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Cited by 74Connective tissue disorders researchOral and gingival health researchDermatological and Skeletal Disorders

Pediatric joint hypermobility: a diagnostic framework and narrative review

Open access
Tofts, Louise Jane, Simmonds, Jane, Schwartz, Sarah B., Richheimer, Roberto M., O’Connor, Constance, Elias, Ellen, Engelbert, Raoul, Cleary, Katie +5 more·2023·Orphanet Journal of Rare Diseases
DOI 10.1186/s13023-023-02717-2PMC PMC10157984
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Abstract

Background: Hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are debilitating conditions. Diagnosis is currently clinical in the absence of biomarkers, and criteria developed for adults are difficult to use in children and biologically immature adolescents. Generalized joint hypermobility (GJH) is a prerequisite for hEDS and generalized HSD. Current literature identifies a large proportion of children as hypermobile using a Beighton score ≥ 4 or 5/9, the cut off for GJH in adults. Other phenotypic features from the 2017 hEDS criteria can arise over time. Finally, many comorbidities described in hEDS/HSD are also seen in the general pediatric and adolescent population. Therefore, pediatric specific criteria are needed. The Paediatric Working Group of the International Consortium on EDS and HSD has developed a pediatric diagnostic framework presented here. The work was informed by a review of the published evidence. Observations: The framework has 4 components, GJH, skin and tissue abnormalities, musculoskeletal complications, and core comorbidities. A Beighton score of ≥ 6/9 best identifies children with GJH at 2 standard deviations above average, based on published general population data. Skin and soft tissue changes include soft skin, stretchy skin, atrophic scars, stretch marks, piezogenic papules, and recurrent hernias. Two symptomatic groups were agreed: musculoskeletal and systemic. Emerging comorbid relationships are discussed. The framework generates 8 subgroups, 4 pediatric GJH, and 4 pediatric generalized hypermobility spectrum disorders. hEDS is reserved for biologically mature adolescents who meet the 2017 criteria, which also covers even rarer types of Ehlers–Danlos syndrome at any age. Conclusions: This framework allows hypermobile children to be categorized into a group describing their phenotypic and symptomatic presentation. It clarifies the recommendation that comorbidities should be defined using their current internationally accepted frameworks. This provides a foundation for improving clinical care and research quality in this population.

AI snapshot

Written from the paper’s full text.

TL;DR

This paper presents a pediatric diagnostic framework for joint hypermobility, developed by the Paediatric Working Group of the International Consortium on EDS and HSD, with four components and eight subgroups. It recommends a Beighton score ≥ 6/9 for GJH in children, reserves hEDS for biologically mature adolescents meeting the 2017 criteria, and defines core comorbidities using existing international frameworks.

Key findings

  • The framework has 4 components—generalized joint hypermobility (GJH), skin and tissue abnormalities, musculoskeletal complications, and core comorbidities—and generates 8 subgroups: 4 pediatric GJH and 4 pediatric generalized hypermobility spectrum disorders. hEDS is reserved for biologically mature adolescents who meet the 2017 criteria; the minimum age for GJH assessment is 5 years.
  • A Beighton score of ≥ 6/9 best identifies children with GJH at 2 standard deviations above average, based on published general population data. Skin involvement requires at least 3 of 5 skin features, with the atrophic scar requirement reduced to one because many young children have not sustained significant scarring.
  • Core comorbidities included if reported in cohort studies at frequencies > 10% are chronic primary pain, persistent fatigue, functional gastrointestinal disorders, functional bladder disorders, dysautonomia, and anxiety. Emerging comorbidities such as inflammatory arthritis, developmental coordination disorder, ADHD, autism spectrum disorder, menorrhagia/dysmenorrhea, and adolescent idiopathic scoliosis were not included because they were considered low frequency (< 10%) or supported by weak evidence.
  • In cited pediatric data: the Sydney cohort of 89 patients aged 6–16 years with Beighton scores ≥ 4 reported joint pain in 94% (mean 6.4 joints, range 0–15), joint instability in 67%, any GI symptom in 54%, stress incontinence in 26%, and orthostatic intolerance in 39%; a pediatric POTS registry found 62% had hEDS/HSD.

