Background: Dystonia is a movement disorder with high heterogeneity regarding phenotypic appearance and etiology that occurs in both sporadic and familial forms. The etiology of the disease remains unknown. However, there is increasing evidence suggesting that a small number of gene alterations may lead to dystonia. Although pathogenic variants to the familial type of dystonia have been extensively reviewed and discussed, relatively little is known about the contribution of single-nucleotide polymorphisms (SNPs) to dystonia. This review focuses on the potential role of SNPs and other variants in dystonia susceptibility.
Methods: We searched the PubMed database for peer-reviewed articles published in English, from its inception through January 2018, that concerned human studies of dystonia and genetic variants. The following search terms were included: "dystonia" in combination with the following terms: 1) "polymorphisms" and 2) "SNPs" as free words.
Results: A total of 43 published studies regarding TOR1A, BDNF, DRD5, APOE, ARSG, NALC, OR4X2, COL4A1, TH, DDC, DBH, MAO, COMT, DAT, GCH1, PRKRA, MR-1, SGCE, ATP1A3, TAF1, THAP1, GNAL, DRD2, HLA-DRB, CBS, MTHFR, and MS genes, were included in the current review.
Discussion: To date, a few variants, which are possibly involved in several molecular pathways, have been related to dystonia. Large cohort studies are needed to determine robust associations between variants and dystonia with adjustment for other potential cofounders, in order to elucidate the pathogenic mechanisms of dystonia and the net effect of the genes.
Keywords: Dystonia; blepharospasm; cervical dystonia; genetic polymorphism; movement disorders; single nucleotide polymorphism; variant.