Huntington Disease as a Neurodevelopmental Disorder and Early Signs of the Disease in Stem Cells

Mol Neurobiol. 2018 Apr;55(4):3351-3371. doi: 10.1007/s12035-017-0477-7. Epub 2017 May 11.


Huntington disease (HD) is a dominantly inherited disorder caused by a CAG expansion mutation in the huntingtin (HTT) gene, which results in the HTT protein that contains an expanded polyglutamine tract. The adult form of HD exhibits a late onset of the fully symptomatic phase. However, there is also a long presymptomatic phase, which has been increasingly investigated and recognized as important for the disease development. Moreover, the juvenile form of HD, evoked by a higher number of CAG repeats, resembles a neurodevelopmental disorder and has recently been the focus of additional interest. Multiple lines of data, such as the developmental necessity of HTT, its role in the cell cycle and neurogenesis, and findings from pluripotent stem cells, suggest the existence of a neurodevelopmental component in HD pathogenesis. Therefore, we discuss the early molecular pathogenesis of HD in pluripotent and neural stem cells, with respect to the neurodevelopmental aspects of HD.

Keywords: ESC; Huntington disease; NSC; Neurodegenerative disease; Neurodevelopmental disease; Polyglutamine diseases; Stem cells; iPS; iPSC; polyQ disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Humans
  • Huntingtin Protein / metabolism
  • Huntington Disease / genetics
  • Huntington Disease / pathology*
  • Neural Stem Cells / pathology*
  • Neurodevelopmental Disorders / genetics
  • Neurodevelopmental Disorders / pathology*
  • Trinucleotide Repeat Expansion / genetics


  • Huntingtin Protein