• 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 DeJesus-Hernandez, Mochtar Pribadi, Giovanni Coppola, Daniel H Geschwind, Rosa Rademakers, Suzee E Lee, William Seeley, Bruce L Miller, and Adam L Boxer.
• Department of Neurology, University of California, San Francisco, USA. ssha@memory.ucsf.edu
• Neurology. 2012 Sep 4; 79 (10): 1002-11.

ObjectiveTo describe the phenotype of patients with C9FTD/ALS (C9ORF72) hexanucleotide repeat expansion.MethodsA 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 behavioral variant FTD [bvFTD], 11 FTD-motor neuron disease [MND], 5 amyotrophic lateral sclerosis [ALS]) and sporadic noncarriers (48 bvFTD, 19 FTD-MND, 6 ALS).ResultsAll 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.ConclusionsPatients 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 novel and unexpected feature.

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