Aicardi-Goutieres Syndrome (AGS)

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Disease Ontology 12 DOID:0050629 KEGG 36 H00290 ICD10 32 G31.8 MESH via Orphanet 44 C535607 ICD10 via Orphanet 33 G31.8

UMLS via Orphanet 72 C0393591 Orphanet 58 ORPHA51 SNOMED-CT via HPO 68 111266001 11934000 128496001 128613002 14648003 16046003 16386004 166603001 166643006 17944005 192781003 192965001 19393004 202264009 204043002 204113001 21850008 22125009 224958001 228158008 233873004 23414001 237836003 240305000 246545002 248315005 25003006 25064002 254024005 26079004 266261006 26825009 26889001 271611007 277473004 278849000 31186001 31216003 312444006 313307000 34911001 36760000 3723001 387712008 40930008 413728006 418143002 423699002 45227007 50219008 51092000 52522001 563001 609225004 64217002 67362008 73211009 75183008 8186001 84757009 85828009 91175000 92814006 95202004 95515009 more UMLS 71 C0393591 C0796126

Genetics Home Reference : ²⁵ Aicardi-Goutières syndrome is a disorder that mainly affects the brain, the immune system, and the skin. Most newborns with Aicardi-Goutières syndrome do not show any signs or symptoms of the disorder. However, about 20 percent are born with a combination of features that include an enlarged liver and spleen (hepatosplenomegaly), elevated blood levels of liver enzymes, a shortage of blood cells called platelets that are needed for normal blood clotting (thrombocytopenia), and neurological abnormalities. While this combination of signs and symptoms is typically associated with the immune system's response to a viral infection that is present at birth (congenital), no actual infection is found in these infants. For this reason, Aicardi-Goutières syndrome is sometimes referred to as a "mimic of congenital infection." Within the first year of life, most individuals with Aicardi-Goutières syndrome experience an episode of severe brain dysfunction (encephalopathy), typically lasting for several months. During this encephalopathic phase of the disorder, affected babies are usually extremely irritable and do not feed well. They may develop intermittent fevers in the absence of infection (sterile pyrexias) and may have seizures. They stop developing new skills and begin losing skills they had already acquired (developmental regression). Growth of the brain and skull slows down, resulting in an abnormally small head size (microcephaly). In this phase of the disorder, white blood cells and other immune system molecules associated with inflammation can be detected in the cerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system). These abnormal findings are consistent with inflammation and tissue damage in the central nervous system. The encephalopathic phase of Aicardi-Goutières syndrome causes permanent neurological damage that is usually severe. Medical imaging reveals loss of white matter in the brain (leukodystrophy). White matter consists of nerve fibers covered by myelin, which is a substance that protects nerves and insures rapid transmission of nerve impulses. Affected individuals also have abnormal deposits of calcium (calcification) in the brain. As a result of this neurological damage, most people with Aicardi-Goutières syndrome have profound intellectual disability. They also have muscle stiffness (spasticity); involuntary tensing of various muscles (dystonia), especially those in the arms; and weak muscle tone (hypotonia) in the torso. Some people with Aicardi-Goutières syndrome have features characteristic of autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own systems and organs. Some of these features overlap with those of another disorder called systemic lupus erythematosus (SLE). A feature of SLE that also occurs in about 40 percent of people with Aicardi-Goutières syndrome is a skin problem called chilblains. Chilblains are painful, itchy skin lesions that are puffy and red, and usually appear on the fingers, toes, and ears. They are caused by inflammation of small blood vessels, and may be brought on or made worse by exposure to cold. Vision problems, joint stiffness, and mouth ulcers are other features that can occur in both disorders. As a result of the severe neurological problems usually associated with Aicardi-Goutières syndrome, most people with this disorder do not survive past childhood. However, some affected individuals who develop the condition later or have milder neurological problems live into adulthood.

