A Novel TBK1 Variant (Lys694del) Presenting With Corticobasal Syndrome in a Family With FTD-ALS Spectrum Diseases: Case Report

• Published in: Frontiers in neurology 2022-03, Vol.13, p.826676
• Main Authors: Seibert, Kaitlin, Smith, Heather, Lapins, Allison, Pytel, Peter, Mastrianni, James A
• Format: Article
• Language: English
• Subjects: corticobasal syndrome; dementia; frontotemporal dementia; motor neuron disease; Neurology; TBK1
• ISSN: 1664-2295; 1664-2295
• DOI: 10.3389/fneur.2022.826676

Several variants of the TANK-Binding Kinase 1 ( ) gene have been associated with frontotemporal dementia - amyotrophic lateral sclerosis (FTD-ALS) spectrum diseases. Corticobasal syndrome (CBS) is characterized by asymmetric limb rigidity, dystonia or myoclonus, in association with speech or limb apraxia, cortical sensory deficit, and/or alien limb. It can result from a variety of underlying pathologies and although typically sporadic, it has been occasionally associated with and variants. We describe here the proband of a family with multiple occurrences of FTD-ALS spectrum disease who developed an isolated right-sided primary asymmetric akinetic-rigid syndrome and subsequent speech and cognitive dysfunction associated with contralateral anterior temporal lobe atrophy on MRI and corresponding hypometabolism by FDG-PET. Genetic testing revealed a novel Lys694del variant of the gene and Type A TDP-43 pathology in a predominantly frontotemporal distribution contralateral to the affected side. To our knowledge this is the first report of CBS as the initial expression of a variant. This case emphasizes the importance of considering genetic screening in patients with CBS, as this may be an underrepresented population on the spectrum of genetic FTD-ALS.