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

• AGS2 (Aicardi-Goutieres Syndrome Type 2)
• RNASEH2B-Related Aicardi-Goutieres Syndrome

What is Aicardi-Goutieres Syndrome Type 2? (Definition/Background Information)

• Aicardi-Goutieres Syndrome Type 2 is an inherited disease that mainly affects the brain, immune system, and the skin
• Loss of white matter in the brain (leukodystrophy) and abnormal deposits of calcium (calcification) in the brain leads to an early-onset severe brain dysfunction (encephalopathy) that usually results in severe intellectual and physical disability
• Additional symptoms may include epilepsy, painful, itchy skin lesion (chilblains), vision problems, and joint and muscle stiffness (spasticity), involuntary muscle twisting and contractions (dystonia), and weak muscle tone (hypotonia) in the torso
• Other signs and symptoms of Aicardi-Goutieres Syndrome Type 2 may include a very small head (microcephaly), presence of white blood cells and other sign of inflammation in thecerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system)
• Symptoms usually progress over several months before the disease course stabilizes. Treatment is symptomatic and supportive
• The prognosis of Aicardi-Goutieres Syndrome Type 2 depends mainly on the severity of neurologic problems and on the age of onset of these problems

(Source: Aicardi-Goutieres Syndrome Type 2; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

• Aicardi-Goutieres Syndrome Type 2 is caused by mutations in the RNASEH2B gene. It is inherited in an autosomal recessive manner

Who gets Aicardi-Goutieres Syndrome Type 2? (Age and Sex Distribution)

• Aicardi-Goutieres Syndrome Type 2 is a rare congenital disorder, with very few cases reported in the medical literature
• The presentation of symptoms may occur at birth or in infancy
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Aicardi-Goutieres Syndrome Type 2? (Predisposing Factors)

• A positive family history may be an important risk factor, since Aicardi-Goutieres Syndrome Type 2 can be inherited
• Currently, no other risk factors have been clearly identified for the syndrome

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-Goutieres Syndrome Type 2? (Etiology)

Aicardi-Goutieres Syndrome Type 2 is a genetic condition that is caused by mutations in the RNASEH2B gene.

• This gene provides instructions for a subunit of RNASEH2 complex complex, which catalyzes breakdown of molecules containing RNA
• A mutation in this gene may cause RNA containing molecules to accumulate in cells and tissues, leading to signs and symptoms of the disease
• The condition is inherited in an autosomal recessive manner

Autosomal recessive: 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).

What are the Signs and Symptoms of Aicardi-Goutieres Syndrome Type 2?

The signs and symptoms of Aicardi-Goutieres Syndrome Type 2 may vary among affected individuals in type and severity. The signs and symptoms may include:

• Dystonia
• Microcephaly
• Spastic paraplegia
• Basal ganglia calcification
• Cerebral atrophy
• Chronic CSF lymphocytosis
• Encephalopathy
• Epilepsy
• Painful, itchy skin lesion (chilblains)
• Vision problems
• Joints and muscle stiffness 
• Involuntary muscle twisting and contractions (dystonia), and 
• Weak muscle tone (hypotonia) in the torso
• Microcephaly
• Presence of white blood cells and other sign of inflammation in the  cerebrospinal fluid

(Source: Aicardi-Goutieres Syndrome Type 2; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How is Aicardi-Goutieres Syndrome Type 2 Diagnosed?

Aicardi-Goutieres Syndrome Type 2 is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

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-Goutieres Syndrome Type 2?

The complications of Aicardi-Goutieres Syndrome Type 2 may include:

• Faiure to thrive in the neonatal period
• Failure to reach developmental milestones
• Problems with movement
• Intellectual deficiency
• Severe physical disabilities

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Aicardi-Goutieres Syndrome Type 2 Treated?

There is no cure for Aicardi-Goutieres Syndrome Type 2, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Aicardi-Goutieres Syndrome Type 2 be Prevented?

Aicardi-Goutieres Syndrome Type 2 may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Aicardi-Goutieres Syndrome Type 2? (Outcomes/Resolutions) 

• The prognosis of Aicardi-Goutieres Syndrome Type 2 is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with early-onset of the disorder may exhibit severe symptoms, when compared to individuals developing the disorder a few months after birth
• The majority of those affected show intellectual and physical disability to varying degrees

Additional and Relevant Useful Information for Aicardi-Goutieres Syndrome Type 2:

The following DoveMed website link is a useful resource for additional information:

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