Muscle Strength, Muscle Mass and Physical Impairment in Women with hypermobile Ehlers-Danlos syndrome and Hypermobility Spectrum Disorder.

OBJECTIVES: To evaluate differences in physical impairment, muscle strength, muscle mass and muscle density between patients with hypermobile Ehlers Danlos Syndrome (hEDS), hypermobile spectrum disorder (HSD), and healthy controls. METHODS: Female adults with hEDS (n=20) and HSD (n=23), diagnosed to the most recent criteria, and age-matched healthy controls (n=28) completed the Arthritis Impact Measurement Scale (physical functioning) and performed maximal muscle strength and strength endurance tests of lower and upper limbs (hand grip, posture maintenance, 30 seconds chair rise and isokinetic tests). Muscle mass and density were evaluated by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. RESULTS: No differences in physical functioning and muscle strength were found between adults with hEDS and HSD. Furthermore, no differences in muscle mass and density were observed between the three groups. Nevertheless, when both patient groups were compared to controls, physical functioning, maximal muscle strength and muscle strength endurance were significantly lower (all p<0.001), except for the hand flexors. CONCLUSION: Physical functioning, muscle strength, density and mass did not significantly differ between individuals with hEDS and HSD. Compared to controls, physical functioning and muscle strength (maximal and endurance) were significantly lower. Consequently, (functional) strength training in individuals with hEDS and HSD is necessary.

International Perspectives on Joint Hypermobility: A Synthesis of Current Science to Guide Clinical and Research Directions.

ABSTRACT: There is exponential clinical and research interest in joint hypermobility due to recognition of the complexity of identification, assessment, and its appropriate referral pathways, ultimately impacting management. This state-of-the-science review provides an international, multidisciplinary perspective on the presentation, etiology, and assessment of joint hypermobility, as it presents in those with and without a systemic condition. We synthesize the literature, propose standardizing the use of terminology and outcome measures, and suggest potential management directions. The major topics covered are (i) historical perspectives; (ii) current definitions of hypermobility, laxity, and instability; (iii) inheritance and acquisition of hypermobility; (iv) traditional and novel assessments; (v) strengths and limitations of current assessment tools; (vi) age, sex, and racial considerations; (vii) phenotypic presentations; (viii) generalized hypermobility spectrum disorder and hypermobility Ehlers-Danlos syndrome; and (ix) clinical implications and research directions. A thorough understanding of these topics will equip the reader seeking to manage individuals presenting with joint hypermobility, while mindful of its etiology. Management of generalized joint hypermobility in the context of a complex, multisystem condition will differ from that of acquired hypermobility commonly seen in performing artists, specific athletic populations, posttrauma, and so on. In addition, people with symptomatic hypermobility present predominantly with musculoskeletal symptoms and sometimes systemic symptoms including fatigue, orthostatic intolerance, and gastrointestinal or genitourinary issues. Some also display skeletal deformities, tissue and skin fragility, and structural vascular or cardiac differences, and these warrant further medical follow-up. This comprehensive review on the full spectrum of joint hypermobility will assist clinicians, coaches/sports trainers, educators, and/or researchers in this area.

Clinical and molecular characteristics of 168 probands and 65 relatives with a clinical presentation of classical Ehlers-Danlos syndrome.

