Aicardi-Goutières syndrome

Also known as: AGS, Aicardi-Goutieres syndrome, Aicardi Goutieres syndrome, Cree encephalitis, encephalopathy with basal ganglia calcification, familial infantile encephalopathy with intracranial calcification and chronic cerebrospinal fluid lymphocytosis, pseudotoxoplasmosis syndrome

Definition

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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 cell fragments 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.

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Orphanet

Aicardi-Goutières syndrome (AGS) is an inherited, subacute encephalopathy characterised by the association of basal ganglia calcification, leukodystrophy and cerebrospinal fluid (CSF) lymphocytosis.

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Symptoms

Medical Term Other Names Description
Abnormality of the nervous system Neurologic abnormalities, Neurological abnormality, Brain and/or spinal cord issue [more] An abnormality of the nervous system.
Microcephaly small cranium, Decreased circumference of cranium, Small head, Small skull, Small head circumference, Reduced head circumference, Decreased size of cranium, Decreased size of skull, Abnormally small skull, Decreased size of head, Abnormally small cranium, small calvarium, Abnormally small head [more] Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Muscle stiffness A condition in which muscles cannot be moved quickly without accompanying pain or spasm.
Pruritus Itching, pruritis, Skin itching, Itchy skin [more] Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased disposition to experience pruritus.
Autoimmunity Autoimmune disorder, Autoimmune condition, Autoimmune disease [more] The occurrence of an immune reaction against the organism's own cells or tissues.
Dystonia Dystonic movements, Dystonic disease An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Thrombocytopenia Low platelet count A reduction in the number of circulating thrombocytes.
Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
Irritability Irritable
Intellectual disability Nonprogressive intellectual disability, Poor school performance, Mental-retardation, Dull intelligence, Nonprogressive mental retardation, Mental deficiency, Mental retardation, nonspecific, Low intelligence [more] Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Seizures Epilepsy Seizures are an intermittent abnormality of the central nervous system due to a sudden, excessive, disorderly discharge of cerebral neurons and characterized clinically by some combination of disturbance of sensation, loss of consciousness, impairment of psychic function, or convulsive movements. The term epilepsy is used to describe chronic, recurrent seizures.
Spasticity Muscle spasticity, Muscular spasticity A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Metatarsus adductus Metatarsus adductovarsus, Metatarsus varus, Forefoot varus, Intoe [more] The metatarsals are deviated medially (tibially), that is, the bones in the front half of the foot bend or turn in toward the body.
Leukodystrophy Degeneration of white matter of brain Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes.
Generalized hypotonia Generalized muscular hypotonia, Decreased muscle tone, Low muscle tone, Hypotonia [more] Generalized muscular hypotonia (abnormally low muscle tone).
Encephalopathy Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Fever Pyrexia, Hyperthermia Elevated body temperature due to failed thermoregulation.
Impulsivity Impulsive Acting on the spur of the moment in response to immediate stimuli; acting on a momentary basis without a plan or consideration of outcomes; difficulty establishing or following plans; a sense of urgency and self-harming behavior under emotional distress.
Developmental regression Psychomotor regression, Psychomotor regression in infants, Psychomotor regression beginning in infancy, Loss of developmental milestones, Mental deterioration in childhood, Psychomotor regression, progressive, Neurodevelopmental regression [more] Loss of developmental skills, as manifested by loss of developmental milestones.
Basal ganglia calcification Basal ganglion calcification, Calcification of the basal ganglia The presence of calcium deposition affecting one or more structures of the basal ganglia.
Lymphocytosis High lymphocyte count Increase in the number or proportion of lymphocytes in the blood.
Hepatosplenomegaly Enlarged liver and spleen Simultaneous enlargement of the liver and spleen.
Episodic fever Increased body temperature, episodic, Hyperthermia, episodic, Intermittent fever [more] Periodic (episodic or recurrent) bouts of fever.
CSF lymphocytic pleiocytosis CSF lymphocytosis An increased lymphocyte count in the cerebrospinal fluid.
Oral ulcer Mouth sore, Mouth ulcer Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue.
Hepatomegaly Enlarged liver Abnormally increased size of the liver.
Joint stiffness Stiff joint Joint stiffness is a perceived sensation of tightness in a joint or joints when attempting to move them after a period of inactivity. Joint stiffness typically subsides over time.
Systemic lupus erythematosus A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes.

Other Classifiers and IDs

  • OrphaNet: ORPHA:51
  • MeSH: C535607
  • UMLS: C0393591