Objective:

To assess the effect of early life conditions and events on age at onset (AAO), severity, and progression in SCA6 patients.

Background:

Caused by pathologically expanded CAG repeats in the CACNA1A gene, SCA6 AAO and clinical progression can vary significantly between individuals with the same size CAG repeat allele. Although this indicates that non-genetic factors can influence the disease course, the impact of these external factors is poorly understood.

Design/Methods:

We performed a survey of social factors in SCA6 patients enrolled at the University of Chicago through consecutive sampling. AAO of ataxia symptoms and Patient-Reported Outcome Measure (PROM) of Ataxia were used as primary outcome measures. Using least absolute shrinkage and selection operation (LASSO) regression, we identified which early life factors are predictive of SCA6 AAO, severity, and progression. We then created multiple linear regression models to assess the degree to which these determinants influence SCA6 health outcomes.

Results:

A total of 105 participants with SCA6 completed the assessments. Maternal difficulty during pregnancy and participation in school sports were found to be predictive of AAO in addition to pathological CAG repeat length. We found a 12.76 year earlier AAO for those with maternal difficulty in pregnancy than those who did not (p = 0.022), and a 16.36 year earlier AAO for those active in school sports than those who were not (p <0.001). Higher education attainment was found to be associated with decreased SCA6 severity and slower progression. Compared to those with only primary education, those receiving post-secondary education were determined to have a 43.64 lower PROM-Ataxia score (p <0.001) and a slower rate of ataxia progression by 3.23 PROM-Ataxia score per year (p <0.001).

Conclusions:

Early life biological, behavioral, and social factors can have a strong influence on the SCA6 disease course and may contribute to the disease course of other monogenetic disorders.