1. Clinical and pathologic features of Aicardi-Goutières syndrome due to an IFIH1 mutation: A pediatric case report
- Author
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Florent Marguet, Thierry Frebourg, Olivier Quenez, Annie Laquerrière, Catherine Vanhulle, Alice Goldenberg, Clémentine Dumant-Forest, Philippe Flahaut, Myriam Vezain, Isabelle Tournier, Françoise Charbonnier, Gaël Nicolas, Anne-Marie Guerrot, and Soumeya Bekri
- Subjects
0301 basic medicine ,Male ,Pediatrics ,medicine.medical_specialty ,Interferon-Induced Helicase, IFIH1 ,Adolescent ,Encephalopathy ,Neuropathology ,Nervous System Malformations ,03 medical and health sciences ,0302 clinical medicine ,Autoimmune Diseases of the Nervous System ,Genetics ,Medicine ,Humans ,Medical history ,Chilblains ,Exome ,Genetics (clinical) ,Exome sequencing ,Paraplegia ,Brain Diseases ,business.industry ,Infant, Newborn ,medicine.disease ,030104 developmental biology ,Mutation ,Etiology ,Aicardi–Goutières syndrome ,business ,030217 neurology & neurosurgery - Abstract
We describe the case of a young patient with calcifying encephalopathy, born to asymptomatic parents. An extensive hypothesis-driven etiological assessment was performed and failed to detect the precise etiology during many years. We therefore decided to perform whole exome sequencing of the child-unaffected parents trio. A de novo pathogenic variant in the IFIH1 gene which has recently been shown to cause autosomal dominant forms of Aicardi-Goutieres syndrome was identified. This child presented with a severe form with neonatal thrombocytopenia and hepatomegaly, the latter having been detected during late gestation. Although first milestones were uneventful, he progressively lost motor skills from the age of 12 months and developed severe spastic paraplegia. Brain imaging revealed white matter abnormalities and extensive calcifications. He also presented atypical skin lesions, different from chilblains. His medical history was marked by two episodes of acute pancreatitis. We provide herein the results of pathological examination including detailed description of the neuropathological hallmarks. To our knowledge, this the first detailed clinico-pathological description of a patient with an IFIH1 pathogenic variant.
- Published
- 2015