Discussion

Here we present a patient with biallelic variants in WARS2 and a clinical phenotype consisting of a severe hyperkinetic movement disorder and cognitive deficits. This case broadens the differential diagnostic approach to juvenile hyperkinetic movement disorders with dystonia, chorea, and ballism. It further substantiates the role of WARS2 in syndromes comprising developmental and cognitive delay combined with hyperkinetic movement disorders. Because the majority of published patients were reported to have had epileptic seizures, the absence of this clinical finding might explain the survival beyond 25 years in our patient. In summary, WARS2-related mitochondrial disease can cause heterogeneous clinical presentations, but developmental cognitive delay and complex movement disorders seem to be a consistent feature. In children and young adults with otherwise unexplained progressive hyperkinetic movement disorders, WARS2-related mitochondrial disease should be included in the list of differential diagnoses.