Phenotype and Genetics of Spinocerebellar Ataxia Type 27B: Novel Movement-disorder Features, Cognitive Impairment, and Repeat Expansion Findings

Spinocerebellar ataxia type 27B is a recently described autosomal dominant, late-onset cerebellar ataxia caused by an intronic GAA repeat expansion in the fibroblast growth factor 14 (FGF14) gene. Despite being recognized as a frequent adult-onset ataxia, its full clinical spectrum remains incompletely understood. To characterize the neurological, cognitive, and paraclinical phenotype of patients with heterozygous FGF14 repeat expansions (>200) and expand the currently known motor and non-motor features, as well as to assess the co-occurrence of other repeat expansions. In this cross-sectional single-center study, patients with heterozygous FGF14 repeat expansions underwent standardized neurological examination and cognitive screening. Paraclinical data were reviewed when available. 18 patients were included in the study (mean age at onset: 64 [37-79], at examination: 76 [61-94]). They all presented with gait ataxia, most commonly a lateral veering gait with corrective sidesteps. In addition to the core known cerebellar phenotype, we identified other movement-disorder manifestations, including myokymia, myoclonus, dystonia, and parkinsonism, with nigrostriatal degeneration confirmed in one patient. Cognitive impairment was common, with two-thirds of patients fulfilling criteria for cerebellar cognitive-affective syndrome (mean MoCA: 25 [21-29], CCAS: 86.9/120 [62-108]). Worse CCAS and MoCA performance was associated with increasing ataxia severity. FGF14 repeat expansions ranged from 210 to 520, and co-occurrence with heterozygous expansions in RFC1 or ATXN8/ATXN8OS were identified in three patients. Earlier diagnostic misclassification as transient ischemic attack was reported in 33%. These findings expand the known phenotype of spinocerebellar ataxia type 27B, emphasizing it as a multisystem movement disorder.