Leisure-Time Physical Activity Interventions for Health Promotion in Individuals With Rett Syndrome: Scoping Review

Introduction

Rett syndrome (RTT) is a rare progressive neurodevelopmental disorder that is prevalent among female individuals [1,2]. RTT is characterized by impairments in motor function, communication, and cognitive abilities [3-5]. Half of individuals with RTT are older than 50 years [6]. Considering that mortality in RTT has been linked with several preventable factors such as declines in physical function and cardiorespiratory issues [7], there is a need to identify interventions that can improve and manage physical health and wellness.

Over 40 years of research have found that leisure-time physical activity (LTPA) participation has been identified as a key behavior for improving and managing physical and mental health among people with mobility disabilities [8,9]. LTPA refers to physical activities performed outside of regular work, including exercise; sports; and physically active hobbies such as walking for exercise, running, and similar activities done during discretionary time [10]. While there is a growing volume of research related to LTPA in more prevalent disability groups (eg, stroke, Parkinson disease, cerebral palsy, and multiple sclerosis) [8,9,11,12], less is known about its potential impact in preserving or improving health in individuals with RTT.

Although there are systematic reviews that highlight the multifaceted benefits of specific rehabilitation interventions in people with RTT [13-18], there has not been a review of LTPA interventions for this population. Compiling a single resource of LTPA interventions for RTT can help health professionals and caregivers quickly identify programs that extend outside the rehabilitation context and promote physical health and wellness across the life span. To provide a foundation that can guide future research in LTPA and telehealth for individuals with RTT, the objectives of this scoping review were as follows:

1. To aggregate and summarize the state of the science regarding LTPA for people with RTT across the lifespan
2. To describe LTPA intervention characteristics and their potential outcomes on physical health, function, and fitness
3. To explore telehealth technologies and their use in LTPA interventions

Methods

Study Design

This scoping review was conducted using the methodological framework developed by Arksey and O’Malley [19], which consists of (1) identifying a research question; (2) identifying relevant studies; (3) selecting studies; (4) charting the data; (5) collating, summarizing, and reporting the results; and (6) an optional consultation exercise. Additionally, recommendations and considerations to improve scoping reviews in health research were implemented [20,21]. This research adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for reporting, and a completed PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist can be found in Multimedia Appendix 1.

Review Questions

The population, intervention, comparison, and outcome framework [22] was used to develop the guiding questions for this scoping review: (1) What is the state of the science regarding LTPA interventions for individuals with RTT? (2) What are the intervention delivery strategies and their outcomes, with a specific focus on health-related fitness [23] (cardiorespiratory fitness, muscular strength, muscular endurance, body composition, and flexibility)? (3) What telehealth strategies have been implemented?

Inclusion Criteria

Studies were deemed eligible for inclusion if they met the following criteria: (1) publications that were primary sources of original, peer-reviewed research; (2) LTPA interventions that incorporated the deliberate use of repetitive large body movements to improve, maintain, or change a component of health (exercise, recreation, and conditioning); (3) interventions that targeted people with RTT and/or caregivers; and (4) LTPA interventions that could be delivered in the community outside a rehabilitation setting and did not require the supervision of a licensed therapist. This study included all types of research designs, from case studies to randomized controlled trials (RCTs). Gray literature articles were excluded from review.

Search Process

A preliminary search of the PubMed database, Cochrane Database of Systematic Reviews, and Scopus database was conducted (CM), and no current or underway systematic or scoping reviews on the topic were identified. The text words contained in the titles and abstracts of relevant articles and the index terms used to describe the articles were used to develop a full search strategy.

The article search was conducted (CM) for all years up to September 30, 2025, in the following databases: MEDLINE, Scopus, and CINAHL Plus. Hand searches also included research found through Google Scholar and from the reference lists of existing RTT reviews.

Search Strategy

Article searches were generally conducted by integrating RTT terms (eg, “Rett syndrome” and “neurodevelopmental disorder”) and LTPA key terms (eg, “physical activity,” “exercise,” and “sedentary activity”). Boolean operators were used to connect RTT terms with physical activity terms depending on the database. The MEDLINE database search string was as follows: “Rett syndrome AND physical activity.”