MalaCards based summary : Aicardi-Goutieres Syndrome, also known as aicardi goutieres syndrome, is related to aicardi-goutieres syndrome 1 and aicardi-goutieres syndrome 3, and has symptoms including seizures and petechiae of skin. An important gene associated with Aicardi-Goutieres Syndrome is RNASEH2B (Ribonuclease H2 Subunit B), and among its related pathways/superpathways are Cytosolic DNA-sensing pathway and DNA replication. The drugs Abacavir and Zidovudine have been mentioned in the context of this disorder. Affiliated tissues include brain, liver and skin, and related phenotypes are global developmental delay and arrhinencephaly

Disease Ontology : ¹² A syndrome that is a genetically heterogeneous encephalopathy characterized in its most severe form by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic cerebrospinal fluid lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infections.

NIH Rare Diseases : ⁵² Aicardi-Goutieres syndrome 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 may include a very small head (microcephaly ), presence of white blood cells and other sign of inflammation in the cerebrospinal 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. There are several types of Aicardi-Goutieres syndrome, depending on the gene that causes the condition: TREX1 , RNASEH2A , RNASEH2B , RNASEH2C , SAMHD1 , ADAR and IFIH1 , genes. Most cases are inherited in an autosomal recessive pattern, although rare autosomal dominant cases have been reported. Treatment is symptomatic and supportive. The prognosis depends mainly on the severity neurologic problems and in the age of onset of these problems.

NINDS : ⁵³ Aicardi-Goutieres syndrome (AGS) is an inherited encephalopathy that affects newborn infants and usually results in severe mental and physical handicap. There are two forms of the syndrome: an early-onset form that is severe, and a late-onset form that has less impact upon neurological function. The early-onset form affects about 20 percent of all babies who have AGS. These infants are born with neurological and liver abnormalities, such as enlargement of the liver and spleen and elevated liver enzymes. Their jittery behavior and poor feeding ability mimic congenital viral infection. Babies with later-onset AGS begin having symptoms after the first weeks or months of normal development, which appear as a progressive decline in head growth, weak or stiffened muscles (spasticity), and cognitive and developmental delays that range from moderate to severe. Symptoms last for several months, and include irritability, inconsolable crying, intermittent fever, seizures, and loss of developmental skills. Children may also have puffy swelling on the fingers, toes, and ears that resemble chilblains. A number of children have a noticeable startle reaction to sudden noise. For babies with the later-onset form, as symptoms lessen, there is no further worsening of the disease. AGS is difficult to diagnose since many of the symptoms are similar to those of other disorders. Diagnosis is made based on the clinical symptoms of the disease, as well as characteristic brain abnormalities that can be seen in an MRI brain scan. Cerebrospinal fluid (CSF), taken using a "spinal tap," can also be tested for increased levels of a specific immune system cell (a lymphocyte), which indicates a condition known as chronic lymphocytosis. These cells are normally only elevated during infection, so that lymphocytosis without evidence of infection can be used as an indicator of AGS. CSF may 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 defective gene responsible for the disease. Parents do not have any symptoms of disease, but with every child they have together, there is a one in four chance that the baby will receive two copies of the defective gene and inherit AGS. NOTE: AGS is distinct from the similarly named Aicardi syndrome (characterized by absence of a brain structure (corpus callosum), and spinal, skeletal, and eye abnormalities).

KEGG : ³⁶ Aicardi-Goutieres Syndrome (AGS) is an autosomal recessive encephalopathy characterized by basal ganglia and white matter calcification in the presence of chronic cerebrospinal fluid lymphocytosis, and a raised level of cerebrospinal fluid IFNalpha. There is progressive neurological dysfunction resulting in a failure of development of expected physical and social skills. AGS presents in infancy and is lethal in ~40% of cases. It can be caused by mutations in the following genes, TREX1, RNaseH2 and SAMHD1 that lead to excessive intracellular accumulation of DNA and abnormal type I IFN metabolism.

Wikipedia : ⁷⁴ Aicardi-Goutières syndrome (AGS), which is completely distinct from the similarly named Aicardi... more...

GeneReviews: NBK1475

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Synthetic lethal with MLN4924 (a NAE inhibitor)	GR00250-A-1	9.4	ERCC6
2	Synthetic lethal with MLN4924 (a NAE inhibitor)	GR00250-A-2	9.4	ERCC6 EXO1 RNASEH2A RNASEH2C
3	Synthetic lethal with MLN4924 (a NAE inhibitor)	GR00250-A-3	9.4	ERCC6 EXO1 KAT5 RNASEH2A RNASEH2B RNASEH2C

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