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Genetics of Primary Torsion Dystonia

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Abstract

Advances in the genetics of dystonia have further elucidated the pathophysiology of this clinically and etiologically heterogeneous group of movement disorders. Currently, 20 monogenic forms of dystonia, designated by the acronym DYT, are grouped as 1) pure dystonias, 2) dystonia-plus syndromes, and 3) paroxysmal dystonias/dyskinesias. We summarize recently discovered genes and loci, including the 1) detection of two primary dystonia genes (DYT6, DYT16), 2) identification of the DYT17 locus, 3) association of a dystonia/dyskinesia phenotype with a gene previously linked to GLUT1 (glucose transporter of the blood–brain barrier) deficiency syndrome (DYT18), 4) designation of paroxysmal kinesigenic and nonkinesigenic dyskinesia as DYT19 and DYT20, and 5) redefinition of DYT14 as DYT5. Further, we review current knowledge regarding genetic modifiers and susceptibility factors. Because recognizing and diagnosing monogenic dystonias have important implications for patients and their families with regard to counseling, prognosis, and treatment, we highlight clinical “red flags” of individual subtypes and review guidelines for genetic testing.

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Authors and Affiliations

  1. Schilling Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Norbert Brüggemann & Christine Klein

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  1. Norbert Brüggemann
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  2. Christine Klein
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Correspondence to Christine Klein.

Glossary

Allele

One of a series of different forms of a gene

Haploinsufficiency

Only a single functional copy of the gene is available, mostly leading to a lack of adequate protein (gene product) levels

Linkage analysis

Common method for the search for disease-causing genes

Gene locus

Specific location of a gene on a chromosome

Penetrance

Describes the proportion of mutation carriers who develop a distinct phenotype

Expressivity

Phenotypic variations in individuals carrying a distinct genotype

Haplotype

Combination of alleles at multiple gene loci transmitted together on the same chromosome

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Brüggemann, N., Klein, C. Genetics of Primary Torsion Dystonia. Curr Neurol Neurosci Rep 10, 199–206 (2010). https://doi.org/10.1007/s11910-010-0107-5

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  • DOI: https://doi.org/10.1007/s11910-010-0107-5

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