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PubMed This is a summary of 29 peer-reviewed journal articles Updated
Rheumatology · Joint Hypermobility

What Tests Rule Out Other Causes of Joint Hypermobility?

At a Glance

There is no single blood test that confirms hEDS or HSD. Doctors use a medical history and physical examination, including the Beighton score, then order targeted blood tests, imaging, or genetic testing only when symptoms or family history suggest another condition.

When you are being evaluated for hypermobile Ehlers-Danlos syndrome (hEDS) or Hypermobility Spectrum Disorder (HSD), you might expect your doctor to order a specific blood test to confirm the diagnosis. However, because there is currently no validated diagnostic biomarker or known gene for hEDS, the diagnosis is primarily clinical [1][2]. hEDS is diagnosed using specific criteria, while HSD is used when you have symptomatic hypermobility that does not meet the strict hEDS criteria; both conditions can cause significant symptoms [1][3].

This means your doctor must carefully evaluate your symptoms and use targeted tests to check for other conditions that can look like hEDS or HSD [1]. There is no universal “hEDS lab panel.” Instead, your care team will use your medical history, a physical examination, and specific blood, imaging, or genetic tests based on your unique symptoms [1][4].

The Physical Examination and Medical History

The foundation of ruling out other conditions is a thorough physical examination and detailed medical history [5]. Your doctor will assess your joint mobility using the Beighton score (a 9-point physical exam measuring flexibility in specific joints), but they will also look for systemic features (traits affecting your whole body) [5].

For example, skin that is highly stretchy and fragile, or scars that are widened and atrophic (papery), might prompt an evaluation for classical Ehlers-Danlos syndrome (cEDS) [6][7]. A history of frequent, low-impact bone fractures, blue-tinted sclerae (the whites of the eyes), or severe bone deformities might point toward osteogenesis imperfecta (OI), a group of genetic disorders that cause bone fragility [8][9].

Targeted Blood Tests for Inflammatory and Autoimmune Conditions

Because the symptoms of hEDS and HSD—such as widespread joint pain and fatigue—can overlap with chronic inflammatory diseases, your doctor may order specific tests if your symptoms suggest an autoimmune or metabolic condition [10]. These are not indiscriminate screening panels, but targeted tests:

  • Inflammatory markers: Tests like Erythrocyte Sedimentation Rate (ESR) or C-Reactive Protein (CRP) check for active inflammation [4].
  • Specific Autoantibodies: Antinuclear antibodies (ANA) might be checked if a condition like lupus is suspected. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) are primarily used to evaluate for rheumatoid arthritis [11][4].
  • Metabolic and muscle tests: Thyroid function tests can help rule out thyroid disease [12]. If you have persistent muscle weakness, a creatine kinase (CK) test—a nonspecific marker of muscle injury—might be used, though normal results do not rule out all muscle diseases (myopathies) [13].

It is important to know that these tests must be interpreted carefully. Some healthy people have positive ANA results, which can lead to false alarms if testing wasn’t targeted based on symptoms [11]. Additionally, some people with true inflammatory arthritis are “seronegative,” meaning their blood tests do not show these specific antibodies [4][14]. Finally, having an autoimmune condition does not mean you cannot also have hEDS/HSD; the conditions can coexist [15].

Imaging and Specialist Examinations

Imaging is not routine for everyone with hypermobility, but may be used when specific symptoms, family history, or physical exam findings warrant it:

  • Cardiovascular imaging: An echocardiogram (ultrasound of the heart) may be ordered to check for mitral valve prolapse (a floppy heart valve) or aortic-root dilation (enlargement of the first part of the main artery leaving the heart) [16][17]. This test is guided by your clinical picture and family history, particularly if a connective tissue disorder like Marfan syndrome or Loeys-Dietz syndrome is suspected [18][19]. A normal echocardiogram does not completely rule out these conditions or other causes of aortic disease, nor does it diagnose hEDS [20].
  • Joint imaging: If your doctor suspects synovitis (inflammation of the joint lining) or crystal deposits (like gout), a musculoskeletal ultrasound can sometimes provide evidence when standard X-rays are normal [21]. However, a normal ultrasound does not rule out all inflammation, and analyzing joint fluid remains the standard for diagnosing crystal arthritis [22].
  • Eye examinations: A formal eye exam can check for ectopia lentis (lens displacement), a distinguishing feature of Marfan syndrome not typically seen in hEDS [18][23].

Safety Alert: When to Seek Immediate Care
While joint hypermobility itself is usually not a medical emergency, certain very rare genetic conditions like vascular EDS (vEDS) or Marfan syndrome carry risks for the blood vessels. If you or a family member experience sudden, severe chest, back, or abdominal pain, fainting, stroke-like symptoms, or unexplained major bleeding, seek emergency medical care immediately [24][16].

When is Genetic Testing Used?

Routine genetic testing is not recommended for everyone with generalized joint hypermobility [2][1]. Because a gene for hEDS has not yet been identified, genetic testing cannot confirm an hEDS diagnosis [25][26].