Methods

  • The Paediatric Working Group and representatives of the hEDS/HSD Working Group of the International Consortium on EDS and HSD met online throughout 2020–22; members represented Europe, The Americas, and Australasia, and medical, nursing, and physical therapy clinical and academic backgrounds. Collectively, the group reported seeing over 5000 pediatric patients for diagnostic evaluation over the last 5 years.
  • Using a codesign methodology, the group reviewed literature, combined it with expert real-world experience, presented drafts at the British Society of Rheumatology Case-based Conference (October 2021), the International Society of Paediatric Pain 13th International Symposium on Paediatric Pain (March 2022), and The Ehlers–Danlos Society Scientific Symposium (Rome, September 2022), then sought stakeholder consultation from the EDS Society Medical and Scientific Board and the AHEAD coalition.
  • The literature review included studies of children alone and both children and adults; studies were not assessed for quality due to wide variety of populations, reporting methods, and study designs, and varying definitions of GJH and diagnostic criteria precluded clinically meaningful systematic reviews.

Limitations

  • Stated: the literature review was limited because varying definitions of GJH and diagnostic criteria precluded clinically meaningful systematic reviews, and included studies were not assessed for quality due to heterogeneity in populations, reporting methods, and designs.
  • Stated: no data are available on piezogenic papules in children; “unusually soft skin” and “mild skin extensibility” are largely subjective; no studies have reported the prevalence of FGID in hypermobile children compared with controls; mechanisms for chronic fatigue, anxiety, and other associations are unknown; evidence is moderate for anxiety and emerging for other mental health disorders.
  • Evident from the text: the framework is consensus/codesign-based and not prospectively validated; the paper calls for future work to test the framework and conduct prospective cohort studies; some cited evidence comes from mixed pediatric and adult studies; and the Beighton cut-off of 6/9 was retained despite reported sex divergence because the cited studies lacked enough information about biological maturity.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/s13023-023-02717-2

Cites

66 of 66 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

44 of 101 cited sources checked · 21 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    The association between GJH and acute onset intermittent MSK pain has been found in several population studies of adolescents and one study in symptomatic children.

    “The association between GJH and acute onset intermittent MSK pain has been found in several population studies of adolescents [19, 20], and one study in symptomatic children [21].”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [19] Tobias JH, Deere K, Palmer S, Clark EM, Clinch J. Joint hypermobility is a risk factor for musculoskeletal pain during adolescence: findings of a prospective cohort study. Arthritis Rheum. 2013;65(4):1107–15. https://doi.org/10.1002/art.37836. source
    • cites [20] Morris SL, O’Sullivan PB, Murray KJ, Bear N, Hands B, Smith AJ. Hypermobility and musculoskeletal pain in adolescents. J Pediatr. 2017;181:213-221.e1. https://doi.org/10.1016/j.jpeds.2016.09.060. source

      The Results and Discussion report an association between GJH and pain in the last month in boys in this adolescent population cohort. The Musculoskeletal Pain methods measured recent pain, pain lasting more than three months, and pain worsened by sport—not acute onset or intermittent pain. The separate claim about symptomatic children is attached to citation [21], not this source. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [21] El-Metwally A, Salminen JJ, Auvinen A, Kautiainen H, Mikkelsson M. Risk factors for traumatic and non-traumatic lower limb pain among preadolescents: a population-based study of Finnish schoolchildren. BMC Musculoskelet Disord. 2006;7:3. https://doi.org/10.1186/1471-2474-7-3. source

      The Results section (page unavailable) reports no association between hypermobility and either traumatic or non-traumatic lower-limb pain in this population-based study of preadolescents. The Discussion likewise says pain occurrence did not differ between children with and without hypermobility. The paper does not report an association with acute-onset intermittent pain in adolescents. (LLM, conf=0.86)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    Children have high levels of joint hypermobility.

    “Children have high levels of joint hypermobility (herewith hypermobility) [3, 4] making it difficult to distinguish those with a normal physical trait from those with an underlying disorder [5].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [3] Clinch J, Deere K, Sayers A, et al. Epidemiology of generalized joint laxity (hypermobility) in fourteen-year-old children from the UK: a population-based evaluation. Arthritis Rheum. 2011;63(9):2819–27. https://doi.org/10.1002/art.30435. source
    • cites [4] Singh H, McKay M, Baldwin J, et al. Beighton scores and cut-offs across the lifespan: cross-sectional study of an Australian population. Rheumatology. 2017;56(11):1857–64. https://doi.org/10.1093/rheumatology/kex043. source
  • Premisecitation

    The 2017 criteria for hEDS and HSD were established based on expert consensus and evidence from adult studies.

