ENOrphanet Journal of Rare Diseases | Personalized Home-Based Exercise Training Improves Aerobic Capacity and Quality of Life in Children with Marfan and Loeys-Dietz Syndromes
Date: March 06, 2026
Classification: Frontiers
Recommend:
This study is the first to evaluate the effectiveness and tolerability of personalized home-based exercise training in children with Marfan and Loeys-Dietz syndromes. Results show that a 6-month training program significantly improves aerobic capacity and health-related quality of life, without affecting aortic sinus diameter, providing key evidence for non-pharmacological interventions in children with rare diseases.
Literature Overview
The article 'A personalized home-based exercise training program in children with Marfan and Loeys-Dietz syndromes improves aerobic exercise capacity and health-related quality of life,' published in the Orphanet Journal of Rare Diseases, reviews and summarizes the effects of a 6-month personalized home-based exercise training program in children with Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). Using a prospective single-center clinical trial design, the study assessed the impact of this training on aerobic capacity, health-related quality of life (HRQoL), and cardiovascular safety. Results indicate that the intervention significantly improved ventilatory anaerobic threshold (VAT) and 6-minute walk distance, enhanced multiple dimensions of quality of life, and did not cause aortic dilation or cardiovascular adverse events. The study highlights the potential of early, safe, and personalized exercise interventions in managing rare connective tissue disorders. It also notes that despite a small sample size, the observed effects are significant, suggesting such non-pharmacological interventions warrant further promotion and optimization.Background Knowledge
Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS) are autosomal dominant connective tissue disorders caused by mutations in FBN1 and genes related to the TGF-β signaling pathway (e.g., TGFBR1/2, SMAD3), respectively. Both share cardiovascular (e.g., aortic root dilation, dissection) and skeletal manifestations, and both involve dysregulation of the TGF-β signaling pathway. Although β-blockers and surgery significantly extend patient lifespan, children often report chronic fatigue, reduced physical endurance, and diminished quality of life. Studies show that MFS patients have reduced muscle mass and strength, possibly due to TGF-β overactivation leading to muscle fiber atrophy and impaired regeneration. Animal models suggest moderate exercise can improve aortic pathology, while high-intensity exercise may worsen elastic fiber damage. While exercise interventions have been studied in adults with MFS, data in children remain limited. Improving fitness and quality of life without increasing aortic risk poses a major clinical challenge. This study addresses this gap by designing a safe, home-based personalized training program and systematically evaluating its physiological and psychological benefits, filling a critical void in pediatric rare disease exercise rehabilitation.
Methods and Experiment
This single-center, single-arm, prospective intervention trial enrolled 28 genetically confirmed children aged 7–18 years with MFS or LDS. The study included a 3-month observational period followed by a 6-month intervention. The primary endpoint was change in ventilatory anaerobic threshold (VAT), with secondary endpoints including 6-minute walk test (6MWT) distance, health-related quality of life (PedsQL™ questionnaire), and cardiovascular safety parameters (aortic sinus diameter, heart rate, blood pressure). The personalized home-based program consisted of two 40-minute sessions per week of cycling on a stationary bike using an intermittent 'base-peak' load pattern, plus one weekly resistance training session with elastic bands. Exercise intensity was based on the ventilatory threshold determined during an initial maximal exercise test. Supervision and adjustments were provided via telephone follow-ups. Data were analyzed using linear mixed models for repeated measures and paired t-tests for pre- and post-intervention comparisons.Key Conclusions and Insights
Significance and Outlook
This study provides the first high-quality evidence that personalized, moderate-intensity home-based exercise training is not only safe but also effective in improving aerobic capacity and quality of life in children with MFS and LDS. It challenges the traditional approach of strictly limiting physical activity in these patients and supports regular, professionally guided exercise.
However, the 29% dropout rate suggests room for improvement in adherence, possibly due to monotonous training formats. Future studies should explore more engaging and individually tailored exercise modes—such as activity integration based on personal interests—to enhance long-term compliance. Although no changes in aortic diameter were observed, longer-term studies are needed to assess potential effects on aortic root progression. This study lays the foundation for multicenter randomized controlled trials and may help establish standardized exercise rehabilitation guidelines for pediatric connective tissue disorders.
Conclusion
This study systematically evaluated the effects of personalized home-based exercise training in children with Marfan and Loeys-Dietz syndromes. Despite significantly lower baseline aerobic capacity compared to healthy peers, a 6-month structured training program significantly improved ventilatory anaerobic threshold and 6-minute walk distance, while enhancing health-related quality of life domains such as physical function and social well-being. No deterioration in aortic sinus diameter or cardiovascular parameters was observed, confirming the safety of the intervention. The study emphasizes that moderate, personalized exercise can be an essential component of comprehensive management for children with MFS and LDS, helping to break the vicious cycle of reduced activity due to fatigue and poor fitness. Although limited by small sample size and high dropout rate, the significant physiological and psychological benefits support further optimization and broader implementation of such non-pharmacological strategies. Future efforts should focus on improving adherence, exploring long-term benefits, and validating applicability across a wider range of rare disease populations. This work provides crucial practical evidence for functional rehabilitation in rare diseases, advancing the paradigm shift from 'activity restriction' to 'scientific exercise'.
