Genetic dystonia-ataxia syndromes: clinical spectrum, diagnostic approach and treatment options

Abstract

Background: Dystonia and ataxia are manifestations of numerous disorders, and indeed, an ever-expanding spectrum of genes causing diseases that encompass dystonia and ataxia are discovered with the advances of genetic techniques. In recent years, a pathophysiological link between both clinical features and the role of the cerebellum in the genesis of dystonia, in some cases, has been proposed. In clinical practice, the genetic diagnosis of dystonia-ataxia syndromes is a major issue for genetic counseling, prognosis and, occasionally, specific treatment. Methods: For this pragmatic and educational review, we conducted a comprehensive and structured literature search in Pubmed, OMIM, and GeneReviews using the key words “dystonia” and “ataxia” to identify those genetic diseases that may combine dystonia with ataxia. Results: There are a plethora of genetic diseases causing dystonia and ataxia. We propose a series of clinico-radiological algorithms to guide their differential diagnosis depending on the age of onset, additional neurological or systemic features, and imaging findings. We suggest a sequential diagnostic approach to dystonia-ataxia syndromes. We briefly highlight the pathophysiological links between dystonia and ataxia and conclude with a review of specific treatment implications. Conclusions: The clinical approach presented in this review is intended to improve the diagnostic success of clinicians when faced with patients with dystonia-ataxia syndromes.