Aicardi-Goutieres Syndrome 1, Autosomal Dominant

Alternative Names

  • AGS1
  • AGS
  • Encephalopathy, Familial Infantile, with Intracranial Calcification and Chronic Cerebrospinal Fluid Lymphocytosis
  • Cree Encephalitis
  • Pseudo-Torch Syndrome
  • Pseudotoxoplasmosis Syndrome
  • Aicardi-Goutieres Syndrome, Autosomal Dominant
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WHO-ICD-10 version:2010

Diseases of the nervous system

Cerebral palsy and other paralytic syndromes

OMIM Number

225750

Mode of Inheritance

Autosomal recessive

Gene Map Locus

3p21.31

Description

Aicardi-Goutieres Syndrome (AGS) is a progressive, early onset encephalopathy, which is transmitted in an autosomal recessive manner. AGS is characterized by mental and physical deformations due to calcifications of the basal ganglia, which sometimes extends to the white matter, cerebral atrophy, chronic CSF leukocytosis, and elevated levels of alpha-interferon in the spinal fluid and blood. Other symptoms include microcephaly, feeding difficulties, vomiting, irritability, spasticity, dystonia, cortical blindness, ocular jerks, poor or no eye contact, and lack of progress of motor and social skills. A quarter of the affected patients may show tonic-clonic or focal tonic seizures, while another quarter may present with chilblain-like swellings at the extremities. The condition is a severe one, with 25% of the patients dying before the age of 17-years. Surviving patients generally persist in a vegetative state, with very little contact with their surroundings.

AGS is a genetically heterogeneous disorder. AGS1 (Aicardi-Goutieres Syndrome 1, Autosomal Dominant) is associated with mutations in TREX1 (3-Prime @Repair Exonuclease 1) gene, which encodes an exonuclease that plays a major role in DNA repair. It is postulated that defects in mismatch repair lead to development of AGS.

Epidemiology in the Arab World

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Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
606609.1ArabFemale Microcephaly; Global developmental delay...NM_033629.6:c.341G>AHomozygousAutosomal, RecessiveAl Mutairi et al. 2018

Other Reports

Algeria

Giroud et al. (1986) reported an affected son of consanguineous Algerian parents. After a period of apparent normality, evidence of encephalopathy began at age 3 months. The CT scan at that time was normal, but the CSF showed lymphocytosis (75 cells per cubic mm; 85% lymphocytes). Serologic studies for the TORCH group showed no evidence of infection. CT scan at 9 months showed frontal atrophy, hypodensity in the white matter, and calcification of the lenticular nuclei. Death occurred before age 4 years.

Oman

Koul et al. (2001) reported two siblings with Aicardia-Goutieres syndrome. The patients were born to healthy consanguineous parents and had eight other normal siblings. The first patient, presented at the age of four months with excessive crying for two weeks, milestones regression (lost social smile) and lower limb stiffness. Her head circumference was 37 cm, below third percentile (at birth - 33cm) and she had increased tone and hyperreflexia in the upper and lower limbs with bilateral ankle clonus. There were no neurocutaneous lesions, and her cranial nerves were normal. Investigations which included complete hemogram, serum biochemistry and bone profile, liver and renal functions, TORCH serology, serum creatinine kinase, serum lactate, serum ammonia, brucella antibodies, blood gases, and aminoacidogram as well as an abdominal ultrasound and EEG, were normal. Cerebrospinal fluid examination revealed lymphocytosis and protein of 0.86g/L, but negative culture. Ct brain revealed cortical atrophy, and she was managed with antibiotics as a case of meningitis. Repeat CSF examination revealed persistant lymphocytosis (10/microL), high protein levels (0.59g/L) and negative cultures. After eight years of follow up, her head circumference remained below the third percentile and she became bedridden with severe spasticity and scissoring of the lower limbs along with upper and lower limb contractures. Calcification of the basal ganglia and cerebellum along with cortical atrophy were seen on a repeat CT brain scan. The other sibling presented at the age of five months with excessive crying and lower limb stiffness. Examination revealed an alert boy with a head circumference of 38cm (below third percentile). He had normal cranial nerves, but had bilateral cortical thumb and increased tone in the lower limbs. All investigations done on his sister were repeated on him and were normal. Similar to case one, CSF examination revealed lymphocytosis (11/microlitre) and high protein of 0.75g/l. CT scan of the brain showed calcifications of the basal ganglia and cerebrum. CSF interferon-alpha level was not measured because of unavailability of facilities and lymphocytic choriomeningitis virus infection was not tested in both patients.

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