Study and Source of Evidence Selection

Following the search, all identified citations were collated and uploaded into EndNote 2025 (Clarivate Analytics), and duplicates were removed. Titles and abstracts were screened by 2 independent reviewers (CM and BL) for assessment against the inclusion criteria for the review. Potentially relevant sources were retrieved in full text and saved as a PDF to a shared digital folder. Rationales for the exclusion of articles were recorded. Any disagreements that arose between the reviewers at each stage of the selection process were resolved through discussion with an additional reviewer (JR) during weekly meetings. The results of the search and the study inclusion process are reported in full and presented in a PRISMA flow diagram.

Data Charting

Data were extracted from the full texts of the articles by 3 reviewers. Extraction was guided by a data template in Microsoft Excel. One reviewer (CM) extracted data from all articles. Two reviewers (RY and AW) each reviewed half of the total articles as a way to ensure that all articles were reviewed by 2 reviewers. After reviewers charted data from the first 2 studies, the research team met to resolve any disputes and aggregate the data extraction results. Extracted data included specific details about the participants, concept, context, study methods, interventions, outcomes, and key findings relevant to the review questions. The final data extraction chart was cross-checked for accuracy by 2 analysts (CM and BL).

Data Analysis and Presentation

The data were organized graphically and in tabular form. These data included study parameters (design and country of origin), participant demographics and clinical characteristics (age, RTT severity, and ambulatory ability), intervention characteristics (duration, type, frequency, setting, and mode of delivery), outcomes and measures, and telehealth characteristics where applicable (mode of delivery and contact frequency). In instances in which there were multiple publications that were associated with a single trial, the extracted data were considered as a single article for the purposes of summation calculation or frequency counts.

A draft of the preliminary results and findings of this work was reviewed by the mother of an individual with RTT. Consistent with expert recommendations [20], she provided feedback to confirm whether the findings aligned with her experiences, identify any misinterpretations, suggest alternative conceptualizations, and add context to this work. Her feedback was documented in writing through email and integrated into this final work.

Results

Search Results

The search strategy yielded 459 records from 122 original research studies. After screening, of the 459 records, 31 (7%) were assessed for eligibility. Of these 31 publications, 8 (26%) were excluded due to not targeting individuals with RTT or caregivers (n=1) [24], not incorporating an LTPA intervention (n=4) [17,25-27], or administering an intervention that required a licensed therapist (n=3) [28-30]. After assessment, 23 articles were included in the final synthesis (Figure 1).

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Study Parameters

General study parameters are shown in Table 1. Most studies (21/23, 91%) were conducted in the last 20 years. The most common research designs were case studies (11/23, 48%) and within-group repeated measures (9/23, 39%). Among the 23 studies, 3 (13%) randomized designs were identified, with only 2 (9%) being RCTs. Almost every study reported at least one favorable result of their interventions, with the most common benefits being improved gross motor function (eg, sitting independently and standing transitions), improved walking ability, or an increase in physical activity or decrease in sedentary time.

Participants

Participant information is shown in Table 2. A total of 200 individuals with RTT were enrolled across the 23 included studies. In total, 13% (3/23) of the publications overlapped and reported separate results from the same sample of participants [40,44,52]. Sample sizes ranged from 1 to 42. Adults were underrepresented, with the mean participant age being 13 (SD 7) years and ages ranging from as young as 2 up to 48 years. A total of 65% (130/200) of the participants were ambulatory (independent or with assistance); 25% (50/200) were nonambulatory; and for 10% (20/200), ambulation was not reported or unknown. In total, 39% (9/23) of the studies reported a measure of RTT severity, which included at least one participant with severe RTT. Only 22% (2/9) of these studies enrolled participants with mild RTT.

