Objective: To report a case of generalized primary dystonia due to a mutation in the histone methyltransferase gene (KMT2B) treated with globus pallidus interna deep brain stimulation (GPi-DBS) with excellent response after 2 years.

Background: Pathogenic variants in the KMT28 gene cause generalized progressive dystonia. The clinical phenotype is of a childhood-onset initially affecting lower limbs, and progressively generalizing with severe bulbar symptoms in some cases. Neurologic features such as impaired cognition, oculomotor abnormalities, spasticity or epilepsy can occur. Symmetrical hypointensities of the globus pallidi in T2WI and SWI MRI have been described. To date 13 patients treated with GPi-DBS have been reported in the literature with good clinical response in most of them.

Methods: Case report.

Results: A 13 years old boy initially presented to us with generalized abnormal movements affecting limbs, cervical muscles and trunk, causing severe disability on speech, gait, and daily live activities. Symptoms started at the age of one, with toe walking and progressed until he became wheelchair bound at 12 years old. There was no previous history of nervous system infection, developmental difficulties or family history of neurodegenerative diseases. On the examination generalized dystonia, ballistic movements of left arm, bulbar and pyramidal signs were observed. The symptoms partially respond to botuline toxine type A injections, and no benefit with oral medications including levodopa was noted. MRI revealed hypointense images on globus pallidus and substantia nigra in T2WI. The genetic testing demonstrated a deletion/insertion mutation in KMT2B gene (c.6515_6518delinsCCCAA p.Val217Alafs*11). At the age of 17, bilateral GPi-DBS was performed using standard electrical parameters followed by excellent improvement of symptoms, recovery of independent walking, and partial recovery of writing and manual dexterity, however dysarthria persisted. After 2 years of follow up the patient shows a persistent and excellent response to pallidal stimulation.

Conclusions: KMT2B-DYT28 dystonia should be suspected in childhood-onset cases with generalized primary dystonia, involving oromandibular and laryngeal muscles. Hypointensities in T2-MRI have been described although they are not specific and its pathological significance is unclear. Bilateral GPi-DBS should be promptly considered as principal treatment.

References: 1. Zech M, Boesch S, Maier EM et al. Haploinsufficiency of KMT2B, encoding the lysine-specific histone methyltransferase 2B, results in early onset generalized dystonia. Am J Hum Genet 2016; 9(6): 1377-1387. 2. Meyer E, Carss KJ, Rankin J et al. Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia. Nat Genet 2017; 49(2): 223-237. 3. Zech M, Jech R, Havránková P et al. KMT2B rare missense variants in generalized dystonia. Mov Disord 2017; 32(7): 1087-1091. 4. Gorman KM, Meyer E, Kurian MA. Review of the phenotype of early-onset generalized progressive dystonia due to mutations in KMT2B. Eur J Paediatr Neurol. 2018 Mar; 22(2): 245-256.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/good-response-to-bilateral-gpi-dbs-after-2-years-in-generalized-dystonia-due-to-a-mutation-in-the-kmt2b-gene-dyt28/