Joint hypermobility syndromes, particularly chronic pain associated with this condition, including Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD), present diagnostic challenges due to their multifactorial origins and remain poorly understood from biomechanical and genomic-molecular perspectives. Recent diagnostic guidelines have differentiated hEDS, HSD, and benign joint hypermobility, providing a more objective diagnostic framework. However, incorrect diagnoses and underdiagnoses persist, leading to prolonged journeys for affected individuals. Musculoskeletal manifestations, chronic pain, dysautonomia, and gastrointestinal symptoms illustrate the multifactorial impact of these conditions, affecting both the physical and emotional well-being of affected individuals. Infrared thermography (IRT) emerges as a promising tool for joint assessment, especially in detecting inflammatory processes. Thermal distribution patterns offer valuable insights into joint dysfunctions, although the direct correlation between pain and inflammation remains challenging. The prevalence of neuropathies among hypermobile individuals accentuates the discordance between pain perception and thermographic findings, further complicating diagnosis and management. Despite its potential, the clinical integration of IRT faces challenges, with conflicting evidence hindering its adoption. However, studies demonstrate objective temperature disparities between healthy and diseased joints, especially under dynamic thermography, suggesting its potential utility in clinical practice. Future research focused on refining diagnostic criteria and elucidating the underlying mechanisms of hypermobility syndromes will be essential to improve diagnostic accuracy and enhance patient care in this complex and multidimensional context.

OBJECTIVE: To co-create expert guidelines for the management of pregnancy, birth, and postpartum recovery in the context of hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD).
METHODS: Scoping Review and Expert Co-creation.
METHODS: United Kingdom, United States of America, Canada, France, Sweden, Luxembourg, Germany, Italy, and the Netherlands.
METHODS: Co-creators (n = 15) included expertise from patients and clinicians from the International Consortium on the Ehlers-Danlos syndromes and Hypermobility Spectrum Disorders, facilitated by the Ehlers-Danlos Society.
METHODS: A scoping review using Embase, Medline, the Cochrane Central Register of Controlled Trials and CINHAL was conducted from May 2022 to September 2023. Articles were included if they reported primary research findings in relation to childbearing with hEDS/HSD, including case reports. No language limitations were placed on our search, and our team had the ability to translate and screen articles retrieved in English, French, Spanish, Italian, Russian, Swedish, Norwegian, Dutch, Danish, German, and Portuguese. The Mixed Methods Appraisal Tool was used to assess bias and quality appraise articles selected. The co-creation of guidelines was based on descriptive evidence synthesis along with practical and clinical experience supported by patient and public involvement activities.
RESULTS: Primary research studies (n = 14) and case studies (n = 21) including a total of 1,260,317 participants informed the co-creation of guidelines in four overarching categories: 1) Preconceptual: conception and screening, 2) Antenatal: risk assessment, management of miscarriage and termination of pregnancy, gastrointestinal issues and mobility, 3) Intrapartum: risk assessment, birth choices (mode of birth and intended place of birth), mobility in labor and anesthesia, and 4) Postpartum: wound healing, pelvic health, care of the newborn and infant feeding. Guidelines were also included in relation to pain management, mental health, nutrition and the common co-morbidities of postural orthostatic tachycardia syndrome, other forms of dysautonomia, and mast cell diseases.
CONCLUSIONS: There is limited high quality evidence available. Individualized strategies are proposed for the management of childbearing people with hEDS/HSD throughout pregnancy, birth, and the postpartum period. A multidisciplinary approach is advised to address frequently seen issues in this population such as tissue fragility, joint hypermobility, and pain, as well as common comorbidities, including dysautonomia and mast cell diseases.

Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Asymptomatic EDSs, joint hypermobility without associated syndromes, EDSs, and hypermobility spectrum disorders are the commonest phenotypes associated with joint hypermobility. Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. JHS can be a sign of a more serious underlying genetic condition, such as EDS, which affects the cartilage, bone, fat, and blood. The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. Membrane proteins are a class of proteins embedded in the cell membrane and play a crucial role in cell signaling, transport, and adhesion. Dysregulated membrane proteins have been implicated in a variety of diseases, including cancer, cardiovascular disease, and neurological disorders; recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. This article presents an exploration of the causative factors contributing to musculoskeletal pain in individuals with hypermobility, based on research findings. It aims to provide an understanding of JHS and its association with membrane proteins, addressing the clinical manifestations, pathogenesis, diagnosis, and management of JHS.

