Historically, the syndrome of primary
paroxysmal dyskinesias was considered a group of disorders as a result of
ion channel dysfunction. This proposition was primarily based on the discovery of mutations in
ion channels, which caused other episodic
neurological disorders such as
epilepsy and
migraine and also supported by the frequent association between
paroxysmal dyskinesias and
epilepsy. However, the discovery of the genes responsible for the 3 classic forms of
paroxysmal dyskinesias disproved this
ion channel theory. On the other hand, novel gene mutations implicating
ion channels have been recently reported to produce episodic
movement disorders clinically similar to the classic
paroxysmal dyskinesias. Here, we review the clinical and pathophysiological aspects of the
paroxysmal dyskinesias, further proposing a pathophysiological framework according to which they can be classified as synaptopathies (
proline-rich transmembrane protein 2 and myofibrillogenesis regulator gene),
channelopathies (
calcium-activated potassium channel subunit alpha-1 and
voltage-gated sodium channel type 8), or transportopathies (solute carrier family 2 member 1). This proposal might serve to explain similarities and differences among the various
paroxysmal dyskinesias in terms of clinical features, treatment response, and natural history. © 2017 International Parkinson and
Movement Disorder Society.