Hypermobility spectrum disorder and Ehlers-Danlos syndromes

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Hypermobility varies with age, sex, ancestry, training and injury. Ask about childhood flexibility, party tricks, dislocations, sprains, poor coordination, pain after activity, fatigue, bruising, scars, hernias, prolapse, dental crowding, autonomic symptoms and gastrointestinal or pelvic-floor problems. Construct a three-generation history of arterial events, bowel or uterine rupture, pneumothorax, sudden young death, extreme skin fragility and diagnosed connective-tissue disease. Examine joints beyond Beighton sites, skin and scars, body proportions, palate, feet, muscle control, neurology and current inflammatory or structural pathology.

Beighton scoring samples passive fifth-finger extension beyond 90 degrees and thumb apposition to forearm on each side, elbow and knee hyperextension of at least 10 degrees on each side, and palms flat on floor with straight knees. It omits shoulders, hips, ankles, ribs and historical mobility. In an adult meeting generalised hypermobility criteria, apply the complete 2017 hEDS framework rather than stopping at the score. Unusual tissue fragility redirects evaluation toward another subtype.

Management improves dynamic stability and reduces secondary harm; it cannot change inherited tissue. Physiotherapy teaches neutral control, progressive closed-chain strength, proprioception and sustainable aerobic conditioning. Occupational therapy adapts work, school and self-care. Splints or tape may support a defined task but should not replace muscle. Pain treatment distinguishes acute injury, tendinopathy, nociplastic and neuropathic mechanisms. Orthostatic, bladder, bowel, sleep and mental-health symptoms deserve ordinary evidence-based assessment without assuming every symptom is caused by EDS.

Key points

Joint hypermobility is a physical trait; HSD or hEDS requires symptoms or associated features after exclusion of another explanation, and neither follows from flexibility alone.
Score Beighton manoeuvres correctly: the 2017 hEDS threshold is at least 5 of 9 from puberty through age 50 and at least 4 after 50; historical questions help when one point below.
All hEDS groups are required: generalised hypermobility; at least two of Feature A with five systemic findings, Feature B with an independently affected first-degree relative, or Feature C with qualifying pain or instability; and complete exclusions.
There is no confirmatory genetic test for hEDS; molecular testing is directed by features of vascular, classical or another monogenic subtype, not ordered as a generic hypermobility panel.
HSD can be as functionally important as hEDS; management is based on instability, pain, fatigue and comorbidity rather than perceived label rank.
Use progressive proprioceptive, strength and movement-control rehabilitation, pacing, task adaptation and selected braces; aggressive stretching or prolonged immobilisation can worsen stability and deconditioning.
Sudden severe chest, abdominal, head or limb pain in suspected vascular EDS is an emergency; state the diagnosis because imaging, access and operative strategy require tissue-fragility expertise.
Pregnancy planning should identify subtype where possible; vascular EDS needs genetics and maternal medicine, while hEDS or HSD benefits from pelvic-health and anaesthetic planning.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Monogenic EDS subtypes

Pathogenic variants in collagen or connective-tissue processing genes cause most defined subtypes, including COL3A1-related vascular and commonly COL5A1 or COL5A2-related classical EDS.

Hypermobile EDS

Hypermobile EDS is strongly familial but has no established single diagnostic molecular test; diagnosis remains clinical using adult criteria and exclusion requirements.

Hypermobility spectrum disorder

HSD describes symptomatic localised, peripheral, generalised or historical hypermobility causing musculoskeletal difficulty after another connective-tissue disorder and relevant alternative are excluded.

