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Late-onset Huntington disease with intermediate CAG repeats: true or false?
  1. Justus L Groen1,
  2. Rob M A de Bie1,
  3. Elisabeth M J Foncke1,2,
  4. Raymund A C Roos3,
  5. Klaus L Leenders4,
  6. Marina A J Tijssen1
  1. 1Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  2. 2Department of Neurology, VU medical centre, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  3. 3Department of Neurology, LUMC, Leiden, The Netherlands
  4. 4Neurology Department, University Medical Center Groningen, The Netherlands
  1. Correspondence to Dr Marina AJ de Koning-Tijssen, Department of Neurology H2-237, Academic Medical Centre, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands; m.a.tijssen{at}


Huntington disease (HD) is a neurodegenerative disorder associated with an expanded CAG trinucleotide repeat length in the huntingtin gene. ‘Intermediate alleles’ with 27 to 35 CAG repeats generally do not cause HD but are unstable upon germ-line transmission. Insights in CAG repeat mosaicism and enhanced trinucleotide expansion in postmitotic neurons indicate that in the intermediate range, other factors than the CAG repeat length in diagnostic tests have to be considered. Here, we report two patients with mild, late onset HD and an intermediate repeat allele. The authors anticipate that intermediate repeats can cause late-onset HD due to disease modifiers and may be more common than previously stated.

  • Huntington disease
  • chorea
  • trinucleotide repeat
  • intermediate repeat
  • molecular biology

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  • Supplemental files: Videos of case 1 and case 2 are published online only at

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Medical Ethics Committee Academic Medical Center.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.