Table 1 Overview of the reviewed sources

Acasuso Diaz et al., 1993

675 teenage soldiers (male only)

Non-clinical healthy sample

Quantitative

Degree of joint hypermobility assessed by 5 criteria

To determine the prevalence of hypermobility (cutoff of 2–3/5 and 4–5/5) among young male soldiers

25.5% of soldiers met 2 or 3 criteria and 7.5% met 4 or 5 criteria; Injury was significantly more frequent than in soldiers with normal joint mobility

Al-Rawi, Al-Aszawi, & Al-Chalabi, 1985

University sample of 1774 young adults

Non-clinical healthy sample

Quantitative

Hypermobility assessed via Beighton Scale; Height/weight

To determine the prevalence of hypermobility (cutoff of 4/9) among university students

Prevalence of hypermobility was high (males = 25.4%; females = 38.5%)

Baeza-Velasco et al., 2011

University sample of 365 young adults

Non-clinical healthy sample

Cross-sectional quantitative

Hypermobility assessed via Beighton Scale; Self-report measures

To determine the frequency of hypermobility among university students; To explore the relationship between hypermobility, somatosensory amplification Scale, depression, and anxiety

Somatosensory amplification was higher in students with hypermobility independent of gender; Depression and anxiety were higher in female students with hypermobility; social anxiety was higher in male students with hypermobility

Bair et al., 2003

Review of studies that included adults only

Chronic pain

Literature review

Search: Depression or depressive disorders and pain

To determine the prevalence of depression and pain and the effects of comorbidity on diagnosis, clinical outcomes, and treatment

65% of patients with depression experienced pain and between 5–85% of patients with pain experienced depression – rates that are higher than when the conditions are examined individually; Both pain and depression were negatively associated with poor pain outcomes and worse prognosis

Barnum, 2014

Pediatric patient

hEDS

Case study

N/A

To discuss the impact of an inaccurate diagnosis of conversion disorder^a in a pediatric patient with hEDS

Diagnosis of conversion disorder can undermine patients’ trust and create defensiveness that may interfere with acquisition of appropriate diagnosis, and related treatment.

Becker et al., 2017

26 adult patients and 26 practitioners

Chronic pain

Qualitative

Semi-structured interview

To identify factors related to whether one utilizes evidence-based non-pharmacologic pain treatment

Patient themes: Barriers – high cost, transportation difficulties, low motivation; Facilitators – greater availability of treatment, team-based treatment with follow-up; Practitioner themes: Barriers – inability to promote non-pharmacologic treatment after opioids, patient skepticism; Facilitators – consistent treatment philosophy, increased patient knowledge about non-pharmacologic treatment

Berglund, Anne-Cathrine, Randers, 2010

22 adults

EDS

Qualitative

Study-specific questionnaire

To describe health-care encounters patients with EDS experienced in which their dignity was not upheld and the long-term consequences associated with these encounters

Themes: Ignored/belittled. assigned psychological explanations, treated as an object, personal space invaded, questioned about family violence; Consequences of these encounters included mistrust and negatively impacting on health

Bulbena et al., 2015

Review of studies that included adults

hEDS

Literature review

N/A

To summarize research concerning the relationship between hypermobility and anxiety disorders

The relationship between hypermobility and anxiety disorders have been well established; Common mechanisms that are involved in include genetics, autonomic nervous system dysfunctions, and interoceptive/exteroceptive processes

Castori, 2015

 N/A

EDS including hEDS

Editorial/ commentary

N/A

To aid in practitioners in the differentiation of trauma due to EDS versus abuse

EDS should be considered in the differential diagnosis of children with a suspect of non-accidental injury such as skin lacerations, bruising, dislocations

Castori et al., 2013

Review of studies that included children and adults

EDS including hEDS

Reinterpretation of the literature

Search: joint laxity/joint instability/EDSand pain, fatigue, or headache

To re-interpret the published literature (based on the authors’ multidisciplinary clinical experience) on pain, fatigue, and headache in EDS based on authors’ multidisciplinary clinical experience

Pathogenic mechanisms of pain, fatigue, and headache in hEDS are offered through comparisons with other functional somatic syndromes

Castori et al., 2017

 N/A

hEDS

Editorial/ commentary

N/A

To propose a framework for the classification for joint hypermobility-related disorders

A continuous spectrum ranging from symptomatic joint hypermobility to hypermobility spectrum disorders to hEDS should be used; This spectrum supports the dynamic nature of condition.

