Aicardi-Goutières syndrome due to a paternal mosaic IFIH1 mutation.

Abstract

Progressive immune-mediated neurodegeneration is a central feature of Aicardi-Goutières syndrome (AGS), a monogenic disorder characterized by chronic activation of antiviral type I interferon (IFN).1 Typically, AGS presents as subacute infancy-onset encephalopathy with microcephaly, leukodystrophy, and basal ganglia calcification, resulting in global developmental delay. AGS is either caused by loss-of-function mutations in TREX1 , RNASEH2B , RNASEH2C , RNASEH2A , SAMHD1 , or ADAR , encoding genes involved in the metabolism of nucleic acids, or by gain-of-function mutations in IFIH1 encoding the cytosolic RNA sensor melanoma differentiation-associated protein 5 (MDA5).1 The phenotypic spectrum of IFIH1 -associated mutations includes intracerebral vasculopathy, bilateral striatal necrosis, and isolated spastic paraparesis. The authors are thankful to the family for participation in this study. The authors thank Diana Federl and Kerstin Engel for excellent technical assistance.