TY - JOUR
T1 - Update on KMT2B-Related Dystonia
AU - Zech, Michael
AU - Lam, Daniel D.
AU - Winkelmann, Juliane
N1 - Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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. Summary: 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.
AB - 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. Summary: 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.
KW - Childhood dystonia
KW - De novo mutation
KW - Deep brain stimulation
KW - Generalized dystonia
KW - Haploinsufficiency
KW - Lysine-specifc methyltransferase family
UR - http://www.scopus.com/inward/record.url?scp=85075496031&partnerID=8YFLogxK
U2 - 10.1007/s11910-019-1007-y
DO - 10.1007/s11910-019-1007-y
M3 - Review article
C2 - 31768667
AN - SCOPUS:85075496031
SN - 1528-4042
VL - 19
JO - Current Neurology and Neuroscience Reports
JF - Current Neurology and Neuroscience Reports
IS - 11
M1 - 92
ER -