Episodic movement disorders: from phenotype to genotype and back

Abstract

Episodic dyskinetic movement disorders are a heterogeneous group of rare conditions. Paroxysmal dyskinesias constitute the core of this group and usually exhibit normal interepisodic neurologic findings. Contrariwise, episodic dyskinesias occur as a particular feature of complex chronic neurologic disorders. Conjunction of accurate phenotyping with up-to-date methods of molecular genetics recently provided remarkable new insights concerning the genetic causes of episodic dyskinesia. The identification of heterozygous mutations in the PRRT2 gene in paroxysmal kinesigenic dyskinesia as well as in benign familial infantile seizures linked episodic movement disorders with epilepsy. Alternating hemiplegia of childhood, the prototype of a chronic multisystem disease with episodic dyskinesia as a clinical hallmark, was recently found to be caused by heterozygous de novo mutations in the ATP1A3 gene. The clinical spectra of PRRT2 as well as of ATP1A3 mutations are still expanding. This review summarizes new genetic findings and clinical aspects in episodic dyskinesias.