    “The 2017 criteria for hypermobile Ehlers–Danlos syndrome (hEDS) [1] and hypermobility spectrum disorders (HSD) [2] were established based on expert consensus and evidence from adult studies.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [1] Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers–Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8–26. https://doi.org/10.1002/ajmg.c.31552. source

      The Introduction says the authors revised the EDS classification after a comprehensive literature review, and the Criterion 1 section describes age-specific hEDS cutoffs proposed by an International Consortium committee. This supports the expert-developed hEDS criteria attributed to citation [1], but our copy does not say they were based specifically on adult studies; it also sets a cutoff for pre-pubertal children and adolescents. The separate HSD citation [2] is outside this verdict. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [2] Castori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A. A framework for the classification of joint hypermobility and related conditions. Am J Med Genet C Semin Med Genet. 2017;175(1):148–57. https://doi.org/10.1002/ajmg.c.31539. source
  • Premisecitation

    Biologically mature adolescents can be diagnosed using the 2017 criteria.

    “Biologically mature adolescents can be diagnosed using these criteria, but they are difficult to use in children and biologically immature adolescents (herewith children), who have not yet developed a stable phenotype.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [1] Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers–Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8–26. https://doi.org/10.1002/ajmg.c.31552. source
    • cites [2] Castori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A. A framework for the classification of joint hypermobility and related conditions. Am J Med Genet C Semin Med Genet. 2017;175(1):148–57. https://doi.org/10.1002/ajmg.c.31539. source
  • Premisecitation

    High levels of joint hypermobility in children make it difficult to distinguish those with a normal physical trait from those with an underlying disorder.

    “Children have high levels of joint hypermobility (herewith hypermobility) [3, 4] making it difficult to distinguish those with a normal physical trait from those with an underlying disorder [5].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [5] Tofts LJ, Elliott EJ, Munns C, Pacey V, Sillence DO. The differential diagnosis of children with joint hypermobility: a review of the literature. Pediatr Rheumatol. 2009. https://doi.org/10.1186/1546-0096-7-1. source
  • Classified as probably not a substantial claim. 23
  • May combine two claims. 26

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Skin and soft tissue features may develop with time post growth, such as stretch marks, or with injury, such as scarring.

    “Skin and soft tissue features may develop with time post growth (stretch marks) or injury (scarring), and musculoskeletal complications and comorbidities can occur in any child [6].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [6] Sperotto F, Brachi S, Vittadello F, Zulian F. Musculoskeletal pain in schoolchildren across puberty: a 3-year follow-up study. Pediatr Rheumatol. 2015. https://doi.org/10.1186/s12969-015-0014-z. source

      The Methods (Clinical assessment) describe examination of pubertal stage and the musculoskeletal system, while the Background and Discussion address musculoskeletal pain across puberty. No passage in our copy addresses stretch marks, scarring, or skin and soft-tissue features developing after growth or injury; searches for those terms found none. (LLM, conf=0.73)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Musculoskeletal complications and comorbidities can occur in any child.

    “Skin and soft tissue features may develop with time post growth (stretch marks) or injury (scarring), and musculoskeletal complications and comorbidities can occur in any child [6].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [6] Sperotto F, Brachi S, Vittadello F, Zulian F. Musculoskeletal pain in schoolchildren across puberty: a 3-year follow-up study. Pediatr Rheumatol. 2015. https://doi.org/10.1186/s12969-015-0014-z. source

      The Background describes musculoskeletal pain as a frequent cause of pain and sometimes disability in childhood, supporting the general point that children can have musculoskeletal problems. It does not establish that complications and comorbidities can occur in any child; the study concerns musculoskeletal pain in a cohort of schoolchildren. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    A diagnosis of hEDS requires generalized joint hypermobility plus at least two of: 5+/12 phenotypic features of mild skin and tissue fragility and a marfanoid habitus; a first-degree relative meeting the criteria; and at least one of daily musculoskeletal pain in 2 or more limbs over 3 months, chronic widespread pain, or joint dislocations or instability.

    “A diagnosis of hEDS requires the presence of generalized joint hypermobility (GJH), with at least two of: 5+/12 of a set of phenotypic features of mild skin and tissue fragility and a marfanoid habitus; a first-degree relative meeting the criteria; and at least one of daily musculoskeletal pain in 2 or more limbs over 3 months, chronic widespread pain, or joint dislocations or instability [1].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers–Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8–26. https://doi.org/10.1002/ajmg.c.31552. source

      The hEDS criteria section supports the stated requirements for generalized joint hypermobility and at least two of Features A–C, including the family-history and musculoskeletal-complication options. But it says diagnosis requires Criteria 1, 2, and 3 together; the claim omits Criterion 3’s mandatory exclusions and absence of unusual skin fragility. Page numbers are not available in our copy. (LLM, conf=0.89)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A prospective study of children aged 9-14 years did not demonstrate an increased risk of injury.

