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

Abstract

AbstractBackgroundHeterozygous 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.ObjectivesTo estimate the prevalence, characterize the phenotypic spectrum, identify discriminative features, and model longitudinal progression of SCA27B in a prospective cohort of SLOCA patients.MethodsFGF14 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.ResultsPrevalence 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.ConclusionsFGF14 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.