Genetic Testing for Dystonia
Genetic testing enables medical professionals to identify significant changes in genes, chromosomes, the genome, or proteins that may be indicative of a genetic condition. This is used for screening, diagnosis, and prognosis of diseases consistent with an underlying genetic cause, permitting guided drug therapy (Franceschini et al., 2018). In recent decades, genetic testing has been utilized to confirm or rule out a host of conditions, including breast cancer, Parkinson’s disease and dystonia. There are currently over 12 types of dystonia exclusively linked to genetic mutations, including primary generalized dystonia, segmental dystonia with laryngeal involvement, and myoclonus dystonia, to name a few. These presentations predominantly exhibit autosomal dominant inheritance; however, the number of autosomal recessive forms, X-linked and mitochondrial, is continuously evolving (Albanese et al., 2013). Genetic testing not only aids in diagnosing dystonia in patients but also in distinguishing the specific type of dystonia. Despite this, the current literature highlights that genetic testing is significantly underutilized in establishing the precise genetic diagnosis in patients with heritable forms of dystonia (Pozojevic et al., 2021).
How many genes have been found exactly?
Dystonia is defined as a movement disorder, causing the muscles to contract involuntarily. This condition has multiple causes, giving to the complicated genetics underlying dystonia. However, it is possible to identify genetic markers that increase a person’s susceptibility to contracting this presentation. It has been proposed that although no single gene can be attributed to all cases of dystonia, an estimated 200 genes or genetic markers have been positively associated with several different types of dystonia. Moreover, with medical technology constantly advancing, it is expected that a host of new genetic markers will be discovered in the future (Dystonia Medical Research Foundation, 2021). Molecular genetic testing is the method by which healthcare staff can confirm a diagnosis of specific inherited forms of dystonia. This screening approach can detect mutations in the previously discussed 200 genes or genetic markers known to cause inherited dystonia (National Organization for Rare Disorders, 2021). Molecular genetic testing can encompass several different approaches, including a multigene panel, comprehensive genomic sequencing, and single-gene testing (Klein C, 2003). The employment of genetic testing has also aided researchers in establishing the wide clinical spectrum of the disorder, including alternating hemiplegia of childhood.
An overview of several genes associated with dystonia can be found here: https://www.ncbi.nlm.nih.gov/books/NBK1155/table/dystoniaov.T.nomenclature_system_for_in/?report=objectonly
Would getting tested help with a previous misdiagnosis?
Despite significant milestones having been achieved regarding the comprehension of dystonia in recent years, primary dystonia is still insufficiently diagnosed in patients, with several patients receiving a misdiagnosis. This has resulted in a large pro portion of dystonia patients receiving a transient or permanent misclassification of their symptoms. A 2015 study assessed the most common reasons for misdiagnosis in dystonia patients, with the primary rationale arising being misdiagnoses in favour of other movement disorders, including Parkinson’s disease, essential tremor, myoclonus, tics, psychogenic movement disorder, and even headache or scoliosis (Lalli and Albanese, 2010). Hence, genetic testing would significantly aid those with a previous misdiagnosis as identification of genes or genetic markers associated with dystonia would lead to a correct diagnosis and treatment approach. Moreover, a positive genetic test for dystonia impacts the approach to treatment depending on the genetic markers identified in the patient.
How does a positive genetic test for dystonia affect the approach to treatment?
The use of genetic testing and the knowledge that this yields for numerous dystonia-related genes, the variants they may contain, associated clinical presentations, and the molecular disease mechanism has significant translational potential for those with a positive genetic test for dystonia. A positive genetic test for dystonia will drastically impact the approach to treatment, with this being crucial to determine the appropriate genetic counselling and also possesses the potential to enhance or resolve at least some of the challenging disease aspects for both patients and their caregivers. In some cases, an early positive genetic test may even indicate a potentially life-changing treatment option (Pozojevic et al., 2021). It is also validated in current research that identification of the specific genetic biomarkers in patients may contribute to translational research and enable participation in gene-tailored clinical trials of potential disease-modifying therapies. Moreover, a positive genetic test, resulting in a diagnosis of dystonia, enables early employment of treatment options, including education, psychological support, and judicious medical management, yielding crucial improvements in quality of life.
ALBANESE, A., BHATIA, K., BRESSMAN, S. B., DELONG, M. R., FAHN, S., FUNG, V. S., HALLETT, M., JANKOVIC, J., JINNAH, H. A., KLEIN, C., LANG, A. E., MINK, J. W. & TELLER, J. K. 2013. Phenomenology and classification of dystonia: a consensus update. Mov Disord, 28, 863-73.