Nongenetic Factors Associated With Onset and Severity of Hereditary Ataxia

Spinocerebellar ataxias (SCAs) are rare neurodegenerative disorders that arise from genetic sequence variants causing progressive imbalance and motor incoordination. Few studies have investigated nongenetic correlates of patient variation in onset and severity of SCA6 and 27B.

Participants with genetic diagnosis of SCA6 or SCA27B were recruited from the University of Chicago Medical Center Ataxia Clinic, National Ataxia Foundation, SCA6 Network, and SCA27b Ataxia Foundation to complete an online survey to explore correlates of disease onset and severity. Age at onset was modeled using Cox proportional hazards regression. Disease severity was measured using the Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia) and modeled using ordinal logistic regression.

A total of 282 participants with SCA6 (mean age 64 years, 60% female) and 127 participants with SCA27B were enrolled (mean age 70 years, 47% female). Female sex, non-White race, and longer CAG repeats were associated with earlier SCA6 onset. Earlier SCA27B onset was associated with longer GAA repeats, early concussion, industrial cleaner, pesticide exposure, and herpes simplex virus infection. Less education, non-White race, and lower current alcohol and higher marijuana use were also significantly associated with SCA6 severity.

Genetic factors primarily influence SCA6 disease onset, while several environmental exposures are correlated with SCA27B disease onset and severity.