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

Abstract

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.

Key words::

• Frontotemporal dementia
• amyotrophic lateral sclerosis
• C9orf72
• clinical characteristics
• psychosis

Acknowledgements

We acknowledge the assistance of A. Gerhard and M. Jones in patient evaluation. We thank neurological and psychiatric colleagues from the North-West Region of UK for referring patients, in particular J. Ealing and H. Hamdalla from the Manchester MND Care Centre. We thank DeNDRoN for assistance in acquisition of blood samples.

SP-B and DMAM receive Medical Research Council and Wellcome Trust support through the Neurodegeneration Programme. The Manchester brain donation scheme is supported by Alzheimer's Research UK and the Alzheimer's Society through the Brains for Dementia Research Initiative.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.