brand logo

Am Fam Physician. 2021;103(8):481-492

Patient information: See related handout on hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder, written by the authors of this article.

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial affiliations.

Hypermobile Ehlers-Danlos syndrome (EDS) and hypermobility spectrum disorders are the most common symptomatic joint hypermobility conditions seen in clinical practice. The 2017 International Classification of the Ehlers-Danlos syndromes replaced previous terms for symptomatic joint hypermobility with hypermobile EDS and introduced the term hypermobility spectrum disorders for patients not meeting diagnostic criteria for hypermobile EDS. Both are diagnosed by applying the 2017 diagnostic criteria, which also excludes other less common conditions presenting with joint hypermobility such as other forms of EDS and heritable connective tissue disorders. Hypermobile EDS is inherited in an autosomal dominant pattern, but it does not have a known genetic mutation to help with diagnosis. Clinical features of hypermobile EDS include joint hypermobility, skin findings, and joint pains or recurrent dislocations. Hypermobile EDS and, less commonly, hypermobility spectrum disorders may also be associated with several extra-articular symptoms, including anxiety disorders, chronic pain, fatigue, orthostatic intolerance, functional gastrointestinal disorders, and pelvic and bladder dysfunction. The central goals of therapy are managing symptoms, preventing joint injury, and educating patients about their condition. Based on limited evidence, patients with hypermobile EDS/hypermobility spectrum disorders may benefit from physical and occupational therapy, psychological support, and self-management. Primary care physicians play a key role not only in initial recognition, diagnosis, and patient education, but by virtue of their ongoing relationship they can also help oversee and coordinate the multidisciplinary team many of these patients require.

Hypermobile Ehlers-Danlos syndrome (EDS) and hypermobility spectrum disorders are the most common symptomatic joint hypermobility conditions seen in clinical practice.1,2 Family physicians play a vital role in the care of patients with these conditions, from initial diagnosis to ongoing care.

WHAT'S NEW ON THIS TOPIC

Hypermobility Spectrum Disorders

The 2017 International Classification of the Ehlers-Danlos syndromes replaced prior terms for symptomatic joint hypermobility with hypermobile Ehlers-Danlos syndrome and introduced the term hypermobility spectrum disorder for patients not meeting hypermobile Ehlers-Danlos syndrome diagnostic criteria.

A 2013 U.K. population survey found that 3.4% of adults endorsed hypermobility and chronic widespread pain using validated instruments.

Generalized joint hypermobility is more common than hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders because patients with generalized joint hypermobility may be asymptomatic. When assessed in student population samples using the 2017 criteria, 4% to 11% of children three to 19 years of age had generalized joint hypermobility.

Definitions

“Ehlers-Danlos syndromes (EDS) … are a group of inherited connective tissue disorders caused by abnormalities in the structure, production, and/or processing of collagen. The new classification, from 2017, includes 13 subtypes of EDS.”3 Table 1 describes these subtypes.1,4,5 Joint hypermobility is a feature common among many EDS subtypes and other heritable connective tissue disorders. Joint hypermobility is defined as the ability of a joint to move “beyond normal limits along physiological axes.”4 Joint hypermobility can involve a few or many joints and may be entirely asymptomatic. Generalized joint hypermobility is more likely to be associated with a genetic syndrome than localized joint hypermobility. The exception is hypermobile EDS, which is the most common EDS variant, representing 80% to 90% of EDS cases,2 with clinical features including joint hypermobility, skin findings (Figure 1), and joint pains or recurrent dislocations (Figure 26 and Figure 31,7 ). The 2017 classification introduced stricter criteria for hypermobile EDS than previously available to distinguish patients with hypermobile EDS from those most likely to have a diagnosable genetic syndrome.1 For patients with symptomatic joint hypermobility satisfying neither the new hypermobile EDS criteria nor another specific condition, the 2017 classification introduced hypermobility spectrum disorders.1

TypeBeighton scoreMusculoskeletal involvement*Notes
Asymptomatic joint hypermobility
Asymptomatic generalized joint hypermobilityPositiveAbsent
Asymptomatic peripheral joint hypermobilityUsually negativeAbsentJoint hypermobility typically limited to hands and/or feet
Asymptomatic localized joint hypermobilityNegativeAbsentJoint hypermobility limited to single joint or body parts
Hypermobility spectrum disorders
Generalized hypermobility spectrum disordersPositivePresentDoes NOT meet criteria for hypermobile EDS based on limited findings in skin and musculoskeletal systems and lack of family history
No genes identified
Screening with echocardiography unnecessary
Peripheral hypermobility spectrum disordersUsually negativePresentJoint hypermobility typically limited to hands and/or feet
Localized hypermobility spectrum disordersNegativePresentJoint hypermobility limited to single joints or body parts
Historical hypermobility spectrum disordersNegativePresentHistorical presence of joint hypermobility
EDS – Joint hypermobility with more pronounced skin and musculoskeletal findings and/or positive family history
1. Hypermobile EDSPositivePossibleMeet criteria based on supportive findings in skin and body systems and/or positive family history (see Figure 2)
No genes identified
AD inheritance pattern
Obtain screening echocardiography
TypeBeighton scoreMajor featuresGene affected

