A number sign (#) is used with this entry because of evidence that Aicardi- Goutieres syndrome-1 (AGS1) is caused by homozygous or compound heterozygous. Aicardi-Goutières syndrome (AGS) is an inherited, subacute encephalopathy characterised by the association of basal ganglia calcification, leukodystrophy and. Aicardi-Goutières syndrome (AGS) is a rare genetic disorder that affects the brain , spinal cord and immune system. Learn about symptoms, diagnosis and.
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CC HPO: C ] – Bilateral, symmetric intracerebral calcifications, especially in the basal ganglia and periventricular areas [UMLS: C ] – Heterozygous mutations reported, see AGS1 has also been reported to be caused by heterozygous mutation in this gene see, e. Aicardi-Goutieres syndrome is a genetically heterogeneous encephalopathy characterized in its most severe form by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic cerebrospinal fluid CSF lymphocytosis, increased CSF alpha-interferon IFNA1;and negative serologic investigations for common prenatal infections Ali et al.
AGS is phenotypically similar to in aicarddi-goutieres viral infection. Aicardi-goutiered neurologic dysfunction becomes clinically apparent in infancy, aicardi-goutieree manifests as progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation, and often death in early childhood.
Outside the nervous system, thrombocytopenia, hepatosplenomegaly, and elevated hepatic transaminases along with intermittent fever may also erroneously suggest an infective process Crow et al.
In a review of AGS, Stephenson noted that an expanded phenotypic spectrum has been recognized and that most of the aicardi-voutieres criteria for diagnosis no longer apply: The appearance of chilblains is an important clinical sign for correct diagnosis. Cree encephalitis was originally considered a separate disorder, but genetic evidence has shown that it is the same as AGS1. AGS is distinct from the similarly named Aicardi syndromewhich is characterized by agenesis of aicarei-goutieres corpus callosum, spinal skeletal abnormalities, and chorioretinal abnormalities.
Aicardi synddome Goutieres reported 8 cases of progressive familial encephalopathy in infancy, with calcification of the basal ganglia and chronic CSF lymphocytosis, occurring in 5 families and leading rapidly to a vegetative state and early death. The authors considered this to be a distinct type of leukodystrophy transmitted as an autosomal recessive. After a period of apparent normality, evidence of encephalopathy began at age 3 months. CT scan at 9 months showed frontal atrophy, hypodensity in the white matter, and calcification of the lenticular nuclei.
Aicardi–Goutières syndrome | British Medical Bulletin | Oxford Academic
Death occurred before age 4 years. The parents of the boy were known to be consanguineous; they were Muslims living in England. They termed this disorder ‘Cree encephalitis’ and distinguished it from another neurologic condition, Cree leukoencephalopathywhich is a form of leukoencephalopathy with vanishing white matter. Cree encephalitis is characterized by severe psychomotor retardation, progressive microcephaly, cerebral atrophy, white matter attenuation, intracerebral calcification, a CSF lymphocytosis, and systemic immune abnormalities.
In 10 of 11 affected children described, premature death resulted in a median age of Although these features were noted as reminiscent of Aicardi-Goutieres syndrome, the conditions were considered distinct because of the observation of immunologic abnormalities and an apparent susceptibility to infection in Cree encephalitis.
They also noted that 1 affected child reported by Black et al. In a review, Tolmie et al. A raised level of CSF interferon-alpha was noted. All presented from infancy to early childhood with progressive moderate to severe developmental delay, postnatal microcephaly, spastic quadriplegia, refractory seizures, and visual handicap.
CSF pleocytosis was present in 3 children. Neuroimaging of 3 boys and a girl showed generalized cortical atrophy, dilatation of the lateral, third, and fourth ventricles, widening of the surface CSF spaces, hypoplasia of the posterior fossa structures, and multiple and solitary calcifications in the cerebral cortex and punctate calcifications involving basal ganglia, cerebellum, and Sylvian fissure. Histopathologic examination of the brain from 3 boys and 1 girl confirmed generalized cortical and cerebellar atrophy with widespread calcifications within the cortical gray and white matter, the basal ganglia, the cerebellum, and in some areas along the capillaries.
Although this autosomal recessive syndrome showed phenotypic overlap with Aicardi-Goutieres syndrome, Kumar et al. Similar microcephaly and intracranial calcification with developmental delay occurs following intrauterine infection but is distinguishable by purpuric rash and associated thrombocytopenia.
The first boy was normocephalic with normal IQ, aicardi-goutieees had spastic diplegia. Brain imaging aicardi-goutieeres the second year of life showed punctate calcification of the basal ganglia and subcortical white matter and CSF pleocytosis. At 21 months, the second boy had dystonic cerebral palsy, slight fall-off in head growth, and cognitive delay.
Imaging abnormalities were more severe than those syndroke the brother, and CSF examination showed pleocytosis and marked increase in IFN-alpha. Although the clinical course was not progressive, McEntagart et al. So striking were the immunologic abnormalities that the disorder was described as ‘familial systemic lupus erythematosus SLE. All 3 had congenital glaucoma. Additionally, neuroimaging demonstrated significant brainstem atrophy in the affected sib pair.
