Hülya MARAŞ-GENÇ, Emek UYUR-YALÇIN, Bülent KARA

Clinical and neuroradiologic variability of Aicardi-Goutiéres syndrome: Two siblings with RNASEH2C mutation and a boy with TREX1 mutation

Uyur-Yalçın E, Maraş-Genç H, Kara B. Clinical and neuroradiologic variability of Aicardi-Goutiéres syndrome: Two siblings with RNASEH2C mutation and a boy with TREX1 mutation. Turk J Pediatr 2015; 57: 504-508.Aicardi-Goutières syndrome (AGS) is a rare, autosomal recessively inherited, immune-mediated neurodevelopmental disorder. The syndrome causes infantileonset progressive encephalopathy characterized by the neuroradiologic features of basal ganglia and periventricular white matter calcification, leucodystrophy and cerebral atrophy. Lymphocytosis and elevated levels of interferon alpha (IFN-alpha) in the cerebrospinal fluid are supplementary findings of AGS. It is frequently misdiagnosed as sequelae of congenital infection (pseudo-TORCH) and mostly recognized later. We describe three AGS cases with different clinical presentation, two male siblings with RNASEH2C mutation and a boy with TREX1 mutation. These cases highlight the importance of considering AGS in the differential diagnosis of unexplained leukoencephalopathy and developmental delay. We suggest to search for intracranial calcification, especially if there are more than one affected cases in a family.

PDF

___

1. Aicardi J, Goutieres F. A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol 1984; 15: 49-54.
2. Aicardi J, Goutières F. Systemic lupus erythematosus or Aicardi-Goutières syndrome? Neuropediatrics 2000; 31: 113.
3. Crow YJ. Aicardi-Goutières Syndrome. 2005 Jun 29 [Updated 2014 Mar 13]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993- 2014. Available from: http://www.ncbi.nlm.nih.gov/ books/NBK1475/
4. Fazzi E, Cattalini M, Orcesi S, et al. Aicardi-Goutiéres syndrome, a rare neurological disease in children: A new autoimmune disorder? Autoimmun Rev 2013; 12: 506-509.
5. Rice G, Patrick T, Parmar R, et al. Clinical and molecular phenotype of Aicardi-Goutières syndrome. Am J Hum Genet 2007; 81: 713-725.
6. Livingston JH, Stivaros S, Warren D, Crow YJ. Intracranial calcification in childhood: a review of aetiologies and recognizable phenotypes. Dev Med Child Neurol 2014; 56: 612-626.
7. Crow YJ, Massey RF, Innes JR, et al. Congenital glaucoma and brain stem atrophy as features of Aicardi-Goutiéres syndrome. Am J Med Genet 2004; 129A: 303-307.
8. Vogt J, Agrawal S, Ibrahim Z, et al. Striking intrafamilial phenotypic variability in Aicardi-Goutières syndrome associated with the recurrent Asian founder mutation in RNASEH2C. Am J Med Genet A 2013; 161A: 338- 342.
9. Lee-Kirsch MA, Wolf C, Günther C. Aicardi-Goutières syndrome: a model disease for systemic autoimmunity. Clin Exp Immunol 2014; 175: 17-24.
10. Lee-Kirsch MA, Chowdhury D, Harvey S et al. A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus. J Mol Med 2007; 85: 531-537.
11. Richards A, van den Maagdenberg AM, Jen JC et al. C-terminal truncations in human 3´-5´ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat Genet 2007; 39: 1068-1070.