Paroxysmal Kinesigenic Dyskinesia Caused by 16p11.2 Microdeletion and Related Clinical Features

Background and Objectives Isolated paroxysmal kinesigenic dyskinesia (PKD) is mainly caused by PRRT2 variants and TMEM151A variants. Patients with proximal 16p11.2 microdeletion (16p11.2MD) (including PRRT2) often have neurodevelopmental phenotypes, whereas a few patients have PKD. Here, we aimed to identify 16p11.2MD in patients with PKD and describe the related phenotypes. Methods Whole-exome sequencing and bioinformatics analysis of copy number variant (CNV) were performed in patients with PKD carrying neither PRRT2 nor TMEM151A variant. Quantitative PCR and low-coverage whole-genome sequencing verified the CNV. Results We identified 9 sporadic patients with PKD and 16p11.2MD (similar to 535 kb), accounting for 9.6% (9/94) of our patients. Together with 9 previously reported patients with PKD and 16p11.2MD, we found that 16p11.2MD was de novo in 11 of 12 tested patients and inherited from a parent in the other patient. And 80% (12/15) of these patients had a mild language delay, 64.3% (9/14) had compromised learning ability, 42.9% (6/14) had a mild motor delay, and 50% (6/12) had abnormal neuroimaging findings. No severe autism disorders were observed. Discussion Mild developmental problems may be overlooked. A detailed inquiry of developmental history and CNV testing are necessary to distinguish patients with 16p11.2MD from isolated PKD.

Automated summary

This study identified a group of patients with isolated paroxysmal kinesigenic dyskinesia (PKD) who also have 16p11.2 microdeletion (16p11.2MD), and described their related phenotypes. The results showed that most of these patients had mild language delay, compromised learning ability, and mild motor delay, as well as abnormal neuroimaging findings in some cases. It is important to conduct a detailed developmental history inquiry and CNV testing to distinguish these patients from those with isolated PKD.