title: Frontotemporal dementia due to C9ORF72 mutations: clinical and imaging features.
abstract: 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 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).
  
  
  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 novel and unexpected feature.
authors.affiliation: Department of Neurology, University of California, San Francisco, USA. ssha@memory.ucsf.edu
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Sha
authors.forename: Leonel T
authors.initials: LT
authors.lastname: Takada
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Rankin
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Yokoyama
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Rutherford
authors.forename: Jamie C
authors.initials: JC
authors.lastname: Fong
authors.forename: Baber
authors.initials: B
authors.lastname: Khan
authors.forename: Anna
authors.initials: A
authors.lastname: Karydas
authors.forename: Matt C
authors.initials: MC
authors.lastname: Baker
authors.forename: Mariely
authors.initials: M
authors.lastname: DeJesus-Hernandez
authors.forename: Mochtar
authors.initials: M
authors.lastname: Pribadi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Suzee E
authors.initials: SE
authors.lastname: Lee
authors.forename: William
authors.initials: W
authors.lastname: Seeley
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.forename: Adam L
authors.initials: AL
authors.lastname: Boxer
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D001284:Atrophy / Q000235:genetics / Q000473:pathology; D001921:Brain / Q000473:pathology*; D000073885:C9orf72 Protein; D042622:DNA Repeat Expansion; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059906:Neuroimaging; D009483:Neuropsychological Tests; D011506:Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins