Pons Calcifications and Striatal Necrosis in ADAR1 Aicardi-Goutières Syndrome.

Abstract

Aicardi-Goutières is an inherited encephalopathy characterized by acquired microcephaly, basal-ganglia calcification, leukodystrophy, cerebral atrophy, and CSF with chronic lymphocytosis and raised interferon-alpha.1 The neuroimage is usually diagnostic, showing basal ganglia and subcortical calcifications on CT and abnormal white matter signal on MRI. The lesions tend to be stable and no treatment is available. A 19-year-old male presented a neurologic condition with pyramidal and extrapyramidal signs associated with cardiomyopathy, livedo, and chilblains that appeared after acute episodes of encephalopathy (age of 2 and 10) precipitated by meningitis vaccine and salmonellosis, followed by neurologic regression and posterior recovering. CT scan (Fig. 1) identified brainstem calcifications (almost confined to the pons), without evident basal ganglia, internal capsule, white matter or dentate nucleus calcifications (faint calcifications could be seen on right putamen). Brain MRI (Fig. 2) showed T2 and T2 FLAIR bilateral hyperintensity on the putamina with atrophy (striatal necrosis), with no white matter signal intensity alterations. The genetic study—WES based gene panel designed for Aicardi-Goutières (including the analysis of MYORG gene)—identified two heterozygous, likely pathogenic, variants in ADAR1 (NM_001111.4:c.577C > G and c.3116A > G). Compound heterozygosity was confirmed by testing both parents, establishing the diagnosis of ADAR1-related Aicardi-Goutières syndrome (Fig. 3). The absence of white matter involvement is described in ADAR1 mutations and further help us to suggest the diagnosis based on image.1, 2 (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique. C.P.: 1A, 1C, 2A A.F.B.: 3B J.F.: 3B M.M.: 1B, 3B The authors confirm that the approval of an institutional review board was not required for this work. The informed consent was waived. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. No funding was used for this work. The authors declare no conflict of interest. No financial disclosures for the previous 12 months to declare.