Acquired symptom modifiers

Injury, deconditioning, pregnancy, hormonal change, repetitive loading, pain amplification and autonomic or gastrointestinal comorbidity influence disability without creating a monogenic subtype.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Reduced passive stability
More compliant capsule, ligament or connective tissue permits excessive translation and end-range movement, requiring greater muscular control to keep a joint centred under load.
2
Proprioceptive and motor load
Impaired position sense and delayed stabilising muscle recruitment contribute to sprains, subluxations, fatigue and inefficient movement even without visible dislocation.
3
Tissue-specific fragility
In classical and vascular EDS, abnormal collagen weakens skin, vessels or hollow organs; complication pattern follows molecular subtype rather than joint laxity alone.
4
Pain and autonomic interaction
Repeated microinjury, muscle overactivity, peripheral nociception, central amplification, sleep disturbance and orthostatic intolerance combine, making pain greater than structural findings alone.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Generalised mobility

A correctly measured Beighton score above the age threshold supports generalised hypermobility, but history matters after injury, ageing or surgery reduces range.

Symptomatic instability

Recurrent atraumatic subluxation, sprains, giving way, poor proprioception and pain after low-load activity distinguish disorder from useful flexibility.

Hypermobile EDS pattern

Generalised hypermobility combines with sufficient systemic, family-history or musculoskeletal criteria after exclusion of another disorder and unusual skin fragility.

Classical EDS pattern

Marked skin hyperextensibility, broad atrophic scars, easy bruising and generalised hypermobility suggest classical EDS and a COL5-related molecular pathway.

Vascular EDS pattern

Thin translucent skin, characteristic facial or acral features, easy bruising and personal or family arterial or hollow-organ rupture suggests COL3A1 disease.

Autonomic symptoms

Orthostatic light-headedness, tachycardia, presyncope, heat intolerance and fatigue occur, but anaemia, arrhythmia, endocrine disease and medicines require assessment.

Mixed pain mechanisms

Local instability, tendon overload, nerve irritation and widespread sensitisation can coexist; examination should identify the active mechanism at each troublesome site.

Red flags requiring action

Arterial rupture or dissection, spontaneous bowel perforation, uterine rupture, pneumothorax or unexplained sudden death in a young first-degree relative raises vascular EDS and warrants specialist genetics assessment.
Marked skin fragility with broad atrophic scars, easy tearing, congenital hip dislocation, severe progressive scoliosis, ocular rupture or early periodontal loss suggests a monogenic subtype.
A hot swollen joint after a procedure or injury, fever, severe unremitting bone pain or progressive neurological loss requires an infection, fracture or compression pathway.
Syncope during exertion, chest pain, sustained tachyarrhythmia or focal neurological events must not be assumed to be benign dysautonomia without acute assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line structured assessmentFirst stepFirst line
Why
Confirm current and historical hypermobility, document functional consequences and detect signs requiring another route.
Interpretation and limitations
Measure Beighton manoeuvres with a goniometer when possible and apply complete hEDS or HSD criteria; score alone neither confirms EDS nor grades disability.
02
Three-generation pedigree
Why
Identify dominant clustering and arterial, organ, skin, ocular or skeletal features that change testing and surveillance.
Interpretation and limitations
Early arterial rupture, bowel perforation, sudden death or fragility prompts genetics referral; absent family history does not exclude a de novo variant.
03
Confirmatory molecular testingConfirmatory
Why
Establish a specific monogenic EDS diagnosis when phenotype suggests vascular, classical or another genetically defined form.
Interpretation and limitations
Genetics selects and interprets testing against phenotype and variant classification; a negative broad panel does not diagnose hEDS, for which no single test exists.
04
Targeted cardiovascular assessment
Why
Evaluate murmur, aortic-root concern, arterial symptoms or a subtype with defined vascular surveillance.
Interpretation and limitations
Echocardiography or vascular imaging is indication- and subtype-specific; repeated whole-arterial imaging for every HSD patient is unsupported.
05
Orthostatic observations and ECG
Why
Characterise postural symptoms and exclude rhythm, blood-pressure, anaemia or endocrine explanations before labelling dysautonomia.
Interpretation and limitations
Record supine and standing heart rate and blood pressure with symptoms; persistent orthostatic tachycardia requires duration and exclusions, not one wearable reading.
06
Site-specific imaging
Why
Investigate fracture, instability, tendon tear, neurological compression or surgical questions rather than hypermobility itself.
Interpretation and limitations
Normal static imaging does not disprove functional instability; incidental labral and degenerative findings need correlation before invasive treatment.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Asymptomatic hypermobility

Many healthy people are flexible without pain, instability or systemic features; a Beighton score identifies mobility, not a disorder requiring medicalisation.

