Clinical heterogeneity of dysphagia in spinocerebellar ataxia type 6 and its relationship with CAG repeat length

Abstract

Spinocerebellar ataxia type 6 (SCA6) is classically regarded as a relatively pure cerebellar ataxia, and dysphagia has therefore been considered uncommon. Consequently, the clinical characteristics of dysphagia in SCA6 remain poorly understood. We retrospectively analyzed 70 patients with genetically confirmed SCA6 to characterize the occurrence and clinical features of dysphagia and to examine its association with expanded CAG repeat length in CACNA1A . The interval from disease onset to patient-reported dysphagia was evaluated using Cox proportional hazards regression and exploratory Kaplan–Meier analysis. Swallowing function was further assessed in eight patients using videofluoroscopic swallowing study (VFSS). During follow-up, 27 of 70 patients (38.6%; 95% confidence interval, 27.2–51.0%) developed patient-reported dysphagia. Cox proportional hazards analysis suggested an association between larger expanded CAG repeat length and earlier patient-reported dysphagia. Exploratory Kaplan–Meier analysis using a median CAG repeat cutoff showed a similar trend. In contrast, VFSS findings in this referred subset showed marked interindividual variability. Notably, the two most severe cases, which required alternative nutritional routes, were characterized by prominent pharyngeal-phase impairment on VFSS despite relatively small expanded CAG repeat lengths. These findings indicate that dysphagia in SCA6 is not necessarily rare but clinically heterogeneous. Instrumental swallowing assessment should be considered when clinically indicated, particularly in patients who report swallowing symptoms.