Category: Ataxia
Objective: The aim of this study was to investigate the presence of pathogenic repeat expansion in the FGF14 gene in patients with adult-onset cerebellar ataxia in the Serbian population.
Background: The newly discovered deep intronic GAA repeat expansion in the Fibroblast Growth Factor (FGF14) gene was recently reported as the cause of autosomal dominant late-onset cerebellar ataxia.
Method: First, the symptomatic and most frequent hereditary ataxias (SCA1, 2, 3, 6, 7, 17 and Friedreich’s ataxia) were excluded in 90 patients with autosomal dominant and sporadic cerebellar ataxia. FGF14 mutation analysis was performed by long-range PCR. All patients were neurologically examined, including nerve conduction studies and MRI of the brain in all patients.
Results: Family history for autosomal dominant inheritance was known to be positive in only four patients. Pathogenic GAA repeat expansions of more than 270 repeats were found in 11 patients (12.2%). The first manifestation started at the age of 27 to 66 years as gait ataxia in 10 of the patients, while one patient had spastic paraparesis at onset and later also developed gait ataxia. Dysarthria and limb ataxia were reported in 73% of patients. All patients had oculomotor abnormalities such as gaze-evoked nystagmus 55%, broken smooth pursuit 36%, and in 27% downbeat nystagmus and slow saccades. Pyramidal signs such as spasticity were seen in 18%, increased deep tendon reflexes 55%, and extensor plantar response in 18% of the expansion carriers. Nerve conduction studies showed signs of sensorimotor neuropathy in 36% of FGF14 patients. Marked global brain atrophy was found in 8 patients, frontal and cerebellar atrophy in one, and isolated cerebellar atrophy in another patient, while one mutation carrier had a normal MRI of the brain.
Conclusion: GAA intronic repeat expansions in the FGF14 gene are the frequent cause (>10%) of autosomal dominant adult-onset cerebellar ataxia, also in patients with sporadic onset of cerebellar ataxia.
To cite this abstract in AMA style:
A. Milovanović, NT. Dragašević Mišković, M. Borsche, A. Westenberger, N. Brueggemann, M. Svetel, I. Petrović, VS. Kostić, K. Lohmann. FGF14 repeat expansions: Case series of adult-onset cerebellar ataxia patients from Serbia [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/fgf14-repeat-expansions-case-series-of-adult-onset-cerebellar-ataxia-patients-from-serbia/. Accessed June 15, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/fgf14-repeat-expansions-case-series-of-adult-onset-cerebellar-ataxia-patients-from-serbia/