Diagnostic value of genetic testing in chorea: a retrospective monocentric study

Chorea is a hyperkinetic movement disorder with a broad differential diagnosis, ranging from acute symptomatic causes to slowly progressive neurogenetic diseases. While Huntington's disease (HD) remains the most prevalent hereditary form, numerous other genetic disorders may mimic its clinical presentation. A major diagnostic challenge arises in patients with a seemingly negative family history, which can obscure the suspicion of a genetic etiology. In patients with sporadic chorea, the potential contribution of genetic testing to the diagnostic process has not yet been systematically analyzed.

We conducted a retrospective analysis of 81 patients presenting with chorea as a prominent symptom at the movement disorders outpatient clinic between 2013 and 2024. Clinical data, family history, laboratory results, imaging, and genetic analyses were evaluated. Genetic testing included a chorea-related gene panel and, if unremarkable, whole-exome or whole-genome sequencing.

Out of 81 patients, 44 presented with slowly progressive chorea and unremarkable family history of HD or chorea-related syndromes. After exclusion of secondary etiologies (n = 8), 36 patients remained, of whom 30 (83, 33%) received a confirmed genetic diagnosis. HD was the most frequent diagnosis (n = 20), followed by rare genetic disorders such as Spinocerebellar Ataxia Type 17 (n = 2), Wilson's Disease (n = 2), Ataxia with Oculomotor Apraxia Type 2 (n = 1), C9orf72-related Neurodegeneration (n = 1), Choreoacanthocytosis (n = 1), KMT2B-related Dystonia (n = 1), ERCC4-related Neurodegeneration (n = 1), and Glutaric Acidemia Type 1 (n = 1).

These findings support the systematic use of genetic testing-even in apparently sporadic cases-and suggest that the prevalence of hereditary choreatic disorders, may be significantly underestimated.