Clinical characteristics of symptomatic hypermobility in children and young people: A scoping review protocol

Abstract

INTRODUCTION:

Joint hypermobility (JH) is a term used to define active or passive joint range of motion that is beyond normal range, accounting for age, sex, and ethnicity. Symptomatic hypermobility is a term that can be used when symptoms are thought to be associated with JH. Children and young people with symptomatic hypermobility complain of musculoskeletal symptoms but also may report symptoms from other domains including gastrointestinal, cardiovascular, psychological, and urogenital. Many of these symptoms are not included in formal diagnostic criteria yet may impact negatively on their quality of life. The pattern of these symptoms may change with age.

PURPOSE:

To map the literature on clinical characteristics of symptomatic hypermobility in an age and developmental context, to improve our understanding and assist in the clinical assessment of children and young people with symptomatic hypermobility.

METHODS:

This systematic scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) methodology. Studies that include children and young people from birth to 24 years with a confirmed diagnosis of symptomatic hypermobility, HSD or hEDS using internationally recognised criteria or equivalent diagnoses will be included. Data extraction and analysis will be undertaken using an iterative process.

DISCUSSION:

Mapping and synthesis of the data will be carried out and gaps and limitations in the literature will be acknowledged. Results will be disseminated in a peer reviewed journal. The search strategy will be made available publicly for transparency.

Keywords

Symptomatic hypermobility children young people clinical characteristics

1 Introduction

Joint Hypermobility (JH) refers to the ability a joint has to move beyond its normal range of movement [1]. JH is a descriptive term, not a diagnosis and varies according to age, sex, and ethnicity [2]. Hypermobile joints as they can be termed, are prevalent in children and young people. The reported prevalence in children and young people ranges between 3.3% and 65%, dependent on population characteristics and study methodology, notably the definition and evaluation of JH [3]. Despite such variances in prevalence, it is evident that JH is a common trait and depends on both environmental and genetic factors [4].

Recognising when JH is clinically relevant, is a challenge to physiotherapists and other clinicians for many reasons. The terminology used to describe JH and symptoms has changed significantly over the years, and remains controversial especially in regard to children and young people. Historically, previous terms have included Joint Hypermobility Syndrome (JHS), Benign Joint Hypermobility Syndrome (BJHS) [5] and Ehlers Danlos Syndrome hypermobility type (EDS-HT) which was thought to overlap JHS and BJHS significantly [6]. In 2017, hypermobile Ehlers Danlos Syndrome (hEDS) was redefined using strict criteria and the term Hypermobility Spectrum Disorder (HSD) was used to define all those not fitting the criteria for hEDS [7], which has been postulated to be inherited as an autosomal dominant disorder of connective tissues [8]. There is no known genetic aetiology for hEDS therefore diagnosis is based on clinical assessment, using current diagnostic criteria [8]. The term ‘symptomatic hypermobility’ will be used in this study, to define clinically relevant signs and symptoms in the presence of JH, where all other diagnoses have been excluded.

Shortcomings have been found in the literature in many of the tools used to identify JH, with tools lacking adequate reliability, and validity [9]. As JH is known to change significantly with age; values should be compared to standardised norms [1]. The Beighton score is commonly used, and despite limitations, is considered one of the most acceptable tools for screening generalised JH in the clinical setting and is used in the criteria determining a diagnosis of hEDS [1, 9]. The Beighton score is used to screen JH through the examination of passive range of movement (bilateral thumb apposition to the flexor side of the forearm, fifth metacarpophalangeal extension, elbow extension, knee extension) and the ability to place both palms to floor [9, 10]. The emphasis on the upper limb is often considered a limitation of this score [11] in addition to the fact that the score is easily influenced by exercise, the sex of the individual and previous trauma [1]. Nonetheless, the Beighton score has been validated in primary school-aged children when using a standardised protocol, and it is recommended that clinicians use these uniform testing procedures with specific cut offs for different age groups [9, 12].

