A semi-standardized music therapy intervention for girls with Rett syndrome: A descriptive essay

Rett syndrome (RTT) is a severe neurodevelopmental disorder resulting in a wide range of functional impairments and therefore greatly impacts the lives of both patients and their families. While genetic and medical aspects have been studied for several decades, rehabilitation intervention research is still in its infancy. In this study, the investigating researchers have presented a rehabilitative framework by using music therapy for girls with RTT. This model is founded upon the use of music therapy in light of Stern’s proposal of subjective experience and affect attunement; it also refers to Rosenbaum’s family-centered rehabilitation medicine perspective. This study both describes the theory behind this intervention and presents a newly developed outcome measure. This novel tool may have future clinical and research applications. Music therapy for patients with RTT has not been well researched yet, and as a result, is not universally recommended. However this study’s findings suggest that music therapy is an important component of multidisciplinary therapy. Further collaborative research should be encouraged in order to study and implement the use of music therapy in the treatment of severe disabilities. Projects such as the Enablin+program with the support from the European Commission constitute fundamental tools in promoting integrative medical research and international networks.

Comparing Advanced with Basic Telerehabilitation Technologies for Patients with Rett Syndrome—A Pilot Study on Behavioral Parameters

The aim of this study is to compare the performances of patients with Rett syndrome that were undergoing advanced telerehabilitation (ATR) and patients that were undergoing basic telerehabilitation (BTR). It was hypothesized that patients that were undergoing ATR training would have better improvement in nearly all the motor and cognitive scale scoring activities that were administered, thus showing reduced disability. A total of 20 young girls and women with a diagnosis of RTT, ranging from age 4 to 31 years old (Median: 12.50; IQR: 9.50–17.25) underwent a pre-test, treatment post-test 1, treatment, and post-test 2 procedure. The treatment consisted of either ATR or BTR, lasting 10 weeks with three sessions a week of about an hour. The results showed that the group with advanced telerehabilitation improved their performance better than the control group only in some neuropsychological measurements. The results are discussed in the light of critical factors of telerehabilitation.

Assistive Technology to Promote Adaptive Skills in Children and Adolescents With Rett Syndrome

Rett syndrome is classified within the rare genetic syndromes, characterised by intellectual delays, extensive motor impairments, lack of speech and communication difficulties, sensorial deficits, and problems in adaptive responding. That clinical conditions may be deleterious on their social image, status, and quality of life. A practice for addressing this problem is technology-based interventions. The use of assistive technologies, in particular microswitches, with children with RTT has been shown to effectively change the impact on their quality of life, facilitating access to recreational activities and improving their performance. Through the use of technology-aided programs, a child with RTT and multiple disabilities will be ensured with an independent access to positive stimulation. In this chapter, a selective literature review was carried out considering Rett Syndrome, assistive technologies, quality of life, and rare genetic syndromes. Empirical data demonstrated the effectiveness and suitability of interventions with AT, allowing participants to increase their level of independence.

Family-Centered Telehealth Supporting Motor Skills and Activity in Individuals With Rett Syndrome

Rett syndrome is a rare genetically caused condition associated with severe disability and impaired motor functions. Local therapists typically see small numbers of affected individuals, and this limits their capacity to gain experience. Telehealth is being used increasingly to counter poor access to rehabilitation services. Moreover, there is a need to develop management plans that support individuals with Rett syndrome over their lifespan. Three projects in which telehealth support was provided by therapists experienced in Rett syndrome and supported by available local resources are presented in this chapter. The three projects responded to locally identified needs in a cost-efficient way and empowered those working with people with Rett syndrome to maintain and improve their clients' physical function and activity. This chapter will discuss the conceptual underpinnings of delivering a service using a telehealth approach and describe the results and the strategies implemented in the projects mentioned above.

