Dystonia genes and their biological pathways

Abstract

The dystonias are a group of disorders characterized by excessive contraction of muscles leading to abnormal involuntary movements. The clinical manifestations are very heterogeneous, with numerous distinct syndromes. The etiologies for dystonia are also heterogeneous with idiopathic, acquired, and inherited forms. Technological advances in genetics over the past two decades have led to a rapid growth in the number of genes associated with dystonia. These genes encode proteins with very diverse biological functions. This review focusses on genes that have contributed to understanding shared biological pathways relevant to specific subgroups of dystonia syndromes. Although many potential shared biological pathways have been proposed, the ones addressed here include defects in dopamine signaling, mitochondrial dysfunction and energy maintenance, toxic accumulation of heavy metals in the brain, and calcium channels and abnormal calcium homeostasis. Elucidation of these and other shared pathways is important for understanding the biological basis for dystonia and for designing novel experimental therapeutics that have the broadest potential for multiple types of dystonia.

Keywords: Biological pathways; Calcium homeostasis; Dopamine; Dystonia; Gene; Genetic variant; Genetics; Mitochondrial disease; Mutation; NBIA; Neurobiology.