Celletti, et al., 2013

42 adult patients

hEDS

Cross-sectional quantitative

Self-report measures

To investigate the impact of kinesiophobia in hEDS and the relationship with pain, fatigue, and QoL

Kinesiophobia is common in hEDS; severity of kinesiophobia was related to severity of fatigue and, generally, related to severity of pain but not to QoL, or to intensity of pain or fatigue

Clinch et al., 2011

Population-based cohort of 6,022 children

Non-clinical healthy sample

Quantitative

Hypermobility assessed via Beighton Scale; Height/weight; Assessment of physical activity, puberty, and SES

To determine the point prevalence and pattern of hypermobility (cutoff of 4/9) in children from a population-based cohort

Prevalence of hypermobility was high in children (girls = 27.5%; boys = 10.6%) suggesting that the cutoff of 4/9 is too low for this population

De Baets et al., 2017

10 adult females who have had at least 2 children

hEDS

Qualitative

Semi-structured interview

To explore the lived experiences of women with hEDS regarding diagnosis, influence on daily life, and motherhood

Themes: Relief in receiving diagnosis/support to become a mother, hEDS emotionally related distress impact on social/physical behavior, adjustment of everyday activities, differing mother/child expectations, importance of supportive social/physical environment, and child decreases illness focus of mother

Eccles et al., 2012

72 adults

Non-clinical healthy sample

Experimental

Hypermobility assessed via Beighton Scale; Self-report measures; fMRI

To examine the relationship between regional cerebral grey matter and hypermobility (cutoff of at least 1/9) using fMRI

Structural differences in the key emotion-processing brain regions and decreased volume within other regions implicated in emotional arousal and attention were found in the group with hypermobility as compared to those without.

Engelbert et al., 2017

 N/A

hEDS

Practice guideline

N/A

To provide education as to the role of PT in the assessment and management of hEDS in both pediatric and adult populations:

Descried the following factors as key for management of pain in hEDS: proprioception, muscle strength and balance; joint instability; extra-articular factors; psychological symptoms; motor development, gait pattern, physical fitness; and participation in hobbies, sports, and social activities

Grahame, 2017

 N/A

EDS including hEDS

Editorial/ commentary

N/A

To correct two misconceptions about hEDS and the resulting hesitancy to diagnose hEDS in pediatric populations

Two misconceptions identified are that symptomatic joint hypermobility occurs in otherwise healthy individuals and the dismissal of an underlying connective tissue disorder; Encouragement provided to consider early diagnosis and intervention

Johnson, Zautra, & Davis, 2006

51 adults (female only)

Fibromyalgia

Quantitative and qualitative

Self-report measures; Weekly semi-structured interview for 10–12 weeks

To examine the relationship between IU in pain coping focusing on weeks with greater pain intensity

For participants with high IU, pain severity predicted increases in coping difficulty; Coping difficulty was associated with lower coping efficacy

Juul-Kristensen et al., 2017

Review of studies that included children and adults

JHS/hEDS

Systematic review

Search one: combinations of joint, laxity, hypermobility, instability, general and evaluation, rate, questionnaire, test, examine, scale, diagnose, assess, observe, measure; Search two: added psychometrics, clinometric, reproducibility, reliability, repeatability, responsiveness, sensitivity, specificity, validity, diagnosis, feasibility

To complete a systematic review of the clinical assessment methods for classifying generalized joint hypermobility

6 measures of hypermobility were identified with most studies using the Beighton Scale; inter-rater reliability was acceptable, however, more research on the validity is needed; when using the Beighton Scale, a cutoff of 5/9 criteria for adults and 6/9 for children is used provided uniformity of testing procedures

Kennedy et al., 2022

Review of studies that included children and adults

EDS including hEDS

Systematic review

Search: Ehlers-Danlos syndrome and psychology or mental disorder

To complete a systematic review of the psychiatric disorders in the EDS population

63.2% of patients with EDS were diagnosed with a language disorder, 52.4% with attention-deficit/hyperactivity disorder, 51.2% with anxiety, 42.4% with a learning disability and 30.2% depression

Klemp & Learmonth, 1984

47 adult ballet dancers and age-/sex-matched controls

Non-clinical healthy sample

Longitudinal (10 years) quantitative

Hypermobility assessed via Beighton Scale; Rate of injury

To determine the prevalence of hypermobility (cutoff of 4/9) among ballet dancers and frequency of injury

Ballet dancers were not found to be more hypermobile and did not sustain more injuries as compared to age-/sex-matched controls

Kohn & Chang, 2020

Review of studies that included children and adults

hEDS, POTS, and MCAS

Literature review

Search one: Various combinations of hEDS, POTS, and MCAS; Search two: Various combinations of all forms of EDS, POTS, and MCAS

To review the comorbidity between hEDS, POTS, and MCAS

An evidence-based pathophysiologic relationship between hEDS and POTS or MCAS does not exist and studies describing a relationship are biased or based on outdated criteria

Malek, Reinhold, & Pearcem, 2021

Review of studies that included adults only

hEDS

Literature review

Search one: Beighton Score and validity, correlation, or reliability; Search two: Expanded to include various joints

To review the validity of the Beighton Score as a diagnostic tool for hypermobility

As the Beighton Score does not

accurately represent the diagnosis definition of and should not be used as a direct indicator of generalized joint hypermobility

Malfait et al., 2017

 N/A

hEDS

Position paper

N/A

To propose a revised hEDS classification system be used for clinical and research purposes

