Objective: To describe the phenotypic spectrum of patients with Spinocerebellar ataxia 27B (SCA27B).

Background: SCA27B is a recently recognized cause of adult-onset ataxia caused by a GAA repeat expansion in intron 1 of the fibroblast growth factor 14 gene [1]. It was first described in 2023 and is a growing cause of adult-onset ataxia, estimated to account for up to 61% of previously undiagnosed adult-onset ataxia [1–3].

Method: This was a retrospective observational study using routine clinical care data from adult patients (≥18 years) seen in the Mayo Clinic Ataxia Clinic from July 2023 to September 2025 with genetic confirmation of SCA27B.

Results: Twenty-eight patients with genetically confirmed SCA27B were identified (13 female, 15 male), with a mean age of onset of 58 years. Episodic symptoms were common at presentation (20/28, 71%), most frequently triggered by exercise. The mean time to diagnosis was 9 years.

Gait ataxia was present in all patients, followed by cerebellar ocular motor abnormalities (19/28, 68%), including downbeat nystagmus (14/28, 50%). Neuropathy was present in over half of the patients (18/28, 64%).

Five patients had a coexisting functional neurological disorder, manifesting as functional tremor or speech disorder, which was confirmed by electrophysiologic testing or formal speech evaluation. MRI findings were subtle, with vermian atrophy in 10/28 (36%) and cerebellar atrophy in 14/28 (50%). A family history of ataxia was present less than half of the cohort (11/28, 39%). Most patients remained ambulatory without gait aids, with only 11/28 (40%) requiring assistance at an average of 10 years after symptom onset.

Conclusion: SCA27B is a recently described genetic ataxia that often begins with episodic symptoms, which can delay recognition and diagnosis [1-3]. In our cohort, many patients did not have a family history and presented with a range of phenotypes, although symptoms most often began episodically over half of the cohort and were frequently triggered by exercise. We found that patient presentation can be clinically heterogeneous, with half of our patients having cerebellar atrophy and a small minority with positive family history. The episodic nature of symptoms, late age of onset, and co-existent functional overlay may further contribute to delays in diagnosis. We hope that our findings increase awareness of this newly recognized cause of adult-onset ataxia, leading to earlier recognition and diagnosis.

References: 1. Pellerin D, Danzi MC, Wilke C, Renaud M, Fazal S, Dicaire MJ, Scriba CK, Ashton C, Yanick C, Beijer D, Rebelo A, Rocca C, Jaunmuktane Z, Sonnen JA, Larivière R, Genís D, Molina Porcel L, Choquet K, Sakalla R, Provost S, Robertson R, Allard-Chamard X, Tétreault M, Reiling SJ, Nagy S, Nishadham V, Purushottam M, Vengalil S, Bardhan M, Nalini A, Chen Z, Mathieu J, Massie R, Chalk CH, Lafontaine AL, Evoy F, Rioux MF, Ragoussis J, Boycott KM, Dubé MP, Duquette A, Houlden H, Ravenscroft G, Laing NG, Lamont PJ, Saporta MA, Schüle R, Schöls L, La Piana R, Synofzik M, Zuchner S, Brais B. Deep Intronic FGF14 GAA Repeat Expansion in Late-Onset Cerebellar Ataxia. N Engl J Med. 2023 Jan 12;388(2):128-141. doi: 10.1056/NEJMoa2207406. Epub 2022 Dec 14. PMID: 36516086; PMCID: PMC10042577.

2. Pellerin D, Danzi MC, Renaud M, et al. Spinocerebellar ataxia 27B: A novel, frequent and potentially treatable ataxia. Clin Transl Med. 2024;14:e1504.

3. Hengel H, Pellerin D, Wilke C, Fleszar Z, Brais B, Haack T, Traschütz A, Schöls L, Synofzik M. As Frequent as Polyglutamine Spinocerebellar Ataxias: SCA27B in a Large German Autosomal Dominant Ataxia Cohort. Mov Disord. 2023 Aug;38(8):1557-1558. doi: 10.1002/mds.29559. Epub 2023 Aug 1. PMID: 37528564.

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