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Disease progression in C9orf72 mutation carriers

Mary K Floeter1, Bryan J Traynor2, Jennifer Farren2

  • 1From the National Institute of Neurological Disorders and Stroke (M.K.F., J.F., L.E.B., M.T., E.A.W., T.W.) and National Institute of Aging (B.J.T.), NIH, Bethesda, MD. floeterm@ninds.nih.gov.

Neurology
|June 16, 2017
PubMed

Insights

Clinical measures like the ALSFRS-R, letter fluency, and FBI track disease progression in C9orf72 mutation carriers. These tools help differentiate between ALS, ALS-FTD, and FTD phenotypes over time.

Area of Science:

  • Neuroscience
  • Genetics
  • Neurology

Background:

  • The C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
  • Understanding the clinical progression in C9orf72 mutation carriers is crucial for developing targeted therapies.

Purpose of the Study:

  • To evaluate longitudinal changes in the Revised ALS Functional Rating Scale (ALSFRS-R), letter fluency, and Frontal Behavioral Inventory (FBI) in C9orf72 mutation carriers.
  • To assess how these clinical measures differentiate between various phenotypic presentations (asymptomatic, ALS, ALS-FTD, FTD) and track disease progression.

Main Methods:

  • A prospective natural history study enrolled 34 C9orf72 mutation carriers.
  • Participants were categorized into asymptomatic, ALS, ALS-FTD, or behavioral-variant FTD groups.
  • ALSFRS-R, letter fluency, and FBI were assessed at baseline and at 6, 12, and 18 months.

Main Results:

  • ALSFRS-R scores correlated with motor function, while letter fluency correlated with cognitive tests and FBI.
  • Significant differences in ALSFRS-R, letter fluency, and FBI were observed among C9orf72 subgroups at baseline.
  • Symptomatic patients showed worsening scores over time, with varying rates across subgroups, impacting survival in ALS and ALS-FTD groups.

Conclusions:

  • The ALSFRS-R, letter fluency, and FBI effectively distinguish between different C9orf72-associated neurodegenerative phenotypes.
  • Longitudinal changes in these measures reflect disease progression and are consistent with the initial clinical presentation.
Abstract

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