Postsynaptic movement disorders: clinical phenotypes, genotypes, and disease mechanisms

Abstract

Movement disorders comprise a group of heterogeneous diseases with often complex clinical phenotypes. Overlapping symptoms and a lack of diagnostic biomarkers may hamper making a definitive diagnosis. Next-generation sequencing techniques have substantially contributed to unraveling genetic etiologies underlying movement disorders and thereby improved diagnoses. Defects in dopaminergic signaling in postsynaptic striatal medium spiny neurons are emerging as a pathogenic mechanism in a number of newly identified hyperkinetic movement disorders. Several of the causative genes encode components of the cAMP pathway, a critical postsynaptic signaling pathway in medium spiny neurons. Here, we review the clinical presentation, genetic findings, and disease mechanisms that characterize these genetic postsynaptic movement disorders.