Intervention Characteristics

The intervention characteristics are shown in Table 3. The mean intervention duration was 30 (SD 35) weeks, ranging from a single week to 3 years. The most common setting was in the home and community, followed by physical therapy clinics. Most interventions were delivered by health professionals directly or indirectly as an activity program designed for a caregiver or parent to deliver. Interventions were delivered from twice per week to daily, with the typical frequency being 5 times per week. Mean session duration was 55 (SD 36) minutes per week, with some durations as short as 5 to 10 minutes. The types of interventions varied. Some studies (20/23, 87%) included therapy-driven programs, hydrotherapy, walking, exercise training, and motor activities. While most studies (19/23, 83%) integrated a single type of intervention, some (4/23, 17%) were multimodal. For example, one study included 5 different intervention types (motor activities, hippotherapy, hydrotherapy, exercise training, and walking) [18]. While intervention characteristics were typically reported in detail (duration, setting, and delivery), protocols were often superficially described and lacked sufficient details to allow for replication. For example, frequency was often reported as recommended times per week without providing actual adherence. Additionally, time per session was typically reported as a range that could vary based on progression or unknown factors. Finally, most interventions relied on tailored, individualized exercise programs that listed the prescribed activities but did not provide specific dose information or movement adaptations.

Measured Outcomes

The primary and secondary outcomes and measures reported in the included studies are shown in Table 4, and frequencies are shown in Table 5. The most frequent primary or secondary outcome was gross motor function (11/23, 48%), followed by LTPA (6/23, 26%) or walking ability (6/23, 26%). Several of the studies (7/23, 30%) assessed behavior, goal attainment, caregiver satisfaction and well-being, fine motor function, or communication as a primary or secondary outcome. Health-related fitness outcomes were not measured thoroughly. Some studies (9/23, 39%) reported body composition, balance, quality of life, flexibility, cardiorespiratory health, intervention feasibility, or mood; however, these variables were typically secondary or tertiary measures. Additionally, very few objective measures were used to support the primary or secondary objectives, with most of the studies (21/23, 91%) relying on clinical observational performance or self-report (parent or caregiver) measures. There were no studies that reported direct measures of strength or cardiorespiratory health.

The studies that reported gross motor function were split between the use of RTT-specific motor assessment tools, including the Rett Syndrome Gross Motor Scale [53] and the Rett Syndrome Motor Evaluation Scale [54]. Physical activity was typically measured through step or activity counts using an accelerometer; however, 9% (2/23) of the studies estimated LTPA using a modified Bouchard activity record [55].

Telehealth Implementation

Among the 23 studies included in this review, 9 (39%) interventions were delivered through telehealth. These studies accounted for 77% (153/200) of the total participant population. Ambulatory participants made up approximately 59% of the total telehealth enrollment. Every telehealth study used a remote video call delivered by a health professional to a caregiver. Only one study augmented the video calls with an online monitoring platform (smartphone app) [47]. The most common frequency of video calls was once every other week (67%). Several studies only used video calls as needed or monthly. Very few telehealth procedural details (eg, communication, behavior change, or technical implementation strategies) were reported across these studies to support replication.

Discussion

State of Research

This scoping review summarized 23 studies involving LTPA for individuals with RTT, with a secondary aim of charting telehealth implementation. The findings reveal a growing body of evidence supporting the feasibility and potential benefits of LTPA interventions across diverse settings, delivery modes, and outcome domains. We discuss the current state of research on LTPA interventions, telehealth implementation, expected benefits, and recommendations for future research that could enhance LTPA interventions for individuals with RTT.

These study findings, similar to those of a recent scoping review of rehabilitation therapies, suggest a lack of studies that could be classified as high-quality evidence [56]. Regarding quality, there appeared to be 2 key limitations: sample size and study design. While many global regions were represented in our review (Table 1), study samples were predominantly small. Over half (12/23, 52%) of the studies included in this review did not incorporate a control or comparison group, and many studies (9/23, 39%) instead used a multiple-baseline design in which the intervention was introduced at different times across participants, settings, or behaviors to demonstrate experimental control (Table 2). Single-group within-subject designs may be appropriate for evaluating the effects of LTPA interventions in neuromuscular disorders, particularly in the context of small sample sizes (eg, 10-40 participants) [57]. On a positive note, our findings suggest that several research design decisions across these studies were consistent with recommendations from the International Rare Diseases Research Consortium for small-population clinical trials, including making use of longitudinal data to show how treatment effects evolve over time, using multiple end points, adjusting follow-up outcomes for baseline values rather than relying on a single change-from-baseline measure, and using registry data to aid in sample size estimates [58]. The only RCTs (2/23, 9%) were implemented by one researcher [34,35]. These studies were able to demonstrate an increase in gross motor skills with environmental enrichment and a small reduction in sedentary time through a telehealth-supported program.

Disappointingly, low rates of physical activity are common in RTT, particularly among people with RTT who have a mobility disability and a higher age [59,60]. A notable finding was that several types of home- and community-based LTPA interventions were successful in achieving their intended outcomes. An encouraging finding was that these interventions were adapted to the needs of individuals with RTT who were ambulatory and nonambulatory. Nonambulatory participants represented 65% of the sample, which was representative of the population [61]. Such adaptations and programs were particularly noteworthy for their inclusion of individuals with more severe levels of disability. However, the lack of depth in reporting intervention and implementation characteristics limits replication of current research efforts in this area. We encourage future LTPA research in RTT to provide more transparent details regarding intervention tailoring strategies, along with successful and unsuccessful lessons that have been learned from intervention delivery.

We found that caregivers were often the primary target for LTPA interventions. This approach likely reflects the severity of the children’s disability, which limits the feasibility of direct participation or communication. Although caregivers play a vital role in fostering LTPA, particularly when communication difficulty in the child is a concern, caregivers experience substantial burden with LTPA interventions, which can manifest in various barriers, including limited time and resources, difficulty obtaining mobility aids, few trained professionals, and a lack of knowledge [62]. Caregivers of children or adult patients with RTT report barriers to LTPA that are consistent with those of other disability groups [62,63], including limited resources in the community, lack of transportation, lack of trained professionals, lack of suitable LTPA modalities and resources, and lack of knowledge [64,65]. Therefore, LTPA programs that are accessible and adaptable to the unique needs of individuals with RTT may promote LTPA and reduce caregiver burden [4].

Many of the targeted outcomes reported across the studies in this review were not objectively measured. There was a lack of health and fitness outcomes that are typical in LTPA interventions. For instance, there was not a single example of an objective muscle strength measure even though arm and leg muscle area measurements are significantly lower in female patients with RTT than in their male counterparts [3]. Gross motor function was a consistent positive finding [18,33,34]. There was little evidence to demonstrate an improvement in cardiopulmonary health, which is concerning because RTT is associated with cardiac arrhythmias that are a potential cause of sudden death [3]. Therefore, benefits as a result of LTPA for people with RTT should be interpreted with caution.

A notable gap identified in this study was the limited information on telehealth implementation. The use of telehealth as an intervention delivery platform may expand intervention reach and address enrollment barriers. Delivery of interventions through telehealth has been shown to be effective and important in neurodevelopmental rehabilitation and disability management [66,67]. Remote interventions in this review demonstrated positive goal achievement and caregiver satisfaction [35,40,41,47,48]. Consistent with findings across all included studies, we observed little to no direct communication with participants with RTT via remote telecommunication. While impaired communication is common in individuals with RTT [68], a major concern of their caregivers [69], and a barrier to LTPA participation [62], it is unclear whether direct participant communication through telehealth is feasible. For example, one study demonstrated significant potential in supplementing telehealth coaching using alternative augmentative communication [70]. While direct interaction with participants is typical in telehealth exercise interventions for individuals with disabilities [71], achieving meaningful communication with participants with RTT may require additional support from speech-language therapists or a family member. Although the intervention characteristics were often superficially reported across studies, the description of telehealth delivery and engagement of participants with RTT was even more limited. A deeper understanding of the factors contributing to telehealth implementation success and failure could help guide future research in this area.

