title: Milestones in dystonia.
abstract: The last 25 years have seen remarkable advances in our understanding of the genetic etiologies of dystonia, new approaches into dissecting underlying pathophysiology, and independent progress in identifying effective treatments. In this review we highlight some of these advances, especially the genetic findings that have taken us from phenomenological to molecular-based diagnoses. Twenty DYT loci have been designated and 10 genes identified, all based on linkage analyses in families. Hand in hand with these genetic findings, neurophysiological and imaging techniques have been employed that have helped illuminate the similarities and differences among the various etiological dystonia subtypes. This knowledge is just beginning to yield new approaches to treatment including those based on DYT1 animal models. Despite the lag in identifying genetically based therapies, effective treatments, including impressive benefits from deep brain stimulation and botulinum toxin chemodenervation, have marked the last 25 years. The challenge ahead includes continued advancement into understanding dystonia's many underlying causes and associated pathology and using this knowledge to advance treatment including preventing genetic disease expression.
authors.affiliation: Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Ozelius
authors.forename: Naomi
authors.initials: N
authors.lastname: Lubarr
authors.forename: Susan B
authors.initials: SB
authors.lastname: Bressman
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D003952:Diagnostic Imaging / Q000379:methods; D004421:Dystonia / Q000175:diagnosis / Q000235:genetics* / Q000266:history* / Q000628:therapy; D049672:History, 19th Century; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D009482:Neurophysiology
chemical_list: D002352:Carrier Proteins