Aicardi–Goutières syndrome (AGS) is an autosomal recessive disease that mimics congenital viral infection and mainly affects the brain, immune system, and skin. The dominant clinical symptom is the subacute onset of severe encephalopathy, which manifests as irritability, loss of ability, slowing of head growth, and poor nutrition. Arteriopathy in AGS is an uncommon manifestation usually associated with mutations in the SAMHD1 gene. We present a rare case of a 3-year-old male due to failure to thrive, global developmental delay, microcephaly, poor vision, upper and lower limbs spasticity, and gastroesophageal reflux disease (GERD), who harbored early stenotic lesions of the large and medium intracranial arteries with ischemic sequelae in the early postnatal life. Performed genetic testing confirmed homozygous gene mutation, SAMHD1 associated with AGS type 5. By reviewing the available literature, we were able to find only one patient whose arterial lesions were diagnosed after 6 months.
WintermarkMHillsNKdeVeberGA, et al.VIPS Investigators. Arteriopathy diagnosis in childhood of the Vascular Effects of Infection in Pediatric Stroke study. Stroke2014; 45: 3597–3605.
5.
GoyalPMalhotraAAlmastJ, et al.Neuroimaging of Pediatric Arteriopathies. J Neuroimaging2019; 29: 1–22. DOI: 10.1111/jon.12614
6.
HenricksonMWangH. Tocilizumab reverses cerebral vasculopathy in a patient with homozygous SAMHD1 mutation. Clin Rheumatol2017; 36: 1445–1451. DOI: 10.1007/s10067-017-3600-2
7.
RameshVBernardiBStafaA, et al.Intracerebral large artery disease in Aicardi-Goutieres syndrome implicates SAMHD1 in vascular homeostasis. Dev Med Child Neurol2010; 52: 725–732.
8.
ThieleHdu MoulinMMBarczykK, et al.Cerebral arterial stenoses and stroke: Novel features of Aicardi-Goutières syndrome caused by the Arg164X mutation in SAMHD1 Are associated with altered cytokine expression. Human Mutation Mutation in Brief2010; 31: E1836–E1850.
9.
BarritS. An Aicardi-Goutières syndrome associated with a quasi-Moyamoya by a biallelic mutation in SAMHD1. Rev Med Brux2018; 39(3): 155–160. DOI: 10.30637/2018.16-030
10.
WuCCPengSSFLeeWT. Intracerebral large artery disease in Aicardi-Goutières syndrome with TREX1 mutation: a case report. Neurol Sci2020; 41(11): 3353–3356. DOI: 10.1007/s10072-020-04516-0
11.
BrarJSVermaRAl-OmariM, et al.Moyamoya Syndrome in an Infant with Aicardi– Goutières and Williams Syndromes. A Case Repor Neuropediatrics2021; 53(3): 204–207. DOI: 10.1055/s-0041-1739131
12.
XinBJonesSPuffenbergerEG, et al.Homozygous mutation in SAMHD1 gene causes cerebral vasculopathy and early onset stroke. Proc Natl Acad Sci U S A2011; 108: 5372–5377. DOI: 10.1073/pnas.1014265108
13.
du MoulinMNürnbergPCrowYJ, et al.Cerebral vasculopathy is a common feature in Aicardi-Goutieres syndrome associated with SAMHD1 mutations. Proc Natl Acad SciU S A2011; 108(26): E232.
14.
XinBLiWBrightA, et al.Reply to du Moulin et al.: Cerebral vasculopathy is a common hallmark in individuals. Proc Natl Acad Sci U S A2011; 108(26): E233.
15.
RiceG IBondJAsipuA, et al.Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as a regulator of the innate immune response. Nature Genet2009; 41: 829–832.
16.
DaleR CGornallHSingh-GrewalD, et al.Familial Aicardi-Goutieres syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures. Am J Med Genet2010; 152A: 938–942.
17.
CrowYJChaseDSLowenstein SchmidtJ, et al.Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet Part A2015; 167: 296–312.
18.
SamantaDand Ramakrishnaiah R. recurrent encephalopathy with spinal cord involvement: an atypical manifestation of Aicardi–Goutières syndromeannals of Indian Academy of Neurology. Ann Indian Acad Neurol2019; 22(1): 111–115. DOI: 10.4103/aian.AIAN_12_18
Coggins SiAAMahboubiBSchinaziRF, et al.SAMHD1 functions and human diseases. Viruses202012(4): 382 doi:10.3390/v1204038.
21.
Leshinsky-SilverEMalingerBen-SiraL, et al.A large homozygous deletion in the SAMHD1 gene causes atypical Aicardi-Goutieres syndrome associated with mtDNA deletions. Europ J Hum Genet2011; 19: 287–292.
22.
HaskellGTMoriMPowellC, et al.Combination of exome sequencing and immune testing confirms Aicardi–Goutieres syndrome type 5 in a challenging pediatric neurology case. Cold Spring Harb Mol Case Stud2018; 4: a002758.
23.
WintermarkMHillsNKDeVeberGA, et al.Clinical and imaging characteristics of arteriopathy subtypes in children with arterial ischemic stroke: results of the VIPS Study. AJNR Am J Neuroradiol2017; 38: 2172–2179.
24.
SebireGFullertonHRiouE, et al.Toward the definition of cerebral arteriopathies of childhood. Curr Opin Pediatr2004; 16: 617–622.
25.
ChabrierSRodeschGLasjauniasP, et al.Transient cerebral arteriopathy: a disorder recognized by serial angiograms in children with stroke. J Child Neurol1998; 13: 27–32.
26.
YeonJYShinHJ. Nonprogressive unilateral intracranial arteriopathy in children with Arterial ischemic stroke. J Korean Neurosurg Soc2015; 57(6): 401–407.
GuerreiroCBellD. Focal cerebral arteriopathy of childhood. Reference article, Radiopaedia.org., DOI: 10.53347/rID-88592, (accessed 14 October 2022).
29.
FullertonHJStenceNHillsNK, et al.Focal cerebral arteriopathy of childhood: novel severity score and natural history. Stroke2018; 49(11): 2590–2596. DOI: 10.1161/STROKEAHA.118.021556
30.
Amlie-LefondCBernardTJSébireG, et al.Predictors of cerebral arteriopathy in children with arterial ischemic stroke: results of the international pediatric stroke study. Circulation2009; 119: 1417–1423.
31.
BernardTJManco-JohnsonMJLoW, et al.Towards a consensus-based classification of childhood arterial ischemic stroke. Stroke2012; 43: 371–377.
