Unravelling Heterogeneity: A Rare PNPT1 Variant in Childhood-Onset Spinocerebellar Ataxia with Sensorineural Hearing Loss.

Abstract

Spinocerebellar ataxias (SCAs) are a diverse and heterogeneous group of inherited neurodegenerative disorders marked by progressive ataxia and cerebellar degeneration. This case report details an 11-year-old Indian boy with childhood-onset ataxia and severe sensorineural hearing loss, a rarely reported concomitance in pediatric neurology. Genetic analysis identified a unique heterozygous 3' splice site variant in the PNPT1 gene (c.2014-3 C > G) of pathogenic significance, confirming the diagnosis of SCA25. This case highlights the phenotypic and genotypic heterogeneity of PNPT1 gene-related SCA25 and suggests an autosomal dominant inheritance pattern with low penetrance. It underscores the need for functional studies to further validate the splice variant reported herein and emphasizes the importance of a high index of suspicion for genetic analysis and genetic counselling in children with concurrent hearing loss and progressive ataxia, even in the absence of a clear autosomal dominant inheritance pattern.