EDS
2. ClassicalPositiveSkin hyperextensibility
Abnormal scarring
COL5A1, COL5A2 genes
Rare COL1A1 gene
AD inheritance
3. Classical-likePositiveSkin hyperextensibility
Easy bruising
TNXB gene
AR inheritance
4. Cardiac-valvularPositive or negative, general hypermobility or restricted to small jointsCardiac valvular problems
Skin involvement
COL1A2 gene
AR inheritance
5. VascularPositive or negativeFamily history of vascular EDS
History of early arterial rupture or uterine rupture, sigmoid colon perforation, or atraumatic carotid-cavernous sinus fistula formation
COL3A1 gene
Rare COL1A1 gene
AD inheritance
6. ArthrochalasiaPositiveCongenital bilateral hip dislocation
Skin hyperextensibility
COL1A1, COL1A2 genes
AD inheritance
7. DermatosparaxisPositive or negativeExtreme skin fragility
Characteristic craniofacial features
ADAMTS2 gene
AR inheritance
8. KyphoscolioticPositive with history of dislocation and subluxationCongenital hypotonia
Kyphoscoliosis
PLOD1, FKBP14 genes
AR inheritance
9. Brittle cornea syndromePositive or negativeThin cornea with or without rupture
Keratoconus
Keratoglobus
Blue sclerae
ZNF469, PRDM5 genes
AR inheritance
10. SpondylodysplasticPositive or negativeShort stature
Muscle hypotonia
Bowing of limbs
B4GALT7, B3GALT6, SLC39A13 genes
AR inheritance
11. MusculocontracturalPositive or negativeCongenital multiple contractures
Characteristic craniofacial features
Skin involvement
CHST14, DSE genes
AR inheritance
12. MyopathicDistal joints affectedCongenital muscle hypotonia and/or atrophy that improves with age
Proximal muscle contractures
COL12A1 gene
AD or AR inheritance
13. PeriodontalPositive or negativePeriodontitis
Lack of attached gingiva
Pretibial plaques
Family history of periodontal EDS
C1R, C1S genes
AD inheritance

Patients with hypermobility spectrum disorders are distinct from those with hypermobile EDS and other syndromes with joint hypermobility in that their symptoms are primarily musculoskeletal; however, limited extra-articular involvement may be seen.4 All previous terms, including EDS type III, EDS hypermobility type, hypermobility syndrome, joint hypermobility syndrome, and benign joint hypermobility syndrome, should no longer be used.4 At one time, these earlier named diagnoses were thought to represent distinct entities, but subsequent studies finding broad overlap of these older named conditions within families demonstrated that they were the same entity.4 In a more recent study, nearly all patients with one of the earlier, now outdated, diagnoses fulfilled either hypermobile EDS or hypermobility spectrum disorders criteria.8 Because they are the most common symptomatic hypermobility conditions, their evaluation and management are the focus of this article; the terms hypermobile EDS and hypermobility spectrum disorders will be used except when clarity dictates reference to an older diagnostic term.

Epidemiology and Pathogenesis

The exact prevalence of hypermobile EDS/hypermobility spectrum disorders is unknown. The best estimates of the population prevalence of these conditions are derived from studies in national or patient registries from Sweden and Wales, United Kingdom, using diagnostic codes for EDS and joint hypermobility syndrome, the latter a prior term for hypermobile EDS, as discussed previously.9,10 The combined hypermobile EDS/hypermobility spectrum disorders prevalence would be expected to be lower than the 0.13% to 0.19% prevalence that these two studies found for all EDS and joint hypermobility syndrome codes combined.9,10 This prevalence equates to about seven to 10 patients out of a 5,000-patient panel. Another estimate of combined hypermobile EDS/hypermobility spectrum disorders prevalence from a U.K. population survey found that 3.4% of adults endorsed hypermobility and chronic widespread pain using validated instruments.11

Already a member/subscriber?  Log In

Subscribe

From $145
  • Immediate, unlimited access to all AFP content
  • More than 130 CME credits/year
  • AAFP app access
  • Print delivery available
Subscribe

Issue Access

$59.95
  • Immediate, unlimited access to this issue's content
  • CME credits
  • AAFP app access
  • Print delivery available

Article Only

$25.95
  • Immediate, unlimited access to just this article
  • CME credits
  • AAFP app access
  • Print delivery available
Purchase Access:  Learn More

Continue Reading

More in AFP

More in Pubmed

Copyright © 2021 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See permissions for copyright questions and/or permission requests.