Neonatal onset Aicardi-Goutières syndrome with congenital corneal edema, expanding the phenotype

Abstract

Background: Type I interferonopathy is a group of autoinflammatory disorders associated with enhanced type I interferon levels, due to upregulation of activation mechanisms or downregulation of negative feedback. Aicardi-Goutières syndrome (AGS) is one of these conditions, characterized by encephalopathy that usually manifests in late infancy. A rarer presentation that mimics congenital trans-placentally acquired infection or a 'pseudo-TORCH' subtype has been described. Clinical Description: A boy of 36-week gestational age with intrauterine growth restriction, nuchal transparency and a normal antenatal microarray assay, was delivered by cesarean section for oligohydramnios and fetal distress. The baby cried at birth, but developed mild respiratory distress and was neurologically depressed. A congenital infection was considered in view of being hypoplastic small for date with microcephaly, encephalopathy, intracerebral calcifications, multiple congenital heart lesions, and hepatosplenomegaly. Bilateral corneal edema was noted. Management: Supportive treatment was initiated. Mother-baby serology for congenital infections was negative. Various differential diagnoses for pseudo ToRCH presentations were considered and genetic testing planned. Exome sequencing identified a homozygous, single base pair insertion (c. 56_57insG variant) in exon 2 of TREX1 gene on chromosome 3, previously reported in AGS. The baby did not survive, Conclusion: This paper describes the clinical approach that was used to establish diagnosis in a neonate with “pseudo ToRCH” phenotype. It also expands the clinical phenotype of AGS by reporting a hitherto undescribed ocular finding of congenital corneal edema.

Keywords

• corneal edema
• pseudo-torch
• trex1
• type 1 interferonopathy