Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-

Please cite this article as: Kaminska M, Perides S, Lumsden DE, Nakou V, Selway R, Ashkan K, Lin J-P, Complications of Deep Brain Stimulation (DBS) for dystonia in children -the challenges and 10 year experience in a large paediatric cohort, European Journal of Paediatric Neurology (2016Neurology ( ), doi: 10.1016Neurology ( / j.ejpn.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. • Lower than previously reported infection rates following DBS for movement disorders in children were identified and no increased susceptibility for patients younger than 7 years. • We report relatively high incidence of technical problems with electrodes and extensions and in particular recharging.• Presentation of heterogeneous phenotypes requires an experienced team to manage and prevent complications. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPTThe paper confirms that DBS in young children is safe and can be offered. Abstract:Deep brain stimulation (DBS) has been increasingly used for primary and secondary movement disorders in children and young people. Reports of hardware related complications have been sparse for this population and from small cohorts of patients.We report DBS complications from a single large DBS centre with 10 year experience.Data was collected as a prospective audit and additionally from a questionnaire on recharging of the stimulators. 129 patients with a minimum 6 months follow up were identified, mean age10.8 y (range 3.0 -18.75), mean follow up 3.3y (range 0.5 -10.3), weight 10.4-94.2kg, 126 new implants (92 Activa RC) and 69 revisions for reasons other than infection. 26 patients were 7y or younger. Surgical site infections (SSI) rates were 10.3% for new implants and revisions, lower 8.6% for new Activa RC and even lower, 4.7%, for new Activa RC in patients under 7y (1/21). SSI occurred within first 6 months and necessitated total system removal in 86% of those infected. Electrode/extension problems were recorded in 18.4% of patients, fracture in 4.6% malfunction in 7.7%, short extension3.8% and electrode migration in 2.3%. Other complications involved clinically silent intracranial bleed in 1 patient, skin erosions (2.3%), unexpected switching off in 18.7% of Soletra/Kinetra and 3.4% of Activa RC, transient seroma at IPG site in postoperative period (8%). Of the 48 returned recharging questionnaires, 38% of families required recharger replacement and 23% experienced frequent problems maintaining connection during recharging. However, 83% of responders considered recharging not at all or only a little care burden.We identified lower than previously reported DBS infection rates ...

In this article, we report four new patients, from three kindreds, with pathogenic variants in RBCK1 and a multisystem disorder characterised by widespread polyglucosan storage. We describe the clinical presentation of progressive skeletal and cardiac myopathy, combined immunodeficiencies and auto‐inflammation, illustrate in detail the histopathological findings in multiple tissue types, and report muscle MRI findings.