Childhood-onset progressive dystonia associated with pathogenic truncating variants in CHD8

Ann Clin Transl Neurol. 2021 Oct;8(10):1986-1990. doi: 10.1002/acn3.51444. Epub 2021 Aug 20.


Originally described as a risk factor for autism, CHD8 loss-of-function variants have recently been associated with a wider spectrum of neurodevelopmental abnormalities. We further expand the CHD8-related phenotype with the description of two unrelated patients who presented with childhood-onset progressive dystonia. Whole-exome sequencing conducted in two independent laboratories revealed a CHD8 nonsense variant in one patient and a frameshift variant in the second. The patients had strongly overlapping phenotypes characterized by generalized dystonia with mild-to-moderate neurodevelopmental comorbidity. Deep brain stimulation led to clinical improvement in both cases. We suggest that CHD8 should be added to the growing list of neurodevelopmental disorder-associated genes whose mutations can also result in dystonia-dominant phenotypes.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • DNA-Binding Proteins / genetics*
  • Deep Brain Stimulation
  • Disease Progression
  • Dystonic Disorders / genetics*
  • Dystonic Disorders / physiopathology
  • Dystonic Disorders / therapy
  • Female
  • Humans
  • Middle Aged
  • Neurodevelopmental Disorders / genetics*
  • Neurodevelopmental Disorders / physiopathology
  • Transcription Factors / genetics*


  • CHD8 protein, human
  • DNA-Binding Proteins
  • Transcription Factors