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

• Published in: Movement disorders Vol. 38; no. 10; pp. 1950 - 1956
• Main Authors: Wirth, Thomas, Clément, Guillemette, Delvallée, Clarisse, Bonnet, Céline, Bogdan, Thomas, Iosif, Andra, Schalk, Audrey, Chanson, Jean-Baptiste, Pellerin, David, Brais, Bernard, Roth, Virginie, Wandzel, Marion, Fleury, Marie-Céline, Piton, Amélie, Calmels, Nadège, Namer, Izzie Jacques, Kremer, Stéphane, Tranchant, Christine, Renaud, Mathilde, Anheim, Mathieu
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-10-2023; Wiley
• Subjects: Ataxia; Cerebellar ataxia; Cerebellum; Clinical trials; Cognitive science; Genetics; Hypotension; Life Sciences; Movement disorders; Neuropathy; Neuroscience; Phenotyping; Sensorimotor system; cerebellar ataxia; FGF14; genetics; SCA27B; natural history; phenotyping; cerebellar ataxia genetics FGF14 natural history phenotyping SCA27B
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.29560

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