Classical Ehlers-Danlos syndrome (cEDS) is a heritable connective tissue disorder mainly caused by pathogenic variants in COL5A1 or COL5A2, encoding type V collagen. Its diagnosis, based on clinical criteria and molecular confirmation, can be challenging. We report the molecular and clinical characteristics of 168 probands (72 clinically evaluated at our center) and 65 relatives with a clinical presentation of cEDS. Type V collagen defects were found in 145 probands, 121 (83.5%) were located in COL5A1 and 24 (16.5%) in COL5A2. Although 85.6% of molecularly confirmed patients presented the two major clinical criteria (generalized joint hypermobility, hyperextensible skin with atrophic scarring), significant inter- and intrafamilial phenotypic variability was noted. COL5A2 variants often caused a more severe phenotype. Vascular complications were rare in individuals with type V collagen defects (1.4%). Among the 72 probands clinically evaluated in our center, the mutation detection rate was 82.0%. The majority (68.1%) harbored COL5A1/COL5A2 defects. Yet, 13.9% harbored a defect in another gene (COL1A1, PLOD1, TNXB, AEBP1) highlighting important clinical overlap and the need for molecular confirmation of the diagnosis as this has implications regarding follow-up and genetic counseling. Eighteen percent of the 72 probands remained molecularly unexplained and a COL5A1 variant of unknown significance was identified in 6.9%.

Pain in the Ehlers-Danlos syndromes: Mechanisms, models, and challenges.

Chronic pain is one of the most common, yet poorly studied, complaints in people suffering from Ehlers-Danlos syndromes (EDS). This heterogeneous group of heritable connective tissue disorders is typically characterized by skin hyperextensibility, joint hypermobility, and generalized connective tissue fragility. Most EDS types are caused by genetic defects that affect connective tissue biosynthesis, thereby compromising collagen biosynthesis or fibrillogenesis and resulting in a disorganized extracellular matrix. Even though chronic pain is a major source of disability, functional impairment, and psychosocial suffering in EDS, currently used analgesics and other treatment strategies provide inadequate pain relief and thus represents an important unmet medical need. An important contributor to this is the lack of knowledge about the underlying mechanisms. In this narrative review, we summarize the current understanding of pain and the associated mechanisms in EDS based on clinical studies focusing on questionnaires and experimental pain testing as well as studies in animal models of EDS. In addition, we highlight the challenges, gaps, and opportunities in EDS-pain research.

Bi-allelic AEBP1 mutations in two patients with Ehlers-Danlos syndrome.

The Ehlers-Danlos syndromes (EDSs) are a clinically and molecularly diverse group of heritable connective tissue disorders caused by defects in a wide range of genes. Recently, bi-allelic loss-of-function mutations in the adipocyte enhancer-binding protein 1 (AEBP1) gene were reported in three families with an autosomal recessive EDS-like condition characterized by thin and hyperextensible skin, poor wound healing with prominent atrophic scarring, joint hypermobility and osteoporosis. Using whole exome sequencing, we identified novel bi-allelic AEBP1 variants in two unrelated adult patients, previously diagnosed with an undefined EDS type, which shows important clinical resemblance to several other EDS subtypes. Our patients present with similar cutaneous and musculoskeletal features as the previously reported patients. They also show unreported clinical features, including pectus deformity, premature aged appearance, sparse and frizzled hair, fatigue and pain. AEBP1 is ubiquitously expressed and encodes the secreted aortic carboxypeptidase-like protein (ACLP) that can bind fibrillar collagens and assist in collagen polymerization. Transmission electron microscopy studies on the patients' skin biopsies show ultrastructural alterations in collagen fibril diameter and appearance, underscoring an important role for ACLP in collagen fibril organization. This report further expands the clinical, molecular and ultrastructural spectrum associated with AEBP1 defects and highlights the complex and variable phenotype associated with this new EDS variant.

Subacromial space outlet in female patients with multidirectional instability based on hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder measured by ultrasound.

