Objective: This study aims to evaluate the functional outcomes and effectiveness of deep brain stimulation (DBS) in patients with genetic dystonia secondary to a KMT2B  mutation.

Background: KMT2B, a heterozygous mutation was identified in 2016 as a cause of progressive childhood-onset dystonia. It is characterized by focal dystonia progressing into generalization with prominent craniofacial and laryngeal involvement. Additional features include intellectual disability, psychiatric symptoms, dysmorphic features, and endocrinopathies. Given the progressive nature of the disease, DBS has emerged as a promising method for improving motor symptoms and functional status. However, improvement in speech varies due to early craniofacial involvement and DBS lead placement.

Method: A retrospective study was conducted for patients with KMT2B gene mutation who underwent DBS, detailing their pre- and post-DBS clinical assessment, radiological, and standardized dystonia scales.

Results: The study included three patients (1 male and 2 female); two with typical KMT2B-dystonic symptoms and the third with parkinsonism. The mean age of onset in patients 1 and 2 was 7.5 years. Patient 1 had normal speech with no evidence of craniofacial dystonia, while patient 2 had debilitating dysarthria. While, patient 3 presented at 22 years with asymmetrical tremor, rigidity, and dysarthria.

Neuroimaging showed nonspecific white matter changes in patient 1. Patient 3 had cerebral volume loss, and given the Parkinsonian features, a DOPA scan performed showing reduced uptake in the basal ganglia.

All patients received symptomatic treatment, with unsatisfactory response promoted the need for DBS. Patients 1 and 2 underwent DBS targeting bilateral globus pallidus internus, and patients 3 underwent DBS targeting subthalamic nuclei.

Post-operatively, all patients showed improved motor function, with ongoing programming adjustments. However, speech symptoms continued to progress despite programming modifications.

Conclusion: Dystonia secondary to KMT2B mutation has a broad clinical presentation. Commonly, dystonia-specific therapy fails to control the symptoms, resulting in an increased utilization of DBS as a method for improving symptoms. Though several reports showed positive outcomes following DBS, our cases reflect that severe pre-operative risk factors, including speech impairment and older age at DBS placement, have a negative impact post-operatively.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/kmt2b-related-dystonia-and-dbs-tertiary-center-experience/