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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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