Pediatric joint hypermobility: a diagnostic framework and narrative review

Tofts et al. Orphanet Journal of Rare Diseases https://doi.org/10.1186/s13023-023-02717-2 (2023) 18:104 Orphanet Journal of Rare Diseases Open Access REVIEW Pediatric joint hypermobility: a diagnostic framework and narrative review Louise Jane Tofts1, Jane Simmonds2,3, Sarah B. Schwartz4, Roberto M. Richheimer5, Constance O’Connor4, Ellen Elias6,7, Raoul Engelbert8, Katie Cleary9, Brad T. Tinkle10, Antonie D. Kline11, Alan J. Hakim12* , Marion A. J. van Rossum13 and Verity Pacey1 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. Keywords Child, Adolescent, Joint hypermobility, Ehlers–Danlos syndrome *Correspondence: Alan J. Hakim Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Tofts et al. Orphanet Journal of Rare Diseases (2023) 18:104 Introduction 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. 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]. 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]. 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. 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]. Hypermobility decreases during pediatric years, probably later in adolescent females than males. 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]. We propose that children should not be assessed with the 2017 criteria or diagnosed with hEDS until they have reached biological maturity, so a pediatric specific framework was developed. 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. 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. 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. 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. Page 2 of 10 Methods The Paediatric Working Group and representatives of the hEDS/HSD Working Group of the International Consortium on EDS and HSD [8] met online throughout 2020–22. The group comprised the authors, with representation from Europe, The Americas, and Australasia, and from medical, nursing, and physical therapy clinical and academic backgrounds. Collectively over the last 5 years the group has seen over 5000 pediatric patients fo (...truncated)