title: Symmetrical thalamic calcification: A trio whole exome sequencing negative series.
abstract: Symmetrical thalamic calcification or bilateral symmetrical thalamic gliosis presents at delivery with hypertonia, fixed flexion contractures and prominent bulbar signs, without preceding perinatal asphyxia. At post-mortem, there is evidence of bilateral symmetrical selective thalamic neuronal encrustation and gliosis. To date, 27 cases are published with no underlying diagnosis identified. Two affected children from singleton pregnancies were reported and therefore, a genetic cause proposed. No previous reports have performed genetic testing to confirm or reject this hypothesis. We report three additional cases of this rare condition, expanding the clinical and pathological phenotype. We performed trio whole exome sequencing, the first in this cohort of patients, and did not identify a pathogenic variant. As postulated in the original report, the likely underlying mechanism is antenatal hypoxia in the third trimester.
authors.affiliation: Department of Neurology and Clinical Neurophysiology, Children's University Hospital, Temple Street, Dublin 1, Ireland; Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Ireland. Electronic address: Kathleen.gorman@cuh.ie.
authors.forename: Kathleen Mary
authors.initials: KM
authors.lastname: Gorman
authors.affiliation: Department of Neuropathology, Beaumont Hospital, Dublin, Ireland.
authors.forename: John James
authors.initials: JJ
authors.lastname: Aird
authors.affiliation: Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Ireland.
authors.forename: Judith
authors.initials: J
authors.lastname: Conroy
authors.affiliation: Department of Pathology, Children's University Hospital, Temple Street, Dublin 1, Ireland.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Devaney
authors.affiliation: Department of Neuropathology, Beaumont Hospital, Dublin, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Farrell
authors.affiliation: Department of Neurology and Clinical Neurophysiology, Children's University Hospital, Temple Street, Dublin 1, Ireland; Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Ireland.
authors.forename: Mary Dolores
authors.initials: MD
authors.lastname: King
mesh_terms: D001927:Brain Diseases / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics; D059472:Exome / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D013788:Thalamus / Q000000981:diagnostic imaging / Q000473:pathology*
keywords: Bilateral symmetrical thalamic gliosis; Symmetrical thalamic calcification; Whole exome sequencing