In the literature, the spectrum and heterogeneity of symptomology in the setting of JH, spans different medical specialities. The onset of symptoms is often reported to occur in the first decade of life, with musculoskeletal pain reported to be among the most common presenting symptom in children and young people with JH [13, 14]. Non-musculoskeletal signs and symptoms including fatigue [15], selected gastrointestinal disorders [16 –18], cardiovascular dysautonomia [19], headaches [20], dysmenorrhea [21] and many others, are also reported to be more common in individuals with JH compared to the general population [1]. However, similar musculoskeletal and non-musculoskeletal symptoms, can also be common in children and young people without JH [22]. Neurodevelopmental issues, including a wide variation of impairments of attention and activity, have been linked to JH [23, 24]. Links between children presenting with developmental co-ordination disorder and JHS have been reported in literature and often observed clinically, but methodological heterogeneity including terminology, assessment, and the lack of standardised outcome measures limit comparison between studies, and the reason(s) for such associations remain unknown [25 –27]. Due to the heterogeneity of presenting symptomology, there is often a significant delay between onset of symptoms and intervention, making the study of symptoms in paediatrics very difficult [14]. Clinicians may have to rely on the patient’s estimation of age-related features, asking the participant to recall progression of clinical characteristics over years, which limits an accurate estimation of the described features [28].

Children and young people with symptomatic hypermobility are often initially referred to tertiary paediatric rheumatology services, however, patients may also present to many other medical domains [29, 30]. Physiotherapists often play a key role in the management of children and young people with symptomatic hypermobility although the current evidence base to guide clinicians is limited [31]. Focus groups carried out on adults with a diagnosis of JHS, attending for physiotherapy within the previous 12 months, described how participants perceived JHS to be often poorly understood by health professionals and reported feeling fraudulent or blamed for their symptoms [32]. A survey conducted to explore knowledge and perceptions of JH and JHS amongst paediatric physiotherapists, reported that respondents reported lacking confidence in differentiating between JH and JHS [33]. This survey was carried out prior to more recent clarity in terminology, but the use of diagnostic criteria for children and young people with symptomatic hypermobility remains controversial.

Literature that describes symptoms in adults cannot be generalised to paediatric and emerging adult populations. Children and adolescents are developing physically, emotionally, and psychologically therefore symptoms may present and impact differently to adults [34]. It is necessary to review the current literature specific to children and young people to consider clinical characteristics in an age and developmental context. The identification of clinical characteristics related to JH the trait, rather than a defined diagnosis further complicates the interpretation of the literature [17]. Mapping the literature over time and across all the clinical domains, specific to children and young people using internationally recognised diagnostic terminology, will help to identify clinical characteristics of this heterogenic cohort.

1.1 Study objectives

This systematic scoping review (ScR) aims to identify and map the existing literature reporting clinical characteristics, study designs and setting, diagnostic criteria, and outcome measures in children and young people with symptomatic hypermobility. Unlike systematic reviews, scoping reviews do not aim to critically appraise and answer a specific question but aim to provide an overview of an area [35]. They can be used when literature exhibits a heterogenous nature which is not as amenable to a systematic review [36]. This ScR will provide a broad perspective, reviewing a large body of literature to identify clinical characteristics of symptomatic hypermobility in children and young people across many medical domains, in an age and developmental context [37].

2 Methods

2.1 Study design

The research question will be addressed using a scoping review methodology. This methodology will be used to follow a systematic approach to explore the literature, mapping, and summarising the evidence available on children and young people with symptomatic hypermobility, such as reporting characteristics and concepts [37]. It will also provide an overview of the evidence, to answer questions about the diversity or heterogeneity of symptomatic hypermobility in children and young people [38]. A ScR allows for broader inclusion criteria, enabling the researcher to answer the research question in a comprehensive manner. This ScR will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) [37]. The ScR framework, initially proposed by Arksey and O’Malley [36], will be followed [38]. This framework consists of five main stages: (1) identifying the research question(s); (2) identifying potentially relevant studies; (3) selecting eligible studies; (4) charting the data and searching for the evidence; and (5) collating, summarising, and reporting the results. This process is not linear but will be an iterative process which requires researchers to adapt to each stage depending on their findings and where necessary review or repeat steps, to ensure that the literature is studied in a comprehensive manner [36]. To ensure this process, regular team meetings will be held during the ScR to seek clarification, discuss, and amend the process if required. The protocol was registered with the Open Science Framework on 20^th September 2021, (https://osf.io/m2h6q).

2.2 Protocol

This ScR protocol was written using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR)[38]. This was designed for systematic reviews but is used for guidance where appropriate for a ScR. The protocol was developed by the research team. The final protocol was registered with the Open Science Framework in an open registration format (https://osf.io/m2h6q).

2.3 ScR framework

2.3.1 Framework stage 1: Identifying the research question

The research question was formulated following team meetings and consultation with the subject librarian. This review will be guided by one main research question and will use the Joanna Briggs institute (JBI) recommended framework to outline this question according to Population, Concept and Context (PCC) [38].

