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

Vlaskamp, D. R. M., Callenbach, P. M. C., Rump, P., Giannini, L. A. A., Brilstra, E. H., Dijkhuizen, T., Vos, Y. J., van der Kevie-Kersemaekers, A-M. F., Knijnenburg, J., de Leeuw, N., van Minkelen, R., Ruivenkamp, C. A. L., Stegmann, A. P. A., Brouwer, O. F. & van Ravenswaaij-Arts, C. M. A., Apr-2019, In : European journal of medical genetics. 62, 4, p. 265-269 5 p.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)265-269
Number of pages5
JournalEuropean journal of medical genetics
Issue number4
Early online date17-Aug-2018
Publication statusPublished - Apr-2019


  • Benign infantile epilepsy, Seizure, Movement disorder, Sequencing, Microarray, PAROXYSMAL KINESIGENIC DYSKINESIA, INFANTILE CONVULSIONS, PRRT2, MUTATIONS, DUPLICATION, LEADS

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