Diagnostic Testing for hEDS and POTS
For hEDS, use the Beighton score as your primary screening tool in the office—no laboratory or imaging tests exist to diagnose hEDS, making it a purely clinical diagnosis based on the 2017 criteria. For POTS, measure orthostatic vital signs with a 10-minute active stand test, which is sufficient for diagnosis in most patients without requiring tilt table testing or specialized autonomic laboratories 1.
Testing for Hypermobile Ehlers-Danlos Syndrome (hEDS)
Primary Screening: Beighton Score
Incorporate the Beighton score into your practice as the foundational screening tool 1. This 9-point assessment evaluates:
- Bilateral 5th finger hyperextension beyond 90° (1 point each side)
- Bilateral thumb-to-forearm apposition (1 point each side)
- Bilateral elbow hyperextension >10° (1 point each side)
- Bilateral knee hyperextension >10° (1 point each side)
- Forward trunk flexion with palms flat on floor without knee bending (1 point)
Age-adjusted cutoffs 1:
- ≥6/9 points: children before puberty
- ≥5/9 points: puberty to age 50
- ≥4/9 points: age 50 and older
Complete Clinical Diagnosis
A positive Beighton score triggers application of the 2017 diagnostic criteria requiring three major criteria 1:
- Generalized joint hypermobility (Beighton score as above)
- Two or more systemic features: soft/velvety skin, skin hyperextensibility, atrophic scarring, striae, hernias, pelvic organ prolapse, dental crowding, high/narrow palate, arachnodactyly, arm span-to-height ratio >1.05, mitral valve prolapse, aortic root dilatation
- Exclusion of alternative diagnoses
Critical Caveat: Genetic Testing
Despite hEDS being a clinical diagnosis, genetic testing plays a crucial exclusionary role. Recent evidence shows that 26.4% of patients meeting clinical hEDS criteria actually had alternative genetic diagnoses requiring different management 2. Order genetic testing to exclude other hereditary connective tissue disorders (Marfan syndrome, vascular EDS, classical EDS, Loeys-Dietz syndrome) before finalizing an hEDS diagnosis 2.
No Routine Laboratory Tests
Do not order routine laboratory tests, imaging, or biopsies for hEDS diagnosis—these cannot confirm or exclude hEDS 1. The diagnosis remains clinical after genetic exclusion.
Testing for Postural Orthostatic Tachycardia Syndrome (POTS)
Primary Diagnostic Test: Active Stand Test
Measure heart rate and blood pressure after 5 minutes supine, then continuously during 10 minutes of standing 3. This bedside test is sufficient for diagnosis in most patients.
POTS diagnostic criteria 1, 3:
- Heart rate increase ≥30 bpm within 10 minutes of standing (≥40 bpm in ages 12-19)
- Sustained increase: must be present on at least 2 consecutive recordings separated by ≥1 minute, after the first minute of standing
- Minimum standing heart rate ≥90 bpm in adults (≥100 bpm in teenagers)
- No orthostatic hypotension (blood pressure drop ≥20/10 mmHg)
- Symptoms of orthostatic intolerance present for ≥6 months
Important technical point: If resting heart rate is <60 bpm, use 60 bpm as the reference baseline. For example, a patient with resting heart rate of 55 bpm needs standing heart rate ≥90 bpm (60+30), not 85 bpm (55+30) 3.
Initial Laboratory Workup
Order these basic tests to exclude secondary causes 3:
- Complete blood count
- Electrolytes (Na+, K+, Cl-)
- Creatinine and urea
- Ferritin (iron deficiency can mimic/exacerbate POTS)
- Thyroid stimulating hormone
- Morning cortisol
When NOT to Order Advanced Testing
Do not routinely order 3:
- Tilt table testing
- Echocardiogram or ECG monitoring (unless suspecting structural heart disease or non-sinus arrhythmia)
- Plasma catecholamines/norepinephrine levels
- 24-hour urine sodium
- Blood volume measurement
- Autoimmune antibody panels
- Neuroimaging
- Electromyography
The 2020 Canadian Cardiovascular Society guidelines explicitly state that detailed autonomic testing should be reserved only for patients who fail initial conventional therapy or when suspecting autonomic neuropathy 3. Most patients do not need these expensive, specialized tests.
When to Consider Advanced Autonomic Testing
Refer for specialized autonomic testing only if 3:
- Symptoms persist despite appropriate initial treatment
- Suspicion of autonomic neuropathy (progressive symptoms, clear neurological deficits)
- Diagnostic uncertainty after basic evaluation
Advanced testing may include: tilt table test, Valsalva maneuver, deep breathing test, thermoregulatory sweat test, quantitative sudomotor axonal reflex test 3.
Testing for Mast Cell Activation Syndrome (MCAS)
When clinical features suggest MCAS (recurrent anaphylaxis, multisystem episodic symptoms), measure serum tryptase during and after symptomatic episodes 1. MCAS diagnosis requires:
- Clinical signs: severe, recurrent, episodic systemic symptoms affecting ≥2 organ systems
- Biochemical documentation: serum tryptase increase from baseline of >20% + 2 ng/mL
- Response to mast cell-directed therapy
Targeted Testing Strategy
Universal testing for POTS/MCAS in all hEDS patients is not supported by evidence 1. Instead, test only when clinical manifestations are present:
- Test for POTS if: orthostatic dizziness, palpitations, lightheadedness, fatigue, tremulousness, blurred vision, or generalized weakness with standing
- Test for MCAS if: recurrent flushing, urticaria, angioedema, wheezing, GI symptoms (nausea, cramping, diarrhea), or anaphylaxis triggered by foods, heat, emotion, or mechanical stimuli
The association between hEDS and POTS is well-documented (31% prevalence in one study 4), but this doesn't justify screening asymptomatic patients 1.
Common Pitfalls to Avoid
Don't diagnose POTS based on transient heart rate increases in the first minute of standing—this may represent initial orthostatic hypotension, not POTS 3.
Don't diagnose POTS in asymptomatic patients who meet hemodynamic criteria but lack symptoms—this is increasingly common with wearable heart rate monitors and requires only reassurance 3.
Don't miss secondary causes of orthostatic tachycardia: dehydration, prolonged bedrest, medications (stimulants, α-blockers, calcium channel blockers), anemia, hyperthyroidism 3.
Don't finalize hEDS diagnosis without genetic testing to exclude alternative diagnoses—26% of clinically diagnosed hEDS patients had different genetic conditions requiring distinct management 2.