Severe Epilepsy and Movement Disorder May Be Early Symptoms of TMEM106B -Related Hypomyelinating Leukodystrophy.

Autor:	Solazzi R; Department of Pediatric Neuroscience (R.S., T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Member of the ERN EpiCARE, Milan, Italy; Neuroradiology Unit (M.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Department of Biomedical Sciences for Health (M.M.), University of Milan, Italy; Neurophysiology Unit (D.R.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Integrated Diagnostics for Epilepsy (L.C.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; and Medical Genetics Laboratory (L.P., M.I.), ASST Papa Giovanni XXIII, Bergamo, Italy., Moscatelli M; Department of Pediatric Neuroscience (R.S., T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Member of the ERN EpiCARE, Milan, Italy; Neuroradiology Unit (M.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Department of Biomedical Sciences for Health (M.M.), University of Milan, Italy; Neurophysiology Unit (D.R.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Integrated Diagnostics for Epilepsy (L.C.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; and Medical Genetics Laboratory (L.P., M.I.), ASST Papa Giovanni XXIII, Bergamo, Italy., Sebastiano DR; Department of Pediatric Neuroscience (R.S., T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Member of the ERN EpiCARE, Milan, Italy; Neuroradiology Unit (M.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Department of Biomedical Sciences for Health (M.M.), University of Milan, Italy; Neurophysiology Unit (D.R.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Integrated Diagnostics for Epilepsy (L.C.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; and Medical Genetics Laboratory (L.P., M.I.), ASST Papa Giovanni XXIII, Bergamo, Italy., Canafoglia L; Department of Pediatric Neuroscience (R.S., T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Member of the ERN EpiCARE, Milan, Italy; Neuroradiology Unit (M.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Department of Biomedical Sciences for Health (M.M.), University of Milan, Italy; Neurophysiology Unit (D.R.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Integrated Diagnostics for Epilepsy (L.C.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; and Medical Genetics Laboratory (L.P., M.I.), ASST Papa Giovanni XXIII, Bergamo, Italy., Pezzoli L; Department of Pediatric Neuroscience (R.S., T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Member of the ERN EpiCARE, Milan, Italy; Neuroradiology Unit (M.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Department of Biomedical Sciences for Health (M.M.), University of Milan, Italy; Neurophysiology Unit (D.R.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Integrated Diagnostics for Epilepsy (L.C.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; and Medical Genetics Laboratory (L.P., M.I.), ASST Papa Giovanni XXIII, Bergamo, Italy., Iascone M; Department of Pediatric Neuroscience (R.S., T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Member of the ERN EpiCARE, Milan, Italy; Neuroradiology Unit (M.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Department of Biomedical Sciences for Health (M.M.), University of Milan, Italy; Neurophysiology Unit (D.R.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Integrated Diagnostics for Epilepsy (L.C.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; and Medical Genetics Laboratory (L.P., M.I.), ASST Papa Giovanni XXIII, Bergamo, Italy., Granata T; Department of Pediatric Neuroscience (R.S., T.G.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Member of the ERN EpiCARE, Milan, Italy; Neuroradiology Unit (M.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Department of Biomedical Sciences for Health (M.M.), University of Milan, Italy; Neurophysiology Unit (D.R.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Integrated Diagnostics for Epilepsy (L.C.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; and Medical Genetics Laboratory (L.P., M.I.), ASST Papa Giovanni XXIII, Bergamo, Italy.
Jazyk:	angličtina
Zdroj:	Neurology. Genetics [Neurol Genet] 2022 Aug 29; Vol. 8 (5), pp. e200022. Date of Electronic Publication: 2022 Aug 29 (Print Publication: 2022).
DOI:	10.1212/NXG.0000000000200022
Abstrakt:	Objective: To report the clinical presentation of the first Italian child affected by hypomyelinating leukodystrophy (HLD) associated with the recurrent variant p.Asp252Asn in the TMEM106B gene. Methods: The methods included clinical case description, neurophysiologic assessment, brain MRI, and whole-exome sequencing (WES). Results: The child presented soon after birth with nystagmus and hyperkinetic movement disorder. Focal seizures appeared from 2 months of age and recurred at high frequency, despite several antiseizure medications, and focal epileptic status frequently required IV phenytoin. Control of seizures was achieved at the age of 8 months by the association of high doses of sodium blockers. Clinical picture worsened over time and was characterized by axial hypotonia, failure to thrive requiring gastrostomy, pyramidal sings, and severe secondary microcephaly. MRI performed at ages 2, 6, and 20 months showed diffuse supratentorial and subtentorial hypomyelination; multimodal evoked potentials showed increased latency. WES performed at 6 months of age identified the p.Asp252Asn de novo variant in the TMEM106B gene. Discussion: Hyperkinetic movement disorders and seizures may be early symptoms of TMEM106B -HLD. Our observation, supported by video EEG recordings, emphasizes that seizures may be difficult to recognize from movement disorders and that epilepsy may be a severe and prominent symptom of the disease. TMEM106B -HLD should be considered in the genetic screening of infants with early-onset seizures and movement disorders. (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Databáze:	MEDLINE
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