This narrative review aims to demonstrate and summarize the complex relationship between Ehlers-Danlos syndromes (EDS) and temporomandibular disorders (TMD) by reviewing the results of observational studies and case reports. EDS are a set of hereditary connective tissue disorders, where generalized joint hypermobility (GJH), especially in the hypermobile subtype (hEDS), is a key symptom. Mutations have been identified in genes that impact the production or assembly of collagen for all subtypes except hEDS. While the correlation between GJH and TMD has been analysed in various studies, fewer studies have examined TMD in patients with EDS, with most showing an increased prevalence of TMD. In case-control studies, an elevated prevalence of myalgia, arthralgia and disc-related disorders was found in individuals with EDS. Various therapeutic interventions have been reported within the literature in the form of case reports and observational studies, but there are no long-term clinical trials with results on the efficacy of different therapeutic approaches to date. This review demonstrates the high prevalence of different TMDs in different subtypes of EDS, but also shows that little is known about the success of treatment thus far. Further clinical research is necessary to provide adequate guidance on targeted treatment.

Heavy menstrual bleeding has a high prevalence and is well documented in adult patients with hypermobile-type Ehlers-Danlos syndrome, but there is limited research surrounding work-up and treatment for the adolescent population. Excessive menstrual blood loss can significantly interfere with emotional and physical quality of life. A provider should acquire a comprehensive medical and menstrual history and focused physical examination, as well as baseline laboratory studies, to determine the presence of anemia or underlying bleeding disorder. Use of a pictorial blood assessment chart may be considered to help quantify the amount of bleeding. Treatment to reduce heavy menstrual flow and referral to specialty care should be initiated swiftly to improve quality of life for this population. [Pediatr Ann. 2024;53(3):e104-e108.].

OBJECTIVE: Postural Orthostatic Tachycardia Syndrome (POTS) is a form of dysautonomia. It may occur in isolation, but frequently co-exists in individuals with hypermobile variants of Ehlers-Danlos Syndrome (EDS) and related conditions (chronic fatigue syndrome [CFS] and fibromyalgia). Exercise is recommended for non-pharmacological POTS management but needs to be individualised. This scoping review explores the current literature on use and effectiveness of exercise-based management for POTS, with specific focus on individuals with joint hypermobility and related conditions who experience hypermobility, and/or pain, and/or fatigue.
METHODS: A systematic search, to January 2023, of Medline, EMBASE, AMED, CINAHL and the Cochrane library was conducted. Studies that reported on adolescents and adults who had been diagnosed with POTS using standard criteria and underwent an exercise-based training intervention were included.
RESULTS: Following full-text screening, 10 articles were identified (2 randomised control trials, 4 comparative studies and 4 case reports). One comparative study reported a small subset of participants with EDS and one case report included an individual diagnosed with CFS; the remainder investigated a wider POTS population. Overall, 3 months of endurance followed by resistance exercise, graduating from the horizontal-to-upright position reduced POTS symptoms and improved quality-of-life.
CONCLUSIONS: The findings highlight a paucity of higher-level studies documenting exercise for POTS management in people with joint hypermobility and related conditions. Results from the wider POTS population demonstrate exercise is safe and effective. Large, well-designed clinical studies exploring exercise for POTS management adapting to meet the complex musculoskeletal and non-musculoskeletal features of symptomatic joint hypermobility are needed.

