated gene from each parent to develop AGS.

Less commonly, AGS may develop due to sporadic mutations that occur without a family history. Some gene mutations are dominant, meaning they only need to be inherited from one parent to develop AGS. They include mutations in the following genes:

  • ADAR
  • TREX1
  • IFIH

AGS seems to occur roughly equally in males and females, and no other risk factors other than a family history have been identified.

A doctor may suspect that your child has AGS based on their signs and symptoms. Imaging and laboratory tests can support their diagnosis.

Magnetic resonance imaging (MRI) and computed tomography (CT) scans are the most used imaging methods. They can reveal typical features such as:

  • calcification of the basal ganglia
  • changes to the white matter throughout your brain
  • loss of cerebral mass

Laboratory findings that can support an AGS diagnosis include:

  • blood cell abnormalities
  • elevated liver enzymes
  • elevated white blood cell count in cerebral spinal fluid
  • increased levels of interferon-alpha and neopterin

The diagnosis can be confirmed with genetic testing to look for gene mutations known to cause AGS.

It’s rare for AGS to be diagnosed before your child is born. Researchers in a 2023 case study diagnosed AGS prenatally in a child using an ultrasound combined with the results of a genetic test.

The treatment for AGS largely revolves around treating symptoms and improving quality of life. Options include:

AGS seems to respond poorly to traditional immunosuppressive medications. Some recent evidence suggests that Janus kinase inhibitors may help suppress interferon activity. A specific Janus kinase inhibitor called baricitinib may help people with AGS develop new motor skills.

In a 2023 study, researchers found promising results with a type of monoclonal antibody called tocilizumab.

Enrolling your child in a clinical trial can help researchers improve their understanding of AGS and may give your child access to new treatments.

You can ask your doctor about clinical trials your child may be eligible for, or you can search for a list of current clinical trials from the National Institutes of Health website.

Children who have AGS often have severe intellectual and physical disability. Most children don’t survive past childhood. People with milder forms of the disease may live into adulthood, and a few cases of people with AGS having normal intelligence have also been reported.

Children with early-onset AGS are particularly unlikely to survive into adulthood. They often pass away within the first year of life.

AGS is a rare neurological condition caused by an autoimmune abnormality. It currently doesn’t have a cure, and many children have severe physical and mental disability.

Enrolling your child in a clinical trial can help researchers improve their understanding of the disease and may give your child access to new treatments. You can talk with your doctor about clinical trials your child might be eligible for.