SCA-17 with 43 CAG-CAA repeats in the TBP gene: a rare cause of young-onset dementia

<h3></h3> Spinocerebellar ataxia type 17 (SCA-17) is a rare, autosomal dominant, neurodegenerative disease associated with CAG/CAA repeat expansion in the TATA-box binding protein (TBP) gene. Core features are dementia and ataxia, with chorea, dystonia, pyramidal signs, seizures, and psychiatric disturbance also reported. We present a diagnostically challenging case of SCA-17, associated with one expanded allele, in the reduced penetrance range, in the TBP gene. A 40-year-old gentleman presented with cognitive decline and behavioural changes. He struggled to use electronic devices, forgot passwords, and could no longer work. He was managed for depression and pseudodementia, but over time his cognition progressively deteriorated. He developed tremor, seizures, somnolence, visual hallucinations, and unsteady gait. He eventually moved to a care home. Extensive investigation initially yielded no clear unifying diagnosis. EEG showed diffuse background slowing. Brain MRI detected right lateral ventricle nodular grey matter heterotopia, right cerebellar hemisphere lacuna infarct, bilateral subcortical supratentorial white matter microangiopathy, and involutional atrophy of the frontal lobe and cerebellar hemispheres. The initial adult-onset neurodegenerative disease gene panel (R58) did not detect a genetic mutation. However, whole genome sequencing detected 43 CAG/CAA repeats in one allele of the TBP gene, finally offering a diagnosis of SCA-17 four years after presentation.