Objective: To assess long term results of GPi-DBS in one patient with generalized dystonia with KMT2B mutation.

Background: Mutations in heterozygosis of the KMT2B gene, which codes for protein lisin-methyltransferases, has recently been described in association with a rare and infrequent form of early-onset complex, combined progressive dystonia. Most of affected people develop cervical, cranial and laryngeal dystonia and can also associate dysmorphic features, cutaneous, cognitive or psychiatric alterations.

Methods: The patient is a 20 year old male carrying a mutation de novo in heterozygosis in the KMT2B gene (c.4955G> A p.Gly1652Asp). The patient had elongated facies with normal cognitive function. At the age of 6, he developed clumsy walking due to abnormal posture of the right leg together with dystonic postures in both hands and progressive motor and gait deterioration with consequent loss of autonomy. In the following 3 years he associated severe dysphagia, dysarthria and urinary retentions needing periodic catheterizations. At age 14, he had severe cachexia and a very poor global clinical situation. L-Dopa , Trihexyphenidyl and a variety of other drugs were tried without benefit. At age 15, he had a bilateral Globus Pallidus pars Interna (GPi) deep brain stimulation (GPi-DBS).

Results: Score on the Burke-Fahn-Marsden Scale Movement (BFMDRS-M) was 91 and 25 on Disability (BFMDRS-D), pre-DBS. Motor and bulbar symptoms improved progressively through the first two years post-DBS and kept improving though slower until his fifth year post-DBS, finally scoring 75% and 52% better in BFMDR-M and BFMDRS-D respectively.

Conclusions: – Gorman KM, Meyer. E, Kurian M.A et al., Review of the phenotype of early-onset generalised progressive dystonia due to mutations in KMT2B, European Journal of Paediatric Neurology (2017). – Meyer E, Carss K.J, Rankin J, et al. Mutations in the histone methyltransferase gene KMT2B cause complex early onset dystonia. Nat Genet. 2017 Feb;49(2):223-237. – Zech M, Boesch S, Maier EM, Borggraefe I, Vill K, Laccone F, et al. Haploinsufficiency of KMT2B, encoding the lysinespecific histone methyltransferase 2B, results in early-onset generalized dystonia. Am J Hum Genet 2016;99(6):1377e87.

References: – Gorman KM, Meyer. E, Kurian M.A et al., Review of the phenotype of early-onset generalised progressive dystonia due to mutations in KMT2B, European Journal of Paediatric Neurology (2017). – Meyer E, Carss K.J, Rankin J, et al. Mutations in the histone methyltransferase gene KMT2B cause complex early onset dystonia. Nat Genet. 2017 Feb;49(2):223-237. – Zech M, Boesch S, Maier EM, Borggraefe I, Vill K, Laccone F, et al. Haploinsufficiency of KMT2B, encoding the lysinespecific histone methyltransferase 2B, results in early-onset generalized dystonia. Am J Hum Genet 2016;99(6):1377e87.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/globus-pallidus-deep-brain-stimulation-gpi-dbs-in-one-patient-with-complex-early-onset-dystonia-and-kmt2b-mutation-a-case-report/