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The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood
Pathogenic variants in PRRT2, encoding the proline-rich transmembrane protein 2, have been associated with an evolving spectrum of paroxysmal neurologic disorders. Based on a cohort of children with PRRT2-related infantile epilepsy, this study aimed at delineating the broad clinical spectrum of PRRT...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719266/ https://www.ncbi.nlm.nih.gov/pubmed/33126500 http://dx.doi.org/10.3390/biomedicines8110456 |
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author | Döring, Jan Henje Saffari, Afshin Bast, Thomas Brockmann, Knut Ehrhardt, Laura Fazeli, Walid Janzarik, Wibke G. Kluger, Gerhard Muhle, Hiltrud Møller, Rikke S. Platzer, Konrad Santos, Joana Larupa Bache, Iben Bertsche, Astrid Bonfert, Michaela Borggräfe, Ingo Broser, Philip J. Datta, Alexandre N. Hammer, Trine Bjørg Hartmann, Hans Hasse-Wittmer, Anette Henneke, Marco Kühne, Hermann Lemke, Johannes R. Maier, Oliver Matzker, Eva Merkenschlager, Andreas Opp, Joachim Patzer, Steffi Rostasy, Kevin Stark, Birgit Strzelczyk, Adam von Stülpnagel, Celina Weber, Yvonne Wolff, Markus Zirn, Birgit Hoffmann, Georg Friedrich Kölker, Stefan Syrbe, Steffen |
author_facet | Döring, Jan Henje Saffari, Afshin Bast, Thomas Brockmann, Knut Ehrhardt, Laura Fazeli, Walid Janzarik, Wibke G. Kluger, Gerhard Muhle, Hiltrud Møller, Rikke S. Platzer, Konrad Santos, Joana Larupa Bache, Iben Bertsche, Astrid Bonfert, Michaela Borggräfe, Ingo Broser, Philip J. Datta, Alexandre N. Hammer, Trine Bjørg Hartmann, Hans Hasse-Wittmer, Anette Henneke, Marco Kühne, Hermann Lemke, Johannes R. Maier, Oliver Matzker, Eva Merkenschlager, Andreas Opp, Joachim Patzer, Steffi Rostasy, Kevin Stark, Birgit Strzelczyk, Adam von Stülpnagel, Celina Weber, Yvonne Wolff, Markus Zirn, Birgit Hoffmann, Georg Friedrich Kölker, Stefan Syrbe, Steffen |
author_sort | Döring, Jan Henje |
collection | PubMed |
description | Pathogenic variants in PRRT2, encoding the proline-rich transmembrane protein 2, have been associated with an evolving spectrum of paroxysmal neurologic disorders. Based on a cohort of children with PRRT2-related infantile epilepsy, this study aimed at delineating the broad clinical spectrum of PRRT2-associated phenotypes in these children and their relatives. Only a few recent larger cohort studies are on record and findings from single reports were not confirmed so far. We collected detailed genetic and phenotypic data of 40 previously unreported patients from 36 families. All patients had benign infantile epilepsy and harbored pathogenic variants in PRRT2 (core cohort). Clinical data of 62 family members were included, comprising a cohort of 102 individuals (extended cohort) with PRRT2-associated neurological disease. Additional phenotypes in the cohort of patients with benign sporadic and familial infantile epilepsy consist of movement disorders with paroxysmal kinesigenic dyskinesia in six patients, infantile-onset movement disorders in 2 of 40 individuals, and episodic ataxia after mild head trauma in one girl with bi-allelic variants in PRRT2. The same girl displayed a focal cortical dysplasia upon brain imaging. Familial hemiplegic migraine and migraine with aura were reported in nine families. A single individual developed epilepsy with continuous spikes and waves during sleep. In addition to known variants, we report the novel variant c.843G>T, p.(Trp281Cys) that co-segregated with benign infantile epilepsy and migraine in one family. Our study highlights the variability of clinical presentations of patients harboring pathogenic PRRT2 variants and expands the associated phenotypic spectrum. |
format | Online Article Text |
