What are the 2017 diagnostic criteria for hypermobile Ehlers‑Danlos syndrome (hEDS)?

2017 Diagnostic Criteria for Hypermobile Ehlers-Danlos Syndrome (hEDS)

The 2017 diagnostic criteria for hEDS require fulfillment of ALL THREE major criteria: (1) generalized joint hypermobility confirmed by Beighton score, (2) presence of systemic manifestations of a connective tissue disorder plus family history, and (3) exclusion of alternative diagnoses. 1

Criterion 1: Generalized Joint Hypermobility (Beighton Score)

The Beighton scoring system uses a 9-point scale to assess joint hypermobility. A positive score requires:

• ≥6/9 points in children before puberty
• ≥5/9 points from puberty to age 50
• ≥4/9 points for those ≥50 years old 1

Beighton Score Components (1 point each):

• Passive dorsiflexion of each 5th finger >90 degrees (2 points total, 1 per side)
• Passive apposition of each thumb to flexor surface of forearm (2 points total, 1 per side)
• Hyperextension of each elbow >10 degrees (2 points total, 1 per side)
• Hyperextension of each knee >10 degrees (2 points total, 1 per side)
• Forward flexion of trunk with palms flat on floor with knees fully extended (1 point) 1

Critical pitfall: Studies show that Beighton scores assessed by primary care practitioners are frequently overestimated compared to specialist assessment—in one cohort, 81% of primary care assessments were higher than specialist re-evaluation 2. This leads to false-positive screening and emphasizes the need for careful, standardized assessment.

Criterion 2: Systemic Manifestations

At least TWO of the following features must be present:

A. Systemic manifestations of a connective tissue disorder:

• Soft or velvety skin with normal or slightly increased extensibility
• Absence of skin or soft tissue fragility (which would suggest other EDS subtypes)
• Unexplained striae distensae or atrophic scarring
• Bilateral piezogenic papules of the heel
• Recurrent or multiple abdominal hernias
• Pelvic floor, rectal, and/or uterine prolapse in nulliparous women or men
• Dental crowding and high or narrow palate
• Arachnodactyly
• Arm span-to-height ratio ≥1.05
• Mitral valve prolapse
• Aortic root dilatation 3, 1

B. Positive family history:

• One or more first-degree relatives independently meeting current diagnostic criteria for hEDS

C. Musculoskeletal complications:

• Musculoskeletal pain in 2 or more limbs, recurring daily for at least 3 months
• Chronic, widespread pain for ≥3 months
• Recurrent joint dislocations or frank joint instability, in the absence of trauma (≥3 atraumatic dislocations in the same joint or ≥2 atraumatic dislocations in 2 different joints occurring at different times)
• ≥3 atraumatic subluxations in the same joint or ≥2 atraumatic subluxations in 2 different joints occurring at different times 3, 1

Important nuance: Research demonstrates that objective systemic manifestations are found less frequently than subjective manifestations in clinical practice, and the number of systemic manifestations does not correlate with Beighton score 2. This creates diagnostic challenges, as many highly symptomatic patients may not meet the stringent criteria.

Criterion 3: Exclusion of Alternative Diagnoses

All alternative heritable and acquired connective tissue disorders must be excluded, including:

• Other EDS subtypes (classical, vascular, etc.)
• Marfan syndrome
• Loeys-Dietz syndrome
• Other genetic syndromes with joint hypermobility
• Autoimmune rheumatologic disorders 1, 4

Critical consideration: Genetic testing identified an alternative or additional diagnosis in 26.4% of patients who initially met clinical criteria for hEDS, with clinical implications requiring distinct management strategies 4. This underscores that genetic testing plays a crucial yet underutilized role in the diagnostic workup, despite hEDS having no identified genetic marker.

Diagnostic Evaluation Required

1. Comprehensive physical examination with standardized Beighton score assessment by experienced clinician
2. Detailed family history of hypermobility and related features
3. Echocardiogram to evaluate for aortic root dilatation and mitral valve prolapse 3
4. Dilated eye examination to exclude Marfan syndrome (ectopia lentis) 3
5. Targeted genetic testing when clinical features suggest alternative diagnoses 4

Common Diagnostic Pitfalls

The 2017 criteria are significantly more stringent than previous Villefranche criteria. In one retrospective study, only 15% of patients with prior hEDS diagnosis based on Villefranche criteria met the 2017 criteria 2. Additionally, generalized joint hypermobility was confirmed in only 46% of patients who had a previous hEDS diagnosis 2.

Beware of diagnostic overlap: In POTS patients, 31% met hEDS criteria, with an additional 24% having generalized joint hypermobility without meeting full hEDS criteria 5. The distinction between hEDS and hypermobility spectrum disorders (HSD) remains debated, with emerging evidence suggesting they may represent a spectrum of the same disorder rather than distinct entities 6, 7.

Sex bias in diagnosis: While hEDS is autosomal dominant and should show 1:1 sex ratio, clinical cohorts show marked female predominance (7:1 to 24:1 female-to-male ratios) 8, suggesting potential underdiagnosis in males or sex-specific expression patterns.

Associated Comorbidities to Screen For

While not part of diagnostic criteria, clinicians should assess for common associated conditions:

• Postural orthostatic tachycardia syndrome (POTS) - present in 31-37.5% 1, 5
• Mast cell activation syndrome (MCAS) 1
• Functional gastrointestinal disorders (IBS, gastroesophageal reflux, dysmotility) - present in >60% 1
• Chronic pain and fibromyalgia 3
• Osteoporosis and increased fracture risk 3, 9
• Neurally mediated hypotension 3

However, universal testing for POTS/MCAS in all hEDS patients is not supported by current evidence—testing should be targeted to those with clinical manifestations 1.