Early-life social determinants of SCA6 age at onset, severity, and progression (P9-11.005) (2023)

<h3>Objective:</h3> To assess the effect of early life conditions and events on age at onset (AAO), severity, and progression in SCA6 patients. <h3>Background:</h3> Caused by pathologically expanded CAG repeats in the <i>CACNA1A</i> 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. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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 (<i>p</i> = 0.022), and a 16.36 year earlier AAO for those active in school sports than those who were not (<i>p</i> &lt;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 (<i>p &lt;</i>0.001) and a slower rate of ataxia progression by 3.23 PROM-Ataxia score per year (<i>p &lt;</i>0.001). <h3>Conclusions:</h3> 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. <b>Disclosure:</b> Tiffany Chen has nothing to disclose. Ms. Casey has nothing to disclose. Dr. Lin has a non-compensated relationship as a Secretary with Broadway for Ataxia Foundation (a 501 (c) (3) non-profit organization) that is relevant to AAN interests or activities. An immediate family member of Dr. Boyle has stock in Ionis Pharmaceuticals. The institution of Dr. Boyle has received research support from Bristol Myers Squibb. Dr. Schmahmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medavante. Dr. Schmahmann has stock in Cadent. The institution of Dr. Schmahmann has received research support from National Ataxia Foundation. The institution of Dr. Schmahmann has received research support from Biohaven. Dr. Schmahmann has received intellectual property interests from a discovery or technology relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Gilbert J. L’Italien has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Gilbert J. L’Italien has received stock or an ownership interest from biohaven pharmaceuticals. Dr. Kuo has nothing to disclose. Dr. Gomez has nothing to disclose.