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Original research
Early life involvement in C9orf72 repeat expansion carriers
  1. Flora Gossink1,
  2. Annemiek Dols2,
  3. Max L Stek2,
  4. Philip Scheltens1,
  5. Bas Nijmeijer3,
  6. Petra Cohn Hokke4,
  7. Anke Dijkstra4,
  8. Fred Van Ruissen5,
  9. Cora Aalfs6,
  10. Yolande A L Pijnenburg1
  1. 1 Alzheimer Center, Department of Neurology, Location VU University Medical Center, Amsterdam University Medical Centres, Amsterdam, The Netherlands
  2. 2 Department of Old Age psychiatry, GGZ inGeest Amsterdam locatie De Nieuwe Valerius, Amsterdam, The Netherlands
  3. 3 Clinical Genetics, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
  4. 4 Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
  5. 5 Department of Clinical Genetics, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
  6. 6 UMC Utrecht, Utrecht, The Netherlands
  1. Correspondence to Ms Flora Gossink, Neurology, Amsterdam UMC Locatie VUmc, Amsterdam 1081 HV, The Netherlands; f.gossink{at}


Objectives The chromosome 9 open reading frame 72 gene (C9orf72) hexanucleotide repeat expansion (C9orf72RE) is the most common genetic cause of behavioural variant frontotemporal dementia (bvFTD). Since the onset of the C9orf72RE-associated disease is sometimes hard to define, we hypothesise that C9orf72RE may cause a lifelong neuropsychiatric vulnerability. The first aim of our study was to explore lifelong behavioural and personality characteristics in C9orf72RE. Second, we aimed to describe distinctive characteristics of C9orf72RE during disease course.

Methods Out of 183 patients from the Amsterdam Dementia Cohort that underwent genetic testing between 2011 and 2018, 20 C9orf72RE bvFTD patients and 23 C9orf72RE 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 C9orf72RE, revealing that subtle personality traits may be present early in life. Our study suggests that C9orf72RE exerts a lifelong neuropsychiatric vulnerability. This may strengthen hypotheses of links between neurodevelopmental and neurodegenerative diseases. Moreover, the presence of a distinct C9orf72RE -associated syndrome within the FTD spectrum opens doors for investigation of vulnerable neuronal networks.

Data availability statement

Data are available on reasonable request. Data are available in written form through contact with FG,

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Data availability statement

Data are available on reasonable request. Data are available in written form through contact with FG,

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  • Correction notice This article has been correcedt since it appeared Online First. Author name has been corrected to "Van Ruissen".

  • Contributors FG, AD, CA and YALP had the idea for thepaper. FG prepared the first draft with YALP. FG prepared the draft figures together with AD. AD, MLS, PS, SN, PC, AD, FVR and CA assistedwith interpretation of the data and critically reviewed the first version of the manuscript. FG, AD, SN, PC, AD, FVR, AC and YALP were involved in the clinical care of the patients. FG wrote the final version of the manuscript together, first reviewed by YALP and it was then critically reviewed for intelectual content by AD, MLS, PS, SN, PC, AD, FVR and CA.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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