“What are the presenting clinical characteristics of children and young people diagnosed with symptomatic hypermobility (including HSD and hEDS and other equivalent diagnoses)?”.

2.3.1.1. Inclusion criteria

The inclusion criteria were guided by the terms included in the research question, incorporating the PCC elements.

2.3.1.2. Population

This ScR will consider studies of children and young people from birth to 24 years. UNICEF (The UN Convention on Rights of the Child) defines a child up until the age 18 years [39]. The World Health Organization defines ‘adolescents’ as individuals in the 10–19-year and ‘youth’ as the 15–24- year age group. These two overlapping age groups are combined in the group ‘young people’, covering the age range 10–24 years [40]. Inclusion of both children and young adult participants ensures that search terms are not restrictive to age limits initially, to allow for inclusion of studies which include a mixed age-group cohort.

For the purposes of the review, and to incorporate historical as well as present day terminology, symptomatic hypermobility was defined as a ‘confirmed diagnosis of Hypermobility Spectrum Disorder (HSD) or hypermobile Ehlers-Danlos Syndrome (hEDS) (using internationally recognised criteria) or equivalent diagnosis Ehlers-Danlos Syndrome- Hypermobility Type (EDS-HT), Ehlers-Danlos Syndrome type III (EDS type III), Joint Hypermobility Syndrome (JHS) or Benign Joint Hypermobility Syndrome (BJHS)’. There are a number of genetic syndromes, most of which present with recognisable features which include JH. These syndromes include classical and vascular types of Ehlers-Danlos syndrome, Marfan syndrome, Stickler syndrome, Loeys-Dietz syndrome, and others [1]. These syndromes will be excluded from this scoping review. As JH is a common trait in children and young people, studies describing asymptomatic JH will also be excluded.

2.3.1.3. Concept

The main concept of this ScR is to map clinical characteristics of this population. The confirmed diagnosis must be a clinical diagnosis, following a clinical assessment which takes place in a clinical setting so that clinical characteristics can be determined. The research team deemed that studies conducted in school or university settings will also be acceptable within the definition of a health care setting if clinical researchers conduct clinical assessments using defined assessments and outcome measures.

2.3.1.4. Context

The aim of the ScR is to allow for broad inclusion criteria, to enable a comprehensive search of the literature. In terms of the type of evidence sources included, this ScR will consider randomised and non-randomised controlled trials, intervention, and observational studies including case reports. A large number of case reports is anticipated, and therefore excluding these reports may restrict the review even though they may represent extreme cases. Review articles will also be included if they fulfil the inclusion criteria and capture data not seen in original articles. Review articles will be excluded if on searching of the primary source, the original data no longer fulfil the inclusion criteria. Editorials, opinion papers, abstracts and posters will not be included. These types of evidence may often be lacking the detail required to fulfil the objectives of the review. Papers written in languages other than English and papers where there is an inability to obtain the full text will be also be excluded. During this process of defining criteria, the iterative nature of the ScR will enable the research team to review and revise inclusion and exclusion criteria, to ensure that the studies included in the process are in line with the objectives of the ScR.

2.3.2 Framework stage 2: Identifying relevant studies

The search strategy will aim to be as comprehensive as possible, to capture all studies considered by the authors to satisfy the research question according to the Joanne Briggs Institute (JBI) PCC framework [38]. Initially, a search of recent literature will be conducted to consider key words which may inform the development of the search strategy. Studies in the following databases will be reviewed: EMBASE, Medline, CINAHL, and Web of Science. These databases were selected to be comprehensive and to cover a broad range of medical disciplines. No limits on date or language will be placed on the initial database search. Based on meetings with the research team, experienced clinicians and in collaboration with an experienced subject librarian, specific search terms for each database will be identified. All information sources will be included in the search including grey literature (http://www.opengrey.eu), conferences, consultation with experts, membership of expert groups, and manual searching of targeted websites (http://www.ehlers-danlos.com, http://www.hedstogether.com, http://www.hypermobility.org). The Google search engine (http://www.google.com) will be used to conduct a search without date restriction. The first 20 hits (deemed most relevant by the Google search engine) will be screened. Review articles will be hand searched to identify articles not yet captured. The full search strategy will aim to include all key words relevant to the research question. Studies must show evidence of a confirmed diagnosis of Hypermobility Spectrum Disorder (HSD) or hypermobile Ehlers-Danlos Syndrome (hEDS) or equivalent diagnosis, using internationally recognised criteria.