    “While a prospective study of children aged 9–14 years did not demonstrate an increased risk of injury it appears underpowered with only 36 of the 999 children classified as hypermobile (Beighton score ≥ 5–9) [28].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [28] Junge T, Larsen LR, Juul-Kristensen B, Wedderkopp N. The extent and risk of knee injuries in children aged 9–14 with generalised joint hypermobility and knee joint hypermobility - the CHAMPS-study Denmark. BMC Musculoskelet Disord. 2015;16:143. https://doi.org/10.1186/s12891-015-0611-5. source

      The Discussion reports no observed impact of generalised joint hypermobility on knee injuries in this prospective cohort of children aged 9–14. The Methods report 999 children tested and 36 meeting the ≥5/9 Beighton criterion on both rounds; the Discussion also notes the low number with hypermobility and knee injuries. The source studied knee injuries, not injury risk generally, so the unqualified wording is broader than its finding. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Recent research has reported divergence between sexes in Beighton scores at a statistically significant level in 14-year-olds and in 14-19-year-olds.

    “Recent research has reported divergence between sexes at a statistically significant level present in 14-year-olds [3] and occurring in 14–19-year olds [4].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [3] Clinch J, Deere K, Sayers A, et al. Epidemiology of generalized joint laxity (hypermobility) in fourteen-year-old children from the UK: a population-based evaluation. Arthritis Rheum. 2011;63(9):2819–27. https://doi.org/10.1002/art.30435. source
    • cites [4] Singh H, McKay M, Baldwin J, et al. Beighton scores and cut-offs across the lifespan: cross-sectional study of an Australian population. Rheumatology. 2017;56(11):1857–64. https://doi.org/10.1093/rheumatology/kex043. source

  • May combine two claims.

    Premisecitation

    Evidence from the literature was reviewed although limited because of varying definitions of GJH and diagnostic criteria, precluding clinically meaningful systematic reviews.

    “Initially, evidence from the literature was reviewed although limited because of varying definitions of GJH and diagnostic criteria, precluding clinically meaningful systematic reviews [10].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [10] Sobhani-Eraghi A, Motalebi M, Sarreshtehdari S, Molazem-Sanandaji B, Hasanlu Z. Prevalence of joint hypermobility in children and adolescents: a systematic review and meta-analysis. J Res Med Sci. 2020;25(1):104. https://doi.org/10.4103/jrms.JRMS_983_19. source

      The Discussion and Limitation sections say that differing diagnostic criteria and cutoffs caused heterogeneity and prevented the authors from including some studies. But the paper conducted a systematic review and meta-analysis of 20 studies; it does not say those differences precluded clinically meaningful systematic reviews. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In a cohort of 47 10-20-year-olds (Beighton score 4-9), self-reported fatigue was greater than controls, with higher fatigue-related disability.

    “In a cohort of 47 10–20-year old's (Beighton score 4–9) self-reported fatigue was greater than controls, with higher fatigue-related disability [42].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [42] Mu W, Muriello M, Clemens JL, et al. Factors affecting quality of life in children and adolescents with hypermobile Ehlers–Danlos syndrome/hypermobility spectrum disorders. Am J Med Genet A. 2019;179(4):561–9. https://doi.org/10.1002/ajmg.a.61055. source

      The Results report 47 self-reporting patients, Beighton scores ranging from 4 to 9, and low fatigue scores indicating greater fatigue-related disability; the Discussion compares fatigue scores with healthy controls. However, the Methods describe the patient participants as aged 12–20 years, not 10–20 years. Page numbers are unavailable in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Children and adolescents with hypermobility reported headache and recurrent abdominal pain.

    “Children and adolescents in these studies also reported headache [42], and recurrent abdominal pain [43].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [42] Mu W, Muriello M, Clemens JL, et al. Factors affecting quality of life in children and adolescents with hypermobile Ehlers–Danlos syndrome/hypermobility spectrum disorders. Am J Med Genet A. 2019;179(4):561–9. https://doi.org/10.1002/ajmg.a.61055. source
    • cites [43] Pacey V, Adams RD, Tofts L, Munns CF, Nicholson LL. Joint hypermobility syndrome subclassification in paediatrics: a factor analytic approach. Arch Dis Child. 2015;100(1):8–13. https://doi.org/10.1136/archdischild-2013-305304. source

  • May combine two claims.

    Premisecitation

    The presence of scarring and stretch marks predicted greater disability at 3 years, whereas soft skin and stretchy skin did not.