Mean age at symptom onset was 3. The neurologic symptoms were progressive in the first year of life and stabilized by the end of syncrome second year in 10 patients; 1 patient died of pneumonia at age 18 months. During the follow-up period, 3 patients developed seizures, 2 patients showed some improvement in psychomotor development and communication, and only 1 patient showed clear worsening.
Five patients had skin lesions consistent with acrocyanosis, more commonly in the colder months. Serial brain imaging of 6 patients showed basal ganglia calcifications that were unchanged in 4 patients but increased in 2 patients.
White matter abnormalities remained stable in all 6 patients.
Aicardi-Goutieres Syndrome Information Page
Diffuse cerebral atrophy remained stable in 4 patients but progressed in 2. Serial CSF studies in 3 patients showed reduction of alpha-interferon levels over time, although the level remained elevated in 1 patient.
He presented at age 4 months with developmental delay. MRI showed demyelination, and calcification of the basal ganglia was aicardi-goutirees on CT scan. At age 7 years the patient was profoundly delayed, with no meaningful communication, and was fed by gastrostomy tube.
He demonstrated severe spasticity with dystonic posturing and was microcephalic.
He had never experienced seizures. He had several chilblain-like lesions on his toes and hands and a more generalized patchy mottling of the skin on all aicardi-gotieres limbs and over his trunk. These lesions first developed around the age of 12 months and, while present throughout the year, were significantly worse in the winter.
A standard exonuclease assay indicated close-to-normal TREX1 enzymatic activity. By means of genomewide linkage analysis in families with AGS, Crow et al. The data suggested the existence of locus heterogeneity in this syndrome. Despite the clinical differences and the difference in mode of inheritance, Lee-Kirsch et al.
Some patients with AGS1 have chilblain-like lesions that resemble those found in the large German family with chilblain lupus. Moreover, AGS1 has been suggested to be a form of systemic lupus erythematosus, because of the findings of hypocomplementemia and antinuclear autoantibodies in addition to lupus-like skin lesions in some patients.
In affected members of 10 unrelated families with AGS1, Crow et al. Seven of the families were of European descent. In a patient with Cree encephalitis, born of consanguineous parents, Crow et al.
To define the molecular spectrum of Aicardi-Goutieres syndrome, Rice et al. In 5 families, Rice et al. In 1 child, the disease occurred because of a de novo heterozygous TREX1 mutation In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe arg to his; The year-old girl had relatively mild AGS, and displayed additional features indicative of mitochondrial dysfunction and peripheral neuropathy.
Two clinical presentations could be delineated: Mortality was correlated with genotype; The data from the study of Rice et al. At the level of its clinical presentation, AGS is a notable mendelian mimic of the sequelae of congenital viral infection. These resemblances are so strong as to suggest the likelihood of common mechanisms involved in the pathogenesis of the inherited and the infectious syndromes Crow et al.
Consistent with this notion, both AGS and a number of placentally acquired viral infections are characterized by the production of high levels of interferon-alpha.
That this IFN-alpha may have a pathogenic role in the disease is indicated by the observation that astrocyte-specific chronic overproduction of IFN-alpha in transgenic mice recapitulates the neuropathologic findings seen in AGS Akwa et al.
Crow and Rehwinkel reviewed the pathogenesis of AGS with respect to the phenotypic overlap both with the sequelae of congenital infection and with systemic lupus erythematosus SLE; Experimental evidence suggested that the nucleases defective in AGS are involved in removing endogenously produced nucleic acid species, and that a failure of this removal results in activation of the immune system.
This hypothesis explains the phenotypic overlap of AGS with congenital infection and some aspects of SLE, where an equivalent type I interferon-mediated innate immune response is triggered by viral and self nucleic acids, respectively. Similarly, TREX1 silencing led to reduced proliferation of endothelial cells, but not of cells involved in angiogenesis. A progressive familial encephalopathy in infancy, with calcifications of the basal ganglia, and chronic cerebrospinal fluid lymphocytosis.
Systemic lupus erythematosus or Aicardi-Goutieres syndrome?
Orphanet: Aicardi Goutières syndrome
Transgenic expression of IFN-alpha in the central nervous system of mice protects against lethal neurotropic viral infection but induces inflammation and neurodegeneration.
A second locus for Aicardi-Goutieres syndrome at chromosome 13q Idiopathic familial cerebrovascular ferrocalcinosis Fahr’s disease and review of differential diagnosis of intracranial calcification in children. Encephalitis among Aicardi-gotieres children in northern Quebec. Cree encephalitis is allelic with Aicardi-Goutieres syndrome: Aicardi-Goutieres syndrome displays aicsrdi-goutieres heterogeneity with one locus AGS1 on chromosome 3p Congenital glaucoma and brain stem atrophy as features of Aicardi-Goutieres syndrome.
Aicardi-Goutieres syndrome and related phenotypes: Phenotypic variation in Aicardi-Goutieres syndrome explained by cell-specific IFN-stimulated gene response and cytokine release.
Familial systemic lupus erythematosus and congenital infection-like syndrome. A case of progressive familial encephalopathy in infancy with calcification of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. A de novo p. Recognizable inherited syndrome of progressive central nervous system degeneration and generalized intracranial calcification with overlapping phenotype of the syndrome of Aicardi and Goutieres.
The natural history of Aicardi-Goutieres syndrome: Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p. Familial calcification of the basal ganglia with cerebrospinal fluid pleocytosis. Brain calcification in patients with cerebral lupus.