Challenges in the diagnosis of spinocerebellar ATAXIA 27B

To characterize the clinical, radiologic, and genetic spectrum of patients with (GAA) repeat expansions in FGF14 gene and to analyze diagnostic challenges associated with spinocerebellar ataxia type 27B (SCA27B).

We retrospectively evaluated a Spanish cohort of 53 adults with idiopathic late-onset cerebellar ataxia. The intronic FGF14 repeat locus was examined by fluorescent long-range PCR to determine allele size, by bidirectional repeat-primed PCR to verify the presence and nature of the expansion. Clinical data, neuroimaging findings, and response to 4-aminopyridine were collected.

Among 53 ataxia patients, 39.62% (21/53) carried uninterrupted >200 (GAA) repeats in FGF14, all in heterozygosity. Of these, 71.42% (15/21) exhibited >250 repeats, corresponding to 28.30% of the total cohort, and 73.33% (11/15) had >300 repeats, representing 20.75% overall. Additionally, 11.32% (6/53) of patients carried (GAA) 200-249 repeats, four of whom presented phenotypes compatible with SCA27B. Neuroimaging showed cerebellar atrophy in 7/21 and superior cerebellar peduncle hyperintensity in MRI of 7/17, including two patients with 200-249 (GAA) repeats. Seventeen patients received 4-aminopyridine; 11 continued therapy and 9 reported clinical improvement.

SCA27B is a frequent cause of idiopathic late-onset cerebellar ataxia. Downbeat nystagmus, episodic symptoms, and superior cerebellar peduncle abnormalities increase diagnostic suspicion. Expansions >250 (GAA) repeats are highly predictive, whereas 200-250 may be pathogenic in compatible phenotypes. Early identification is difficult but crucial given the potential therapeutic benefit of 4-aminopyridine.