    “In terms of outcomes, the presence of scarring and stretch marks predicted greater disability at 3 years whereas soft skin and stretchy skin did not [17].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [17] Scheper MC, Nicholson LL, Adams RD, Tofts L, Pacey V. The natural history of children with joint hypermobility syndrome and Ehlers–Danlos hypermobility type: a longitudinal cohort study. Rheumatology. 2017;56(12):2073–83. https://doi.org/10.1093/rheumatology/kex148. source

      The Multi-systemic complaints section and Table 3 show that scarring and stretch marks were more frequent in the severely affected group, while soft skin and stretchy skin were not significantly associated with group severity. However, the Statistics section says these groups were identified at baseline; the paper does not show that the skin features predicted disability at the 3-year follow-up. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Pain-related disability was found in the Sydney cohort and in 47 10-20-year-olds with hypermobility (Beighton score 4-9).

    “Pain-related disability was found in the Sydney cohort [17] as well as 47 10–20-year-olds with hypermobility (Beighton score 4–9).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [17] Scheper MC, Nicholson LL, Adams RD, Tofts L, Pacey V. The natural history of children with joint hypermobility syndrome and Ehlers–Danlos hypermobility type: a longitudinal cohort study. Rheumatology. 2017;56(12):2073–83. https://doi.org/10.1093/rheumatology/kex148. source

  • Classified as probably not a substantial claim.

    Premisecitation

    The core comorbidities identified (chronic primary pain, persistent fatigue, functional GI disorders, functional bladder disorders, dysautonomia, anxiety) have established diagnostic definitions.

    “The core comorbidities identified have established diagnostic definitions, and include chronic primary pain by the ICD-11 [37], CDC Institute of Medicine persistent fatigue [31], Rome Foundation Rome IV Criteria for functional gastrointestinal (GI) disorders [38]”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [37] Treede RD, Rief W, Barke A, et al. A classification of chronic pain for ICD-11. Pain. 2015;156(6):1003–7. https://doi.org/10.1097/j.pain.0000000000000160. source
    • cites [31] Centres for Disease Control and Prevention. ME/CFS. Accessed 30 Nov 2022. https://www.cdc.gov/me-cfs/index.html.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [38] Rome Foundation. Rome IV criteria. Accessed 30 November 2022. https://theromefoundation.org/rome-iv/rome-iv-criteria/.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Eccles et al. reported structural brain differences between subjects with and without JH in areas involved in emotion processing, attention, cognitive control of pain, and negative emotions which may be relevant.

    “Eccles et al. reported structural brain differences between subjects with and without JH in areas involved in emotion processing, attention, cognitive control of pain, and negative emotions which may be relevant.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [68] Eccles JA, Beacher FD, Gray MA, et al. Brain structure and joint hypermobility: relevance to the expression of psychiatric symptoms. Br J Psychiatry. 2012;200(6):508–9. https://doi.org/10.1192/bjp.bp.111.092460. source

  • May combine two claims.

    Premisecitation

    In a retrospective case series, Kindgren et al. reviewed data from 201 children with hypermobility disorders. Significantly more with a registered ICD-10 Q79.6 EDS diagnosis had ADHD compared to children with M35.7 hypermobility syndrome diagnosis (p = 0.02).

    “In a retrospective case series, Kindgren et al. reviewed data from 201 children with hypermobility disorders. Significantly more with a registered ICD-10 Q79.6 EDS diagnosis had ADHD compared to children with M35.7 hypermobility syndrome diagnosis (p = 0.02).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [66] Kindgren E, Perez AQ, Knez R. Prevalence of ADHD and autism spectrum disorder in children with hypermobility spectrum disorders or hypermobile Ehlers-Danlos syndrome: a retrospective study. Neuropsychiat Dis Treat. 2021;17:379–88. https://doi.org/10.2147/NDT.S290494. source

  • May combine two claims.

    Premisecitation

    A recent systematic review found no association between isolated musculoskeletal hypermobility and adolescent idiopathic scoliosis, and the "wide variation in methods of musculoskeletal hypermobility" made study comparisons difficult so it was somewhat inconclusive.

    “A recent systematic review found no association, the “wide variation in methods of musculoskeletal hypermobility” made study comparisons difficult so it was somewhat inconclusive.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [71] Shere C, Clark EM. Systematic review of the association between isolated musculoskeletal hypermobility and adolescent idiopathic scoliosis. Arch Orthop Trauma Surg. 2022. https://doi.org/10.1007/s00402-022-04508-z. source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationnone given

    The framework generates 8 subgroups: 4 pediatric GJH and 4 pediatric generalized hypermobility spectrum disorders.

