DOI: 10.1055/a-2321-0597
Short Communication

Neurological Findings and a Brief Review of the Current Literature in a Severe Case of Aicardi-Goutières Syndrome Due to an IFIH1 Mutation

1   Division of Pediatrics, Department of Neonatology, University Medical Centre Ljubljana, Ljubljana, Slovenia
Tina Vipotnik Vesnaver
2   Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
David Neubauer
3   Division of Pediatrics, Adolescent and Developmental Neurology, Department of Child, University Medical Centre Ljubljana, Ljubljana, Slovenia
Aneta Soltirovska-Šalamon
1   Division of Pediatrics, Department of Neonatology, University Medical Centre Ljubljana, Ljubljana, Slovenia
4   Department of Pediatrics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
› Author Affiliations


Aicardi-Goutières syndrome (AGS) is a rare genetic early-onset progressive encephalopathy with variable clinical manifestations. The IFIH1 mutation has been confirmed to be responsible for type I interferon production and activation of the Janus kinase signaling pathway. We herein stress neurological observations and neuroimaging findings in a severe case report of an infant with AGS type 7 due to an IFIH1 mutation who was diagnosed in the first month of life. We also review neurological characteristics of IFIH1 mutations through recent literature.

Publication History

Received: 10 April 2024

Accepted: 06 May 2024

Accepted Manuscript online:
07 May 2024

Article published online:
31 May 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 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 (01) 49-54
  • 2 Oda H, Nakagawa K, Abe J. et al. Aicardi-Goutières syndrome is caused by IFIH1 mutations. Am J Hum Genet 2014; 95 (01) 121-125
  • 3 Rice GI, Del Toro Duany Y, Jenkinson EM. et al. Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling. Nat Genet 2014; 46 (05) 503-509
  • 4 Al Mutairi F, Alfadhel M, Nashabat M. et al. Phenotypic and molecular spectrum of Aicardi-Goutières syndrome: a study of 24 patients. Pediatr Neurol 2018; 78: 35-40
  • 5 Gilani A, Adang LA, Vanderver A, Collins A, Kleinschmidt-DeMasters BK. Neuropathological findings in a case of IFIH1-related Aicardi-Goutières syndrome. Pediatr Dev Pathol 2019; 22 (06) 566-570
  • 6 Crow YJ, Chase DS, Lowenstein Schmidt J. et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A 2015; 167A (02) 296-312
  • 7 Vanderver A, Adang L, Gavazzi F. et al. Janus kinase inhibition in the Aicardi-Goutières syndrome. N Engl J Med 2020; 383 (10) 986-989
  • 8 Adang LA, Gavazzi F, Jawad AF. et al. Development of a neurologic severity scale for Aicardi Goutières syndrome. Mol Genet Metab 2020; 130 (02) 153-160
  • 9 Železnik M, Soltirovska Šalamon A, Debeljak M. et al. Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi-Goutières syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency. Front Immunol 2023; 13: 1033513
  • 10 Rice GI, Park S, Gavazzi F. et al. Genetic and phenotypic spectrum associated with IFIH1 gain-of-function. Hum Mutat 2020; 41 (04) 837-849
  • 11 Adang LA, Frank DB, Gilani A. et al. Aicardi Goutières syndrome is associated with pulmonary hypertension. Mol Genet Metab 2018; 125 (04) 351-358
  • 12 National Center for Biotechnology Information (NCBI). ClinVar [Internet]. Assessed June 16, 2023 at:
  • 13 Crow YJ, Zaki MS, Abdel-Hamid MS. et al. Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia. Neuropediatrics 2014; 45 (06) 386-393
  • 14 Amari S, Tsukamoto K, Ishiguro A, Yanagi K, Kaname T, Ito Y. An extremely severe case of Aicardi-Goutières syndrome 7 with a novel variant in IFIH1. Eur J Med Genet 2020; 63 (02) 103646
  • 15 Funabiki M, Kato H, Miyachi Y. et al. Autoimmune disorders associated with gain of function of the intracellular sensor MDA5. Immunity 2014; 40 (02) 199-212