Update on KMT2B-Related Dystonia

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• KMT2B-related dystonia (DYT-KMT2B) is a recently identified genetic disorder.
• Over 66 KMT2B variants have been reported in 76 patients since 2016.
• Mutations often lead to KMT2B haploinsufficiency and epigenetic dysregulation.

Purpose of the Study:

• To review the molecular and clinical findings of DYT-KMT2B.
• To highlight the diagnostic and therapeutic implications of KMT2B mutations.

Main Methods:

• Literature review of KMT2B-related dystonia cases.
• Analysis of reported KMT2B variants and associated phenotypes.
• Evaluation of treatment outcomes, particularly deep brain stimulation (DBS).

Main Results:

• DYT-KMT2B presents as childhood-onset, progressive limb dystonia, often involving cranio-cervical regions.
• Intellectual disability is a frequent co-occurring symptom.
• Deep brain stimulation (DBS) shows a high success rate (93%) in improving motor function.

Conclusions:

• DYT-KMT2B is an increasingly recognized cause of monogenic dystonia.
• Prompt genetic testing for KMT2B mutations is recommended for childhood-onset dystonia.
• KMT2B mutational status may predict DBS outcomes, warranting further multicenter studies.