Paroxysmal dyskinesias revisited: a review of 500 genetically proven cases and a new classification

Abstract

Paroxysmal movement disorders are a heterogeneous group of conditions manifesting as episodic dyskinesia with sudden onset and lasting a variable duration. Based on the difference of precipitating factors, three forms are clearly recognized, namely, paroxysmal kinesigenic (PKD), non-kinesigenic (PNKD), and exercise induced (PED). The elucidation of the genetic cause of various forms of paroxysmal dyskinesia has led to better clinical definitions based on genotype-phenotype correlations in the familial forms. However, it has been increasingly recognized that (1) there is a marked pleiotropy of mutations in such genes with still expanding clinical spectra; and (2) not all patients clinically presenting with either PKD, PNKD, or PED have mutations in these genes. We aimed to review the clinical features of 500 genetically proven cases published to date. Based on our results, it is clear that there is not a complete phenotypic-genotypic correlation, and therefore we suggest an algorithm to lead the genetic analyses. Given the fact that the reliability of current clinical categorization is not entirely valid, we further propose a novel classification for paroxysmal dyskinesias, which takes into account the recent genetic discoveries in this field.

Keywords: GLUT-1; KCNMA1; MR-1; PED; PKD; PNKD; PRRT2; SLC2A1; paroxysmal choreo-athetosis; paroxysmal dyskinesia; paroxysmal dystonia.