Unveiling the Spectrum: Clinical and Molecular Insights from a Spanish Pediatric Cohort with Hypermobility Disorders and Ehlers-Danlos Syndrome.

Diagnosing hypermobility disorders and Ehlers-Danlos syndrome (EDS) in children is challenging due to overlapping features with generalized joint hypermobility (GJH) and the lack of biomarkers. Background/

Objectives

This study aims to describe the clinical and genetic features of pediatric EDS patients and identify key comorbidities and correlations.

Methods

This is a single-center observational study of patients under 18 diagnosed with suspicion of EDS (2018-2024) at a tertiary pediatric hospital. Diagnoses were made using 2017 criteria.

Results

Forty-one patients (46% female; mean age 11.1 ± 2.8 years) were included. Based on 2017 criteria, 61% had hypermobile EDS (hEDS)/hypermobility spectrum disorder (HSD), 22% classical EDS, 7.3% vascular, and 9.7% other subtypes. Musculoskeletal (90.2%), cutaneous (68.3%), and psychiatric (56.1%) symptoms were most frequent. Significant associations included older age with psychiatric symptoms (p = 0.029), Beighton score with dislocations (p = 0.026), and less atrophic scarring in hEDS (p < 0.008). Genetic testing (73% performed) confirmed pathogenic variants (11 novel) in EDS with a known molecular cause.

Conclusions

This study proposes a clinically guided approach and diagnostic algorithm for youth hypermobility, emphasizing precision medicine principles, while highlighting the urgent need for further research to identify hEDS biomarkers.