    “The framework generates 8 subgroups, 4 pediatric GJH, and 4 pediatric generalized hypermobility spectrum disorders.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The pediatric diagnostic framework has 4 components: GJH, skin and tissue abnormalities, musculoskeletal complications, and core comorbidities.

    “The framework has 4 components, GJH, skin and tissue abnormalities, musculoskeletal complications, and core comorbidities.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    This framework allows hypermobile children to be categorized into a group describing their phenotypic and symptomatic presentation.

    “This framework allows hypermobile children to be categorized into a group describing their phenotypic and symptomatic presentation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    hEDS is reserved for biologically mature adolescents who meet the 2017 criteria, which also covers even rarer types of Ehlers-Danlos syndrome at any age.

    “hEDS is reserved for biologically mature adolescents who meet the 2017 criteria, which also covers even rarer types of Ehlers–Danlos syndrome at any age.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    HSD is described in individuals with any of generalized, peripheral, localized or historic joint hypermobility and associated symptoms in the absence of other cause or diagnosis.

    “HSD is currently described in individuals with any of generalized, peripheral (hands and/or feet), localized (any single joint) or historic joint hypermobility and associated symptoms in the absence of other cause/diagnosis [2].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Castori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A. A framework for the classification of joint hypermobility and related conditions. Am J Med Genet C Semin Med Genet. 2017;175(1):148–57. https://doi.org/10.1002/ajmg.c.31539. source

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    The framework supports identifying those with hypermobility as a physical trait, those with musculoskeletal issues related to their hypermobility, and those who may develop hEDS as they mature.

    “The framework supports identifying those with hypermobility as a physical trait, which is relatively common, those with musculoskeletal issues related to their hypermobility, and those who may develop the rarer hypermobile Ehlers–Danlos syndrome as they mature.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    This framework provides a foundation for improving clinical care and research quality in this population.

    “This provides a foundation for improving clinical care and research quality in this population.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    FGID are diagnosed using the Rome criteria.

    “These conditions are diagnosed using the Rome criteria [38].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Rome Foundation. Rome IV criteria. Accessed 30 November 2022. https://theromefoundation.org/rome-iv/rome-iv-criteria/.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Constipation is the commonest GI symptom, followed by diarrhea and recurrent abdominal pain, in pediatric hypermobility.

    “Constipation is the commonest symptom, followed by diarrhea and recurrent abdominal pain, with 54% of the Sydney cohort reporting any GI symptom and 17% reporting more than one [22].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Pacey V, Tofts L, Adams R, Munns C, Nicholson L. Quality of Life prediction in children with joint hypermobility syndrome. J Paed Child Health. 2015;51(7):689–95. source

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    Studies of children alone, and both children and adults, were included and were not assessed for quality due to the wide variety of populations studied, reporting methods, and study designs.

    “Studies of children alone, and both children and adults were included and were not assessed for quality due to the wide variety of populations studied, reporting methods, and study designs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the Sydney cohort, patients commonly reported joint instability (67% overall) at the knee (predominantly patella) (35%), ankle (32%), shoulder (26%), hand (18%), and wrist (14%).

    “In the Sydney cohort [22] patients commonly reported joint instability (67% overall) at the following sites knee (predominantly patella) (35%), ankle (32%), shoulder (26%), hand (18%), and wrist (14%).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Pacey V, Tofts L, Adams R, Munns C, Nicholson L. Quality of Life prediction in children with joint hypermobility syndrome. J Paed Child Health. 2015;51(7):689–95. source

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationcitation

    This framework will support targeted genetic testing and improved consistency when researching epidemiology, symptom evolution, complications, and interventions.

    “This framework will support targeted genetic testing, which currently has an 11.5% yield [7], and improved consistency when researching epidemiology, symptom evolution, complications, and interventions.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    The diagnoses are fluid, allowing children with GJH to be reclassified over time as typical if GJH resolves, asymptomatic GJH as symptoms improve, or pediatric generalized HSD upon presentation of new signs and symptoms.

    “The diagnoses are fluid, allowing children with GJH to be reclassified over time as: typical if GJH resolves, asymptomatic GJH as symptoms improve, or pediatric generalized HSD (pgHSD) upon presentation of new signs and symptoms.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Hypermobility decreases during pediatric years, probably later in adolescent females than males.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The framework clarifies the recommendation that comorbidities should be defined using their current internationally accepted frameworks.