Consultation Exercise

The consultation exercise reinforced and contextualized several key gaps identified in the literature. The consulted caregiver emphasized that effective LTPA interventions for individuals with RTT must be tailored to age and ambulation status, echoing the heterogeneity observed across the included studies. Their insights highlighted the potential value of telehealth in supporting participation and accountability for families, particularly given the heavy caregiving demands that limit opportunities for structured physical activity. Importantly, the caregiver identified a critical service gap wherein adolescents and adults with RTT often lose access to outpatient therapy services, underscoring the need for accessible, home‑based, or remotely delivered programs. The consultation also drew attention to the lack of standardized severity classifications in existing research and the absence of key outcome domains—such as muscle strength, cardiovascular health, balance, and quality of life—that families consider essential for daily functioning. These perspectives align with the broad variability in intervention characteristics and outcome measures found in our review and further support the need for consistent reporting and comprehensive assessment frameworks. Collectively, the consultation emphasized the urgency of developing adaptable, evidence-informed LTPA resources and best practice guidelines across the life span, particularly for nonambulatory individuals and those aging out of pediatric services.

Future Recommendations

The most promising outcomes observed in this scoping review were improvements in physical activity and walking ability. To advance the field and address existing gaps, future research should consider the following. First, studies should include more adults with RTT to better understand age-related changes in LTPA participation and intervention responsiveness across the life span. Second, while the feasibility of interventions was often reported as good, future research should add greater levels of detail in their protocols and modalities to increase the reproducibility of their design. For example, the walking trials administered by Schaefer-Campion and Johnson [32] illustrated nuanced differences in walking aids for a child with RTT that can inform decisions for future studies to foster walking ability. Conducting larger and more frequent multisite RCTs with appropriate control conditions may strengthen causal inferences. Adopting objective measures for aspects of health-related fitness such as strength across studies would facilitate cross-study comparisons and meta-analyses. Because low physical fitness, gait abnormalities, and comorbidities such as scoliosis and osteoporosis can be potential barriers to participation in LTPA [4,72,73], it is important to confirm the short-term efficacy of interventions that may mitigate barriers and increase LTPA in RTT.

Moreover, the addition of telehealth communications and remotely delivered interventions at home may be ideal for overcoming community barriers to LTPA among people with RTT. Telehealth LTPA clinical trials bypass the need for on-site visitation and have reached the largest sample sizes among people with physical disabilities, which would be ideal for rare diseases and conditions such as RTT [74,75].

Limitations

Several limitations should be acknowledged. Many of the included studies partially reported or did not report at all critical variables such as RTT severity, exercise protocols, or outcome frequency, thereby making it difficult to generalize the findings of this scoping review. Due to the lack of randomized trials, this review focused on non-RCTs, and the heterogeneity in study designs, sample sizes, and intervention protocols limits the generalizability of the findings. Classifying interventions as LTPA was challenging because the studies often involved a mixture of community-based exercise and physical therapy. This limitation reflects the field itself rather than being a limitation of this review specifically. Different operational definitions of LTPA could yield different conclusions. The heterogeneity of RTT (eg, variability in severity, age, and functional ability), combined with small sample sizes and diverse study designs, limits comparability across studies and complicates the synthesis of findings and interpretation of overall effects. Reliance on observational measures and caregiver-reported outcomes introduces potential bias. Finally, with a strong focus on pediatric populations, this review highlights the lack of evidence related to adults with RTT despite over half of individuals with RTT living beyond 50 years of age [6].

Conclusions

This review underscores the potential of LTPA interventions to enhance wellness and functional outcomes in individuals with RTT. Telehealth strategies show promise for improving accessibility and caregiver engagement. Nevertheless, further research is needed to establish best practices, optimize delivery models, and ensure inclusivity across the life span. Future studies should incorporate objectively measured health outcomes to verify both short- and long-term benefits while also providing detailed reporting on intervention tailoring and implementation strategies, including factors contributing to both successes and challenges.