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.
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.
We identified 9 sporadic patients with PKD and 16p11.2MD (~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.
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.