    “It clarifies the recommendation that comorbidities should be defined using their current internationally accepted frameworks.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    An accurate pgHSD diagnosis provides the foundation for appropriate current treatment and support.

    “An accurate pgHSD diagnosis provides the foundation for appropriate current treatment and support, but not a lifelong diagnosis which may result in over medicalization and potential harms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In the Sydney clinical cohort of 89 patients aged 6-16 years with Beighton scores ≥ 4 at inception, the commonest complaint was joint pain, with 94% reporting pain in multiple joints (mean 6.4 joints, range 0-15).

    “In the Sydney clinical cohort of 89 patients aged 6–16 years, with Beighton scores ≥ 4 at inception, the commonest complaint was joint pain with 94% reporting pain in multiple joints (mean 6.4 joints, range 0–15), at the knee 63%, foot 50%, ankle 48%, hand 36%, wrist 33%, back 27%, hip 26%, shoulder 22%, and elbow 21% [22].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Pacey V, Tofts L, Adams R, Munns C, Nicholson L. Quality of Life prediction in children with joint hypermobility syndrome. J Paed Child Health. 2015;51(7):689–95. source

  • May combine two claims.

    Interpretationreasoning

    Comorbidities have multiple potential associations and are not independent of each other.

    “A fundamental challenge is that comorbidities have multiple potential associations and are not independent of each other; for example, widespread musculoskeletal pain and dysautonomia are both common comorbidities of chronic fatigue (Table 2).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Study design and conductnone given

    Collectively over the last 5 years the group has seen over 5000 pediatric patients for diagnostic evaluation and contributed substantially to the peer-reviewed literature on hypermobility-related epidemiology, disorders, and treatment.

    “Collectively over the last 5 years the group has seen over 5000 pediatric patients for diagnostic evaluation and contributed substantially to the peer-reviewed literature on hypermobility-related epidemiology, disorders, and treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Neither the study on 14-year-olds nor the study on 14-19-year-olds provided enough information about biological maturity to assess the relevance of the sex divergence findings to biologically immature adolescents.

    “Neither study provided enough information about biological maturity to assess the relevance of these findings to biologically immature adolescents, so the cut off at 6/9 was retained.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Nair et al. showed ADHD affects 5% of school-aged children and often occurs before age 4.

    “Nair et al. showed ADHD affects 5% of school-aged children and often occurs before age 4 (Nair et al., 2006).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Nair J, Ehimare U, Beitman BD, Nair SS, Lavin A. Clinical review: evidence-based diagnosis and treatment of ADHD in children. Mo Med. 2006;103(6):617–21.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The term juvenile episodic arthritis/arthralgia for patients with hypermobility and recurrent symptoms of arthritis was introduced in 1985 and further described in 2005 and 2017.

    “The term juvenile episodic arthritis/arthralgia for patients with hypermobility and recurrent symptoms of arthritis was introduced in 1985 and further described in 2005 and 2017.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [57] Gedalia A, Person DA, Brewer EJ Jr, Giannini EH. Hypermobility of the joints in juvenile episodic arthritis/arthralgia. J Pediatr. 1985;107(6):873–6. https://doi.org/10.1016/s0022-3476(85)80178-5. source
    • cites [58] Adib N, Davies K, Grahame R, Woo P, Murray KJ. Joint hypermobility syndrome in childhood. A not so benign multisystem disorder? Rheumatology. 2005;44(6):744–50. https://doi.org/10.1093/rheumatology/keh557s. source

      Not checked in the free run.

    • cites [59] Cecchin V, Sperotto F, Balzarin M, Vittadello F, Martini G, Zulian F. Joint hypermobility and oligoarticular juvenile idiopathic arthritis: What relationship? J Paediatr Child Health. 2017;53(4):374–7. https://doi.org/10.1111/jpc.13450. source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    There is weak to very weak evidence for possible mechanistic links with local connective tissue, anatomical, and physiological abnormalities.

    “There is weak to very weak evidence for possible mechanistic links with local connective tissue, anatomical, and physiological abnormalities.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The evidence is moderate in quality for anxiety and emerging for other mental health disorders.

    “Overall, the evidence is moderate in quality for anxiety and emerging for other mental health disorders, so the consensus decision was to include anxiety only at this stage.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Shetreat et al. found that children with ASD had significantly greater joint mobility (p < .002), more gait abnormalities (p < .0001), and on average walked 1.6 months later than their non-autistic peers.