OBJECTIVE: The objective of the study was to compare the acromiohumeral distance (AHD) between patients diagnosed with hypermobility type of the Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSD) and healthy controls by evaluating the relative amount the tendon occupies in the subacromial area. Furthermore, the aim was to evaluate if there was a change in AHD with arm elevation within and between groups. METHODS: Twenty-nine female patients with hEDS/HSD (aged 34 ± 12.9 years) and 20 healthy controls (aged 33 ± 10.8 years) participated in the study. The supraspinatus tendon (SST) thickness and AHD were measured using ultrasound. The interplay between the SST and the AHD was expressed as the occupation ratio (OcAHD), calculated as the SST thickness as a percentage of AHD. The measures were performed in the resting position and in subsequently 45° and 60° of active arm elevation in the scapular plane. RESULTS: The main finding is that patients with hEDS/HSD have a larger subacromial space outlet compared with the controls when measured by ultrasound. Furthermore, in both groups, we found an increased OcAHD during active arm elevation compared with the resting position, which indicates that similar mechanisms occur for patients with hEDS/HSD and healthy controls. CONCLUSION: Patients with hEDS/HSD have a larger available subacromial space outlet compared with healthy individuals. OcAHD increased during active arm elevation compared with the resting position in both groups. This knowledge is important when designing rehabilitation exercise programs for shoulder instability patients with abnormal glenohumeral biomechanics.

Correction: Arterial tortuosity syndrome: 40 new families and literature review.

In the published version of this paper the author Neus Baena's name was incorrectly given as Neus Baena Diez. This has now been corrected in both the HTML and PDF versions of the paper.

Arterial tortuosity syndrome: 40 new families and literature review.

PURPOSE: We delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10. METHODS: We retrospectively characterized 40 novel ATS families (50 patients) and reviewed the 52 previously reported patients. We performed histology and electron microscopy (EM) on skin and vascular biopsies and evaluated TGF-ß signaling with immunohistochemistry for pSMAD2 and CTGF. RESULTS: Stenoses, tortuosity, and aneurysm formation are widespread occurrences. Severe but rare vascular complications include early and aggressive aortic root aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric perforation. Thus far, no reports unequivocally document vascular dissections or ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome (IRDS) are frequently observed. Skin and vascular biopsies show fragmented elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a fragmented elastin core and a peripheral mantle of microfibrils of random directionality. Skin and end-stage diseased vascular tissue do not indicate increased TGF-ß signaling. CONCLUSION: Our findings warrant attention for IRDS and diaphragmatic hernia, close monitoring of the aortic root early in life, and extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific abnormalities.

Cardiac Autonomic Function and Reactivity Tests in Physically Active Subjects with Moderately Severe COPD.

Patients with chronic obstructive pulmonary disease (COPD) show impairments in the autonomic nervous systems (ANS) function, which is responsible for cardiac autonomic regulation. This study assessed the autonomic function and cardio-vagal reactivity in conveniently sampled subjects with COPD participating in a pulmonary rehabilitation (PR) program. Twenty-six subjects with COPD and 22 age and gender matched control subjects were evaluated. R-R intervals were collected at rest in supine position. Thereafter, resting autonomic function parameters comprising linear and nonlinear analyses of heart rate variability (HRV) and baroreceptor sensitivity (BRS) were calculated. Autonomic reactivity tests comprising deep breathing (DB), Valsalva maneuver (VM), and head up tilt (HUT) were also performed. The results of this study indicated that resting autonomic function variables were generally reduced in COPD compared to controls. However, this difference was only statistically significant for a few HRV parameters: mean RR intervals, low frequency (LF), standard deviation of dispersion of points perpendicular to the line-of-identity (SD1), and approximate entropy (ApEn) (p < 0.05). The results also indicated that all cardio-vagal indices following the autonomic reactivity tests were comparable between COPD and controls (p > 0.05). It was concluded that subtle autonomic impairments exists in physically active COPD patients, and these autonomic function deficits were mainly recognized by resting HRV indices and not autonomic reactivity tests.

Cardiovascular autonomic dysfunction in Ehlers-Danlos syndrome-Hypermobile type.

