Dystonia

INDEX

  1. Genetic forms of dystonia have traditionally been classified according to the gene or locus involved, from which the names for the various forms of dystonia, DYT1, DYT2 etc were then derived. Historically, clinical disorders were linked to chromosomal regions before a gene would be discovered. However, the current list of DYTs not only represents an assortment of clinically and genetically heterogeneous disorders but also includes duplicated loci, as well as missing and unconfirmed loci.  Several DYT loci were assigned on the basis of single families and a causal gene was never subsequently identified1.  Furthermore, the genetic locus symbols (e.g., DYT1) were later also used as synonyms for not only the respective phenotype such as “DYT1 dystonia”, but also for the underlying genetic cause (mutation in the “DYT1” gene).
  2. A further flaw with the DYT nomenclature scheme is that it implies that disorders with a DYT assignment are necessarily dystonic disorders, even though the movement disorder may not necessarily be predominantly dystonic. Disorders such as myoclonus-dystonia syndrome (previously termed DYT11) are dominated by myoclonus, but have a DYT designation because there is no locus naming convention for myoclonic disorders.
  3. As a counterpart to this concern, many disorders in which dystonia is both a consistent and dominant feature of the clinical phenotype were described before the DYT convention was developed. As a result, these disorders lack DYT designations. Examples of dystonic disorders without DYT loci include Wilson’s disease, Lesch-Nyhan disease, and glutaric aciduria.  The list using DYT naming implies that there are 29 dystonia genes, but it neglects numerous disorders in which dystonia is a consistent or dominant clinical feature10.
  4. In addition, specific genetic mutations or rare variants will increasingly be identified in individuals with a familial disorder without the antecedent discovery of a linked chromosomal region. Furthermore, genome-wide association studies have identified loci that contain frequent variations (genetic polymorphisms) as being associated with disease risk on a population level, leading to the identification of genetic risk factors rather than disease-determining gene mutations.