PRRT2-related paroxysmal dyskinesia with overlapping paroxysmal kinesigenic and paroxysmal non-kinesigenic dyskinesia-like phenotypes: a case report

Background Paroxysmal dyskinesias (PDs) are a heterogeneous group of episodic movement disorders classified according to their clinical features into paroxysmal kinesigenic dyskinesia (PKD), paroxysmal non-kinesigenic dyskinesia (PNKD), and paroxysmal exercise-induced dyskinesia (PED). Distinct genetic causes have been identified for these subtypes, with PRRT2 being a major causative gene for PKD. Although PRRT2 -related PD typically presents as PKD and responds well to low-dose carbamazepine, atypical phenotypes and variable treatment responses have been reported. Case presentation A male patient with a history of self-limited infantile epilepsy developed exercise-triggered involuntary movements at 6 years of age. At 7 years and 3 months, the attacks became more frequent and were predominantly triggered by anxiety and stress. They occurred multiple times daily, lasted from several minutes to hours, and comprised choreoathetoid and ballistic movements of the limbs and face. Neurological examination, brain magnetic resonance imaging, and electroencephalogram findings were unremarkable. The clinical features overlapped with those of PKD and PNKD, precluding conventional subtype classification. Carbamazepine monotherapy was insufficient, whereas the addition of clonazepam markedly reduced attack frequency. Genetic testing identified a heterozygous PRRT2 NM_145239.3:c.649dup (p.Arg217ProfsTer8) variant. Conclusions This case demonstrates the phenotypic and therapeutic variability in PRRT2 -related PDs. Despite having a common pathogenic PRRT2 variant, the patient exhibited age-dependent change in dyskinetic phenomenology, coexistence of PKD- and PNKD-like features within a single attack, and a favourable response to combined carbamazepine and clonazepam therapy. These findings highlight the importance of considering the clinical phenotype, in addition to genotype, in the management of PDs.