Autonomic dysfunction contributes to health-related impairment of quality of life in the hypermobile type of Ehlers-Danlos syndrome (hEDS). Typical signs and symptoms include tachycardia, hypotension, gastrointestinal dysmotility, and disturbed bladder function and sweating regulation. Cardiovascular autonomic dysfunction may present as Orthostatic Intolerance, Orthostatic Hypotension, Postural Orthostatic Tachycardia Syndrome, or Neurally Mediated Hypotension. The incidence, prevalence, and natural history of these conditions remain unquantified, but observations from specialist clinics suggest they are frequently seen in hEDS. There is growing understanding of how hEDS-related physical and physiological pathology contributes to the development of these conditions. Evaluation of cardiovascular symptoms in hEDS should include a careful history and clinical examination. Tests of cardiovascular function range from clinic room observation to tilt-table assessment to other laboratory investigations such as supine and standing catecholamine levels. Non-pharmacologic treatments include education, managing the environment to reduce exposure to triggers, improving cardiovascular fitness, and maintaining hydration. Although there are limited clinical trials, the response to drug treatments in hEDS is supported by evidence from case and cohort observational data, and short-term physiological studies. Pharmacologic therapy is indicated for patients with moderate-severe impairment of daily function and who have inadequate response or tolerance to conservative treatment. Treatment in hEDS often requires a focus on functional maintenance. Also, the negative impact of cardiovascular symptoms on physical and psycho-social well-being may generate a need for a more general evaluation and on-going management and support. © 2017 Wiley Periodicals, Inc.

Chronic fatigue in Ehlers-Danlos syndrome-Hypermobile type.

Chronic fatigue is an important contributor to impaired health-related quality of life in Ehlers-Danlos syndrome. There is overlap in the symptoms and findings of EDS and chronic fatigue syndrome. A proportion of those with CFS likely have EDS that has not been identified. The evaluation of chronic fatigue in EDS needs to include a careful clinical examination and laboratory testing to exclude common causes of fatigue including anemia, hypothyroidisim, and chronic infection, as well as dysfunction of major physiological or organ systems. Other problems that commonly contribute to fatigue in EDS include sleep disorders, chronic pain, deconditioning, cardiovascular autonomic dysfunction, bowel and bladder dysfunction, psychological issues, and nutritional deficiencies. While there is no specific pharmacological treatment for fatigue, many medications are effective for specific symptoms (such as headache, menstrual dysfunction, or myalgia) and for co-morbid conditions that result in fatigue, including orthostatic intolerance and insomnia. Comprehensive treatment of fatigue needs to also evaluate for biomechanical problems that are common in EDS, and usually involves skilled physical therapy and attention to methods to prevent deconditioning. In addition to managing specific symptoms, treatment of fatigue in EDS also needs to focus on maintaining function and providing social, physical, and nutritional support, as well as providing on-going medical evaluation of new problems and review of new evidence about proposed treatments. © 2017 Wiley Periodicals, Inc.

The evidence-based rationale for physical therapy treatment of children, adolescents, and adults diagnosed with joint hypermobility syndrome/hypermobile Ehlers Danlos syndrome.

New insights into the phenotype of Joint Hypermobility Syndrome (JHS) and Ehlers-Danlos Syndrome-hypermobile type (hEDS) have raised many issues in relation to classification, diagnosis, assessment, and treatment. Within the multidisciplinary team, physical therapy plays a central role in management of individuals with hypermobility related disorders. However, many physical therapists are not familiar with the diagnostic criteria, prevalence, common clinical presentation, and management. This guideline aims to provide practitioners with the state of the art regarding the assessment and management of children, adolescents, and adults with JHS/hEDS. Due to the complexity of the symptoms in the profile of JHS/hEDS, the International Classification of Functioning, Disability and Health (ICF) is adopted as a central framework whereby the umbrella term of disability is used to encompass functions, activities and participation, as well as environmental and personal factors. The current evidence-based literature regarding the management of JHS/hEDS is limited in size and quality and there is insufficient research exploring the clinical outcomes of a number of interventions. Multicenter randomized controlled trials are warranted to assess the clinical and cost-effectiveness of interventions for children and adults. Until further multicenter trials are conducted, clinical decision-making should be based on theoretical and the current limited research evidence. For all individuals diagnosed with JHS/hEDS, international consensus and combined efforts to identify risk profiles would create a better understanding of the pathological mechanisms and the potential for optimizing health care for affected individuals. © 2017 Wiley Periodicals, Inc.

