The natural history of children with joint hypermobility syndrome and Ehlers-Danlos hypermobility type: a longitudinal cohort study
Open accessAbstract
Objectives: The objective of the manuscript was to describe the natural history of complaints and disability in children diagnosed with joint hypermobility syndrome (JHS)/Ehlers-Danlos-hypermobility type (EDS-HT) and to identify the constructs that underlie functional decline. Methods: One hundred and one JHS/EDS-HT children were observed over 3 years and assessed at three time points on the following: functional impairments, quality of life, connective tissue laxity, muscle function, postural control and musculoskeletal and multi-systemic complaints. Cluster analysis was performed to identify subgroups in severity. Clinical profiles were determined for these subgroups, and differences were assessed by multivariate analysis of covariance. Mixed linear regression models were used to determine the subsequent trajectories. Finally, an exploratory factor analysis was used to uncover the underlying constructs of functional impairment. Results: Three clusters of children were identified in terms of functional impairment: mild, moderately and severely affected. Functional impairment at baseline was predictive of worsening trajectories in terms of reduced walking distance and decreased quality of life (P ⩽ 0.05) over 3 years. Multiple interactions between the secondary outcomes were observed, with four underlying constructs identified. All four constructs (multi-systemic effects, pain, fatigue and loss of postural control) contributed significantly to disability (P ⩽ 0.046). Conclusion: Children diagnosed with JHS/EDS-HT who have a high incidence of multi-systemic complaints (particularly, orthostatic intolerance, urinary incontinence and diarrhoea) and poor postural control in addition to high levels of pain and fatigue at baseline are most likely to have a deteriorating trajectory of functional impairment and, accordingly, warrant clinical prioritization.
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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].”
From Pediatric joint hypermobility: a diagnostic framework and narrative review (2023) · cites this paper as [17]
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 measuredWorse fatigue correlated with more functional impairment at 3 years in the prospective Sydney cohort.
“Worse fatigue correlated with more functional impairment at 3 years in the prospective Sydney cohort [17] and worse quality of life at inception [43].”
From Pediatric joint hypermobility: a diagnostic framework and narrative review (2023) · cites this paper as [17]
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).”
From Pediatric joint hypermobility: a diagnostic framework and narrative review (2023) · cites this paper as [17]
The presence of diarrhea at baseline in the Sydney cohort was significantly more common in children with severe functional disability compared to those with milder functional disability.
“The presence of diarrhea at baseline in the Sydney cohort was significantly more common in the children with severe functional disability compared to those with milder functional disability [17].”
From Pediatric joint hypermobility: a diagnostic framework and narrative review (2023) · cites this paper as [17]
A subsequent 3-year longitudinal study traced functional impairment trajectories in 81 JHS children.
“The same group also traced the trajectories of functional impairment of a similar cohort of 81 patients in a subsequent 3 year longitudinal study [12].”
From Severity classes in adults with hypermobile Ehlers–Danlos syndrome/hypermobility spectrum disorders: a pilot study of 105 Italian patients (2019) · cites this paper as [12]
Inclusion of adult patients only did not allow exploration of the impact of the developmental trajectories proposed by others on the resulting phenotype.
“Inclusion of adult patients only did not allow us to explore the impact of the developmental trajectories proposed by others [11,12] on the resulting phenotype.”
From Severity classes in adults with hypermobile Ehlers–Danlos syndrome/hypermobility spectrum disorders: a pilot study of 105 Italian patients (2019) · cites this paper as [12]
In that longitudinal study, JHS children with higher multisystemic involvement and poor postural control more often had a deteriorating trajectory with increased functional impairment.
“In this work, they found that JHS children with a higher incidence of multisystemic involvement and poor postural control more commonly present a deteriorating trajectory with increased functional impairment [12].”
From Severity classes in adults with hypermobile Ehlers–Danlos syndrome/hypermobility spectrum disorders: a pilot study of 105 Italian patients (2019) · cites this paper as [12]
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“Worse fatigue correlated with more functional impairment at 3 years in the prospective Sydney cohort [17] and worse quality of life at inception [43].”
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Self-citation
- Authors
- Scheper, M. C., Nicholson, L. L., Adams, R. D., Tofts, L., & Pacey, V.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- The University of Sydney (AU)
- Children's Hospital at Westmead (AU)
- Corresponding author
- Scheper, Mark C.
- Venue
- Rheumatology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-04-18
- Volume
- 56
- Issue
- 12
- Pages
- 2073-2083
- ISSN
- 1462-0324 (ISSN-L)
- 1462-0332
- OpenAlex
- W2606515288
- Cited by
- 68
- References
- 41
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 6 · 2020: 17 · 2019: 9 · 2018: 5 · 2017: 1
- FWCI
- 5.82
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- Locations
- Lara D. Veeken (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (acceptedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- NWO (023.002.094)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pediatric Pain Management Techniques
- Keywords
- joint hypermobility syndrome, children, natural history (disease), functional decline, disability, quality of life, postural control, orthostatic intolerance, urinary incontinence, diarrhea, pain, fatigue, walking distance
- MeSH terms
- Adolescent, Child, Diarrhea, Disability Evaluation, Ehlers-Danlos Syndrome, Factor Analysis, Statistical, Female, Humans, Joint Instability, Longitudinal Studies, Male, Quality of Life, Surveys and Questionnaires, Syndrome, Urinary Incontinence, Multivariate Analysis, Cluster Analysis, Linear Models, Walking, Orthostatic Intolerance
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