Other heritable disorders

Marfan, Loeys-Dietz, osteogenesis imperfecta and skeletal dysplasias have overlapping laxity, proportions, vascular, ocular or fracture features but different surveillance and genetic consequences.

Inflammatory or neurological disease

Inflammatory arthritis, myopathy, neuropathy and neuromuscular hypotonia cause pain, weakness or apparent instability; examination, inflammation and neurophysiology distinguish acquired pathology.

Nociplastic and regional pain

Fibromyalgia, tendinopathy and mechanical spinal pain frequently coexist or mimic HSD; identify each pain mechanism rather than treating all symptoms as ligament injury.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First-line classificationSeparate trait, HSD, hEDS and rare subtypeFirst stepFirst lineRecurrent pain, instability or systemic connective-tissue features accompany current or historical hypermobility.

1Measure Beighton score correctly, document non-Beighton and historical mobility, and establish whether symptoms are plausibly related rather than incidental.
2AlternativeApply all hEDS criteria groups, examining systemic features and excluding inflammatory, neuromuscular, skeletal and alternative heritable disorders.
3Diagnose HSD when symptomatic hypermobility remains important but hEDS and another defined disorder are not met, explaining that treatment need is not label-dependent.
4Refer to clinical genetics when vascular, classical, ocular, skeletal or other distinctive fragility makes a molecular subtype plausible.

02Preferred rehabilitationBuild active joint controlPreferredInstability, pain, fatigue or movement fear limits function without fracture, unreduced dislocation or emergency.

1Begin proprioception, neutral-position awareness, low-load closed-chain strength and movement quality, progressing repetitions, resistance and complexity gradually.
2Use pacing and aerobic conditioning to reduce boom-and-bust activity while avoiding repeated end-range demonstrations and aggressive stretching.
3Add occupational adaptation, footwear, tape or task-specific brace when it improves function, and maintain active muscle support rather than permanent immobilisation.
4Treat each acute sprain, tendon lesion, nociplastic component and sleep or mood disorder according to its own mechanism.

03Vascular emergencyProtect fragile tissue during rescueConfirmed or suspected vascular EDS develops sudden internal pain, collapse, bleeding, neurological loss or respiratory compromise.

1Activate emergency transfer and communicate possible vascular EDS so experienced vascular, anaesthetic, surgical and interventional teams coordinate diagnosis.
2Obtain rapid non-invasive imaging suited to the territory while avoiding unnecessary arterial puncture, repeated instrumentation and excessive blood-pressure swings.
3Balance operative and endovascular rescue individually because tissue fragility alters suturing, access and haemostasis; involve a recognised vascular-EDS service.

04Pregnancy and proceduresPlan before tissue stressPregnancy, surgery, endoscopy, dentistry or anaesthesia is planned in EDS or significant symptomatic hypermobility.

1Clarify subtype and personal history before conception where possible, offer genetic counselling and refer vascular EDS to high-risk maternal medicine.
2Share skin fragility, bleeding, positioning, dysautonomia, reflux and previous local-anaesthetic response with procedural and anaesthetic teams.
3Use careful positioning, padding, wound closure and mobilisation plans, monitoring for haematoma, dehiscence or instability.
4Arrange pelvic-health support and postpartum rehabilitation in hEDS or HSD while vascular EDS follows a distinct delivery and surveillance strategy.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Provides short-term relief after sprain, subluxation or procedure while protection and rehabilitation address mechanics.

Paracetamol for acute local pain

Use 500 mg–1 g orally at intervals of at least four hours when required, maximum 4 g in 24 hours for a suitable adult; lower the ceiling with low weight, frailty or liver risk.

Avoid duplicated combination products and chronic automatic use without benefit; adjust for liver disease and alcohol. It does not stabilise collagen or prevent dislocation.

