OBJECTIVE: PRRT2 gene variations are commonly associated with paroxysmal kinesigenic dyskinesia (PKD) and epilepsy (EP). This study compares the clinical phenotypes of PKD and EP in relation to PRRT2, focusing on the association of the hotspot mutation c.649dupC (p.Arg217Profs*8). METHODS: We retrospectively analyzed PRRT2 cases from our hospital (2017-2025) and reviewed literature from major databases up to 2025. Pediatric patients (≤ 18 years) with either PKD or EP were included and categorized into sporadic and familial groups. Data on gender, onset age, and c.649dupC mutation prevalence were analyzed. RESULTS: In our cohort (41 patients), EP onset typically occurred in infancy (0.3-2.6 years), while PKD onset was during school age (8-13 years). The c.649dupC mutation rate was numerically higher in the PKD group (57%) than in the EP group (44%), but it was not statistically significant. From literature data (95 sporadic, 436 familial cases), EP was more frequent than PKD. The c.649dupC mutation rate was higher in PKD patients (77%) than in EP patients (66%) overall. This difference reached statistical significance in familial cases (84% vs. 71%, p < 0.05) but not in sporadic cases. SIGNIFICANCE: Among children with PRRT2 variations, EP is more common than PKD. The onset of EP is concentrated in early childhood, whereas PKD typically begins at school age, indicating age-dependent expression. The c.649dupC mutation shows a stronger association with the PKD phenotype in familial cases.
Sun et al. (2026) studied this question.