The role of genes in causing dystonia

Background: In recent years, the identification of several new dystonia genes has provided important insights into the nature of this clinically and genetically heterogeneous disorder. Aims: To identify the role of genes in the pathophysiology of dystonia. Materials and Methods: Literature review from 1985 to 2009. Results: Early-onset dystonia is overall rare, often monogenic and tends to spread to become generalized. In contrast, adult-onset dystonia is relatively common, typically sporadic and usually remains focal. To date, 19 different forms of monogenic dystonia (primary dystonias and dystonia-plus syndromes) have been identified and classified as DYT loci. Likewise, secondary dystonia is a feature of a large number of hereditary conditions, such as Wilson disease or neuroacanthocytosis. This review focuses on the eight monogenic primary dystonias, six of which are associated with an early-onset generalized phenotype (DYT1, 2, 4, 6, 16 and 17), while the remaining two are characterized by an adolescent- or adult-onset focal or segmental form of dystonia (DYT7 and 13). Discussion: Primary dystonias have a strong genetic component that is most obvious in the rare monogenic early-onset generalized forms. However, genetic risk factors also are likely to play an important role in the pathophysiology of the much more common late-onset focal and segmental primary dystonias. Conclusion: The identification of these genetic factors is a critical future aim in dystonia research.