Management and Evaluation of Generalized Joint Hypermobility in a 39-Year-Old Female
This patient requires immediate evaluation with the Beighton scale (≥5/9 points diagnostic for joint hypermobility at her age), followed by systematic exclusion of serious connective tissue disorders—particularly vascular Ehlers-Danlos syndrome—before establishing a diagnosis of hypermobile EDS or hypermobility spectrum disorder. 1, 2
Initial Clinical Assessment
Beighton Scale Evaluation (Required First Step)
Systematically assess all nine points to quantify joint hypermobility 1, 2:
- Passive dorsiflexion of each fifth finger >90 degrees (1 point per side) 2
- Passive apposition of each thumb to flexor forearm surface (1 point per side) 2
- Hyperextension of each elbow >10 degrees (1 point per side) 2
- Hyperextension of each knee >10 degrees (1 point per side) 2
- Ability to place palms flat on floor with knees fully extended (1 point) 1, 2
A score ≥5/9 confirms generalized joint hypermobility in adults under 50 years 1, 2.
Skin and Tissue Examination
Evaluate for features distinguishing different connective tissue disorders 1:
- Soft or velvety skin with normal or slightly increased extensibility suggests hypermobile EDS 1
- Thin, translucent skin with visible veins raises concern for vascular EDS (life-threatening) 2
- Absence of skin fragility or atrophic scarring helps exclude other EDS subtypes 1
- Easy bruising patterns without significant trauma 1, 3
Three-Generation Family History
Document autosomal dominant inheritance patterns 1, 2:
- Sudden deaths, arterial ruptures, or organ perforations (suggests vascular EDS—urgent) 2
- Similar joint hypermobility without skin abnormalities in relatives 1
- Recurrent joint dislocations or chronic pain in family members 1, 3
Mandatory Exclusion Testing
Cardiovascular Evaluation (Cannot Be Skipped)
Echocardiogram is required for all patients with generalized joint hypermobility to evaluate aortic root diameter, as dilation occurs in 25-33% of hypermobile and classic EDS cases 1, 2, 3. This is critical because aortic complications can be life-threatening.
If aortic root is normal: Repeat echocardiogram every 2-3 years until adult height reached, then only if cardiovascular symptoms develop or major increase in physical activity planned 1.
If aortic root dilation present (>2 SD for age/body size): 1
- Echocardiogram every 6 months if diameter >4.5 cm or growth rate >0.5 cm/year
- Annual echocardiogram if diameter <4.5 cm and growth <0.5 cm/year
- Refer to skilled cardiologist for β-blocker therapy consideration
- MR angiography of entire aorta if dilation significant
Ophthalmologic Evaluation
Dilated eye examination is mandatory to exclude ectopia lentis (lens dislocation), which would indicate Marfan syndrome rather than EDS 1, 2.
Genetic Testing Strategy
If clinical features suggest vascular EDS (thin translucent skin, arterial/organ rupture history, early-onset varicose veins): Urgent COL3A1 gene mutation testing is required, as this is a life-threatening subtype with median survival 48 years 2. Avoid invasive vascular procedures in suspected vascular EDS—fatal complications have been reported 2.
For typical hypermobile presentation: Genetic testing is NOT routinely recommended, as no causative genes have been identified for hypermobile EDS 2, 4. However, multi-gene panel testing (COL3A1, COL5A1, COL5A2, TGFBR1, TGFBR2) may be considered if clinical features are atypical or overlap with other syndromes 2.
Recent evidence shows that 26.4% of patients meeting clinical criteria for hypermobile EDS had alternative genetic diagnoses requiring different management 4. This supports selective genetic testing when phenotype is unclear.
Establishing the Diagnosis
Hypermobile EDS Diagnostic Criteria (2017)
All three criteria must be met 1, 2:
Criterion 1: Generalized joint hypermobility (Beighton score ≥5/9 for adults <50 years) 1, 2
Criterion 2: Two or more of the following features 1:
- Soft or velvety skin with normal or slightly increased extensibility
- Absence of skin or soft tissue fragility
- Recurrent joint dislocations or subluxations
- Chronic joint or limb pain
- Easy bruising
- Functional bowel disorders (irritable bowel syndrome, functional gastritis)
- Neurally mediated hypotension or postural orthostatic tachycardia syndrome
- High narrow palate with dental crowding
Criterion 3: Exclusion of alternative diagnoses (Marfan syndrome, vascular EDS, other EDS subtypes, other heritable connective tissue disorders) 1, 2, 4
Hypermobility Spectrum Disorder
If patient has symptomatic joint hypermobility but does not meet all three criteria for hypermobile EDS, diagnose as hypermobility spectrum disorder 5, 6.
