Motor Neuron Disease-Frontotemporal Dementia Spectrum Disorder: A Different Phenotype Related With a Novel TBK1 Gene Variant

The association of frontotemporal dementia (FTD) and motor neuron disease (MND) is a clinical continuum with genetic and neuropathological overlap. Cohort analysis has been broadening our phenotypic and genotypic knowledge on amyotrophic lateral sclerosis-frontotemporal dementia spectrum disorders. A 57-year-old woman presented with a progressive speech disturbance followed by the development of progressive upper MND in the next 2 years. Rapid progression of disease included anarthria, severe dysphagia requiring a gastrostomy tube and a tetrapyramidal syndrome without lower motor neuron signs. Death occurred within 4 years. Complementary investigation showed a left mesial temporal and frontal lobe atrophy, as well as a corticospinal tract hyperintensity on magnetic resonance imaging (MRI). Hypometabolism in the left parietal-temporal and frontal lobes was also evident in FDG-PET. The association of progressive apraxia of speech with upper motor neuron signs in our patient prompted genetic testing and the finding of a novel TBK1 gene variant. Genetic testing should be considered in patients presenting with FTD, particularly with a positive family history or secondarily associated with an MND. Population-based studies are needed to clarify the prevalence and clinical phenotypes of TBK1 variant carriers. J Neurol Res. 2024;14(1):43-47 doi: https://doi.org/10.14740/jnr765