FBXO7 pathogenic variants in early-onset parkinsonism: insights from a neuroimaging perspective and review of the literature

Abstract

BackgroundEarly onset parkinsonism caused by F-box only protein7 (FBXO7) pathogenic variants is a rare autosomal recessive disorder presenting with a combination of parkinsonism, pyramidal signs, dystonia, cognitive impairment, and psychiatric features. Although previous case reports have mentioned neuroimaging findings, there is no comprehensive study characterizing the radiological spectrum of FBXO7 pathogenic variants.CasesTen patients from seven families followed at two tertiary centers in Turkey were included. The cohort included six males and four females with a mean onset age of 21.1 years. Frontal atrophy was the most common MRI finding, followed by global cortical and cerebellar atrophy. One patient showed iron accumulation in the pallidum, and two exhibited severe dopaminergic deficit on DaTSCAN.Literature ReviewPathogenic variants in the FBXO7 gene have been identified in diverse populations over the past 15 years, contributing to a broader understanding of clinical and radiological spectrum. Global cortical atrophy has emerged as the most frequently reported neuroimaging finding in FBXO7-related parkinsonism.ConclusionsFBXO7 pathogenic variants are associated with heterogeneous neuroimaging findings. Frontal and global cortical atrophy are common, while iron deposition and DaTSCAN abnormalities offer additional diagnostic clues. Larger, longitudinal studies are necessary to establish specific imaging biomarkers for FBXO7-related neurodegeneration.