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LETTER TO EDITOR
Year : 2013  |  Volume : 61  |  Issue : 1  |  Page : 77-78

Aicardi-Goutieres syndrome: A genetic disorder which mimics congenital intrauterine infection


1 Department of Pediatrics, CHILDS Trust Medical Research Foundation, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India
2 Department of Genetics, CHILDS Trust Medical Research Foundation, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India
3 Department of Pediatric Neurology, CHILDS Trust Medical Research Foundation, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India

Date of Submission09-Nov-2012
Date of Decision02-Dec-2012
Date of Acceptance07-Dec-2012
Date of Web Publication4-Mar-2013

Correspondence Address:
Venkateswari Ramesh
Department of Pediatrics, CHILDS Trust Medical Research Foundation, Kanchi Kamakoti CHILDS Trust Hospital, Chennai
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.108018

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How to cite this article:
Ramesh V, Sankar J, Gowrishankar K, Ganapathy K. Aicardi-Goutieres syndrome: A genetic disorder which mimics congenital intrauterine infection. Neurol India 2013;61:77-8

How to cite this URL:
Ramesh V, Sankar J, Gowrishankar K, Ganapathy K. Aicardi-Goutieres syndrome: A genetic disorder which mimics congenital intrauterine infection. Neurol India [serial online] 2013 [cited 2020 Feb 21];61:77-8. Available from: http://www.neurologyindia.com/text.asp?2013/61/1/77/108018


Sir,

Basal ganglia and cortical calcification is commonly found in children with TORCH infection. Aicardi-Goutieres syndrome (AGS), an autosomal recessive disorder presents with multiple intracranial calcifications and can mimic of a congenital viral infection. [1] Misdiagnosis of this condition can result in false counseling of a low risk of recurrence. This report presents two children with AGS confirmed by molecular genetic testing [Table 1].
Table 1: Clinical and lab data of both patients


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AGS is an early onset encephalopathy associated with severe intellectual and physical handicap. The characteristics of this syndrome are microcephaly, bilateral basal ganglia calcification, cerebral white matter abnormalities, cerebrospinal fluid (CSF) lymphocytosis and elevated levels of CSF interferon. [2] The clinical phenotype of AGS resembles sequelae of congenital infection. Presence of microcephaly, neonatal hepatitis, thrombocytopenia, and normal CSF examination generally favors the diagnosis of intrauterine infection. However, prenatal microcephaly, elevation of liver enzymes, and thrombocytopenia have also been reported in children with AGS, [3] suggesting an overlap between the two. Chilblain lesions on the hands, feet [4] and intermittent sterile pyrexias have been reported and can be clues for the diagnosis of AGS.

The hypothesis is that in AGS a defect in DNA damage response results in accumulation of endogenous DNA which triggers the interferon-alpha-mediated immune response. AGS is due to mutations in five genes: TREX1 on chromosome 3 (AGS1); RNaseH2B/FLJ11712 on chromosome 13 (AGS2); RNaseH2C/AYP1 on chromosome 11, (AGS3), and RNaseH2A on chromosome 19 (AGS4 and SAMHD1 mutation). [5] An early onset neonatal form highly reminiscent of congenital infection is seen particularly with TREX1 mutation. [1] Mutations in SAMHD1 are associated with cerebral vasculopathy, suggesting a particular role for this gene in vascular homeostasis. [6][Figure 1]
Figure 1: CT brain showing multiple intracranial calcifications

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Cerebral calcification, white matter abnormalities, and cerebral atrophy are the three cardinal features that are universally described in children with AGS. [1],[7],[8] Calcifications frequently involve the basal ganglia and extend in to the white matter. The extent of calcification does not correlate with neurologic outcome and cases without intracranial calcification also have been reported. [2] CSF lymphocytosis and raised CSF interferon-alpha levels, are features of AGS and can give a clue to the diagnosis. [9] The possibility of this genetic disorder should be considered in children who present with developmental delay and intracranial calcification, with background history of consanguinity.


 » Acknowledgment Top


Our sincere thanks to Prof. Yanick Crow, Professor of Genetic Medicine, University of Manchester, who did the molecular genetic testing for both our patients on a research basis.

 
 » References Top

1.Crow YJ, Livingston JH. Aicardi-Goutieres syndrome: An important mendelian mimic of congenital infection. Dev Med Child Neurol 2008;50:410-6.  Back to cited text no. 1
    
2.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.  Back to cited text no. 2
    
3.Goutières F, Aicardi J, Barth PG, Lebon P. Aicardi-Goutières syndrome: An update and results of interferon-alpha studies. Ann Neurol 1998;44:900-7.  Back to cited text no. 3
    
4.Rice G, Patrick T, Parmar R, Taylor CF, Aeby A, Aicardi J, et al. Clinical and molecular phenotype of Aicardi-Goutières syndrome. Am J Hum Genet 2007;81:713-25.  Back to cited text no. 4
    
5.Crow YJ, Hayward BE, Parmar R, Robins P, Leitch A, Ali M, et al. Mutations in the gene encoding the 3´-5´ DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus. Nat Genet 2006;38:917-20.  Back to cited text no. 5
    
6.Ramesh V, Bernardi B, Stafa A, Garone C, Franzoni E, Abinun M, et al. Intracerebral large artery disease in Aicardi-Goutières syndrome implicates SAMHD1 in vascular homeostasis. Dev Med Child Neurol 2010;52:725-32.  Back to cited text no. 6
    
7.Lanzi G, Fazzi E, D'Arrigo S. Aicardi-Goutières syndrome: A description of 21 new cases and a comparison with the literature. Eur J Paediatr Neurol 2002;6:A9-22.  Back to cited text no. 7
    
8.Goutières F. Aicardi-Goutières syndrome. Brain Dev 2005;27:201-6.  Back to cited text no. 8
    
9.Lebon P, Badoual J, Ponsot G, Goutières F, Hémeury-Cukier F, Aicardi J. Intrathecal synthesis of interferon-alpha in infants with progressive familial encephalopathy. J Neurol Sci 1988;84:201-8.  Back to cited text no. 9
    


    Figures

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    Tables

  [Table 1]

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