Paroxysmal kinesigenic dyskinesia: clinical report of 10 cases from three pedigrees with literature review.

objectiveTo characterize the clinical and genetic features of 10 paroxysmal kinesigenic dyskinesia (PKD) patients from three Chinese pedigrees, with emphasis on intrafamilial phenotypic variability and the broader PRRT2-associated disease spectrum.

methodsClinical data were collected from PKD patients attending the Department of Neurology, Second Hospital of Hebei Medical University (January 2023 - December 2024). Targeted next-generation sequencing of PKD-associated genes (PRRT2, TMEM151A, SCN8A, KCNA1, etc.) was performed for probands, followed by Sanger sequencing validation and family segregation analysis in available family members. Clinical features were analyzed in conjunction with literature review.

resultsTen PKD cases from three families were identified. All patients exhibited exercise-induced dystonia, chorea, or athetosis without impaired consciousness; each episode lasted < 1 min. Interictal EEG and brain MRI were normal. Inheritance was autosomal dominant. Pathogenic variants were identified in PRRT2 (chromosome 16), including frameshift mutations c.649dup (p.Arg217ProfsTer8) and c.641delC (p.Arg217Glufs*12). Intrafamilial phenotypic variability was notable: the same c.649dup mutation produced clinically silent carriage in one father but severe daily attacks with secondary depression in another family member. In family 3, cold exposure was identified as a novel trigger.

conclusionThis study expands the mutational spectrum of PRRT2-associated PKD in the Chinese population by documenting a relatively rare c.641delC variant. The marked intrafamilial variability observed supports the role of additional modifiers influencing clinical expression beyond the primary PRRT2 mutation.