Hypermobility, the Ehlers-Danlos syndromes and chronic pain.

Chronic widespread pain is a common complaint among individuals affected by generalised joint hypermobility. In the absence of other conditions that cause chronic pain, these individuals are usually diagnosed with joint hypermobility syndrome (JHS). JHS is a multifactorial trait with a strong genetic basis, but no specific genetic markers. Clinical overlap of JHS is seen with heritable connective tissue disorders, particularly with the Ehlers-Danlos syndrome, hypermobile type (hEDS). The Ehlers-Danlos syndromes (EDS) comprise a heterogeneous group of rare monogenic conditions that are characterised by joint hypermobility, skin and vascular fragility and generalised connective tissue friability, and are caused by genetic defects in an array of extracellular matrix genes. The genetic basis of hEDS remains however unknown, in contrast to other well-described EDS subtypes. In view of the considerable clinical overlap with JHS, many consider it and hEDS to be a single clinical entity. Clinical experience and a limited number of clinical studies show that chronic pain also is common in EDS patients, especially in hEDS. The specific underlying causes and mechanisms of pain in JHS and EDS remain poorly understood. Factors likely contributing to the generation and chronicity of pain include nociceptive pain, directly based on structural changes in affected joints, muscle and connective tissue; neuropathic pain; impaired proprioception and muscle weakness; and central sensitisation. These mechanisms are not mutually exclusive, and likely more than one mechanism may be present. Furthermore, anxiety, depression, and other variables may influence the phenotype. Chronic pain in JHS and EDS patients often is inadequately controlled by traditional analgesics and physical therapy. In view of the high prevalence of these underrecognised conditions, future studies addressing the nature and mediators of chronic pain are needed in order to potentially identify novel targets for therapeutic intervention and optimise treatment.

Orthostatic intolerance and fatigue in the hypermobility type of Ehlers-Danlos Syndrome.

OBJECTIVE: To investigate whether orthostatic intolerance (OI) is a significant predictor for fatigue in Ehlers-Danlos Syndrome, hypermobility type (EDS-HT). METHODS: Eighty patients with EDS-HT and 52 controls participated in the first part of the study, which consisted of questionnaires. Fatigue was evaluated using the Checklist Individual Strength (CIS). As possible fatigue determinants OI [Autonomic Symptom Profile (ASP)], habitual physical activity (Baecke), affective distress [Hospital Anxiety and Depression Scale (HADS)], pain (SF36), medication use and generalized hypermobility (5-point score of Grahame and Hakim regarding generalized joint hypermobility) were studied. Next, a 20 min head-up tilt (70°) was performed in a subsample of 39 patients and 35 controls, while beat-to-beat heart rate and blood pressure were monitored (Holter, Finometer Pro). Before and after tilt, fatigue severity was assessed using a numeric rating scale. RESULTS: Patients scored significantly higher on the CIS [total score: EDS: 98.2 (18.63) vs controls: 45.8 (16.62), P < 0.001] and on the OI domain of the ASP [EDS: 22.78 (7.16) vs controls: 6.5 (7.78)]. OI was prevalent in EDS-HT (EDS: 74.4%, controls: 34.3%, P = 0.001), and frequently expressed as postural orthostatic tachycardia (41.0% of the EDS group). Patients responded to tilt with a higher heart rate and lower total peripheral resistance (p < 0.001; p = 0.032). This altered response correlated with fatigue in daily life (CIS). In the EDS-HT group, tilt provoked significantly more fatigue [numeric rating scale increase: EDS: +3.1 (1.90), controls: +0.5 (1.24), P < 0.001]. Furthermore, the factors OI, pain, affective distress, decreased physical activity and sedative use explained 47.7% of the variance in fatigue severity. CONCLUSION: OI is an important determinant of fatigue in EDS-HT.