SCN1A Mutation—Beyond Dravet Syndrome: A Systematic Review and Narrative Synthesis

Background:SCN1A is one of the most common epilepsy genes. About 80% of SCN1A gene mutations cause Dravet syndrome (DS), which is a severe and catastrophic epileptic encephalopathy. More than 1,800 mutations have been identified in SCN1A. Although it is known that SCN1A is the main cause of DS and genetic epilepsy with febrile seizures plus (GEFS+), there is a dearth of information on the other related diseases caused by mutations of SCN1A.Objective: The aim of this study is to systematically review the literature associated with SCN1A and other non-DS-related disorders.Methods: We searched PubMed and SCOPUS for all the published cases related to gene mutations of SCN1A until October 20, 2021. The results reported by each study were summarized narratively.Results: The PubMed and SCOPUS search yielded 2,889 items. A total of 453 studies published between 2005 and 2020 met the final inclusion criteria. Overall, 303 studies on DS, 93 on GEFS+, three on Doose syndrome, nine on the epilepsy of infancy with migrating focal seizures (EIMFS), six on the West syndrome, two on the Lennox–Gastaut syndrome (LGS), one on the Rett syndrome, seven on the nonsyndromic epileptic encephalopathy (NEE), 19 on hemiplegia migraine, six on autism spectrum disorder (ASD), two on nonepileptic SCN1A-related sudden deaths, and two on the arthrogryposis multiplex congenital were included.Conclusion: Aside from DS, SCN1A also causes other epileptic encephalopathies, such as GEFS+, Doose syndrome, EIMFS, West syndrome, LGS, Rett syndrome, and NEE. In addition to epilepsy, hemiplegic migraine, ASD, sudden death, and arthrogryposis multiplex congenital can also be caused by mutations of SCN1A.

Mirtazapine treatment in a young female mouse model of Rett syndrome identifies time windows for the rescue of early phenotypes during development

Rett Syndrome (RTT) is a rare X-linked neurodevelopmental disorder, mainly caused by mutations in the MECP2 gene. Reduction in monoamine levels in RTT patients and mouse models suggested the possibility to rescue clinical phenotypes through antidepressants. Accordingly, we tested mirtazapine (MTZ), a noradrenergic and specific-serotonergic tetracyclic antidepressant (NaSSA). In previous studies, we showed high tolerability and significant positive effects of MTZ in male Mecp21m1.1Bird-knock-out mice, adult female Mecp2tm1.1Bird-heterozygous (Mecp2+/-) mice, and adult female RTT patients. However, it remained to explore MTZ efficacy in female Mecp2+/- mice at young ages. As RTT-like phenotypes in young Mecp2+/- mice have been less investigated, we carried out a behavioural characterization to analyze Mecp2+/- mice in "early adolescence" (6 weeks) and "late adolescence/young adulthood" (11 weeks) and identified several progressive phenotypes. Then, we evaluated the effects of either a 15- or a 30-day MTZ treatment on body weight and impaired motor behaviours in 11-week-old Mecp2+/- mice. Finally, since defective cortical development is a hallmark of RTT, we performed a histological study on the maturation of perineuronal nets (PNNs) and parvalbuminergic (PV) neurons in the primary motor cortex. The 30-day MTZ treatment was more effective than the shorter 15-day treatment, leading to the significant rescue of body weight, hindlimb clasping and motor learning in the accelerating rotarod test. Behavioral improvement was associated with normalized PV immunoreactivity levels and PNN thickness. These results support the use of MTZ as a new potential treatment for adolescent girls affected by RTT and suggest a possible mechanism of action.

Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models

Models of MECP2 dysfunction in Rett syndrome (RTT) assume that transcription rate changes directly correlate with altered steady-state mRNA levels. However, limited evidence suggests that transcription rate changes are buffered by poorly understood compensatory post-transcriptional mechanisms. Here we measure transcription rate and mRNA half-life changes in RTT patient neurons using RATE-seq, and reinterpret nuclear and whole-cell RNAseq from Mecp2 mice. Genes are dysregulated by changing transcription rate only or half-life only and are buffered when both are changed. We utilized classifier models to understand the direction of transcription rate changes based on gene-body DNA sequence, and combined frequencies of three dinucleotides were better predictors than contributions by CA and CG. MicroRNA and RNA-Binding Protein (RBP) motifs were enriched in 3ʹUTRs of genes with half-life changes. Motifs for nuclear localized RBPs were enriched on buffered genes with increased transcription rate. Our findings identify post-transcriptional mechanisms in humans and mice that alter half-life only or buffer transcription rate changes when a transcriptional modulator gene is mutated in a neurodevelopmental disorder.