The importance of genetic testing for dystonia patients and translational research

Abstract

Genetic testing through a variety of methods is a fundamental but underutilized approach for establishing the precise genetic diagnosis in patients with heritable forms of dystonia. Our knowledge of numerous dystonia-related genes, variants that they may contain, associated clinical presentations, and molecular disease mechanism may have significant translational potential for patients with genetically confirmed dystonia or their family members. Importantly, genetic testing permits the assembly of patient cohorts pertinent for dystonia-related research and developing therapeutics. Here we review the genetic testing approaches relevant to dystonia patients, and summarize and illustrate the multifold benefits of establishing an accurate molecular diagnosis for patients imminently or for translational research in the long run.

Keywords: Dystonia; Genetic modifiers; Genetic testing; Precision medicine.

Fig. 1

Individuals eligible for genetic testing. a Patients seeking genetic diagnoses should be screened by diagnostic genetic testing. b Individuals suspected to carry a pathogenic variant in a single copy of a gene related to autosomal recessive dystonia forms may undergo carrier genetic testing to determine their chance of having an affected offspring. c Clinically unaffected individuals whose family members suffer from dystonia are at risk of carrying a variant that will predispose them to developing symptoms over time (i.e., later in life) and are thus eligible for predictive/presymptomatic genetic testing. d Prenatal genetic testing is performed to assess the presence of a presumed disease-causing change (or changes) in a fetus prenatally. Affected individuals are shown in red and unaffected in white

Fig. 2

Depending on the causative gene defect, some forms of dystonia can be successfully treated and show considerable disease symptom improvements upon gene-defect-determined dietary treatment, medication, or a particular medical procedure. Affected individuals are shown in red and individuals with less severe symptoms upon treatment in light red