Screening for Common Comorbidities
Autonomic Dysfunction (POTS)
Measure postural vital signs with active stand test 2, 3:
- Document heart rate increase ≥30 beats/min within 10 minutes of standing without orthostatic hypotension
- POTS affects up to 37.5% of hypermobile EDS patients 2
- Symptoms include lightheadedness, generalized weakness, blurred vision, cognitive dysfunction, palpitations 3
- If positive, refer for tilt table testing and expanded autonomic function assessment 2
Gastrointestinal Manifestations
Up to 98% of hypermobile EDS patients experience GI symptoms 2, 3. Systematically assess for:
- Nausea and abdominal pain (predictive of abnormal GI motility) 3
- Severe constipation, bloating, early satiety 3
- Gastroesophageal reflux and gastritis 3
Celiac disease serological testing should be performed earlier in hypermobile EDS patients with any GI symptoms, as risk is elevated 2.
Consider anorectal manometry, balloon expulsion test, or defecography for incomplete evacuation symptoms, given high prevalence of pelvic floor dysfunction 2.
Gastric emptying studies for chronic upper GI symptoms after excluding structural disease 2.
Mast Cell Activation Syndrome (MCAS)
Only test if patient presents with episodic multisystem symptoms involving ≥2 physiological systems (flushing, urticaria, wheezing, multisystem symptoms triggered by foods, alcohol, temperature changes) 2, 3.
Do NOT perform routine MCAS testing in all hypermobile EDS patients with isolated GI symptoms 2.
If indicated, obtain baseline serum tryptase level, with diagnostic threshold of 20% increase above baseline plus 2 ng/mL during symptomatic flares 2.
Bone Density
Order DXA scan if height loss >1 inch, as osteoporosis is associated with hypermobile EDS 1, 2.
Management Strategy
Musculoskeletal Management
Low-resistance exercise is the cornerstone to improve joint stability by increasing muscle tone 1, 7.
Physical therapy for myofascial release is often necessary before patients can participate in low-resistance exercise 1.
Orthopedic surgery should be delayed if possible in favor of physical therapy and bracing, as patients with hypermobile EDS have decreased stabilization, reduced pain reduction, and shorter duration of improvement compared to those without EDS 1.
Vitamin C supplementation may improve hypermobility as it is a cofactor for collagen fibril cross-linking 1.
Pain Management
Avoid opioids in patients with chronic pain, as they contribute to fatigue and worsen outcomes 2, 7.
Pain management specialist involvement is crucial for chronic pain in hypermobile EDS 1, 7.
Pain can be classified topographically as articular limb (acute/chronic), muscular limb (myofascial/fibromyalgia), neuropathic, back/neck, abdominal/pelvic, or headache—each requiring specific approaches 7.
Gastrointestinal Management
Gastritis and reflux: Proton pump inhibitor, H2-blocker, or sucralfate 1
Delayed gastric emptying: Promotility agent 1
Irritable bowel: Antispasmodics, antidiarrheals, and laxatives as needed 1
Bone Health
Encourage calcium and vitamin D supplementation 1
Low-impact weight-bearing exercise 1
Lifestyle Modifications
Provide structured education about 8, 5:
- Joint protection techniques
- Activity modification to prevent injury
- Recognition of symptom triggers
- Importance of adherence to physical therapy
Critical Pitfalls to Avoid
Never miss vascular EDS—this carries significant mortality risk from arterial or organ rupture 2. Thin translucent skin with visible veins mandates urgent COL3A1 testing.
Do not perform invasive vascular procedures in suspected vascular EDS without genetic confirmation, as fatal complications have been reported 2.
Recognize that hypermobility may be a shared phenotype across multiple disorders including inflammatory diseases, monogenic syndromes, and chromosomal abnormalities—genetic testing identified alternative diagnoses in 26.4% of patients meeting clinical criteria for hypermobile EDS 4.
Avoid escalating to invasive nutrition support (feeding tubes, parenteral nutrition) in pain-predominant presentations without clear evidence of true dysmotility, as many hypermobile EDS patients have visceral hypersensitivity rather than true small bowel dysmotility 1.
Progress is often slow and hampered by physical and emotional setbacks—set realistic expectations with patients 8, 7.
Multidisciplinary Coordination
Given the multisystem nature of hypermobile EDS, coordinate care with 1, 5:
- Cardiology for aortic surveillance
- Gastroenterology for refractory GI symptoms
- Physical therapy/occupational therapy for joint stability
- Pain management for chronic pain
- Psychology/psychiatry for anxiety, depression, and coping strategies (common comorbidities)
- Medical genetics if diagnosis uncertain or family planning considerations
Primary care physicians play the key role in ongoing coordination of this multidisciplinary team 5.