Neuropathy in GAA-FGF14 Late-Onset Cerebellar Ataxia (SCA27B): Prevalence and Characteristics

This study aimed to investigate the prevalence, characteristics, and determinants of peripheral neuropathy in a large cohort of patients affected by spinocerebellar ataxia type 27B (SCA27B), a late-onset cerebellar ataxia caused by heterozygous GAA repeat expansions in the first intron of the FGF14 gene.

A retrospective, multicenter study in which medical records of SCA27B patients diagnosed between January 2023 and July 2024 in 21 French ataxia/neurogenetic centers were reviewed. Those who had undergone electrodiagnostic study were included.

Among 332 SCA27B patients, 170 had undergone an electrodiagnostic study and were included. Forty-two (25%) were diagnosed with neuropathy: 16 with length-dependent axonal sensorimotor neuropathy, 24 with length-dependent axonal sensory neuropathy, one with sensory, and one with motor neuronopathy. Neuropathy was associated with male sex, older age at electrodiagnostic study, and risk factors for neuropathy but not with GAA expansion sizes. Patients with neuropathy had more severe disability at the last visit (median SARA score 12 vs. 8, p = 0.0024).

The prevalence of neuropathy in SCA27B patients was similar to that reported in the elderly general population. Neuropathies were predominantly non-specific length-dependent axonal neuropathies, primarily driven by aging and known risk factors rather than the underlying genetic abnormality.