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 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.

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar
Author:Jan Henje Döring, Afshin Saffari, Thomas BastGND, Knut BrockmannORCiD, Laura Ehrhardt, Walid FazeliORCiDGND, Wibke Gesine Janzarik, Gerhard Kluger, Hiltrud MuhleORCiDGND, Rikke S. MøllerORCiDGND, Konrad PlatzerORCiDGND, Joana Larupa SantosORCiD, Iben Bache, Astrid BertscheORCiDGND, Michaela Bonfert, Ingo Borggräfe, Philip Julian Broser, Alexandre N. Datta, Trine Bjørg Hammer, Hans Hartmann, Anette Hasse-Wittmer, Marco Henneke, Hermann Kühne, Johannes Rudolph LemkeORCiDGND, Oliver Maier, Eva Matzker, Andreas Merkenschlager, Joachim Opp, Steffi Patzer, Kevin Rostasy, Birgit Stark, Adam StrzelczykORCiDGND, Celina Steinbeis-von StülpnagelORCiDGND, Yvonne G. Weber, Markus Wolff, Birgit Zirn, Georg Friedrich Hoffmann, Stefan Kölker, Steffen SyrbeORCiDGND
Parent Title (English):Biomedicines
Place of publication:Basel
Document Type:Article
Date of Publication (online):2020/10/28
Date of first Publication:2020/10/28
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/11/16
Tag:BFIS; PKD; PKD/IC; PRRT2; familial infantile epilepsy; hemiplegic migraine; phenotypic spectrum
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0