Outlined clinical criteria for hEDS to allow for greater distinction from other heritable connective tissue disorders

Mallorqui-Bague et al., 2014

36 adults

Non-clinical healthy sample

Experimental

Hypermobility assessed via Beighton Scale; Self-report measures; Interoceptive sensitivity assessed via heartbeat detection task; fMRI

To examine the relationship between anxiety, interoceptive sensitivity, and hypermobility (cutoff of 5/9 for women and 4/9 ≥ 4 for men) using fMRI

Anxiety and hypermobility are related, and the relationship is mediated by interoceptive sensitivity; Participants who were hypermobile displayed heightened neural reactivity to brain regions implicated in anxious feeling states

Neville et al., 2019

20 pediatric patients and their parents

Chronic pain

Qualitative

Semi-structured interview

To explore the lived experience of IU in pediatric patients their parents

Themes included IU associated with the function/meaning of the diagnosis, worry surrounding something missing, search for an alternative diagnosis, and mistrust in the medical system

Neville, et al., 2021

152 children and their parents

Chronic pain

Longitudinal (3 months) quantitative

Self-report measures

To examine the association between IU and the Interpersonal Fear Avoidance Model of Pain

Parent and child IU were identified as risk factors in the maintenance of pediatric chronic pain at 3 months through parent and child pain catastrophizing, parent protectiveness, and youth fear of pain.

Palmer et al., 2016

25 adult patients and 14 practitioners

hEDS²

Qualitative

Focus groups (conducted separately for patients and practitioners)

To explore patient and practitioner views on PT in the treatment of hEDS

Themes included PT is ineffective for acute joint problems and if diagnosis is delayed, and effective PT included therapist who is familiar with hEDS, patient led, flexible, and takes a long-term approach

Ploghaus et al., 2001

8 adults (male only)

Non-clinical healthy sample

Experimental

Self-reported pain intensity, Event-related fMRI

To examine the neural mechanisms of induced anxiety and nociceptive stimulation

perception of pain via event-related fMRI

Anxiety-induced hyperalgesia is associated with increased activation of portions of the hippocampal formation (consistent with Gray-McNaughton Theory). Authors suggest that interventions which modulate hippocampal activation may be valuable for management of both procedural and chronic pain.

Reich et al., 2006

51 adults

Fibromyalgia

Quantitative and qualitative

Self-report measures; Weekly semi-structured interview for 10–12 weeks

To examine relationship between IU and depression, anxiety, affect, and coping styles

IU was associated with anxiety, negative affect, avoidant coping, and passive coping and, during stress, IU was found to be a risk factor for negative affect

Rhudy & Meagher, 2000

University sample of 60 young adults

Non-clinical healthy sample

Experimental

Exposure to electric shock was used to induce fear,

whereas anticipation of shock (without exposure) was

used to induce anxiety.

Exposure to electric shock was used to induce fear; Anticipation of shock (without exposure) was used to induce anxiety

To examine the effects of experimentally induced fear and anxiety pain thresholds using fMRI

Experimentally induced anxiety increased pain reactivity while experimentally induced fear resulted in decreased pain reactivity

Sawamoto et al., 2000

10 adults (male only)

Non-clinical healthy sample

Experimental

Self-reported pain intensity and pain unpleasantness; Event-related fMRI

To examine whether the expectation of pain amplifies brain responses to somatosensory stimulation in areas of the brain that regulates behavioral reaction to pain using fMRI

Uncertain expectation of pain amplifies areas of the brain (anterior cingulate cortex, parietal operculum, and posterior insula) which regulates behavioral reaction to pain

Singh et al., 2017

1000 children and adults

Non-clinical healthy sample

Cross-sectional quantitative

Hypermobility assessed via Beighton Scale

To evaluate distribution of Beighton scores (cutoff of 4/9) in a healthy population

Beighton score of 4/9 yielded a high false positive rate of 60% suggesting overestimation of prevalence with this cutoff; Cutoffs should be varied across the life span with age-/sex-specific values cutoffs

Smits-Engelsman, Klerks, & Kirby, 2011

551 elementary school-aged children

Non-clinical healthy sample

Quantitative

Hypermobility assessed via Beighton Scale

To determine the prevalence of hypermobility and the validity of the Beighton scale (cutoff of 5/9) in elementary school aged children

Prevalence of hypermobility was high (35.6%; no sex differences) suggesting that a stricter cutoff score be used; Complaints of join pain and pain after exercise were not significantly different between children with more or less hypermobility

Tanna et al., 2020

91 pediatric patients and 126 of their parents

Varied pain locations/diagnoses including hEDS

Quantitative

Self-report measures

To examine the prevalence and familial concordance of IU and the relationship between parent and child IU with several parent and child psychological factors

Parent IU was associate with higher avoidance of pain-related activities and lower pain acceptance in their children; Parent and child IU was related to the child’s functioning