Recurrent encephalopathy with spinal cord involvement: An atypical manifestation of Aicardi-Goutières syndrome

• Published in: Annals of the Indian Academy of Neurology Vol. 22; no. 1; pp. 111 - 115
• Main Authors: Samanta, Debopam, Ramakrishnaiah, Raghu
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01-01-2019; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Acute necrotizing encephalopathy; ADAR gene; ADAR mutation; Age; Aicardi–Goutières syndrome; Atrophy; Bone marrow; Calcification; Calcification (ectopic); Care and treatment; Case Report; Case studies; Cerebellum; Complications and side effects; Consent; Convulsions & seizures; Development and progression; Disease; dyschromatosis symmetrica hereditaria; Dystonia; Encephalitis; Encephalopathy; Enzymes; Family medical history; Gangrene; Genes; Genetic screening; Infections; Influenza; Influenza B; influenza encephalopathy; Liver diseases; Magnetic resonance imaging; Mesencephalon; Microencephaly; Mutation; Myelosuppression; Neonates; Neostriatum; Neuroimaging; NMR; Nuclear magnetic resonance; Patients; Phenotypes; Pons; Proteins; Seizures; Skin diseases; Spectrum analysis; Spinal cord; Spinal cord diseases; Thalamus; dyschromatosis symmetrica hereditaria; Acute necrotizing encephalopathy; ADAR mutation; Aicardi-Goutières syndrome; influenza encephalopathy; Aicardi–Goutières syndrome
• ISSN: 0972-2327; 1998-3549
• DOI: 10.4103/aian.AIAN_12_18

Aicardi-Goutières syndrome (AGS) is a rare, genetic inflammatory disease due to mutations in any of the seven genes discovered to date (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1). Clinical onset is seen most commonly in utero or in infancy; irritability, feeding difficulties, jitteriness, microcephaly, abnormal movements, seizures, bone marrow suppression, and liver dysfunction are seen either during the neonatal age group or within the first few months of life with abrupt onset of neurologic regression and slowing of head growth. Diffusely abnormal white matters with swelling of frontal or temporal lobes, cerebral atrophy, and intracranial calcification are typical neuroradiologic abnormalities. However, ADAR mutation, a recently discovered AGS gene, can cause late-onset acute or subacute onset of severe dystonia and features of bilateral striatal necrosis on neuroimaging, in the absence of other typical features of AGS. We report a detailed description of a 5-year-old boy who had a recurrent encephalopathic presentation in the setting of infection. Magnetic resonance imaging (MRI) of brain revealed prominent and fairly symmetrical signal abnormalities in the cerebellar peduncles, thalamus, midbrain, and pons. His throat swab was positive for influenza B, and he was initially diagnosed with influenza encephalopathy. He had a recurrence after 18 months of his initial presentation, and his brain MRI showed extensive areas of signal abnormality similar to, but more extensive than, his previous scan. Extensive spinal cord swelling was also seen. His chronic skin finding was recognized as dyschromatosis symmetrica hereditaria (DSH), and genetic testing revealed compound heterozygous mutations of ADAR gene - causative for AGS. This is the first presentation of recurrent acute encephalopathy in the setting of documented ADAR mutation with the longest interval documented between two acute presentations. This is also the first documentation of extensive spinal cord involvement, which will expand its phenotype. This case also highlights the importance of early identification of DSH, a subtle but characteristic skin lesion of ADAR mutations, for prompt diagnosis of this rare condition.