Spinocerebellar ataxia 27B (FGF14 repeat expansion): Clinical spectrum, diagnostic pitfalls, and implications for late-onset ataxia

Abstract

Spinocerebellar ataxia 27B (SCA27B; OMIM 620174) is an autosomal dominant late-onset cerebellar ataxia (LOCA) caused by intronic GAA repeat expansions in FGF14 , first described in 2023. Since its discovery, SCA27B has emerged as a major genetic cause of previously unexplained LOCA across multiple populations. We conducted a narrative review following the Scale for the Assessment of Narrative Review Articles (SANRA) guidance. PubMed, Embase, and Scopus were searched from January 2022 to April 2026 using terms related to SCA27B, FGF14 , GAA repeat expansions, downbeat nystagmus, and aminopyridine therapy. Reference lists of key studies were hand-searched. Human peer-reviewed studies were included, and evidence was synthesized qualitatively by domain. SCA27B typically presents with slowly progressive cerebellar ataxia, prominent downbeat nystagmus, and episodic symptoms such as vertigo, oscillopsia, and transient ataxia that may precede fixed deficits by years. These features are important diagnostic clues in patients otherwise labeled as having idiopathic ataxia or multiple system atrophy of cerebellar type. Prevalence among unsolved LOCA cohorts varies geographically, ranging from 1.2–1.3% in Japan and 1.83% in India to 15–30% in Europe and up to 60% in French-Canadians because of a founder effect. SCA27B is clinically actionable, as many patients experience symptomatic improvement with aminopyridines, particularly 4-aminopyridine. However, evidence remains observational, with no randomized controlled trials available. We review the genetics, epidemiology, clinical spectrum, imaging findings, differential diagnosis, and management of SCA27B, and support routine FGF14 testing in patients with unexplained late-onset ataxia, downbeat nystagmus, or episodic cerebellar symptoms.