Spastic Paraparesis and Marked Improvement of Leukoencephalopathy in Aicardi–Goutières Syndrome

Abstract

Aicardi–Goutières syndrome (AGS) is a rare genetic disorder with inflammatory immune-mediated pathogenesis. Disease onset is most commonly marked by recurrent fevers, irritability, and developmental regression in the 1st year of life. A stable phase characterized by severe spastic quadriparesis and cognitive deficit follows. Brain calcifications, leukoencephalopathy, and cerebral atrophy are the radiological hallmarks of AGS and often show progression over time. We present an atypical patient with late-onset AGS characterized by spastic paraparesis and a leukoencephalopathy that markedly improved during follow-up, demonstrating a nonprogressive disease course and the exceptional amelioration of the white matter abnormalities.

Keywords

Aicardi–Goutières syndrome - leukoencephalopathy - spastic paraparesis

^* Roberta La Piana and Luan T. Tran share first authorship and contributed equally to this manuscript.

• 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 (1) 49-54
• 2 Crow YJ, Hayward BE, Parmar R , et al. Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus. Nat Genet 2006; 38 (8) 917-920
• 3 Crow YJ, Leitch A, Hayward BE , et al. Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection. Nat Genet 2006; 38 (8) 910-916
• 4 Rice GI, Bond J, Asipu A , et al. Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response. Nat Genet 2009; 41 (7) 829-832
• 5 Rice GI, Kasher PR, Forte GM , et al. Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature. Nat Genet 2012; 44 (11) 1243-1248
• 6 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 (5) 503-509
• 7 Rice G, Patrick T, Parmar R , et al. Clinical and molecular phenotype of Aicardi-Goutieres syndrome. Am J Hum Genet 2007; 81 (4) 713-725
• 8 Orcesi S, Pessagno A, Biancheri R , et al. Aicardi-Goutières syndrome presenting atypically as a sub-acute leukoencephalopathy. Eur J Paediatr Neurol 2008; 12 (5) 408-411
• 9 D'Arrigo S, Riva D, Bulgheroni S , et al. Aicardi-Goutières syndrome: description of a late onset case. Dev Med Child Neurol 2008; 50 (8) 631-634
• 10 Orcesi S, La Piana R, Fazzi E. Aicardi-Goutieres syndrome. Br Med Bull 2009; 89: 183-201
• 11 Crow YJ, Livingston JH. Aicardi-Goutières syndrome: an important Mendelian mimic of congenital infection. Dev Med Child Neurol 2008; 50 (6) 410-416
• 12 Uggetti C, La Piana R, Orcesi S, Egitto MG, Crow YJ, Fazzi E. Aicardi-Goutieres syndrome: neuroradiologic findings and follow-up. AJNR Am J Neuroradiol 2009; 30 (10) 1971-1976
• 13 Kothare SV, Pungavkar SA, Patkar DP, Sainani NI, Naik MH, Gadani S. Regression of white matter hypodensities with age in Aicardi-Goutierés syndrome: a case report. Childs Nerv Syst 2006; 22 (11) 1503-1506
• 14 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 (2) 338-342
• 15 Dale RC, Gornall H, Singh-Grewal D, Alcausin M, Rice GI, Crow YJ. Familial Aicardi-Goutières syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures. Am J Med Genet A 2010; 152A (4) 938-942
• 16 Crow YJ, Vanderver A, Orcesi S, Kuijpers TW, Rice GI. Therapies in Aicardi-Goutières syndrome. Clin Exp Immunol 2014; 175 (1) 1-8