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

Frontiers in Neurology

Kaitlin Seibert¹  Allison Lapins¹  James A. Mastrianni¹  Peter Pytel²  Heather Smith² 

[1] Department of Neurology, Center for Comprehensive Care and Research on Memory Disorders, University of Chicago, Chicago, IL, United States;Department of Pathology, University of Chicago, Chicago, IL, United States;

关键词: frontotemporal dementia;    corticobasal syndrome;    TBK1;    motor neuron disease;    dementia;   

DOI  :  10.3389/fneur.2022.826676

来源: DOAJ

【 摘 要 】

Several variants of the TANK-Binding Kinase 1 (TBK1) 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 MAPT and GRN 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 TBK1 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 TBK1 variant. This case emphasizes the importance of considering TBK1 genetic screening in patients with CBS, as this may be an underrepresented population on the spectrum of genetic FTD-ALS.

【 授权许可】

Unknown