Aicardi-Goutières syndrome, RNASEH2B-related

What is Aicardi-Goutières syndrome, RNASEH2B-related?

Aicardi-Goutières syndrome (AGS), RNASEH2B-related, is an inherited condition that affects the brain, immune system, and skin. It is caused by harmful genetic changes (variants) in the RNASEH2B gene. These changes result in the overactivity of certain cells of the immune system. This overactivity causes inflammation and damage to the organs, especially the brain and spinal cord, which leads to symptoms of the disease.

AGS, RNASEH2B-related, is associated with a wide range of symptom severity. There is a severe classic form as well as a milder atypical form of the condition.

Classic form

The majority of individuals with AGS, RNASEH2B-related, have symptoms that begin within the first few months of life. Early onset brain disease (encephalopathy) causes irritability, slow head growth, and loss of developmental skills. Individuals have severe intellectual and physical disabilities. Brain imaging will often show differences such as areas with increased calcium deposits (calcifications). Other common features can include tight muscles, abnormal muscle tone, seizures, enlarged liver and spleen (hepatosplenomegaly), unexplained fevers (sterile pyrexias), and a shortage of blood cells called platelets (thrombocytopenia). Some individuals will develop painful, itchy skin lesions (chilblains) on the fingers, toes, and ears.

Atypical form

The atypical form of AGS, RNASEH2B-related, is generally characterized by milder features that may start at later ages. The age of symptom onset can range from infancy through the teenage years.

Some people with an atypical form have normal intelligence, while others will have developmental delays. Symptoms related to inflammation, such as unexplained fevers and chilblains, are common and may worsen over time. Many individuals will have a period where their neurological function suddenly declines. This often results in new symptoms such as muscle weakness and stiffness (spastic paraparesis), abnormal muscle tone (dystonia), and declines in speech and communication skills.

There have been several reports of individuals whose only symptoms are related to tightness and stiffness of the leg muscles. These individuals may have difficulty walking due to their muscle symptoms but otherwise have normal development.

How common is Aicardi-Goutières syndrome, RNASEH2B-related?

Several genes are known to cause Aicardi-Goutières syndrome, which has an incidence of less than 1 in 100,000 births. Approximately 36% of Aicardi-Goutières syndrome is caused by RNASEH2B.

How is Aicardi-Goutières syndrome, RNASEH2B-related treated?

There is no cure for Aicardi-Goutières syndrome, RNASEH2B-related. Treatment for the condition is directed at managing an individual's specific symptoms. This often means receiving care through a team of specialists, including physicians, speech therapists, occupational therapists, physical therapists, and social workers.   Individuals will often benefit from receiving early intervention and other supportive services beginning at a young age. Other common interventions may include treating breathing problems, managing feeding problems by focusing on diet to ensure adequate caloric intake, and using medications to prevent seizures.

What is the prognosis for an individual with Aicardi-Goutières syndrome, RNASEH2B-related?

Prognosis depends in part on which form of the condition a person has. The overall lifespan of this condition is not well researched, though there are reports of individuals surviving into adulthood. Milder forms of the condition are expected to be associated with longer survival than the classic form.