2.3.3 Framework stage 3: Study selection

The study selection will be carried out according to the criteria specified above, which follow the PCC framework of this ScR [39]. All identified studies will be uploaded to Covidence™ software, 2016 (http://www.covidence.org) where duplicates will be automatically removed at time of upload. The next process will consist of two separate stages; 1. title and abstract screening and 2. full text screening. Two independent reviewers will apply the criteria to all the citations and subsequently to the full text. Inter-rater reliability will be tested at both stages to assess the interpretation of the criteria and ensure an accepted level of agreement between reviewers. Any disagreements regarding interpretation of the criteria will be discussed with the reviewing team and clarified following reliability testing. Conflicts following each stage, will be resolved with a third independent reviewer. The results of the search and study selection phase will be reported in the full ScR and will be presented in a Preferred Reporting Items for Systematic Meta-analyses extension for ScR (PRISMA-ScR) flow diagram.

2.3.4 Framework stage 4: Charting the data

To meet the objectives and answer the research question, data will be extracted using a data extraction template created using Covidence™ software, 2016 (http://www.covidence.org). A pilot data extraction step will be conducted with 20 randomly selected articles to ensure consensus between two independent reviewers. When consensus is achieved, one reviewer will complete the data extraction process [36]. Lead authors will be contacted if there is missing data, or where further information is required, where necessary. The data extraction template will include the following fields: title and author(s), year of publication, lead author contact details, country/countries in which study was conducted, aims of the study, study design, clinical setting, method of recruitment of participants, diagnostic criteria used, total number of participants, biological sex, mean or median and range of ages, inclusion criteria, exclusion criteria, outcome measures used, clinical characteristics of the participants. This template will be modified if necessary, during the process, especially as reviewers reflect on the objectives of the ScR as part of the iterative process [38].

2.3.5 Framework stage 5: Collating, summarising, and reporting the results

The purpose of this ScR is to map the data and present an overview of the research specific to the research question [36]. Due to the anticipated large volume of literature, and consistent with the process for scoping reviews [34], a quality analysis will not be carried out. When the data has been extracted, it will be coded and grouped, and a narrative account of the results will be presented. The results will be categorised into three main areas: 1. mapping of clinical characteristics according to clinical domains in an age, sex, and developmental context with consideration to method of recruitment; 2. detailed descriptions of specific inclusion, diagnostic criteria and outcome measures used including any evidence of standardisation such as standardised testing positions, or use of goniometry, as per recommendations [9, 12]; and 3. numerical listing of country in which the studies were conducted, publication date, journal type, study design and the clinical setting. Each area will be described in a narrative form, and results will be further reported through bubble plots, charts, and tables.

2.4 Ethics and dissemination

Ethical approval is not required for this ScR as human participants are not involved. There are no safety considerations with regard to conducting this ScR. The review findings will be published in relevant peer-reviewed journals and presented at national and international conferences. The findings will also be disseminated at meetings for stakeholders including clinicians working in tertiary paediatric centres and also secondary and primary care, where children and young people present with symptomatic hypermobility. It is hoped that the ScR results will be of relevance to clinical staff in multiple disciplines. It is anticipated that results will also be presented to patient support groups, where appropriate. The search strategy will be made available publicly for transparency.

3 Discussion

This ScR aims to contribute to the understanding in this heterogenous cohort of children and young people who present with a wide spectrum of symptomology. This review will map clinical characteristics spanning different medical domains presented in the literature. The research team aims to chart the evidence using a systematic approach, following an exhaustive search, using well defined criteria, and presenting the data in a structured way to inform physiotherapists, clinicians, and other researchers.

3.1 Limitations

Some studies will not define clinical characteristics by specific age groups, and therefore data pertaining to some children and young people may not be possible to extract. The research team have chosen to exclude studies describing clinical characteristics in children and young people with JH the trait i.e., asymptomatic. The research team accept that some with JH may become symptomatic in the future or may have another diagnosis whereby JH has not been recognised to be clinically relevant at such time.

Author contributions

SW, SD, JD, JS and EMD conceived the study, developed the protocol, and formulated the research question. SW drafted the protocol. All authors were involved in the revisions to the paper and approved the final text for submission.

Conflict of interest

The authors have no conflict of interest to report.

Funding

This work is supported by a National Children’s Research Centre (NCRC) Clinical Fellowship (Project Code –D/19/5). The NCRC have been in existence for more than 50 years and has been funded since its inception by the Children’s Health Foundation Crumlin, Dublin, Ireland.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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