Dystonia as a prominent presenting feature in developmental and epileptic encephalopathies: A case series.
Autor: | Dzinovic I; Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany., Škorvánek M; Department of Neurology, P.J. Safarik University, Kosice, Slovak Republic; Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovak Republic., Necpál J; Department of Neurology, Zvolen Hospital, Slovakia., Boesch S; Department of Neurology, Medical University Innsbruck, Innsbruck, Austria., Švantnerová J; Second Department of Neurology, Faculty of Medicine, Comenius University, University Hospital Bratislava, Bratislava, Slovakia., Wagner M; Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany; Technical University of Munich, Munich, Germany; School of Medicine, Institute of Human Genetics., Havránková P; Department of Neurology, Charles University, 1st Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic., Pavelekova P; Department of Neurology, P.J. Safarik University, Kosice, Slovak Republic; Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovak Republic., Haň V; Department of Neurology, P.J. Safarik University, Kosice, Slovak Republic; Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovak Republic., Janzarik WG; Department of Neuropediatrics and Muscle Disorders, University Medical Center, Faculty of Medicine, University of Freiburg, Germany., Berweck S; Ludwig Maximilian University of Munich, Munich, Germany; Hospital for Neuropediatrics and Neurological Rehabilitation, Centre of Epilepsy for Children and Adolescents, Schoen Klinik Vogtareuth, Vogtareuth, Germany., Diebold I; MGZ - Medical Genetics Center Munich, Munich, Germany; Department of Pediatrics, Technical University of Munich School of Medicine, Munich, Germany., Kuster A; Inborn Errors of Metabolism, Pediatric Intensive Care Unit, University Hospital of Nantes, Nantes, France., Jech R; Department of Neurology, Charles University, 1st Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic., Winkelmann J; Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany; Technical University of Munich, Munich, Germany; School of Medicine, Institute of Human Genetics; Lehrstuhl für Neurogenetik, Technische Universität München, Munich, Germany; Munich Cluster for Systems Neurology, SyNergy, Munich, Germany., Zech M; Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany; Technical University of Munich, Munich, Germany; School of Medicine, Institute of Human Genetics. Electronic address: michael.zech@mri.tum.de. |
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Jazyk: | angličtina |
Zdroj: | Parkinsonism & related disorders [Parkinsonism Relat Disord] 2021 Sep; Vol. 90, pp. 73-78. Date of Electronic Publication: 2021 Aug 11. |
DOI: | 10.1016/j.parkreldis.2021.08.007 |
Abstrakt: | Introduction: Although there has been increasing recognition of the occurrence of non-epileptic involuntary movements in developmental and epileptic encephalopathies (DEEs), the spectrum of dystonic presentations associated with these conditions remains poorly described. We sought to expand the catalogue of dystonia-predominant phenotypes in monogenic DEEs, building on the recently introduced concept of an epilepsy-movement disorder spectrum. Methods: Cases were identified from a whole-exome-sequenced cohort of 45 pediatric index patients with complex dystonia (67% sequenced as parent-child trios). Review of molecular findings in DEE-associated genes was performed. For five individuals with identified DEE-causing variants, detailed information about presenting phenotypic features and the natural history of disease was obtained. Results: De-novo pathogenic and likely pathogenic missense variants in GABRA1, GABBR2, GNAO1, and FOXG1 gave rise to infantile-onset persistent and paroxysmal dystonic manifestations, beginning in the limb or truncal musculature and progressing gradually to a generalized state. Coexisting, less prominent movement-disorder symptoms were observed and included myoclonic, ballistic, and stereotypic abnormal movements as well as choreoathetosis. Dystonia dominated over epileptic neurodevelopmental comorbidities in all four subjects and represented the primary indication for molecular genetic analysis. We also report the unusual case of an adult female patient with dystonia, tremor, and mild learning disability who was found to harbor a pathogenic frameshift variant in MECP2. Conclusions: Dystonia can be a leading clinical manifestation in different DEEs. A monogenic basis of disease should be considered on the association of dystonia and developmental delay-epilepsy presentations, justifying a molecular screening for variants in DEE-associated genes. (Copyright © 2021 Elsevier Ltd. All rights reserved.) |
Databáze: | MEDLINE |
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