Clinical and Genetic Characteristics of SCA27B: A Global Systematic Review and Meta- Analysis

Background Spinocerebellar ataxia 27B (SCA27B) has been recognised as a major cause of sporadic late-onset cerebellar ataxias, accounting for 9–61% of previously unexplained cases. Objectives To describe clinical, radiological and genetic spectrum of SCA27B through a systematic review of the global literature. Methods A systematic literature search of PubMed, Embase (Ovid), Ovid Medline and Scopus was conducted. Studies including genetically confirmed SCA27B patients were selected. Individual patient and aggregate data were extracted, pooled and summarised. Results A total of 45 studies including 1364 patients were analysed. The pooled mean age at onset was 53.9 ± 14.7 years. Cerebellar ataxia (pooled prevalence 0.91; 95% CI: 0.78–0.97), oculomotor abnormalities [excluding nystagmus] (0.74; 95% CI: 0.64–0.82), overall nystagmus (0.67; 95% CI: 0.57–0.75), downbeat nystagmus (0.48; 95% CI: 0.34–0.63), dysarthria (0.46 [0.38–0.54]), episodic symptoms (0.38 [0.29–0.48]), vertigo/dizziness (0.34 [0.29–0.39]), and tremors (0.31 [0.19–0.47]) were the most frequent clinical features. Substantial heterogeneity was present across outcomes. Genotype-phenotype correlation analysis showed that ≤ 249 repeats were associated with significantly higher odds of downbeat nystagmus (OR = 0.56, p = 0.002), nystagmus (OR = 0.45, p = 0.002) and pyramidal signs (OR = 0.25, p < 0.001). Larger expansions (≥ 250 repeats) were significantly linked to episodic manifestations (OR = 1.54, p = 0.049) and broader oculomotor involvement (OR = 3.70, p < 0.001). Conclusions SCA27B is a common and genetically defined cause of late-onset cerebellar ataxia with a heterogeneous phenotype. Vestibular and episodic features often precede gait ataxia. Recognition of key clues, including downbeat nystagmus, oculomotor abnormalities, episodic symptoms and triggers, is essential to facilitate timely diagnosis and appropriate genetic testing.