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Rett syndrome (RTT) is an X‐linked neurogenetic disorder caused by mutations of the MECP2 (methyl‐CpG‐binding protein 2) gene. Over two decades of work established MeCP2 as a protein with pivotal roles in the regulation of the epigenome, neuronal physiology, synaptic maintenance, and behaviour. Given the genetic aetiology of RTT and the proof of concept of its reversal in a mouse model, considerable efforts have been made to design therapeutic approaches to re‐express MeCP2. By being at the forefront of the development of innovative gene therapies, research on RTT is of paramount importance for the treatment of monogenic neurological diseases. Here we discuss the recent advances and challenges of promising genetic strategies for the treatment of RTT including gene replacement therapies, gene/RNA editing strategies, and reactivation of the silenced X chromosome. What this paper adds: Recent advances shed light on the promises of gene replacement therapy with new vectors designed to control the levels of MeCP2 expression.New developments in DNA/RNA editing approaches or reactivation of the silenced X chromosome open the possibility to re‐express the native MeCP2 locus at endogenous levels.Current strategies still face limitations in transduction efficiency and future work is needed to improve brain delivery. [ABSTRACT FROM AUTHOR]

Aim: To evaluate early dystonic features in children and adolescents with SGCE‐myoclonus–dystonia. Method: In this cross‐sectional study, 49 patients (26 females and 23 males) with SGCE‐myoclonus–dystonia (aged 15y 2mo, SD 12y) with childhood‐onset (2y 10mo, SD 1y 10mo) dystonia were examined using a standardized video recorded protocol. Dystonia was rated using the Writer's Cramp and Gait Dystonia Rating Scales. Disability and impairment for handwriting and walking were also rated. Results: Dystonia was present at rest (n=1), posture (n=12), and during specific motor tasks (n=45) such as writing (n=35), walking (n=23), and running (n=20). Most children reported disability while performing these tasks. Early dystonic patterns were identified for writer's cramp and gait dystonia, the latter named the 'circular shaking leg', 'dragging leg', and 'hobby‐horse gait' patterns. Sensory tricks were used by five and eight children to improve dystonia and myoclonus during writing and walking respectively. The rating scales accurately measured the severity of action dystonia and correlated with self‐reported disability. Interpretation: Children with SGCE‐myoclonus–dystonia show recognizable dystonic patterns and sensory tricks that may lead to an early diagnosis and timely therapeutic approach. Isolated writer's cramp is a key feature in childhood and should prompt SCGE analysis. The proposed action dystonia scales could be used to monitor disease course and response to treatment. What this paper adds: Most children with SGCE‐myoclonus–dystonia got writer's cramp and had walking and running dystonia.Writer's cramp was a key feature and should prompt SGCE genetic investigation.'Circular shaking leg', 'dragging leg', and 'hobby‐horse gait' were recognized as early gait patterns.Children used sensory tricks to improve myoclonus and dystonia, suggesting common pathophysiological mechanisms.Action dystonia rating scales are valid tools to assess severity in children. [ABSTRACT FROM AUTHOR]