Knowledge, assessment, and management of adults with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type among Flemish physiotherapists.

Physiotherapy plays a fundamental role in managing adults with the joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT). However, it is a challenge for both the patient and the physiotherapist as the condition is poorly understood and treatment for JHS/EDS-HT is currently undefined. Insight into current practice is, therefore, necessary in order to establish baseline knowledge in this area and in the long term to improve the standard of patient care. Therefore, the purpose of this study was to evaluate current physiotherapists' knowledge of JHS/EDS-HT and to gain insight into current physiotherapy practice with emphasis on assessment, management, and treatment efficacy. Three hundred twenty-five Flemish physiotherapists participated in the study by filling out electronically a modified version of the "Hypermobility and Hypermobility Syndrome Questionnaire" (HHQ), which covered theoretical constructs such as general knowledge, assessment, management, and learning in relation to generalized joint hypermobility and JHS/EDS-HT. The results show that physiotherapists report a low level of confidence with regard to assessment and management of JHS/EDS-HT. Knowledge of hypermobility and JHS/EDS-HT is weak, especially regarding the features associated with JHS/EDS-HT. Many treatment approaches are used by physiotherapists with the majority showing preference for education, reassurance, muscle strengthening, proprioceptive and core stability training. Almost all approaches were perceived as being clinically effective by the physiotherapists, highlighting a lack of consensus. In conclusion, this study in Flemish physiotherapists confirms that JHS/EDS-HT is under-recognized, not well known and deemed difficult to treat. Further education is required and sought by the physiotherapists surveyed, and future research is needed.

Impaired muscle parameters in adults with mild to severe types of osteogenesis imperfecta: a cross-sectional study.

Impaired muscle parameters may further compromise the already compromised skeleton in individuals with OI. This cross-sectional study aimed to compare muscle function and body composition in adults with various OI types and healthy controls. Sixty-eight adults with OI (mean age 42.2 yr; 27 men) and 68 healthy age- and sex-matched controls were recruited. Maximal isometric muscle force was assessed by handheld dynamometry (hand grip, hip flexors, shoulder abductors, and ankle dorsiflexors), muscle endurance by posture maintenance tests (shoulder abduction, hip flexion, and wall sit), and functional lower limb strength by 30-s chair rise test. In a sub cohort, dynamic muscle function (peak power and force) was assessed by a ground reaction force plate, and lean and fat mass, muscle and fat cross-sectional area (CSA), and muscle density by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Multiple linear regression models were fitted with group (OI type I, III, IV/V, or controls), country, sex, and age in the fixed effects part. Overall, adults with various types of OI had lower isometric, endurance, and functional muscle strength (mean difference [MD] = OI type I: 19-43%, OI type IV/V: 25-68%, OI type III: 20-72%) compared to controls. Furthermore, adults with OI type I had lower dynamic muscle function (peak force [MD = 25-29%] and power [MD = 18-60%]), lean mass (MD = 10-17%), muscle CSA (MD = 9-21%), and muscle density (MD = 2-3%) but higher adiposity indices (MD = 24-42%) compared to controls. Functional lower limb strength and maximal muscle force were significantly different between OI types, whereas muscle endurance was not. To conclude, adults with OI present with markedly impaired muscle function which may partially be explained by their altered body composition. Our findings emphasize the need for proper assessment of various muscle parameters and (research into) appropriate and safe muscle strengthening approaches in this population.

Home-based exercise therapy for treating shoulder instability in patients with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders. A randomized trial.

