Schizophrenia Phenotype Preceding Behavioral Variant Frontotemporal Dementia Related to C9orf72 Repeat Expansion

Cogn Behav Neurol. 2019 Jun;32(2):120-123. doi: 10.1097/WNN.0000000000000189.


Behavioral variant frontotemporal dementia (bvFTD) shares a constellation of clinical features with primary psychiatric disorders. The discovery of new FTD-related genetic mutations has brought attention to this overlap between bvFTD and psychotic disorders. The case reported here raises the question of whether C9orf72 repeat expansion may be involved in neuropsychiatric syndromes beyond the spectrum of neurodegenerative disease. A 61-year-old woman was referred to our memory clinic for behavioral changes and progressive cognitive decline over the last 3 years. Her medical history was significant for schizophrenia since age 36, with an exacerbation of psychotic symptoms at age 55, at which time she slowly worsened, became disorganized and apathetic, and presented new perseverative behaviors. Brain MRI showed mild bilateral frontal and temporal cortical atrophy, and F-fluorodeoxyglucose PET showed bilateral frontal and anterior temporal hypometabolism. Genetic analysis revealed C9orf72 hexanucleotide repeat expansion with more than 80 G4C2 repeats. Recently, FTD due to C9orf72 repeat expansion has been reported to show a high frequency of psychotic presentations. C9orf72 repeat expansion has previously been identified as a rare but possible cause of schizophrenia spectrum disorders. Our case report is characterized by a C9orf72-associated schizophrenia phenotype preceding bvFTD by 2 decades, which might reflect early prodromal neurodegeneration or neurodevelopmental and neurobiological effects of C9orf72 repeat expansion. Analysis of C9orf72 hexanucleotide repeat expansion may be appropriate in patients with schizophrenia spectrum disorders showing new behavioral and/or cognitive changes.

Publication types

  • Case Reports

MeSH terms

  • C9orf72 Protein / genetics*
  • DNA Repeat Expansion / genetics*
  • Female
  • Frontotemporal Dementia / diagnostic imaging
  • Frontotemporal Dementia / genetics*
  • Genetic Variation / genetics*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Middle Aged
  • Phenotype*
  • Positron-Emission Tomography / methods
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / genetics*


  • C9orf72 Protein
  • C9orf72 protein, human