The phenotype of the C9ORF72 expansion carriers according to revised criteria for bvFTD
Open accessAbstract
BACKGROUND: The C9ORF72 expansion is one of the most common genetic etiologies observed with behavioural variant frontotemporal dementia (bvFTD). Revised diagnostic criteria for bvFTD (FTDC) were recently introduced but only a few studies have evaluated the accuracy of these criteria. OBJECTIVE: The objective of the study was to evaluate the applicability of the FTDC criteria and assess the psychiatric history of these patients. METHODS: The study examined 36 patients carrying the C9ORF72 expansion and suffering from bvFTD (N = 32) or from bvFTD with motor neuron disease (bvFTD-MND, N = 4). Neuropsychological, neuropsychiatric, structural brain imaging and PET/SPECT data were evaluated. RESULTS: We found 0.75 sensitivity (SD 0.44, 95%CI 0.57-0.87) for possible bvFTD and 0.64 (SD 0.44, 95%CI 0.57-0.87) for probable bvFTD. The sensitivity was even higher in bvFTD patients without MND, i.e., 0.81 for possible bvFTD and 0.69 for probable bvFTD. PET/SPECT was normal in 17.6% of scanned patients with bvFTD. A history of psychiatric symptoms (psychotic and/or mood symptoms) was detected in 61% of cases. CONCLUSIONS: The FTDC possible and probable bvFTD criteria seem to identify the majority of the C9ORF72 expansion carriers with bvFTD, even though they exhibit only a limited number of behavioral criteria but a significant amount of psychiatric symptoms. The presence of a normal PET/SPECT does not exclude the possibility the C9ORF72 associated bvFTD.
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C9orf72 repeat expansion carriers can present with psychiatric symptoms and form a diagnostic challenge given their slow progressive course and atypical findings in neuroimaging.
“C9orf72 repeat expansion carriers can present with psychiatric symptoms and form a diagnostic challenge given their slow progressive course and atypical findings in neuroimaging (see 'Genetic testing' section) (Khan et al. , 2012; Solje et al. , 2015; Ducharme et al. , 2017).”
From Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders (2020) · cites this paper as Solje et al., 2015
The Results (page unavailable) report psychiatric symptoms in 61.1% of carriers, a mean 4.6-year delay from psychiatric symptoms to bvFTD diagnosis, and some imaging findings that did not meet bvFTD criteria. These findings support the psychiatric presentation and diagnostic difficulty. They do not establish a generally slow progressive course: the Results describe one patient with a 40-year progressive disorder, while Table 1 reports a mean 2.1 years from symptom onset to diagnosis. (LLM, conf=0.85)
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References 19 · Cited by 46
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- Authors
- Solje, E., Aaltokallio, H., Koivumaa-Honkanen, H., Suhonen, N. M., Moilanen, V., Kiviharju, A., Traynor, B., Tienari, P. J., Hartikainen, P., & Remes, A. M.
- Affiliations
- University of Eastern Finland (FI)
- Oulu University Hospital (FI)
- University of Helsinki (FI)
- National Institutes of Health (US)
- Kuopio University Hospital (FI)
- Corresponding author
- Remes, Anne M.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-07-06
- Volume
- 10
- Issue
- 7
- Pages
- e0131817
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4493025
- OpenAlex
- W2225889451
- Cited by
- 46
- References
- 19
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 4 · 2015: 2
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Työväentutkimus Vuosikirja (submittedVersion)
- Funders
- ALS Association
- Microsoft Research
- Helsingin ja Uudenmaan Sairaanhoitopiiri
- Suomen Lääketieteen Säätiö
- Kuopion Yliopistollinen Sairaala
- National Institutes of Health (Z01‐AG000949‐02, Z01-AG000949)
- National Institute on Aging (Z01AG000949)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- C9orf72 expansion, behavioral variant frontotemporal dementia, diagnostic sensitivity, psychiatric symptoms, psychosis, mood symptoms, motor neuron disease, genetic frontotemporal dementia
- MeSH terms
- C9orf72 Protein, Aged, Mental Disorders, Genetic Carrier Screening, Humans, Magnetic Resonance Imaging, Middle Aged, Phenotype, Proteins, Cohort Studies, Tomography, Emission-Computed, Single-Photon, Positron-Emission Tomography, Frontotemporal Dementia
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