Aicardi-Goutieres syndrome

Definition: Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection.

AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3’—>5’ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex (RNASEH2A, RNASEH2B, and RNASEH2C).

This autosomal recessive disease is allelic to Cree encephalitis (MIM.608505) and pseudo-TORCH syndrome (MIM.251290) .

Types

 Aicardi-Goutieres syndrome type 1 (AGS1) is caused by mutation in the TREX1 gene (MIM.606605) at 3p21

 Aicardi-Goutieres syndrome type 2 (AGS2) is caused by mutation in the gene encoding subunit B of ribonuclease H2 (RNASEH2B)(MIM.610326) at 13q14-q21

Synopsis

 onset within first year of life
 rapidly progressive to persistent vegetative state or death
 death within first year of life in 25%
 acquired and progressive microcephaly
 acrocyanosis of the feet in some patients
 chilblains
 progressive encephalopathy
 profound developmental retardation
 truncal hypotonia
 tetraplegic spasticity
 dystonia
 visual inattention
 abnormal eye movements
 seizures
 progressive cerebral atrophy
 bilateral, symmetric intracerebral calcifications, especially in the basal ganglia and periventricular areas
 deep white matter hypodensities
 leukoencephalopathy
 no evidence of common prenatal infections

Etiology

 germline mutations in

• the gene TREX1 encoding the 3’—>5’ exonuclease TREX1
• the genes encoding the three subunits of the RNASEH2 endonuclease complex (RNASEH2A, RNASEH2B, and RNASEH2C).

Laboratory

 Increased serum alpha-interferon (IFNA1) (MIM.147660)
 Increased CSF alpha-interferon
 CSF lymphocytosis

References

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