Objective: The primary objective is to describe movement disorder phenomenology, genotypic correlates and treatment outcomes in patients with KMT2B-related disorder.
Background: KMT2B-related dystonia is a well-recognized monogenic dystonia with favorable response to GPi-DBS.
Method: We are conducting an international multicentric retrospective study between March-Dec 2026 across 35 identified centres with a target sample size of 125. This preliminary report presents data from 17 patients from the lead site and two additional centres. Ethics approval has been obtained.
Results: Seventeen patients with pathogenic KMT2B variants were evaluated (median age at onset of dystonia- 4.5 years, 65%- female). Phenomenology included isolated dystonia in 11/16 (69%) and combined movement disorders in 5/16, 31% (myoclonus-2, chorea-2, tremor-1, parkinsonism-1). One patient presented with pure neurodevelopmental phenotype without dystonia. Limb-onset and cranio-cervical dystonia were seen in 57% (8/14; 7-lower limb, 1-upper limb) and 36% (5/14; dysarthria/dysphonia/cervical-onset) patients respectively. Baseline BFMDRS-M scores were 56, range 19-112 (n=15). All patients had developmental delay/intellectual disability (14/14) and 8/14 (57%) had facial dysmorphism. Brain MRI was abnormal in 2/7. Genetic testing revealed predominantly missense variants and deletions in KMT2B. Twelve of fourteen patients required two or more medications with limited clinical response. Fourteen patients underwent bilateral GPi-DBS for progressive dystonia. Follow-up BFMDRS-M scores, post-DBS were 36 (range 9–89.5, n = 11) at median follow-up duration of 20.5 months (range, 6-66 months), representing a median improvement of 61% (range 36–80%). Notably, two patients demonstrated increased BFMDRS scores, indicating disease progression, and one patient required DBS electrode removal at 3 months due to infection.
Conclusion: GPi-DBS provides sustained benefit in KMT2B-related dystonia, with significant reduction in BFMDRS scores. Nonetheless, disease progression can occur, highlighting the importance of understanding the natural disease course and genetic determinants.
To cite this abstract in AMA style:
S. Roychowdhury, H. Alfaris, A. Menetrey, D. Munoz, P. Bisarad, M. Huynh, J. Ganguly, M. Kruer, A. Leblanc-Millar, G. Ibrahim, C. Gorodetsky. Phenotypic Spectrum, Neuroimaging Findings, Genotypic Correlates, and Treatment Outcomes in KMT2B-Related Disorder: A Multicenter Retrospective Cohort Study [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/phenotypic-spectrum-neuroimaging-findings-genotypic-correlates-and-treatment-outcomes-in-kmt2b-related-disorder-a-multicenter-retrospective-cohort-study/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/phenotypic-spectrum-neuroimaging-findings-genotypic-correlates-and-treatment-outcomes-in-kmt2b-related-disorder-a-multicenter-retrospective-cohort-study/