Frontotemporal dementia due To C9ORF72 mutations clinical and imaging features

Sharon J. Sha, Leonel T. Takada, Katherine P. Rankin, Jennifer S. Yokoyama, Nicola J. Rutherford, Jamie C. Fong, Baber Khan, Anna Karydas, Matt C. Baker, Mariely De Jesus-Hernandez, Mochtar Pribadi, Giovanni Coppola, Daniel H. Geschwind, Rosa Rademakers, Suzee E. Lee, William Seeley, Bruce L. Miller, Adam L. Boxer

Research output: Contribution to journalArticlepeer-review

128 Scopus citations


Objective: To describe the phenotype of patients with C9FTD/ALS (C9ORF72) hexanucleotide repeat expansion. Methods: A total of 648 patients with frontotemporal dementia (FTD)-related clinical diagnoses and Alzheimer disease (AD) dementia were tested for C9ORF72 expansion and 31 carried expanded repeats (C9+). Clinical and neuroimaging data were compared between C9+ (15 behavoral variant FTD [bvFTD], 11 FTD-motor neuron disease [MND], 5 amyotrophic lateral sclerosis [ALS]) and sporadic noncarriers (48 bvFTD, 19 FTD-MND, 6 ALS). Results: All C9+ patients displayed clinical syndromes of bvFTD, ALS, or FTD-MND. At first evaluation, C9+ bvFTD patients had more delusions and greater impairment of working memory, but milder eating dysregulation compared to bvFTD noncarriers. C9 + FTD-MND patients had a trend for longer survival and had an earlier age at onset than FTD-MND noncarriers. Voxel-based morphometry demonstrated more thalamic atrophy in FTD and FTD-MND carriers than in noncarriers. Conclusions: Patients with the C9ORF72 hexanucleotide repeat expansion develop bvFTD, ALS, or FTD-MND with similar clinical and imaging features to sporadic cases. Other FTD spectrum diagnoses and AD dementia appear rare or absent among C9+ individuals. Longer survival in C9+ FTD-MND suggests slower disease progression and thalamic atrophy represents a nove and unexpected feature.

Original languageEnglish (US)
Pages (from-to)1002-1011
Number of pages10
Issue number10
StatePublished - Sep 4 2012

ASJC Scopus subject areas

  • Clinical Neurology


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