BACKGROUND: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder characterized by joint hypermobility and other systemic manifestations, such as cardiovascular symptoms, musculoskeletal pain, and joint instability. Cardiovascular symptoms, such as lightheadedness and palpitations, and types of dysautonomia, including postural orthostatic tachycardia syndrome (POTS), are frequently reported in adults with hEDS and have been shown to negatively impact quality of life (QoL).
OBJECTIVE: This brief review will be an overview of co-occurring symptoms in POTS and hEDS to inform potential cardiovascular screening procedures.
RESULTS: While many patients with hEDS report cardiovascular symptoms, few have structural abnormalities, suggesting that dysautonomia is likely responsible for these symptoms. One validated screening measure for dysautonomia symptom burden is the Composite Autonomic Symptom Scale (COMPASS-31). Studies have found that adults with POTS, hEDS, and both POTS and hEDS have higher COMPASS-31 scores than the general population, suggesting a high symptom burden due to dysautonomia, which leads to impaired QoL.
CONCLUSIONS: While studies have examined cardiovascular symptoms and the impact of dysautonomia in adults with and without hEDS, there is scant literature on dysautonomia in pediatric patients with hEDS. Therefore, more studies on cardiovascular symptoms and dysautonomia, as they relate to the quality of life in pediatric patients with hEDS, are needed. This brief review summarizes the current literature on dysautonomia and cardiovascular symptoms in pediatric and adult populations with hEDS.

Conditions such as hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndrome (EDS) are most often diagnosed when an individual has joint flexibility beyond the normal physiological limits. Additional characteristics and symptoms include pain and fatigue with individuals also being more likely to report feelings of anxiety and depression. Due to the varied presentation of these conditions, there is a lack of understanding amongst the various healthcare professionals (HCPs) individuals present to, leading to delayed diagnoses and negative experiences for the individuals themselves. This scoping review therefore aims to map the known biopsychosocial impact of adults with HSD and EDS.
The scoping review will follow the six-step framework as outlined by Arskey and O\'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) checklist. The search will be conducted using the following databases: AMED, CINAHL, Cochrane Library, Embase, MEDLINE, PsycINFO, PubMed PEDro. Full-text published articles in the English language (excluding literature and systematic reviews) with adult samples (over the age of 18 years) and a diagnosis of a HSD or EDS, published between 2012 and 2022, will be included in the review.
This review will aim to explore the existing literature for the reported biopsychosocial impact of adults with a HSD or EDS. It will also aim to further acknowledge the gaps in understanding of the condition, how the condition and the impact of the condition is being measured and what HCPs are involved in supporting such individuals. These gaps will be used to inform a future systematic review. It is the overall goal to increase the knowledge of HCPs and the quality of life of adults living with a joint hypermobility condition.

Hypermobility spectrum disorders (HSD) affect individuals across physical, psychological and social domains, making assessment and management difficult. Management for this condition primarily focuses on addressing the musculoskeletal complaints using physiotherapy rather than the additional manifestations such as fatigue, anxiety and depression. This systematic review aims to identify psychological interventions and assess whether they improve the lived experiences of individuals with HSD. It also aims to assess which psychological interventions were most effective, which symptoms were most effectively managed by a psychological intervention, and whether there were differences between children and adults. Studies were included if they were a randomised controlled trial or pre/post-test design, a sample of any age and clinical diagnosis of HSD (including Ehlers-Danlos syndrome), used a psychological intervention and assessed the effect of the intervention on lived experiences using appropriate outcome measures. Risk of bias was assessed using the Mixed Methods Appraisal Tool. The results were narratively synthesised. Six studies were included in the review, one isolated psychological intervention and five incorporated a psychological intervention within a multidisciplinary programme. The interventions predominantly aimed to reduce pain including intensity, interference, pain-related fear and catastrophising, with anxiety and depression, affect, daily living, fatigue also being evaluated. The most beneficial psychological interventions were those delivered alongside physiotherapy in an outpatient or community setting, improving both the physical and psychological aspects of pain, subsequently improving quality of life. However, there lacks randomised controlled trials with larger samples to definitively confirm the significant findings discussed in this review.

Connective tissue disorders, including Marfan syndrome (MS) and Ehlers-Danlos syndrome (EDS), are characterized by genetic mutations affecting connective tissue structural integrity. These disorders significantly elevate the risk of aortic dissection, a life-threatening condition. This comprehensive review delves into the intricate interplay between connective tissue disorders and aortic dissection, shedding light on the clinical features, pathophysiology, genetic underpinnings, diagnostic approaches, clinical management, associated comorbidities, and prognosis, mainly focusing on MS and EDS, while also exploring rare connective tissue disorders and forms of cutis laxa contributing to aortic pathology.