Objective: To present the first reported case of Spinocerebellar Ataxia 27B (SCA27B) and clinically probable Multiple System Atrophy-Cerebellar subtype (MSA-C) with skin biopsy positive for alpha synuclein.

Background: SCA27B is a recently identified cause of late onset cerebellar ataxia¹. Symptoms may include parkinsonism and autonomic dysfunction, making phenotypic overlap with MSA a diagnostic challenge.  Pathogenic GAA expansions in FGF14 have been found in pathologically confirmed cases of MSA².  We report, to our knowledge, the first case of SCA27B presenting with clinical phenotype consistent with MSA-C and positive phosphorylated alpha synuclein on skin biopsy.

Method: Patient developed urinary frequency at age 60. Three years later, he developed postural dizziness, frequent falls, erectile dysfunction, and urinary incontinence. Over time, he noted decreased dexterity, shuffling gait, and dysphagia. His exam was notable for cerebellar findings, including direction changing nystagmus, dysmetria on finger-to-nose and heel-to-shin testing, and dysdiadochokinesia with rapid alternating movements. Gait was wide based with inability to tandem walk, and postural instability. Autonomic testing was consistent with neurogenic orthostatic hypotension. Post void residual was >500cc.

The patient met criteria for clinically probable MSA-C with core features of autonomic dysfunction and cerebellar syndrome, with supportive features of rapid progression and moderate postural instability within three years³.

Family history was notable for his mother with episodic dizziness and frequent falls in her 80s, and maternal grandmother with similar episodic dizziness and hand tremors.

Results: Skin biopsy revealed phosphorylated alpha-synuclein deposition in all three skin biopsy sites. Genetic testing demonstrated heterozygous pathogenic 346 GAA repeat expansion detected in the FGF14 gene, consistent with SCA27B. The patient was responsive to midodrine for orthostatic hypotension, and mirabegron for urinary symptoms. Treatment with 4-aminopyridine was offered but declined.

Conclusion: The clinical and genetic overlap of MSA and SCA27B is an evolving area of investigation and discovery. This case highlights the importance of considering SCA27B in patients with a family history of ataxia, even when the clinical presentation fulfills diagnostic criteria for MSA-C and alpha-synuclein is detected on skin biopsy.

References: 1. Pellerin D, Danzi MC, Wilke C, et al. Deep Intronic FGF14 GAA Repeat Expansion in Late-Onset Cerebellar Ataxia. New England Journal of Medicine. 2023;388(2):128-141. doi:https://doi.org/10.1056/nejmoa2207406
2. Viorica Chelban, Pellerin D, Nirosen Vijiaratnam, et al. Intronic FGF14 GAA repeat expansions impact progression and survival in multiple system atrophy. Brain. 2025;148(9):3252-3265. doi:https://doi.org/10.1093/brain/awaf134
3. Wenning GK, Stankovic I, Vignatelli L, et al. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy. Mov Disord. 2022;37(6):1131-1148. doi:10.1002/mds.29005

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sca27b-and-msa-c-with-positive-alpha-synuclein-skin-biopsy-case-report/