Update on KMT2B -Related Dystonia

AbstractPurpose of ReviewTo summarize the molecular and clinical findings ofKMT2B-related dystonia (DYT-KMT2B), a newly identified genetic dystonia syndrome.Recent FindingsSince first described in 2016, 66 differentKMT2B-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 inducingKMT2B 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.SummaryDYT-KMT2B is emerging as a prevalent monogenic dystonia. Childhood-onset dystonia presentations should prompt a search forKMT2B mutations, preferentially via next-generation-sequencing and genomic-array technologies, to enable specific counseling and treatment. Prospective multicenter studies are desirable to establishKMT2B mutational status as a DBS outcome predictor.
Source: Current Neurology and Neuroscience Reports - Category: Neuroscience Source Type: research