The Right Temporal Variant of Frontotemporal Dementia Is Not Genetically Sporadic: A Case Series

Abstract

Background: Right temporal variant frontotemporal dementia (rtvFTD) has been generally considered as a right sided variant of semantic variant primary progressive aphasia (svPPA), which is a genetically sporadic disorder. Recently, we have shown that rtvFTD has a unique clinical syndrome compared to svPPA and behavioral variant frontotemporal dementia.

Objective: We challenge the assumption that rtvFTD is a sporadic, non-familial variant of FTD by identifying potential autosomal dominant inheritance and related genes in rtvFTD.

Methods: We collected all subjects with a diagnosis of FTD or primary progressive aphasia who had undergone genetic screening (n = 284) and subsequently who had a genetic variant (n = 48) with a diagnosis of rtvFTD (n = 6) in 2 specialized memory clinics.

Results: Genetic variants in FTD related genes were found in 33% of genetically screened rtvFTD cases; including MAPT (n = 4), GRN (n = 1), and TARDBP (n = 1) genes, whereas only one svPPA case had a genetic variant in our combined cohorts. Additionally, 4 out of 6 rtvFTD subjects had a strong family history for dementia.

Conclusion: Our results demonstrate that rtvFTD, unlike svPPA, is not a pure sporadic, but a heterogeneous potential genetic variant of FTD, and screening for genetic causes for FTD should be performed in patients with rtvFTD.

Keywords: Dementia; GRN; MAPT; TARDBP; frontotemporal dementia; frontotemporal lobar degeneration; genetic; right temporallobe.

Fig. 1

Patient selection.

Fig. 2

Pathological features of Case 3. Anterior cingulate cortex stained with phospho-tau (p-tau) monoclonal antibody (AT8: Pierce Biotechnology, Rockford, IL, USA). Extensive 3R and 4R tauopathy which is characteristic for MAPT related frontotemporal lobar degeneration is observed in neurons across all layers.