Recent discoveries in dystonia genetics have led to greater ability to provide genetic testing, as well promise for better, more focused therapeutic interventions. However, identified genes, such as DYT1, account for only a fraction of dystonia and mostly for early-onset forms. This chapter focuses on the phenotype-genotype relationships as phenotype drives gene discovery, and despite phenotypic heterogeneity, the phenotype is paramount in choice of genetic testing and sometimes treatment. Decisions about testing for DYT1 are made based primarily on age of onset of dystonia and family history. For dopa-responsive dystonia, the diagnosis may be made by the empiric response to levodopa rather than genetic testing, and diagnostic considerations for dopa-responsive dystonia are addressed. The tremendous strides that have recently been made in understanding the Neurogenetics of primary dystonia and dystonia-plus syndromes are also discussed. These include an increased understanding of factors that affect penetrance of genetic forms of dystonia, which are mostly autosomal dominant but are incompletely penetrant. The recent identification of a genetic modifier for DYT1 dystonia partially accounts for the decreased penetrance observed in DYT1, and maternal imprinting of the SGCE gene in myoclonus-dystonia explains decreased penetrance in this disorder. For other genetic forms of dystonia, such as dopa-responsive dystonia, the decreased penetrance is still not well understood.
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