title: Distinct clinical characteristics of C9orf72 expansion carriers compared with GRN, MAPT, and nonmutation carriers in a Flanders-Belgian FTLD cohort.
abstract: OBJECTIVE
  To characterize patients with frontotemporal lobar degeneration (FTLD) with a repeat expansion mutation in the gene C9orf72, and to determine whether there are differences in the clinical presentation compared with FTLD carriers of a mutation in GRN or MAPT or with patients with FTLD without mutation.
  
  
  METHODS
  Patient series.
  
  
  METHODS
  Dementia clinics in Flanders, Belgium.
  
  
  METHODS
  Two hundred seventy-five genetically and phenotypically thoroughly characterized patients with FTLD.
  
  
  METHODS
  Clinical and demographic characteristics of 26 C9orf72 expansion carriers compared with patients with a GRN or MAPT mutation, as well as patients with familial and sporadic FTLD without mutation.
  
  
  RESULTS
  C9orf72 expansion carriers developed FTLD at an early age (average, 55.3 years; range, 42-69 years), significantly earlier than in GRN mutation carriers or patients with FTLD without mutation. Mean survival (6.2 years; range, 1.5-17.0 years) was similar to other patient groups. Most developed behavioral variant frontotemporal dementia (85%), with disinhibited behavior as the prominent feature. Concomitant amyotrophic lateral sclerosis is a strong distinguishing feature for C9orf72 -associated FTLD. However, in most patients (73%), amyotrophic lateral sclerosis symptoms were absent. Compared with C9orf72 expansion carriers, nonfluent aphasia and limb apraxia were significantly more common in GRN mutation carriers.
  
  
  CONCLUSIONS
  C9orf72 -associated FTLD most often presents with early-onset behavioral variant frontotemporal dementia with disinhibition as the prominent feature, with or without amyotrophic lateral sclerosis. Based on the observed genotype-phenotype correlations between the different FTLD syndromes and different genetic causes, we propose a decision tree to guide clinical genetic testing in patients clinically diagnosed as having FTLD.
authors: VIB–Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, University of Antwerp–CDE, Universiteitsplein 1, Antwerp, Belgium. christine.vanbroeckhoven@molgen.vib-ua.be
authors: Tim
authors: T
authors: Van Langenhove
authors: Julie
authors: J
authors: van der Zee
authors: Ilse
authors: I
authors: Gijselinck
authors: Sebastiaan
authors: S
authors: Engelborghs
authors: Rik
authors: R
authors: Vandenberghe
authors: Mathieu
authors: M
authors: Vandenbulcke
authors: Jan
authors: J
authors: De Bleecker
authors: Anne
authors: A
authors: Sieben
authors: Jan
authors: J
authors: Versijpt
authors: Adrian
authors: A
authors: Ivanoiu
authors: Olivier
authors: O
authors: Deryck
authors: Christiana
authors: C
authors: Willems
authors: Lubina
authors: L
authors: Dillen
authors: Stéphanie
authors: S
authors: Philtjens
authors: Githa
authors: G
authors: Maes
authors: Veerle
authors: V
authors: Bäumer
authors: Marleen
authors: M
authors: Van Den Broeck
authors: Maria
authors: M
authors: Mattheijssens
authors: Karin
authors: K
authors: Peeters
authors: Jean-Jacques
authors: JJ
authors: Martin
authors: Alex
authors: A
authors: Michotte
authors: Patrick
authors: P
authors: Santens
authors: Peter
authors: P
authors: De Jonghe
authors: Patrick
authors: P
authors: Cras
authors: Peter P
authors: PP
authors: De Deyn
authors: Marc
authors: M
authors: Cruts
authors: Christine
authors: C
authors: Van Broeckhoven
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001530:Belgium / Q000453:epidemiology; D000073885:C9orf72 Protein; D015331:Cohort Studies; D042622:DNA Repeat Expansion / Q000235:genetics*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000453:epidemiology / Q000235:genetics*; D006580:Genetic Carrier Screening; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D000077153:Progranulins; D011506:Proteins / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D011506:Proteins; D016875:tau Proteins