    “A systematic study by Shetreat et al. found that children with ASD had significantly greater joint mobility (p < .002), more gait abnormalities (p < .0001), and on average walked 1.6 months later than their non-autistic peers.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Shetreat-Klein M, Shinnar S, Rapin I. Abnormalities of joint mobility and gait in children with autism spectrum disorders. Brain Dev. 2014;36(2):91–6. https://doi.org/10.1016/j.braindev.2012.02.005. source
38 of 38

  • The paper relies on this without support.

    Diagnosis of hEDS and HSD is currently clinical in the absence of biomarkers.

    “Diagnosis is currently clinical in the absence of biomarkers, and criteria developed for adults are difficult to use in children and biologically immature adolescents.”

  • The paper relies on this without support.

    Children and biologically immature adolescents have not yet developed a stable phenotype.

    “Biologically mature adolescents can be diagnosed using these criteria, but they are difficult to use in children and biologically immature adolescents (herewith children), who have not yet developed a stable phenotype.”

  • The paper relies on this without support.

    Hypermobility decreases during pediatric years, probably later in adolescent females than males.

    “Hypermobility decreases during pediatric years, probably later in adolescent females than males.”

  • The paper relies on this without support.

    Many comorbidities described in hEDS/HSD are also seen in the general pediatric and adolescent population.

    “Finally, many comorbidities described in hEDS/HSD are also seen in the general pediatric and adolescent population.”

  • The paper relies on this without support.

    No data are available on piezogenic papules in children.

    “The group consensus was to retain the 5 skin items in alignment with the 2017 hEDS adult criteria despite “unusually soft skin” and “mild skin extensibility” being largely subjective and no data being available on piezogenic papules in children.”

  • The paper relies on this without support.

    Many young children have not sustained injuries resulting in significant scarring.

    “As many young children have not sustained injuries resulting in significant scarring the requirement for 2 atrophic scars was agreed to be reduced to one.”

  • The paper relies on this without support.

    Unexplained striae would be an unusual finding prior to adolescence.

    “Clinically, unexplained striae would be an unusual finding prior to adolescence.”

  • The paper relies on this without support.

    Congenital umbilical hernia is a common phenomenon in the pediatric population.

    “Congenital umbilical hernia is a common phenomenon in the pediatric population”

  • The paper relies on this without support.

    Inguinal and umbilical hernia are common post neonatal intensive care.

    “inguinal and umbilical hernia are common post neonatal intensive care”

  • The paper relies on this without support.

    Recurrent hernias are unusual and suggest a degree of tissue fragility.

    “However, recurrent hernias are unusual and suggest a degree of tissue fragility.”
10 of 10

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Chronic-fatigue anxiety rate differs from Table 2

    Minor

    Table 2 reports anxiety in 29% of the chronic-fatigue population, but its note says 20%.

1 of 1

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Authors
Tofts, L. J., Simmonds, J., Schwartz, S. B., Richheimer, R. M., O’Connor, C., Elias, E., Engelbert, R., Cleary, K., Tinkle, B. T., Kline, A. D., Hakim, A. J., van Rossum, M. A. J., & Pacey, V.
Affiliations
  • Macquarie University (AU)
  • University College London (GB)
  • Hospital for Sick Children (CA)
  • Children's Hospital Colorado (US)
  • Amsterdam UMC Location University of Amsterdam (NL)
  • Peyton Manning Children’s Hospital at St.Vincent (US)
  • Greater Baltimore Medical Center (US)
Corresponding author
Hakim, Alan J.
ORCID
Venue
Orphanet Journal of Rare Diseases
Publisher
Springer Science and Business Media LLC
Published
2023-05-04
Volume
18
Issue
1
Pages
104-104
ISSN
1750-1172 (ISSN-L)
DOI
10.1186/s13023-023-02717-2
PMC
PMC10157984
OpenAlex
W4368368290
Semantic Scholar
b4e4eb91deadfe88d9b2ce6f1be7340230eb3a5d
Cited by
74
References
65
Citations by year
2026: 17 · 2025: 26 · 2024: 27 · 2023: 4
FWCI
3.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Orphanet Journal of Rare Diseases (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Pure Amsterdam UMC (submittedVersion, other-oa)
Funders
Ehlers-Danlos Society
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
  • Health Sciences › Health Professions › Pharmacy › Oral and gingival health research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
Keywords
hypermobile Ehlers-Danlos syndrome, hypermobility spectrum disorders, generalized joint hypermobility, Beighton score, diagnostic criteria, musculoskeletal complications, comorbidities
MeSH terms
Adolescent, Adult, Child, Connective Tissue Diseases, Ehlers-Danlos Syndrome, Humans, Joint Instability, Skin

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-13.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-13.

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