Exploring fatigue in Marfan and hypermobile Ehlers-Danlos syndromes: an analytical cross-sectional study in two Italian healthcare centres

Abstract Objective: This study investigates the prevalence and underlying factors of fatigue in individuals with Marfan syndrome (MFS) and hypermobile Ehlers-Danlos syndromes (hEDS), highlighting the necessity for focused research on this symptom within these patient populations. Design: Cross-sectional, multicentre study. Setting: Data were collected from participants diagnosed with MFS or hEDS across multiple healthcare centres. Participants: The study enrolled 282 participants (127 with MFS and 155 with hEDS). Primary and secondary outcome measures: Fatigue was measured using the Fatigue Severity Scale (FSS). Additional assessments included the Patient Health Questionnaire-9 (PHQ-9) for depression and the Insomnia Severity Index (ISI) for sleep disturbances. Results: Participants with hEDS exhibited significantly higher median fatigue scores (FSS median=5.9, IQR=5.00-6.44) compared with the MFS group (FSS median=4.0, IQR=2.88-5.00). Significant predictors of fatigue included being female, having hEDS, participating in psychotherapy, and elevated scores on depression and insomnia scales. In the overall sample, hEDS significantly predicted fatigue (B=0.430, p=0.022), with depression and insomnia as strong influencers (PHQ-9: B=0.12, p