Movement disorders in patients with Rett syndrome: A systematic review of evidence and associated clinical considerations

Abstract

Aim This systematic review identified and thematically appraised clinical evidence of movement disorders in patients with Rett syndrome (RTT). Method Using PRISMA criteria, six electronic databases were searched from inception to April 2021. A thematic analysis was then undertaken on the extracted data to identify potential themes. Results Following the thematic analysis, six themes emerged: (i) clinical features of abnormal movement behaviors; (ii) mutational profile and its impact on movement disorders; (iii) symptoms and stressors that impact on movement disorders; (iv) possible underlying neurobiological mechanisms; (v) quality of life and movement disorders; and (vi) treatment of movement disorders. Current guidelines for managing movement disorders in general were then reviewed to provide possible treatment recommendations for RTT. Conclusion Our study offers an enriched data set for clinical investigations and treatment of fine and gross motor issues in RTT. A detailed understanding of genotype–phenotype relationships of movement disorders allows for more robust genetic counseling for families but can also assist healthcare professionals in terms of monitoring disease progression in RTT. The synthesis also showed that environmental enrichment would be beneficial for improving some aspects of movement disorders. The cerebellum, basal ganglia, alongside dysregulation of the cortico‐basal ganglia‐thalamo‐cortical loop, are likely anatomical targets. A review of treatments for movement disorders also helped to provide recommendations for treating and managing movement disorders in patients with RTT.

Inconsolability in a Nonverbal Adolescent

“…5 Management depends on the severity and etiology of agitation, with options for acute treatment including antihistamines and/or benzodiazepines. 5,6 Antipsychotics are "first line" for maintenance pharmacological therapy for severe agitation or agitation related to neurodevelopmental disorders. 8 Other monotherapy options include clonidine and N-acetylcysteine, both of which are theorized to reduce excitatory signaling that may contribute to aggressive behavior.…”

“…8 Other monotherapy options include clonidine and N-acetylcysteine, both of which are theorized to reduce excitatory signaling that may contribute to aggressive behavior. 5,8 Trofinetide is a novel, investigational drug currently awaiting FDA approval that shows promise in targeting the core symptom domains of RTT. 7…”

“…A majority of evidence-based and Food and Drug Administration (FDA)-approved treatments target the irritability associated with autism; these data are often extrapolated to behaviors associated with other neurodevelopmental disorders. 5 Management depends on the severity and etiology of agitation, with options for acute treatment including antihistamines and/or benzodiazepines. 5,6 Antipsychotics are “first line” for maintenance pharmacological therapy for severe agitation or agitation related to neurodevelopmental disorders.…”

Evidence Synthesis of Gene Therapy and Gene Editing from Different Disorders—Implications for Individuals with Rett Syndrome: A Systematic Review

“…Hence, potential gene therapies related to TSC were also searched for. To make the search as expansive as possible, we also searched for gene therapies and other disorders using the methodology described previously [26]. In brief, snowballing was used so that as much of the literature related to gene therapy studies could be traced as possible.…”

Psychological aspects of being a parent of an individual with Rett syndrome: A scoping review

“…After the period of regression, eye contact improves, but spoken language and purposeful use of the hands are often severely reduced. Individuals with RTT may develop a range of comorbidities and clinical characteristics including episodes of laughing or crying spells (Neul et al, 2010), epilepsy (Glaze et al, 2010; Henriksen et al, 2018), sleep disturbances (Wong et al, 2015), and severe movement disorders (Singh et al, 2021). Gross motor function is also affected but to differing degrees, thus some can walk independently, some with assistance, while others are wheelchair bound.…”