Work

Elucidating the Molecular Basis in a Cohort of Patients With Combined Bleeding Tendencies and Joint Hypermobility Manifestations

Year: 2025

Type: article

Abstract: BACKGROUND: In patients with unexplained bleeding and normal haemostatic parameters, heritable disorders of connective tissue (HDCT) may be an underlying cause due to vascular fragility, as observed in Ehlers-Danlos syndrome (EDS) or Marfan syndrome (MS). This study aims to investigate the molecular profile of patients with joint hypermobility (JH) and unexplained bleeding and to establish genotype-phenotype associations. METHODS: Forty-three female patients with JH and bleeding symptoms were recruited from the haemophilia unit and rehabilitation service at Vall d'Hebron University Hospital. Whole-exome sequencing (WES) was performed to identify genetic variants. RESULTS: Candidate variants in HDCT-related genes were identified in 47% of cases, predominantly in genes associated with EDS and MS. A complete genotype-phenotype concordance was established in 37%, emphasizing the importance of assessing JH in patients presenting with unexplained bleeding. CONCLUSION: The results underscore the need for systematic assessment of JH in patients with bleeding and normal haemostatic tests, as well as for bleeding evaluation in those showing HDCT signs. WES proved valuable in identifying genetic contributors to these complex phenotypes, supporting a multidisciplinary approach to achieve accurate diagnosis and improved patient care.

Source: Haemophilia

DOI: 10.1111/hae.70160