Frontotemporal dementia with amyotrophic lateral sclerosis: a clinical comparison of patients with and without repeat expansions in C9orf72.

Julie S Snowden, Jennifer Harris, Anna Richardson, Sara Rollinson, Jennifer C Thompson, David Neary, David M A Mann, Stuart Pickering-Brown

    Research output: Contribution to journalArticlepeer-review


    Repeat expansions in C9orf72 are a major cause of frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS). Not all FTD-ALS patients show expansions. The study examined whether there are clinical differences between FTD-ALS patients with and without expansions in C9orf72. We examined case notes from consecutive FTD-ALS patients, screened for C9orf72 expansions, and documented demographic, neurological, behavioural and cognitive characteristics. Sixty patients met the selection criteria, of whom 11 showed expanded repeats (C9-positive) and 49 did not (C9-negative). A strong male bias was present in the C9-negative group only. A family history of FTD or ALS was recorded in both groups, but was significantly more common in C9-positive cases. Psychotic and irrational behaviours, apathy, disinhibition and loss of empathy were significantly more common in C9-positive cases, with a trend towards more frequent bulbar signs. No differences were found in onset age, presentation (ALS or FTD first), or cognitive changes (language and executive impairments). In conclusion, FTD-ALS is not clinically uniform. Phenotypic differences exist between patients with and without C9orf72 expansions, suggesting that FTD-ALS may be underpinned by distinct neurobiological substrates. The presence of psychiatric symptoms in the context of FTD-ALS should alert clinicians to the possibility of C9orf72 expansions.
    Original languageEnglish
    Pages (from-to)172-176
    Number of pages4
    JournalAmyotrophic lateral sclerosis & frontotemporal degeneration
    Issue number3
    Publication statusPublished - 2013


    • Aged
    • Amyotrophic Lateral Sclerosis/diagnosis/*epidemiology/*genetics
    • Cohort Studies
    • DNA Repeat Expansion/*genetics
    • Female
    • Frontotemporal Dementia/diagnosis/*epidemiology/*genetics
    • Genetic Testing/methods
    • Humans
    • Male
    • Middle Aged
    • Proteins/*genetics


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