Potential Biomarker for the Diagnosis of Hypermobility Spectrum Disorders

Lilian White, MD
Posted on September 23, 2024

Hypermobile Ehlers-Danlos syndrome (EDS) is fairly common, estimated to affect 1 in 600 to 900 people. A patient with hypermobile EDS may present with atraumatic joint pain, joint hypermobility, and skin hyperextensibility, in addition to other signs and symptoms. The diagnosis is made using a set of clinical criteria, as outlined in an American Family Physician (AFP) article on hypermobile EDS and hypermobility spectrum disorders; however, distinguishing hypermobile EDS from other conditions that present with joint hypermobility can be a challenge. Recently, a study published in the American Journal of Medical Genetics demonstrated the promise of a blood test to aid in the diagnosis of hypermobile EDS.

The study compared fragments of proteins in the blood (e.g., fibronectin, type 1 collage) of patients with hypermobile EDS, vascular and classical EDS, psoriatic arthritis, rheumatoid arthritis, osteoarthritis, and healthy individuals. Patients with hypermobile EDS were found to have a unique signature of protein fragments, potentially leading to future use as a diagnostic tool.

Currently, patients with hypermobility spectrum disorders are distinguished from those with hypermobile EDS by not meeting the full hypermobile EDS criteria. However, the results from this study demonstrated significant similarities in the protein fragments appreciated in patients with hypermobile EDS and hypermobility spectrum disorders. This may result in the two diagnoses becoming more unified in the future.

Even more common than hypermobile EDS or hypermobility spectrum disorders is generalized joint hypermobility, which is distinguished from hypermobile EDS and hypermobility spectrum disorders by the absence of symptomatic joint pain. Children and young adults tend to be most affected, with a prevalence of 4% to 11% in those 3 to 19 years old. As people age, joints tend to become less extensible, reducing the incidence of generalized joint hypermobility. This age-related change is accounted for by reducing the points on the Beighton score for the assessment of hypermobility that are required for a positive score as age increases.

Limitations preventing near-term application of this test in clinical practice include the smaller study design (466 participants and only 174 with hypermobile EDS and hypermobility spectrum disorders) and need to further validate the biomarker’s performance in patients with additional diagnoses or other testing conditions that may affect results. Currently, the median time to diagnosis of hypermobile EDS is 10 years, making a blood test a desirable asset to potentially facilitate earlier diagnosis and improve patient quality of life.

Support for the treatment of hypermobile EDS can be found in the AFP article on hypermobile EDS and hypermobility spectrum disorders as well as the Ehlers-Danlos Society GP Toolkit. Additionally, in 2024, AFP published a Photo Quiz to test reader’s knowledge on the topic.