Purpose of review: The discovery of new disease-causing genes and availability of next-generation sequencing platforms have both progressed rapidly over the last few years. For the practicing neurologist, this presents an increasingly bewildering array both of potential diagnoses and of means to investigate them. We review the latest newly described genetic conditions associated with dystonia, and also address how the changing landscape of gene discovery and genetic testing can best be approached, from both a research and a clinical perspective.
Recent findings: Several new genetic causes for disorders in which dystonia is a feature have been described in the last 2 years, including ZNF142, GSX2, IRF2BPL, DEGS1, PI4K2A, CAMK4, VPS13D and VAMP2. Dystonia has also been a newly described feature or alternative phenotype of several other genetic conditions, notably for genes classically associated with several forms of epilepsy. The DYT system for classifying genetic dystonias, however, last recognized a new gene discovery (KMT2B) in 2016.
Summary: Gene discovery for dystonic disorders proceeds rapidly, but a high proportion of cases remain undiagnosed. The proliferation of rare disorders means that it is no longer realistic for clinicians to aim for diagnosis to the level of predicting genotype from phenotype in all cases, but rational and adaptive use of available genetic tests can certainly expedite diagnosis.