Aicardi-Goutièresyndroom (AGS)
- Article
- 2021-03-02
Aicardi-Goutieres Syndrome (AGS) is a hereditary encephalopathy that affects newborn babies and usually results in severe mental and physical disability. There are two forms of the syndrome: an early-onset form that is severe and a late-onset form that has less impact on neurological function. The early-onset form affects about 20 percent of all babies with AGS. These babies are born with neurological and liver abnormalities such as enlargement of the liver and spleen and elevated liver enzymes. Their nervous behavior and poor nutritional ability mimic congenital viral infection.
Babies with AGS in later life begin to have symptoms after the first weeks or months of normal development, which appear as a gradual decline in head growth, weak or stiff muscles (spasticity), and cognitive and developmental delays ranging from moderate to severe . Symptoms last for several months and include irritability, inconsolable crying, periodic fever, seizures, and loss of developmental skills. Children may also have swollen fingers, toes, and ears that resemble winters. A number of children have a noticeable startle reaction to sudden noises. In babies with a later onset form, there is no further worsening of the disease as symptoms diminish.
AGS is difficult to diagnose because many of its symptoms are similar to those of other conditions. Diagnosis is made based on the clinical symptoms of the disease as well as characteristic brain abnormalities that can be seen on an MRI brain scan. Cerebrospinal fluid (CSF) taken using an "epidural" can also be tested for elevated levels of a specific cell of the immune system (a lymphocyte), indicating a condition known as chronic lymphocytosis. These cells are normally only elevated during infection, so lymphocytosis without signs of infection can be used as an indicator of AGS. CSF can also be tested for elevated levels of a substance known as interferon gamma, which can also support a diagnosis of AGS.
The mutations of four different genes are associated with AGS:
- Aicardi-Goutieres syndrome-1 (AGS1) and AGS5 (an autosomal dominant form) are caused by a mutation in the TREX1 gene,
- AGS2 is caused by a mutation in the RNASEH2B gene,
- AGS3 is caused by a mutation in the RNASEH2C gene,
- AGS4 is caused by a mutation in the RNASEH2A gene.
Most cases of AGS are inherited in an autosomal recessive manner, which means that both parents of a child with AGS must carry a single copy of the faulty gene responsible for the disease. Parents have no symptoms of disease, but with every child they have together, there is a one in four chance that the baby will get two copies of the faulty gene and inherit AGS.
NOTE : AGS differs from the eponymous Aicardi syndrome (characterized by the absence of a brain structure (corpus callosum) and spinal, skeletal and eye abnormalities).
Therapy
Depending on the severity of the symptoms, children may require chest physiotherapy and treatment for respiratory complications. To ensure adequate nutrition and caloric intake, some babies may require special diet and feeding adjustments. Seizures can be treated with standard anticonvulsant medications. Children should be monitored for signs of glaucoma in the first few months of life and later for signs of scoliosis, diabetes, and an underactive thyroid. Prognosis depends on the severity of the symptoms.
Prognosis
Prognosis depends on the severity of the symptoms. Children with early-onset AGS have the greatest risk of death. Children with the later form may be left with weakness or stiffness in the peripheral muscles and arms, weak muscles in the trunk of the body, and poor head control. Almost all children with AGS have a mild to severe mental and physical disability.
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