Abstract
Background: Spinocerebellar ataxias (SCAs) are a diverse group of hereditary neurodegenerative disorders marked by progressive degeneration of the cerebellum and other nervous system parts. In this study, we aimed to reveal the genotype‒phenotype correlations in SCAs within the Brazilian population by leveraging a comprehensive dataset of 763 individuals from the SARAH Network of Rehabilitation Hospitals.
Methods: Using a retrospective, cross-sectional, observational, multicentric approach, we analysed medical records and conducted standardized molecular testing to explore the epidemiological characteristics, clinical manifestations, and genetic profiles of SCAs in Brazil.
Results: Our findings revealed the predominance of SCA3, followed by SCA7 and SCA2, aligning with global trends and reflecting the specific genetic landscape of Brazil. A significant inverse relationship between the age of symptom onset and CAG repeat length in the mutated allele was observed across SCAs 2, 3, and 7. The study also highlights a trend towards paternal inheritance in SCA2 and details the distribution of CAG repeat expansions, correlating larger expansions with earlier onset and specific symptomatology.
Conclusion: This extensive analysis underscores the critical importance of genetic testing in the diagnosis and management of SCAs, shedding light on intricate genotype‒phenotype interplay within a genetically diverse population. Despite certain limitations, such as potential selection bias and the retrospective nature of the study, our research provides invaluable insights into the prevalence, genetic underpinnings, and clinical variability of SCAs in Brazil. We suggest a broader demographic scope and investigations into nonmotor symptoms in future studies to obtain a more comprehensive understanding of SCAs.