However, testing is appropriate if your examination or family history raises suspicion for a different heritable connective tissue disorder [1][2]. If you have features suggesting Marfan syndrome, Loeys-Dietz syndrome, osteogenesis imperfecta, or a non-hypermobile subtype of EDS (like classical or vascular EDS), your doctor may recommend a multigene sequencing panel (a blood or saliva test looking at multiple specific genes) [27][28].

When interpreted alongside your physical exam and with the help of a genetics specialist or genetic counselor, these panels can help support or establish an alternative diagnosis [18][29]. Keep in mind that a negative panel does not perfectly rule out every inherited connective-tissue disorder, as panels may not detect every variant type, and some diagnoses remain purely clinical [28].

By methodically checking for inflammatory, metabolic, and other genetic causes, your care team can assess alternative diagnoses, identify any coexisting conditions, and tailor the best management plan for your symptoms. Importantly, normal diagnostic tests do not mean your pain, fatigue, or joint instability are imaginary.

Common questions in this guide

Can a blood test confirm hypermobile Ehlers-Danlos syndrome?
No. There is currently no validated blood test, biomarker, or known gene that confirms hEDS. Clinicians diagnose it using established clinical criteria and use targeted tests to look for other conditions.
What blood tests might be used when joint hypermobility has other symptoms?
Depending on your symptoms, a clinician may order ESR or CRP for inflammation, ANA for possible lupus, rheumatoid factor or anti-CCP for rheumatoid arthritis, thyroid tests, or creatine kinase when muscle weakness suggests muscle injury. These are targeted tests rather than a universal hypermobility panel, and normal results do not rule out every condition.
How does the physical exam help distinguish hEDS from other disorders?
The examination includes the nine-point Beighton score to measure flexibility, but it also checks the skin, scars, bones, joints, and other whole-body features. Very stretchy or fragile skin, widened papery scars, frequent low-impact fractures, or blue-tinted eye whites may point to another connective-tissue or bone disorder.
When should someone with joint hypermobility have genetic testing?
Genetic testing is not routine for generalized joint hypermobility or hEDS because no hEDS gene has been identified. A clinician may recommend a multigene panel when examination findings or family history suggest Marfan syndrome, Loeys-Dietz syndrome, osteogenesis imperfecta, classical EDS, or vascular EDS. A genetics specialist or counselor can help interpret the results, and a negative panel does not exclude every inherited disorder.
When are an echocardiogram, eye exam, or joint scan useful?
These tests are selected when symptoms, family history, or examination findings suggest another condition. An echocardiogram can assess the heart valve and aortic root, an eye exam can look for lens displacement associated with Marfan syndrome, and ultrasound may look for joint-lining inflammation. If crystal arthritis is suspected, joint-fluid analysis remains the standard test, and normal imaging does not diagnose hEDS or exclude every disorder.
Can autoimmune disease occur alongside hEDS or HSD?
Yes. An autoimmune or inflammatory condition can coexist with hEDS or HSD, and some people with inflammatory arthritis have negative antibody tests. Persistent pain, fatigue, swelling, redness, or heat still deserves medical follow-up even when initial tests are normal.
When should symptoms with hypermobility be treated as an emergency?
Seek emergency care for sudden severe chest, back, or abdominal pain, fainting, stroke-like symptoms, or unexplained major bleeding. These symptoms are uncommon but can signal a serious blood-vessel problem in conditions such as vascular EDS or Marfan syndrome.

Related questions

What Kind of Doctor Diagnoses hEDS or HSD? How to Prepare Can Older Adults Be Diagnosed With hEDS If Less Flexible? Can You Have hEDS or HSD With a Borderline Beighton Score? Do hEDS and HSD Get Worse Over Time? Long-Term Outlook How Are hEDS and HSD Diagnosed in Children and Adolescents?
Show more
How Do I Get an hEDS or HSD Evaluation From a Doctor? How Common Are hEDS and Hypermobility Spectrum Disorder? Is Hypermobile EDS Hereditary? Family and Child Evaluation Is Joint Hypermobility Just Flexibility—or HSD or hEDS? Is Treatment Different for HSD vs. Hypermobile EDS? Can I Safely Do Beighton Score Tests for hEDS at Home? What Causes hEDS and HSD If There Is No Genetic Test? What Exercises Are Safe for Hypermobile EDS and HSD? What Is the 5PQ for hEDS and How Is It Scored in Practice? How Do hEDS, Classical EDS, vEDS, Marfan, and LDS Differ? What Should You Do for a Dislocated or Subluxing Joint? When Is Genetic Testing Recommended for Suspected EDS? Why Does Exercise Worsen hEDS or HSD Symptoms and Flares? Why Do Joints Sublux or Dislocate with hEDS or HSD?

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This page is for informational purposes only and does not constitute medical advice. Your clinician should decide which tests are appropriate and interpret them in the context of your symptoms, examination, and family history.