Early life involvement in C9orf72 repeat expansion carriers

Abstract

Objectives The chromosome 9 open reading frame 72 gene (C9orf72) hexanucleotide repeat expansion (C9orf72 RE ) is the most common genetic cause of behavioural variant frontotemporal dementia (bvFTD). Since the onset of the C9orf72 RE -associated disease is sometimes hard to define, we hypothesise that C9orf72 RE may cause a lifelong neuropsychiatric vulnerability. The first aim of our study was to explore lifelong behavioural and personality characteristics in C9orf72 RE . Second, we aimed to describe distinctive characteristics of C9orf72 RE during disease course. Methods Out of 183 patients from the Amsterdam Dementia Cohort that underwent genetic testing between 2011 and 2018, 20 C9orf72 RE bvFTD patients and 23 C9orf72 RE negative bvFTD patients were included. Patients and their relatives were interviewed extensively to chart their biography. Data analysis was performed through a mixed-methods approach including qualitative and quantitative analyses. Results Education, type of professional career and number of intimate partners were not different between carriers and non-carriers. Carriers were more often described by their relatives as having ‘fixed behavioural patterns in daily life’ and with limited empathy already years before onset of bvFTD symptoms. In carriers, disease course was more often characterised by excessive buying and obsessive physical exercise than in non-carriers. Conclusion This is the first study thoroughly exploring biographies of bvFTD patients with C9orf72 RE , revealing that subtle personality traits may be present early in life. Our study suggests that C9orf72 RE exerts a lifelong neuropsychiatric vulnerability. This may strengthen hypotheses of links between neurodevelopmental and neurodegenerative diseases. Moreover, the presence of a distinct C9orf72 RE -associated syndrome within the FTD spectrum opens doors for investigation of vulnerable neuronal networks.