PRRT2-related phenotypes in patients with a 16p11.2 deletion |
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Authors: | Danique RM Vlaskamp Petra MC Callenbach Patrick Rump Lucia AA 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 AL Ruivenkamp Alexander PA Stegmann Oebele F Brouwer Conny MA van Ravenswaaij-Arts |
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Institution: | 1. University of Groningen, University Medical Center Groningen, Department of Neurology, Groningen, The Netherlands;2. University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands;3. University Medical Center Utrecht, Department of Genetics, Utrecht, The Netherlands;4. Academic Medical Center, Department of Genetics, Amsterdam, The Netherlands;5. Erasmus Medical Center, Department of Genetics, Rotterdam, The Netherlands;6. Radboud University Medical Center, Department of Genetics, Nijmegen, The Netherlands;7. Leiden University Medical Center, Department of Genetics, Leiden, The Netherlands;8. Maastricht University Medical Center, Department of Genetics, Maastricht, The Netherlands |
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Abstract: | 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. |
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Keywords: | Benign infantile epilepsy Seizure Movement disorder Sequencing Microarray |
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