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.


OBJECTIVE
To identify the role of genes in the pathophysiology of dystonia.


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).


CONCLUSIONS
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.


CONCLUSIONS
The identification of these genetic factors is a critical future aim in dystonia research.
Schmidt
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A
Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lübeck, Lübeck, Germany.
Klein
C
C
D017668:Age of Onset; D004421:Dystonia / Q000209:etiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation / Q000235:genetics; D010641:Phenotype