Abstract
Spinocerebellar ataxia 19 (SCA19) represents a rare autosomal dominant genetic disorder resulting in progressive ataxia and cerebellar atrophy. SCA19 is caused by variants in the KCND3 gene, which encodes a voltage-gated potassium channel subunit essential for cerebellar Purkinje cell function. We describe six cases from Chile and Mexico, representing the largest report on SCA19 in Latin America. These cases encompass a range of clinical presentations, highlighting the phenotypic variability within SCA19 from an early-onset, severe disease to a late-onset, slowly progressive condition with normal lifespan. While some patients present with pure ataxia, others also show cognitive impairment, dystonia, and other neurological symptoms. The correlations between specific KCND3 variants and phenotypic outcomes are complex and warrant further investigation. As the genomic landscape of spinocerebellar ataxias evolves, comprehensive genetic testing is becoming pivotal in improving diagnostic accuracy. This study contributes to a better understanding of the clinical spectrum of SCA19, laying the groundwork for further genotype-phenotype correlations and functional studies to elucidate the underlying pathophysiology.
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Acknowledgements
We thank Professor Laura Jardim for fostering the contact between the clinicians from Chile and Mexico and for initial insights regarding this report.
Funding
This work was supported in part by a Grant “Fondo SAVAL para investigación en la Universidad de Chile” awarded to DAJ.
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DAJ, FM, MLA, JMF, DDOM, and MM performed the clinical assessment of cases.
MLB, DV, and MM conceived the study and analyzed the data.
DAJ and FM drafted the initial version of the manuscript under the supervision of MLB and MM.
All authors reviewed and approved the final version of the manuscript.
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This study was performed according to the principles of the Declaration of Helsinki. All participants provided informed consent for genetic studies and publication of their clinical information.
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Avila-Jaque, D., Martin, F., Bustamante, M.L. et al. The Phenotypic Spectrum of Spinocerebellar Ataxia Type 19 in a Series of Latin American Patients. Cerebellum (2024). https://doi.org/10.1007/s12311-023-01654-x
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DOI: https://doi.org/10.1007/s12311-023-01654-x