title: Atypical, slowly progressive behavioural variant frontotemporal dementia associated with C9ORF72 hexanucleotide expansion.
abstract: BACKGROUND
  Some patients meeting behavioural variant frontotemporal dementia (bvFTD) diagnostic criteria progress slowly and plateau at mild symptom severity. Such patients have mild neuropsychological and functional impairments, lack characteristic bvFTD brain atrophy and have thus been referred to as bvFTD 'phenocopies' or slowly progressive (bvFTD-SP). The few patients with bvFTD-SP that have been studied at autopsy have demonstrated no evidence of FTD pathology, suggesting that bvFTD-SP is neuropathologically distinct from other forms of FTD. Here, two patients with bvFTD-SP with chromosome 9 open reading frame 72 (C9ORF72) hexanucleotide expansions are described.
  
  
  METHODS
  384 patients with an FTD clinical spectrum and Alzheimer's disease diagnoses were screened for C9ORF72 expansion. Two bvFTD-SP mutation carriers were identified. Neuropsychological and functional data, as well as brain atrophy patterns, assessed using voxel based morphometry (VBM), were compared with 44 patients with sporadic bvFTD and 85 healthy controls.
  
  
  RESULTS
  Both patients were aged 48 years at baseline and met possible bvFTD criteria. In the first patient, VBM revealed thalamic and posterior insula atrophy. Over 7 years, his neuropsychological performance and brain atrophy remained stable. In the second patient, VBM revealed cortical atrophy with subtle frontal and insular volume loss. Over 2 years, her neuropsychological and functional scores as well as brain atrophy remained stable.
  
  
  CONCLUSIONS
  C9ORF72 mutations can present with a bvFTD-SP phenotype. Some bvFTD-SP patients may have neurodegenerative pathology, and C9ORF72 mutations should be considered in patients with bvFTD-SP and a family history of dementia or motor neuron disease.
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Baber K
authors.initials: BK
authors.lastname: Khan
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Yokoyama
authors.forename: Leonel T
authors.initials: LT
authors.lastname: Takada
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Sha
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Rutherford
authors.forename: Jamie C
authors.initials: JC
authors.lastname: Fong
authors.forename: Anna M
authors.initials: AM
authors.lastname: Karydas
authors.forename: Teresa
authors.initials: T
authors.lastname: Wu
authors.forename: Robin S
authors.initials: RS
authors.lastname: Ketelle
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Baker
authors.forename: Mariely-Dejesus
authors.initials: MD
authors.lastname: Hernandez
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: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.forename: Gil D
authors.initials: GD
authors.lastname: Rabinovici
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Rankin
authors.forename: Adam L
authors.initials: AL
authors.lastname: Boxer
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics; D001931:Brain Mapping; D000073885:C9orf72 Protein; D042622:DNA Repeat Expansion; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D011506:Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins