Objective: .

Background: KMT2B-related dystonia (DYT-28) is a complex childhood-onset movement disorder, characterized by a limb onset dystonia progressing to generalized dystonia with cranio-cervical involvement with frequent cognitive impairment. While medications have limited efficacy, DBS has been successful.

Method: An 8-y.o. male presented to the University of Arkansas for Medical Sciences (UAMS) movement disorder clinic for evaluation of progressive abnormal movements. At the age of 6, he noticed left foot and toe inversion, followed by progression to left arm posturing and development of dysphonia.  At 8 years old, lip pursing started, and a year later, dystonic contractions were present in the right hemibody. He started to fall and became wheelchair-bound. Initial dystonia panel was normal as well as 44 kb microarray. Exam showed lip pursing with closing jaw dystonia when attempted to speak, dystonic posturing of arms and legs, increased tone, bradykinesia and MCI with normal MRI brain.
At the age of 12, he underwent a bilateral GPi placement with six months of continual stimulation,with significant improvement in dystonia.  He went from using a wheelchair to playing basketball for the varsity team. Spasmodic dysphonia remained the only persistent feature that worsened with any changes in DBS settings (Table 1) for which he receives OnabotulinumtoxinA injections with moderate improvement. In 2018, Whole Exome Sequencing showed a pathogenic mutation in the KMT2B gene. After switching his battery to a rechargeable type, he developed hyperkinetic tongue movements. These subsequently resolved after switching to bipolar configuration and reducing overall charge density. Current symptoms remain well controlled without side effects at lower charge density.

Results: KMT2B gene in patients with early-onset, progressive dystonia, represents an important and frequent cause of childhood-onset progressive generalized dystonia and may account for up to 10% of early-onset generalized dystonia. Few cases have been reported with improvement with DBS.

Conclusion: Our report demonstrates significant improvement in primary generalized dystonia with the attainment of independence with bilateral GPi DBS with continual benefits at 7 years. Switching from Primary Cell to Rechargeable IPG led to significant hyperkinetic movements that improved after lowering the charge density by using bipolar configuration.

References: 1. Zech, M et all. Haploinsufficiency of KMT2B, Encoding the Lysine-Specific Histone Methyltransferase 2B, Results in early-onset generalized Dystonia. The American Journal of Human Genetics 2016, 99:1377-1387. 2. Abela, L., Kurian, M, KMT2B-Related Dystonia –Gene Reviews®, University of Washington, Seattle, 2016. https://www.genereviews.org/ 3. Gorman, K.M., Meyer, E., Kurian, M.A, Review of the phenotype of early-onset generalized progressive dystonia due to mutations in KMT2B, European Journal of Paediatric Neurology 2018, 22: 245-256. 4. Baizabal-Carvallo, J.F, Alonso-Juarez, M, Generalized dystonia associated with mutation in the histone methyltransferase gene KMT2B (DYT28 and white matter abnormalities

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MDS Abstracts - https://www.mdsabstracts.org/abstract/bilateral-gpi-dbs-for-the-treatment-of-severe-generalized-genetic-dystonia-caused-by-kmt2b-mutation-dyt-28/