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Aicardi-Goutieres syndrome

MIM.225750 and MIM.610181

Friday 16 March 2007

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

- Rice G, Patrick T, Parmar R, Taylor CF, Aeby A, Aicardi J, Artuch R, Montalto SA, Bacino CA, Barroso B, Baxter P, Benko WS, Bergmann C, Bertini E, Biancheri R, Blair EM, Blau N, Bonthron DT, Briggs T, Brueton LA, Brunner HG, Burke CJ, Carr IM, Carvalho DR, Chandler KE, Christen HJ, Corry PC, Cowan FM, Cox H, D’Arrigo S, Dean J, De Laet C, De Praeter C, Dery C, Ferrie CD, Flintoff K, Frints SG, Garcia-Cazorla A, Gener B, Goizet C, Goutieres F, Green AJ, Guet A, Hamel BC, Hayward BE, Heiberg A, Hennekam RC, Husson M, Jackson AP, Jayatunga R, Jiang YH, Kant SG, Kao A, King MD, Kingston HM, Klepper J, van der Knaap MS, Kornberg AJ, Kotzot D, Kratzer W, Lacombe D, Lagae L, Landrieu PG, Lanzi G, Leitch A, Lim MJ, Livingston JH, Lourenco CM, Lyall EG, Lynch SA, Lyons MJ, Marom D, McClure JP, McWilliam R, Melancon SB, Mewasingh LD, Moutard ML, Nischal KK, Ostergaard JR, Prendiville J, Rasmussen M, Rogers RC, Roland D, Rosser EM, Rostasy K, Roubertie A, Sanchis A, Schiffmann R, Scholl-Burgi S, Seal S, Shalev SA, Corcoles CS, Sinha GP, Soler D, Spiegel R, Stephenson JB, Tacke U, Tan TY, Till M, Tolmie JL, Tomlin P, Vagnarelli F, Valente EM, Van Coster RN, Van der Aa N, Vanderver A, Vles JS, Voit T, Wassmer E, Weschke B, Whiteford ML, Willemsen MA, Zankl A, Zuberi SM, Orcesi S, Fazzi E, Lebon P, Crow YJ. Clinical and molecular phenotype of Aicardi-Goutieres syndrome. Am J Hum Genet. 2007 Oct;81(4):713-25. PMID: 17846997