Paroxysmal Kinesigenic Dyskinesia: Genetics and Pathophysiological Mechanisms

Abstract

Paroxysmal kinesigenic dyskinesia (PKD), the most common type of paroxysmal movement disorder, is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary movements. PKD is mainly caused by mutations in the PRRT2 or TMEM151A gene. The exact pathophysiological mechanisms of PKD remain unclear, although the function of PRRT2 protein has been well characterized in the last decade. Based on abnormal ion channels and disturbed synaptic transmission in the absence of PRRT2, PKD may be channelopathy or synaptopathy, or both. In addition, the cerebellum is regarded as the key pathogenic area. Spreading depolarization in the cerebellum is tightly associated with dyskinetic episodes. Whereas, in PKD, other than the cerebellum, the role of the cerebrum including the cortex and thalamus needs to be further investigated.

Exploring the Genetic Landscape of Chorea in Infancy and Early Childhood: Implications for Diagnosis and Treatment

“…PKD may also be a feature of more complex chronic neurological disorders [ 48 , 49 ]. The gene thought to be responsible for PKD has been identified as the proline-rich transmembrane protein 2 ( PRRT2 ), which may also be involved in other paroxysmal disorders [ 52 , 53 ]. It is an autosomal dominant condition, in which male patients far outnumber female patients.…”