id | pubmed-7719266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77192662020-12-07 The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood Döring, Jan Henje Saffari, Afshin Bast, Thomas Brockmann, Knut Ehrhardt, Laura Fazeli, Walid Janzarik, Wibke G. Kluger, Gerhard Muhle, Hiltrud Møller, Rikke S. Platzer, Konrad Santos, Joana Larupa Bache, Iben Bertsche, Astrid Bonfert, Michaela Borggräfe, Ingo Broser, Philip J. Datta, Alexandre N. Hammer, Trine Bjørg Hartmann, Hans Hasse-Wittmer, Anette Henneke, Marco Kühne, Hermann Lemke, Johannes R. Maier, Oliver Matzker, Eva Merkenschlager, Andreas Opp, Joachim Patzer, Steffi Rostasy, Kevin Stark, Birgit Strzelczyk, Adam von Stülpnagel, Celina Weber, Yvonne Wolff, Markus Zirn, Birgit Hoffmann, Georg Friedrich Kölker, Stefan Syrbe, Steffen Biomedicines Article Pathogenic variants in PRRT2, encoding the proline-rich transmembrane protein 2, have been associated with an evolving spectrum of paroxysmal neurologic disorders. Based on a cohort of children with PRRT2-related infantile epilepsy, this study aimed at delineating the broad clinical spectrum of PRRT2-associated phenotypes in these children and their relatives. Only a few recent larger cohort studies are on record and findings from single reports were not confirmed so far. We collected detailed genetic and phenotypic data of 40 previously unreported patients from 36 families. All patients had benign infantile epilepsy and harbored pathogenic variants in PRRT2 (core cohort). Clinical data of 62 family members were included, comprising a cohort of 102 individuals (extended cohort) with PRRT2-associated neurological disease. Additional phenotypes in the cohort of patients with benign sporadic and familial infantile epilepsy consist of movement disorders with paroxysmal kinesigenic dyskinesia in six patients, infantile-onset movement disorders in 2 of 40 individuals, and episodic ataxia after mild head trauma in one girl with bi-allelic variants in PRRT2. The same girl displayed a focal cortical dysplasia upon brain imaging. Familial hemiplegic migraine and migraine with aura were reported in nine families. A single individual developed epilepsy with continuous spikes and waves during sleep. In addition to known variants, we report the novel variant c.843G>T, p.(Trp281Cys) that co-segregated with benign infantile epilepsy and migraine in one family. Our study highlights the variability of clinical presentations of patients harboring pathogenic PRRT2 variants and expands the associated phenotypic spectrum. MDPI 2020-10-28 /pmc/articles/PMC7719266/ /pubmed/33126500 http://dx.doi.org/10.3390/biomedicines8110456 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Döring, Jan Henje Saffari, Afshin Bast, Thomas Brockmann, Knut Ehrhardt, Laura Fazeli, Walid Janzarik, Wibke G. Kluger, Gerhard Muhle, Hiltrud Møller, Rikke S. Platzer, Konrad Santos, Joana Larupa Bache, Iben Bertsche, Astrid Bonfert, Michaela Borggräfe, Ingo Broser, Philip J. Datta, Alexandre N. Hammer, Trine Bjørg Hartmann, Hans Hasse-Wittmer, Anette Henneke, Marco Kühne, Hermann Lemke, Johannes R. Maier, Oliver Matzker, Eva Merkenschlager, Andreas Opp, Joachim Patzer, Steffi Rostasy, Kevin Stark, Birgit Strzelczyk, Adam von Stülpnagel, Celina Weber, Yvonne Wolff, Markus Zirn, Birgit Hoffmann, Georg Friedrich Kölker, Stefan Syrbe, Steffen The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood |
title | The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood |
title_full | The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood |
title_fullStr | The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood |
title_full_unstemmed | The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood |
title_short | The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood |
title_sort | phenotypic spectrum of prrt2-associated paroxysmal neurologic disorders in childhood |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719266/ https://www.ncbi.nlm.nih.gov/pubmed/33126500 http://dx.doi.org/10.3390/biomedicines8110456 |
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