What are the other Names for this Condition? (Also known as/Synonyms)

• AGS (Aicardi-Goutières Syndrome)
• AGS Syndrome (2), Subclassifications 1-7
• Familial Infantile Encephalopathy, with Calcification of Basal Ganglia and Chronic Cerebrospinal Fluid Lymphocytosis

What is Aicardi-Goutières Syndrome? (Definition/Background Information)

• Aicardi-Goutières Syndrome (AGS) is a genetic disorder that affects the immune system and causes inflammation in the brain and other parts of the body. It is characterized by signs and symptoms, such as fever, rash, weakness, muscle-wasting, and neurological problems, including developmental delays, intellectual disability, and seizures
• The syndrome is caused by mutations in seven different genes, that play a critical role in the immune system’s response to viral infections. These mutations lead to the overactivation of the immune system, causing inflammation in the brain and other parts of the body. The signs and symptoms of Aicardi-Goutières Syndrome vary depending on the specific gene mutation and the severity of the disorder
• Aicardi-Goutières Syndrome is a rare disorder that affects young children, particularly during infancy. The risk factor for AGS is a family history of mutation(s) in one of the AGS-associated genes. Inheritance in most cases is autosomal recessive, while in some cases it can be autosomal dominant
• The complications of Aicardi-Goutières Syndrome may include chronic inflammation, damage to the brain/other organs, seizures, and vision and hearing problems. The treatment of AGS focuses on controlling inflammation and managing the symptoms, and this may include the use of steroids, Immunosuppressants, along with supportive care
• The prognosis of Aicardi-Goutières Syndrome depends on the specific gene mutation and the severity of the disorder. This can vary from one individual to another. However, with adequate treatment, some individuals may have better outcomes; although, in some cases, severe brain damage, lifelong disability, and early demise may be noted

Who gets Aicardi-Goutières Syndrome? (Age and Sex Distribution)

• Aicardi-Goutières Syndrome (AGS) is a rare disorder that affects infants and young children, with most cases diagnosed in the first year of life
• The disorder affects both males and females equally
• The racial/ethnic distribution and frequency of AGS are not yet known

What are the Risk Factors for Aicardi-Goutières Syndrome? (Predisposing Factors)

• The risk factor for Aicardi-Goutières Syndrome is a family history of the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others. 

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Aicardi-Goutières Syndrome? (Etiology)

Aicardi-Goutières Syndrome (AGS) is caused by mutations in several different genes including, TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, DSRAD, and IFIH1 that play critical roles in the immune system’s response to viral infections.

• These mutations lead to the overactivation of the immune system, causing inflammation in the brain and other parts of the body
• Genes involved with neonatal onset and high mortality are TREX1 (AGS1), RNASEH2C (AGS3), and RNASEH2A (AGS4) genes
• Genes involved with later onset and lower mortality are RNASEH2B, SAMDH1 (AGS5), DSRAD (ASG6), and IFIH1 (AGS7) genes

Many forms of AGS are inherited in an autosomal recessive manner, while AGS1 and AGS6 can also be inherited in an autosomal dominant manner.

Autosomal recessive mode of inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

Autosomal dominant mode of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Aicardi-Goutières Syndrome?

The signs and symptoms of Aicardi-Goutières Syndrome vary depending on the specific gene mutation and the severity of the disorder. Some of the common signs and symptoms include:

• High fever
• Rash
• Chilblains (reddish purple rash with or without ulceration of fingers, toes, and ears)
• Seizures
• Calcification of the basal ganglia or white matter of the brain
• Vision and hearing problems
• Weakness and muscle-wasting

How is Aicardi-Goutières Syndrome Diagnosed?

Aicardi-Goutières Syndrome is diagnosed through a combination of the following:

• Clinical examination and medical history evaluation
• Assessment of the presenting signs and symptoms
• Blood tests
• Electroencephalogram (EEG) and cerebrospinal fluid (CSF) studies
• Imaging studies
• Genetic testing

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Aicardi-Goutières Syndrome?

The complications of Aicardi-Goutières Syndrome may include:

• Chronic inflammation
• Inflammation of the brain and spinal cord (encephalopathy) resulting in brain damage
• Damage to various organs that are affected by the condition
• Developmental delays
• Intellectual disability
• Severe vision and hearing problems
• Auto-amputation of the fingers and toes from chilblains

How is Aicardi-Goutières Syndrome Treated?

The treatment for Aicardi-Goutières Syndrome focuses on controlling inflammation and managing the associated signs and symptoms, which may include:

• Steroids to reduce inflammation
• Immunosuppressants to suppress the immune system
• Supportive care to manage symptoms

How can Aicardi-Goutières Syndrome be Prevented?

• Currently, it is not possible to prevent Aicardi-Goutières Syndrome (AGS) as it is a genetic disorder
• Families with a history of AGS may be recommended genetic counseling and testing

What is the Prognosis of Aicardi-Goutières Syndrome? (Outcomes/Resolutions)

• The prognosis for Aicardi-Goutières Syndrome varies depending on the specific gene mutation and the severity of the disorder
• Some individuals may have better outcomes with proper treatment, while others may have severe brain damage and lifelong disability.

According to literature, the percentage of children who succumb to AGS during the first year of their life is about 25%.

Additional and Relevant Useful Information for Aicardi-Goutières Syndrome:

The following link is a useful resource for further information on rare diseases and disorders:

https://www.dovemed.com/diseases-conditions/rare-disorders/