Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review

Aicardi-Goutières Syndrome

Yanick J Crow  1   2
Margaret P Adam, Jerry Feldman, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Anne Amemiya
, editors.
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].
Affiliations
Free Books & Documents
Review

Aicardi-Goutières Syndrome

Yanick J Crow.
Free Books & Documents

Excerpt

Clinical characteristics: Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical disability. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with pathogenic variants in the AGS-related genes is not yet known.

Diagnosis/testing: The diagnosis of AGS is established in a proband with typical clinical findings and characteristic abnormalities on cranial CT (calcification of the basal ganglia and white matter) and MRI (leukodystrophic changes); AND/OR by identification of one of the following:

  1. Biallelic pathogenic variants in ADAR, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, or TREX1

  2. Specific heterozygous autosomal dominant pathogenic variants in TREX1 and ADAR

  3. A variety of heterozygous autosomal dominant pathogenic variants in IFIH1

Management: Treatment of manifestations: Chest physiotherapy and treatment of respiratory complications; attention to diet and feeding methods to assure adequate caloric intake and avoid aspiration; management of seizures using standard protocols.

Surveillance: Monitoring for signs of diabetes insipidus in the neonatal period; repeat ophthalmologic examinations at least for the first few years of life to evaluate for evidence of glaucoma; monitoring for evidence of scoliosis, insulin-dependent diabetes mellitus, and hypothyroidism.

Genetic counseling: AGS is most frequently inherited in an autosomal recessive manner; in a few instances the disease can result from specific de novo or inherited autosomal dominant pathogenic variants in ADAR or TREX1, and a variety of heterozygous autosomal dominant pathogenic variants in IFIH1. At conception, each sib of an affected individual with autosomal recessive AGS has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Individuals with AGS do not typically reproduce. Once the pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk for AGS, and preimplantation genetic testing are possible.

PubMed Disclaimer

Similar articles

  • Adenosine Deaminase Deficiency.
    Hershfield M, Tarrant T. Hershfield M, et al. 2006 Oct 3 [updated 2024 Mar 7]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2006 Oct 3 [updated 2024 Mar 7]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301656 Free Books & Documents. Review.
  • Megalencephalic Leukoencephalopathy with Subcortical Cysts.
    Min R, Abbink TEM, van der Knaap MS. Min R, et al. 2003 Aug 11 [updated 2023 Jul 27]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2003 Aug 11 [updated 2023 Jul 27]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301707 Free Books & Documents. Review.
  • Citrullinemia Type I.
    Quinonez SC, Lee KN. Quinonez SC, et al. 2004 Jul 7 [updated 2022 Aug 18]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2004 Jul 7 [updated 2022 Aug 18]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301631 Free Books & Documents. Review.
  • Permanent Neonatal Diabetes Mellitus.
    De León DD, Pinney SE. De León DD, et al. 2008 Feb 8 [updated 2024 Nov 14]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2008 Feb 8 [updated 2024 Nov 14]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301620 Free Books & Documents. Review.
  • Shwachman-Diamond Syndrome.
    Nelson A, Myers K. Nelson A, et al. 2008 Jul 17 [updated 2024 Sep 19]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2008 Jul 17 [updated 2024 Sep 19]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301722 Free Books & Documents. Review.
See all similar articles

References

    1. Abdel-Salam GM, Zaki MS, Saleem SN, Gaber KR. Microcephaly, malformation of brain development and intracranial calcification in sibs: pseudo-TORCH or a new syndrome. Am J Med Genet A. 2008;146A:2929–36. - PubMed
    1. Abe J, Izawa K, Nishikomori R, Awaya T, Kawai T, Yasumi T, Hiragi N, Hiragi T, Ohshima Y, Heike T. Heterozygous TREX1 p.Asp18Asn mutation can cause variable neurological symptoms in a family with Aicardi-Goutieres syndrome/familial chilblain lupus. Rheumatology (Oxford) 2013;52:406–8. - PubMed
    1. Abe J, Nakamura K, Nishikomori R, Kato M, Mitsuiki N, Izawa K, Awaya T, Kawai T, Yasumi T, Toyoshima I, Hasegawa K, Ohshima Y, Hiragi T, Sasahara Y, Suzuki Y, Kikuchi M, Osaka H, Ohya T, Ninomiya S, Fujikawa S, Akasaka M, Iwata N, Kawakita A, Funatsuka M, Shintaku H, Ohara O, Ichinose H, Heike T. A nationwide survey of Aicardi-Goutieres syndrome patients identifies a strong association between dominant TREX1 mutations and chilblain lesions: Japanese cohort study. Rheumatology (Oxford) 2014;53:448–58. - PubMed
    1. Aicardi J, Goutières F. A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol. 1984;15:49–54. - PubMed
    1. Aicardi J, Goutières F. Systemic lupus erythematosus or Aicardi-Goutieres syndrome? Neuropediatrics. 2000;31:113. - PubMed