Chapter 24 - Dystonia: Phenotypes and Genetics

Abstract

Dystonia has been defined as a syndrome of involuntary, sustained muscle contractions affecting one or more sites of the body, frequently causing twisting and repetitive movements or abnormal postures. Dystonia is also a clinical sign that can be the presenting or prominent manifestation of many neurodegenerative and neurometabolic disorders. Etiological categories include primary dystonia, secondary dystonia, heredodegenerative diseases with dystonia, and dystonia-plus. Primary dystonia includes syndromes in which dystonia is the sole phenotypic manifestation with the exception that tremor can also be present. Most primary dystonia begins in adults, and approximately 10% of probands report one or more affected family members. Many cases of childhood- and adolescent-onset dystonia are due to mutations in TOR1A and THAP1, respectively. Although significant recent progress has been made in defining the genetic basis for most of the dystonia-plus and heredodegenerative diseases with dystonia, a major gap remains in understanding the genetic etiologies for most cases of adult-onset primary dystonia. Common themes in the cellular biology of dystonia include G1/S cell cycle control, monoaminergic neurotransmission, mitochondrial dysfunction, and the neuronal stress response.