The phenotypic spectrum of prrt2-associated paroxysmal neurologic disorders in childhood
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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; PRRT2-Study-Group.
In: Biomedicines, Vol. 8, No. 11, 456, 2020, p. 1-14.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The phenotypic spectrum of prrt2-associated paroxysmal neurologic disorders in childhood
AU - Döring, Jan Henje
AU - Saffari, Afshin
AU - Bast, Thomas
AU - Brockmann, Knut
AU - Ehrhardt, Laura
AU - Fazeli, Walid
AU - Janzarik, Wibke G.
AU - Kluger, Gerhard
AU - Muhle, Hiltrud
AU - Møller, Rikke S.
AU - Platzer, Konrad
AU - Santos, Joana Larupa
AU - Bache, Iben
AU - Bertsche, Astrid
AU - Bonfert, Michaela
AU - Borggräfe, Ingo
AU - Broser, Philip J.
AU - Datta, Alexandre N.
AU - Hammer, Trine Bjørg
AU - Hartmann, Hans
AU - Hasse-Wittmer, Anette
AU - Henneke, Marco
AU - Kühne, Hermann
AU - Lemke, Johannes R.
AU - Maier, Oliver
AU - Matzker, Eva
AU - Merkenschlager, Andreas
AU - Opp, Joachim
AU - Patzer, Steffi
AU - Rostasy, Kevin
AU - Stark, Birgit
AU - Strzelczyk, Adam
AU - von Stülpnagel, Celina
AU - Weber, Yvonne
AU - Wolff, Markus
AU - Zirn, Birgit
AU - Hoffmann, Georg Friedrich
AU - Kölker, Stefan
AU - Syrbe, Steffen
AU - PRRT2-Study-Group
PY - 2020
Y1 - 2020
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.
AB - 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 - BFIS
KW - Familial infantile epilepsy
KW - Hemiplegic migraine
KW - Phenotypic spectrum
KW - PKD
KW - PKD/IC
KW - PRRT2
U2 - 10.3390/biomedicines8110456
DO - 10.3390/biomedicines8110456
M3 - Journal article
C2 - 33126500
AN - SCOPUS:85094604979
VL - 8
SP - 1
EP - 14
JO - Biomedicines
JF - Biomedicines
SN - 2227-9059
IS - 11
M1 - 456
ER -
ID: 251182841