Corticobasal syndrome associated with a novel Lys694del variant of the TBK1 gene.

Abstract

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), characterized by asymmetric limb rigidity, dystonia or myoclonus, in association with speech or limb apraxia, cortical sensory deficit, and/or alien limb can result from a variety of underlying pathologies. It is most commonly sporadic, although it has been rarely described in association with genetic defects, especially MAPT and GRN genes. Case study. We describe the proband of a family with multiple occurrences of FTD-ALS spectrum disease who presented with a primary asymmetric akinetic-rigid syndrome with later speech involvement and cognitive dysfunction, contralateral anterior temporal lobe atrophy on MRI and corresponding hypometabolism by FDG-PET, who carried a novel Lys694del variant of the TBK1 gene and predominant Type A TDP-43 pathology in a frontotemporal distribution that was contralateral to the affected side. Although CBS has been described as a late feature of agrammatic primary progressive aphasia (PPA) in a patient carrying a different variant TBK1, to our knowledge our case is the first report of a patient presenting with asymmetric akinetic rigidity as the initial expression of a TBK1 variant. This case provides further support to consider TBK1 genetic screening in patients with CBS and a family history suggestive of FTD-ALS spectrum diseases, as this may be an underrepresented population on the spectrum of genetic FTD-ALS.