Genetics and treatment of dystonia

The torsion dystonias encompass a broad collection of etiologic subtypes, often divided into primary and secondary classes. Tremendous advances have been made in uncovering the genetic basis of dystonia, including discovery of a gene causing early onset primary torsion dystonia-a GAG deletion in exon 5 of the DYT1 gene that encodes torsinA. Although the exact function of torsinA remains elusive, evidence suggests aberrant localization and interaction of mutated protein; this may result in an abnormal response to stress or interference with cytoskeletal events and the development of neuronal brain pathways. Breakthroughs include the discovery of a genetic modifier that protects against clinical expression in DYT1 dystonia and the identification of the gene causing DYT6, THAP1. The authors review genetic etiologies and discuss phenotypes as well as counseling of patients regarding prognosis and progression of the disease. They also address pharmacologic and surgical treatment options for various forms of dystonia.