Molecular Genetics of the Paroxysmal Dyskinesias

Abstract

Paroxysmal or episodic neurological disorders are frequent in the population and include many common conditions such as migraine, epilepsy and movement disorders. Paroxysmal movement disorders are particularly heterogeneous and difficult to accurately diagnose, but the identification of many new genes and the advent of genetic testing have improved accuracy significantly. Many disease genes in paroxysmal disorders are critical to synaptic function, particularly at the presynaptic terminal where defects in a number of genes that are channels, involved in vesicle release and neurotransmitter receptors have been identified. Key Concepts Paroxysmal dyskinesias are clinically complex and often difficult to define. The genotype–phenotype correlations are not reliable. Paroxysmal dyskinesias are different from channelopathies. The major genes are PRRT2, SLC2A1 and MR1. Multigene diagnostic panels should be used in genetic analysis.