A JOURNAL OF NEUROLOGY REVIEW ARTICLE The monogenic primary dystonias

Presently, 17 distinct monogenic primary dystonias referred to as dystonias 1 – 4, 5a,b, 6–8, 10–13 and 15–18 (loci DYT 1–4, 5a,b, 6–8, 10–13, 15–18) have been recognized. Twelve forms are inherited as autosomal dominant, four as autosomal recessive and one as an X-linked recessive trait. Three additional autosomal dominant forms (DYT9, DYT19 and DYT20) might exist based on linkage mapping to regions apparently different from, yet in close proximity to or overlapping with the known loci DYT18, DYT10 and DYT8. Clinically, this group of movement disorders includes pure dystonias and dystonia plus syndromes. In addition, dyskinesias (paroxysmal dystonias), although phenotypically distinct from classical dystonias, are discussed within this group. In pure dystonias, dystonia is occasionally accompanied by tremor. In dystonia plus syndromes, dystonia as the prominent sign concurs with other movement abnormalities such as myoclonus and parkinsonism. In the dyskinesias, dystonia occurs as a paroxysmal sign in association with other movement anomalies and sometimes seizures. While gross neuropatho-logical changes are absent in most primary dystonias, including the paroxysmal forms, striking morphological alterations are found in some, such as in the X-linked dystonia–parkinsonism syndrome (DYT3). Neuropathological findings at the microscopic level have also been reported in several cases of dystonia 1 and 5, both of which were previously thought to be morphologically normal. One locus, DYT14 had been erroneously assigned, by linkage mapping, in a family with dystonia 5. There are two forms of dystonia 5, one autosomal dominant and one autosomal recessive. These forms are designated here as dystonia 5a and dystonia 5b (DYT5a, DYT5b), respectively. The disease gene has been identified in 10 primary dystonias, seven autosoma