PRRT2-related phenotypes in patients with a 16p11.2 deletion

Danique R M Vlaskamp, Petra M C Callenbach, Patrick Rump, Lucia A A Giannini, Eva H Brilstra, Trijnie Dijkhuizen, Yvonne J Vos, Anne-Marie F van der Kevie-Kersemaekers, Jeroen Knijnenburg, Nicole de Leeuw, Rick van Minkelen, Claudia A L Ruivenkamp, Alexander P A Stegmann, Oebele F Brouwer, Conny M A van Ravenswaaij-Arts

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5 Citaten (Scopus)
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We studied the presence of benign infantile epilepsy (BIE), paroxysmal kinesigenic dyskinesia (PKD), and PKD with infantile convulsions (PKD/IC) in patients with a 16p11.2 deletion including PRRT2 or with a PRRT2 loss-of-function sequence variant. Index patients were recruited from seven Dutch university hospitals. The presence of BIE, PKD and PKD/IC was retrospectively evaluated using questionnaires and medical records. We included 33 patients with a 16p11.2 deletion: three (9%) had BIE, none had PKD or PKD/IC. Twelve patients had a PRRT2 sequence variant: BIE was present in four (p = 0.069), PKD in six (p <0.001) and PKD/IC in two (p = 0.067). Most patients with a deletion had undergone genetic testing because of developmental problems (87%), whereas all patients with a sequence variant were tested because of a movement disorder (55%) or epilepsy (45%). BIE, PKD and PKD/IC clearly showed incomplete penetrance in patients with 16p11.2 deletions, but were found in all and 95% of patients with a PRRT2 sequence variant in our study and a large literature cohort, respectively. Deletions and sequence variants have the same underlying loss-of-function disease mechanism. Thus, differences in ascertainment have led to overestimating the frequency of BIE, PKD and PKD/IC in patients with a PRRT2 sequence variant. This has important implications for counseling if genome-wide sequencing shows such variants in patients not presenting the PRRT2-related phenotypes.

Originele taal-2English
Pagina's (van-tot)265-269
Aantal pagina's5
TijdschriftEuropean journal of medical genetics
Nummer van het tijdschrift4
Vroegere onlinedatum17-aug-2018
StatusPublished - apr-2019

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