FBXO7- associated parkinsonism: clinical, genetic, and radiological insights from a case report and literature review.

backgroundVariants in the FBXO7 gene are a recognized cause of juvenile-onset autosomal recessive parkinsonism (PARK15) with a heterogeneous phenotype. There is limited number of reported cases in the literature.

objectiveTo report a 19-year-old Indian man with juvenile-onset parkinsonism harbouring a novel FBXO7 variant and to review the published literature on FBXO7-associated parkinsonism/parkinsonism-pyramidal syndrome, focusing on the clinical, imaging, and genetic spectrum and possible genotype-phenotype correlations.

methodsWe evaluated an Indian male with FBXO7-associated juvenile parkinsonism and reviewed previously published cases from the literature to assess the clinical, imaging, and genetic spectrum.

resultsA total of 32 cases of FBXO7-associated parkinsonism, including our patient, were identified. The median age at onset was 17 years, median age at presentation was 28 years, with slight male predominance and a median disease duration of 5 years. Symmetrical juvenile-onset parkinsonism with tremor and postural instability was the commonest presentation. Dementia, dystonia, pyramidal signs, and gaze abnormalities were less frequent associated features. Most patients showed levodopa responsiveness, although motor complications and psychiatric adverse effects were common. Neuroimaging findings were heterogeneous, ranging from cortical atrophy to pallidal hypointensity and presynaptic dopaminergic deficits on dopamine transporter imaging. Twenty variants were identified, with the homozygous nonsense variant c.1492 C > T (p.Arg498*) being the most frequently reported.

conclusionFBXO7-associated parkinsonism typically presents as symmetrical juvenile-onset levodopa-responsive parkinsonism, although early-onset parkinsonism is known. Dementia, dystonia, and pyramidal signs are less frequent associated features. FBXO7 variants should be considered in patients with symmetrical juvenile/early-onset parkinsonism, especially when accompanied by levodopa-induced psychiatric adverse effects.