Spinocerebellar ataxia type 19: a series of patients from Latin America. Phenotypic spectrum from early-onset to late-onset slowly progressive ataxia

Abstract

Abstract Spinocerebellar ataxia 19 (SCA19) represents a rare autosomal dominant genetic disorder resulting in progressive ataxia and cerebellar atrophy. It is caused by variants in the KCND3 gene, which encodes a voltage-gated potassium channel subunit, essential for cerebellar Purkinje cell function. We present 6 cases from Chile and México, representing the largest report of SCA19 in Latin America. These cases encompass a range of clinical presentations, highlighting the phenotypic variability within SCA19, from an early-onset more severe disease to a late-onset slowly progressive condition with normal lifespan. While some cases manifest with pure ataxia, others present with cognitive impairment, dystonia and other neurological symptoms. The correlation between specific KCND3 variants and phenotypic outcomes is complex and warrants further investigation. Whole exome sequencing has emerged as a valuable diagnostic tool, aiding in the identification of genetic causes of ataxia. As the genetic landscape of spinocerebellar ataxias evolves, comprehensive genetic testing becomes pivotal in improving diagnosis accuracy. This study contributes to a better understanding of SCA19’s clinical spectrum, for future genotype-phenotype correlations and potential functional studies that could elucidate the underlying pathophysiology of this condition.