Description:
Abstract Background X-Linked dystonia-parkinsonism (XDP) is a movement disorder characterized by the presence of both dystonia and parkinsonism with one or the other more prominent in the initial stages and later on manifesting with more parkinsonian features towards the latter part of the disease. XDP patients show oculomotor abnormalities indicating prefrontal and striatal impairment. This study investigated oculomotor behavior in non-manifesting mutation carriers (NMC). We hypothesized that oculomotor disorders occur before the appearance of dystonic or parkinsonian signs. This could help to functionally identify brain regions already affected in the prodromal stage of the disease. Methods Twenty XDP patients, 13 NMC, and 28 healthy controls (HC) performed different oculomotor tasks typically affected in patients with parkinsonian signs. Results The error rate for two types of volitional saccades, i.e., anti-saccades and memory-guided saccades, was increased not only in XDP patients but also in NMC compared to HC. However, the increase in error rates of both saccade types were highly correlated in XDP patients only. Hypometria of reflexive saccades was only found in XDP patients. Initial acceleration and maintenance velocity of smooth pursuit eye movements were only impaired in XDP patients. Conclusions Despite being asymptomatic, NMC already showed some oculomotor deficits reflecting fronto-striatal impairments, typically found in XDP patients. However, NMC did not show saccade hypometria and impaired smooth pursuit as seen in advanced Parkinson’s disease and XDP, suggesting oculomotor state rather than trait signs in these mutation carriers. Neurodegeneration may commence in the striatum and prefrontal cortex, specifically the dorsolateral prefrontal cortex.