Jiao‑Jiao Xu1,2 · Hong‑Fu Li1,2 · Zhi‑Ying Wu1,21 Department of Medical Genetics and Center for Rare Diseases, The Second Afliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
2 Department of Neurology in the Second Afliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310009, China
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.
Keywords
Paroxysmal kinesigenic dyskinesia; PRRT2; TMEM151A; Genetics; Pathophysiological mechanisms
