Aicardi–Goutières syndrome is a rare genetic disorder

Genetic disorder

A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....

. It is also known as Cree encephalitis and pseudo-TORCH syndrome, both of which were once considered separate disorders. It is a type of leukodystrophy

Leukodystrophy

Leukodystrophy refers to a group of disorders characterized by dysfunction of the white matter of the brain. The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers...

 and is usually fatal within the first few years. It is autosomal recessive and presents within the first few weeks of life.

History

Aicardi–Goutières syndrome was initially described by Jean Aicardi

Jean Aicardi

Jean Aicardi is a French doctor.Aicardi syndrome and Aicardi-Goutieres syndrome are named after him.Aicardi syndrome only affects females, and in very rare cases, males with Klinefelter syndrome .-References:...

 and Françoise Goutières in 1984, based on observations of eight cases of early-onset progressive familial encephalopathy

Encephalopathy

Encephalopathy means disorder or disease of the brain. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of global brain dysfunction; this syndrome can be caused by many different illnesses.-Terminology:...

, with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Further clinical studies included 11 cases of early-onset progressive encephalopathy in a Cree

Cree

The Cree are one of the largest groups of First Nations / Native Americans in North America, with 200,000 members living in Canada. In Canada, the major proportion of Cree live north and west of Lake Superior, in Ontario, Manitoba, Saskatchewan, Alberta and the Northwest Territories, although...

 community in Canada, described in 1988, which were given the name Cree encephalitis .

Causes

Later work mapped the Aicardi–Goutières syndrome to chromosome 3p21 and suggested that the two, along with the pseudo-TORCH (toxoplasmosis

Toxoplasmosis

Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself...

, rubella

Rubella

Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...

, cytomegalovirus

Cytomegalovirus

Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...

, and herpes simplex

Herpes simplex

Herpes simplex is a viral disease caused by both Herpes simplex virus type 1 and type 2 . Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores or fever...

 virus types 1 and 2) syndrome were the same disorder.

The condition has been associated with TREX1

TREX1

Three prime repair exonuclease 1 is an enzyme that in humans is encoded by the TREX1 gene.- Function :This gene encodes the major 3'->5' DNA exonuclease in human cells. The protein is a non-processive exonuclease that may serve a proofreading function for a human DNA polymerase...

. Due to the rarity of mutations in the genes associated with the disease, and its autosomal recessive nature, cases are isolated to consanguineous families. As such, it is frequently described as an autozygosity disease.

Types include:

Type	OMIM	Gene	Locus
AGS1		TREX1 TREX1 Three prime repair exonuclease 1 is an enzyme that in humans is encoded by the TREX1 gene.- Function :This gene encodes the major 3'->5' DNA exonuclease in human cells. The protein is a non-processive exonuclease that may serve a proofreading function for a human DNA polymerase...	3p21.3-p21.2
AGS2		RNASEH2B	13q
AGS3		RNASEH2C	11q13.2
AGS4		RNASEH2A RNASEH2A RRibonuclease H2 subunit A, also known as RNase H2 subunit A, is an enzyme that in humans is encoded by the RNASEH2A gene.- Function :...	19p13.13
AGS5		SAMHD1 SAMHD1 SAM domain and HD domain-containing protein 1 is a protein that in humans is encoded by the SAMHD1 gene.-External Links:* *...	20

Epidemiology

Aicardi–Goutières syndrome is very rare, with only about 50 cases having been described.

Treatment and prognosis

Current treatment is supportive, involving management of seizures and spasticity associated with the syndrome.

External Links

• GeneReviews/NCBI/NIH/UW entry on Aicardi-Goutières Syndrome
• OMIM entries on Aicardi-Goutieres syndrome
• Aicardi-Goutieres Syndrome at United Leukodystrophy Foundation website