Offers local symptom relief for selected acute soft-tissue or mechanical pain with lower systemic exposure than oral NSAID.

Topical diclofenac gel

Apply a product-specific amount to focal pain, commonly 2–4 g of 1.16% gel three or four times daily for a brief trial, without exceeding the product maximum.

Avoid fragile damaged skin, NSAID hypersensitivity and excess combined NSAIDs; systemic harms remain possible. In pregnancy use only when clearly necessary and avoid during the third trimester.

Supports intravascular volume in selected orthostatic intolerance alongside compression, conditioning and cause-directed management rather than treating EDS itself.

Oral rehydration for orthostatic symptoms

When appropriate, use regular fluids and a standard oral rehydration solution according to sachet instructions during heat, illness or predictable orthostatic stress; individual salt targets need cardiovascular and renal review.

Do not increase salt or fluid indiscriminately in hypertension, heart failure, kidney disease or pregnancy complications; syncope, arrhythmia, bleeding and endocrine disease need diagnosis.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Recurrent instability

Sprains, subluxations and dislocations can damage labrum, cartilage and tendon, reduce confidence and lead to repeated emergency attendance or avoidable immobilisation.

Chronic multisystem burden

Pain, fatigue, orthostatic intolerance, headache, pelvic-floor symptoms and gastrointestinal dysmotility can interact, limiting education, work, sleep and daily function.

Procedural difficulty

Fragile skin, bruising, variable local-anaesthetic response, positioning and dysautonomia may complicate surgery or dentistry; vascular EDS adds arterial and hollow-organ risk.

Pregnancy and vascular harm

Pelvic girdle symptoms, prolapse and bleeding may worsen in pregnancy, while vascular EDS carries much greater arterial, bowel and uterine rupture risk.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Use outcomes such as subluxation frequency, recovery after activity, walking, work or self-care, and progress strength only when movement quality is controlled.
Review braces and tape for skin injury, nerve compression and dependence; retain devices solving a defined task and build active support around them.
Reassess new swelling, inflammatory stiffness, neurological loss or night pain as possible additional disease rather than extending the HSD explanation.
For molecular EDS, follow surveillance issued by genetics and the relevant specialist service; surveillance is not interchangeable across subtypes.
In orthostatic symptoms, monitor standing heart rate, blood pressure, hydration response and exercise tolerance while checking anaemia, medicines and arrhythmia when indicated.
Before pregnancy or major procedure, update the diagnosis evidence, anaesthetic history and named specialist contacts so tissue precautions are actionable.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Beighton is a sample

The nine-point score omits shoulders, hips and ankles and falls with age or injury; history and non-scored joints prevent false exclusion.

Flexibility is not disease

An asymptomatic dancer may score highly without HSD or EDS, while a lower-scoring older adult can have important historical hypermobility.

HSD is not lesser

Failing one hEDS criterion does not make instability, fatigue or pain trivial; rehabilitation follows impairment and goals.

hEDS lacks molecular confirmation

A negative connective-tissue panel neither proves nor excludes hEDS; adult diagnosis depends on the clinical and exclusion framework.

Acute pain changes the frame

In vascular EDS sudden internal pain can precede shock; the diagnosis should accelerate careful emergency evaluation, not invite reassurance.

11Common pitfallsFrequent interpretation and management errors.

01
Do not diagnose hEDS from Beighton score alone; all criteria groups and exclusion of alternative disease are required.
02
Do not order a generic genetic panel to confirm hEDS because no single molecular test currently establishes it.
03
Do not describe HSD as benign merely because hEDS criteria are not met; disability can be substantial.
04
Do not prescribe repeated aggressive stretching, end-range manipulation or long immobilisation for lax joints.
05
Do not attribute every gastrointestinal, postural or neurological symptom to EDS without assessment for common and dangerous alternatives.
06
Do not manage suspected vascular EDS as routine hypermobility when arterial, bowel, uterine or family sudden-death red flags are present.