Paroxysmal Movement Disorders: An Update on Clinical approach, Pathophysiology and Genetic Underpinnings

Abstract Paroxysmal movement disorders (PxMDs) are a clinically, genetically, and pathophysiologically a diverse group of disorders, characterized by their sudden, short-lasting, episodic nature, onset in early childhood, reduced severity during adulthood, and often a normal neurological examination between episodes. PxMDs include paroxysmal dyskinesias (PxD), which present with sudden episodes of dystonia and chorea, and episodic ataxias (EA), which present with episodes of cerebellar dysfunction. PxDs can also be precipitated by secondary causes, including metabolic or immunological factors, and structural lesions. Newer genetic advances, such as next-generation sequencing, have revolutionized how we classify and investigate PxMDs. However, a significant proportion of patients still remain undiagnosed despite current advances in genetic testing. In this review, we revisit the updated genetic underpinnings of paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, paroxysmal exercise-induced dyskinesia, and the EAs, review the recently described individual genes causing PxD, discuss the causes of secondary PxMD, describe a pragmatic, clinically based approach to ordering genetic tests in PxMD, and conclude with a brief overview of all cases of PxMD reported from India to date.