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. 2023 Oct;38(10):1950-1956.
doi: 10.1002/mds.29560. Epub 2023 Jul 20.

Natural History and Phenotypic Spectrum of GAA-FGF14 Sporadic Late-Onset Cerebellar Ataxia (SCA27B)

Thomas Wirth  1   2   3 , Guillemette Clément  4 , Clarisse Delvallée  1   2   3 , Céline Bonnet  5   6 , Thomas Bogdan  1 , Andra Iosif  7 , Audrey Schalk  2   8 , Jean-Baptiste Chanson  1   2   9 , David Pellerin  10   11 , Bernard Brais  10 , Virginie Roth  5 , Marion Wandzel  5 , Marie-Céline Fleury  1   2 , Amélie Piton  2   3   8 , Nadège Calmels  2   8 , Izzie Jacques Namer  12   13   14 , Stéphane Kremer  13   15 , Christine Tranchant  1   2   3 , Mathilde Renaud  4   6   16 , Mathieu Anheim  1   2   3
Affiliations

Natural History and Phenotypic Spectrum of GAA-FGF14 Sporadic Late-Onset Cerebellar Ataxia (SCA27B)

Thomas Wirth et al. Mov Disord. 2023 Oct.

Abstract

Background: Heterozygous GAA expansions in the FGF14 gene have been related to autosomal dominant cerebellar ataxia (SCA27B-MIM:620174). Whether they represent a common cause of sporadic late-onset cerebellar ataxia (SLOCA) remains to be established.

Objectives: To estimate the prevalence, characterize the phenotypic spectrum, identify discriminative features, and model longitudinal progression of SCA27B in a prospective cohort of SLOCA patients.

Methods: FGF14 expansions screening combined with longitudinal deep-phenotyping in a prospective cohort of 118 SLOCA patients (onset >40 years of age, no family history of cerebellar ataxia) without a definite diagnosis.

Results: Prevalence of SCA27B was 12.7% (15/118). Higher age of onset, higher Spinocerebellar Degeneration Functional Score, presence of vertigo, diplopia, nystagmus, orthostatic hypotension absence, and sensorimotor neuropathy were significantly associated with SCA27B. Ataxia progression was ≈0.4 points per year on the Scale for Assessment and Rating of Ataxia.

Conclusions: FGF14 expansion is a major cause of SLOCA. Our natural history data will inform future FGF14 clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: FGF14; SCA27B; cerebellar ataxia; genetics; natural history; phenotyping.

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References

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