Update on KMT2B-Related Dystonia

Curr Neurol Neurosci Rep. 2019 Nov 25;19(11):92. doi: 10.1007/s11910-019-1007-y.


Purpose of review: To summarize the molecular and clinical findings of KMT2B-related dystonia (DYT-KMT2B), a newly identified genetic dystonia syndrome.

Recent findings: Since first described in 2016, 66 different KMT2B-affecting variants, encompassing a set of frameshift, nonsense, splice-site, missense, and deletion mutations, have been reported in 76 patients. Most mutations are de novo and expected to mediate epigenetic dysregulation by inducing KMT2B haploinsufficiency. DYT-KMT2B is characterized phenotypically by limb-onset childhood dystonia that tends to spread progressively, resulting in generalized dystonia with cranio-cervical involvement. Co-occuring signs such as intellectual disability are frequently observed. Sustained response to deep brain stimulation (DBS), including restoration of independent ambulation, is seen in 93% (27/29) of patients. DYT-KMT2B is emerging as a prevalent monogenic dystonia. Childhood-onset dystonia presentations should prompt a search for KMT2B mutations, preferentially via next-generation-sequencing and genomic-array technologies, to enable specific counseling and treatment. Prospective multicenter studies are desirable to establish KMT2B mutational status as a DBS outcome predictor.

Keywords: Childhood dystonia; De novo mutation; Deep brain stimulation; Generalized dystonia; Haploinsufficiency; Lysine-specifc methyltransferase family.

Publication types

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

MeSH terms

  • Child
  • Deep Brain Stimulation / methods
  • Deep Brain Stimulation / trends
  • Dystonia / diagnosis
  • Dystonia / genetics
  • Dystonia / therapy
  • Dystonic Disorders / diagnosis*
  • Dystonic Disorders / genetics*
  • Dystonic Disorders / therapy
  • Genetic Testing / methods
  • Genetic Testing / trends
  • Genomics / methods
  • Genomics / trends
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Mutation / genetics*
  • Phenotype
  • Prospective Studies


  • Histone-Lysine N-Methyltransferase
  • KMT2B protein, human