Aicardi-Goutieres Syndrome (AGS)
Inheritance:
Usually Autosomal recessive
Inheritance from both parents will result in the disease. May be Autosomal Dominant Inheritance from one parent results in the disease
Age range at onset:
Birth, first few years of life, occasionally later childhood
Late onset at around 1 year
Specialists you may see:
Symptoms
Aicardi Goutieres syndrome (AGS) usually presents at birth or in the first year of life although later onset may occur. Those presenting at birth usually have the most severe symptoms with neurological abnormalities, a skin rash, enlarged liver and spleen and a fever.
Alternatively there may be a period of normal development followed by a rapid onset of irritability, regression of development, epileptic seizures, feeding difficulties and fever. There is usually a period of several months of extreme irritability and the onset of neurological abnormalities such as stiffness and spasticity of the arms and legs, abnormal eye movements, swallowing difficulties and slowing of head growth. Fever is common and initially a brain infection is suspected. The exclusion of infection and abnormal brain scan appearances (CT and MRI) usually lead to the diagnosis.
The disease course usually stabilises but neurological problems such as stiffness, feeding difficulties, speech problems, poor vision and learning difficulties persist. Around a third of patients develop chilblain like skin lesions.
Atypical and later onset forms of the condition can occur and the clinical course may be milder.
Those with the most severe form usually do not live past 10 years of age, those with a milder form have been known to survive into adulthood.
Note: Aicardi-Goutieres Syndrome differs from Aicardi Syndrome which is not a leukodystrophy
Cause
There are seven different genes associated with Aicardi-Goutieres Syndrome, mutations of any of these could lead to the condition and symptoms described. These are TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1 and IFIH1. Mutations in these genes cause an increase in the production of a chemical called interferon which is thought to play a central role in the brain injury that occurs in AGS.
Mutations in these genes may sometimes cause neurological conditions that are different from AGS and that do not primarily affect the white matter of the brain.
News, research and treatment
Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1