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The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood

Authors :
Doering, Jan Henje
Saffari, Afshin
Bast, Thomas
Brockmann, Knut
Ehrhardt, Laura
Fazeli, Walid
Janzarik, Wibke G.
Kluger, Gerhard
Muhle, Hiltrud
Moller, Rikke S.
Platzer, Konrad
Santos, Joana Larupa
Bache, Iben
Bertsche, Astrid
Bonfert, Michaela
Borggraefe, Ingo
Broser, Philip J.
Datta, Alexandre N.
Hammer, Trine Bjorg
Hartmann, Hans
Hasse-Wittmer, Anette
Henneke, Marco
Kuehne, Hermann
Lemke, Johannes R.
Maier, Oliver
Matzker, Eva
Merkenschlager, Andreas
Opp, Joachim
Patzer, Steffi
Rostasy, Kevin
Stark, Birgit
Strzelczyk, Adam
von Stuelpnagel, Celina
Weber, Yvonne
Wolff, Markus
Zirn, Birgit
Hoffmann, Georg Friedrich
Koelker, Stefan
Syrbe, Steffen
Doering, Jan Henje
Saffari, Afshin
Bast, Thomas
Brockmann, Knut
Ehrhardt, Laura
Fazeli, Walid
Janzarik, Wibke G.
Kluger, Gerhard
Muhle, Hiltrud
Moller, Rikke S.
Platzer, Konrad
Santos, Joana Larupa
Bache, Iben
Bertsche, Astrid
Bonfert, Michaela
Borggraefe, Ingo
Broser, Philip J.
Datta, Alexandre N.
Hammer, Trine Bjorg
Hartmann, Hans
Hasse-Wittmer, Anette
Henneke, Marco
Kuehne, Hermann
Lemke, Johannes R.
Maier, Oliver
Matzker, Eva
Merkenschlager, Andreas
Opp, Joachim
Patzer, Steffi
Rostasy, Kevin
Stark, Birgit
Strzelczyk, Adam
von Stuelpnagel, Celina
Weber, Yvonne
Wolff, Markus
Zirn, Birgit
Hoffmann, Georg Friedrich
Koelker, Stefan
Syrbe, Steffen
Publication Year :
2020

Abstract

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.

Details

Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1238104308
Document Type :
Electronic Resource