Update on KMT2B-Related Dystonia

  • Michael Zech
  • Daniel D. Lam
  • Juliane WinkelmannEmail author
Genetics (V. Bonifati, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Genetics


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.


Generalized dystonia Childhood dystonia De novo mutation Haploinsufficiency Lysine-specifc methyltransferase family Deep brain stimulation 



M.Z. was supported by an internal research program at Helmholtz Center Munich, Germany (“Physician Scientists for Groundbreaking Projects”). D.D.L. was supported by DFG grant LA 3830/1-1.

Compliance with Ethical Standards

Conflict of Interest

Michael Zech, Daniel D. Lam, and Juliane Winkelmann each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal subjects performed by any of the authors. Signed informed consent for publication of clinical and genetic findings was obtained in accordance with institutional review board regulations and protocols from all the patients (or their legal representatives) who were investigated by the authors and their cooperation partners.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Michael Zech
    • 1
    • 2
  • Daniel D. Lam
    • 1
  • Juliane Winkelmann
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Institut für NeurogenomikHelmholtz Zentrum MünchenMunichGermany
  2. 2.Institut für HumangenetikKlinikum rechts der Isar, Technische Universität MünchenMunichGermany
  3. 3.Lehrstuhl für NeurogenetikTechnische Universität MünchenMunichGermany
  4. 4.Munich Cluster for Systems NeurologySyNergyMunichGermany

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