69-Year-Old Female with Progressive Supranuclear Palsy, Frontotemporal Dementia, Focal Hyperkinesia and one variant in the GCH1 gene and in the CSF1R gene

Abstract

How insignificant is the detection of gene variants in a novel clinical presentation of an atypical Parkinson’s syndrome with positive family history? We present the case of a 69-year-old woman with Progressive Vertical Supranuclear Palsy (PSP), focal hyperkinesia, non-L-dopa-responsive asymmetrical Parkinsonism, postural instability as well as apraxia, cognitive, speech and frontal disorder, with a positive family history, MRI evidence of mesial temporal atrophy and tau-PET evidence of tau pathology as well as identification of one variant in the GCH1 gene and one variant in the CSF1R gene. The fact that the clinical presentation and radiological finding of our patients are not compatible with a known and well described genetic disorder caused by pathogenic mutations of these genes, supports the notion that the detected gene variants have an uncertain significance in the pathogenesis of our patient’s disease. Nevertheless, the novel description of the phenotype of our case of PSP with frontal lobe features, focal hyperkinesia and a positive family history, points to an in-vivo tauopathy, in which a genetic burden may play a role. The follow-up of the patient und her family may offer further insights into the pathophysiology of complex neurodegenerative diseases in the spectrum of tauopathies, offering possible new therapeutic targets.