TY  - JOUR
A1  - Döring, Jan Henje
A1  - Saffari, Afshin
A1  - Bast, Thomas
A1  - Brockmann, Knut
A1  - Ehrhardt, Laura
A1  - Fazeli, Walid
A1  - Janzarik, Wibke Gesine
A1  - Kluger, Gerhard
A1  - Muhle, Hiltrud
A1  - Møller, Rikke S.
A1  - Platzer, Konrad
A1  - Larupa Santos, Joana
A1  - Bache, Iben
A1  - Bertsche, Astrid
A1  - Bonfert, Michaela
A1  - Borggräfe, Ingo
A1  - Broser, Philip Julian
A1  - Datta, Alexandre N.
A1  - Hammer, Trine Bjørg
A1  - Hartmann, Hans
A1  - Hasse-Wittmer, Anette
A1  - Henneke, Marco
A1  - Kühne, Hermann
A1  - Lemke, Johannes Rudolph
A1  - Maier, Oliver
A1  - Matzker, Eva
A1  - Merkenschlager, Andreas
A1  - Opp, Joachim
A1  - Patzer, Steffi
A1  - Rostasy, Kevin
A1  - Stark, Birgit
A1  - Strzelczyk, Adam
A1  - Stülpnagel, Celina von
A1  - Weber, Yvonne G.
A1  - Wolff, Markus
A1  - Zirn, Birgit
A1  - Hoffmann, Georg Friedrich
A1  - Kölker, Stefan
A1  - Syrbe, Steffen
T1  - The phenotypic spectrum of PRRT2-associated paroxysmal neurologic disorders in childhood
T2  - Biomedicines
N2  - 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.
KW  - PRRT2
KW  - BFIS
KW  - PKD
KW  - PKD/IC
KW  - hemiplegic migraine
KW  - familial infantile epilepsy
KW  - phenotypic spectrum
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/56837
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-568378
SN  - 2227-9059
VL  - 8
IS  - 456
PB  - MDPI
CY  - Basel
ER  -