PURPOSE: To investigate the effectiveness of two home-based exercise programs for treating multidirectional shoulder instability (MDI) in patients diagnosed with Hypermobile Ehlers-Danlos syndrome (hEDS) or Hypermobility Spectrum Disorders (HSD). METHODS: Twenty-one hEDS/HSD patients with MDI were recruited from the Center for Medical Genetics of the Ghent University Hospital. Patients were randomly assigned to either the experimental or the control group. Both groups received a 6-month home-based exercise program. The primary outcome measure was the Western Ontario Shoulder Index (WOSI). Secondary outcomes included the Disabilities of the Arm, Shoulder and Hand (DASH), Tampa Scale for Kinesiophobia (TSK), Patient-Specific Functional Scale (PSFS), Global Rating of Change (GROC), and pain pressure thresholds. Outcomes were assessed at baseline, after 6 weeks, 12 weeks, and 24 weeks. RESULTS: Significant main effects for time were observed for all questionnaires, except for the TSK (p = 0.12). Patients improved 240 and 325 points on the WOSI after 12 (p = 0.02) and 24 weeks (p = 0.001), respectively. Additionally, patients improved 8.6 points on the DASH (p = 0.002), 4.3 points on the PSFS (p = 0.01), and 1.02 points on the GROC (p = 0.001) after 24 weeks. CONCLUSION: No significant differences were found between group A and B. Both home-based exercise programs led to significant improvements in shoulder function. IMPLICATIONS FOR REHABILITATIONHome-based exercise therapy may be effective for treating MDI in the hEDS/HSD population.Home-based training is beneficial for improving shoulder function, but a multidisciplinary, supervised approach might be more effective for altering kinesiophobia in this patient population.

Bone parameters in hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder: A comparative cross-sectional study.

OBJECTIVE: To compare bone parameters between individuals with hypermobile Ehlers-Danlos syndrome (hEDS) and generalized joint hypermobility spectrum disorder (G-HSD), both diagnosed according to the most recent diagnostic criteria, and with controls. METHODS: Twenty female adults with hEDS (mean age 43.8 years), 20 with G-HSD (mean age 41.8 years), and 37 healthy controls (mean age 40.8 years) participated. Body composition and bone parameters at whole body and lumbar spine were assessed by dual-energy X-ray absorptiometry. Peripheral quantitative computed tomography at the lower leg evaluated body composition (66 % site), and trabecular (4 % site) and cortical (66 % site) bone parameters at the tibia. RESULTS: No significantly different body composition and bone parameters were observed between hEDS and G-HSD. Compared to controls, individuals with hEDS and G-HSD had lower muscle mass (p = 0.004 and p < 0.001, respectively) and cross-sectional area (p = 0.025 and p < 0.001, respectively), cortical bone mineral content (BMC; p = 0.024 and p = 0.027, respectively) and area (p = 0.019 and p = 0.010, respectively). Additionally, individuals with hEDS had lower muscle density (p = 0.009), trabecular BMC (p = 0.027) and bone mineral density (p = 0.022), and individuals with G-HSD lower stress-strain index (p = 0.019), and periosteal and endosteal circumference (p = 0.002 and 0.025, respectively), compared to controls. CONCLUSION: Results indicated lower cortical bone mineral content and smaller cortices in hEDS and G-HSD compared to controls. Individuals with hEDS and G-HSD had no different bone parameters, suggesting that these impairments might not be reflected by the different diagnostic classification. Therefore, we recommend regular physical activity, and training to reduce the risk of falling in both hEDS or G-HSD.

Sensory profiling in classical Ehlers-Danlos syndrome: a case-control study revealing pain characteristics, somatosensory changes, and impaired pain modulation.

Pain is one of the most important, yet poorly understood complaints in heritable connective tissue disorders (HCTD) caused by monogenic defects in extracellular matrix molecules. This is particularly the case for Ehlers-Danlos syndromes (EDS), paradigm collagen-related disorders. This study aimed to identify the pain signature and somatosensory characteristics in the rare classical type of EDS (cEDS) caused by defects in type V or rarely type I collagen. We used static and dynamic quantitative sensory testing and validated questionnaires in 19 individuals with cEDS and 19 matched controls. Individuals with cEDS reported clinically relevant pain/discomfort (VAS ≥5/10 in 32% for average pain intensity the past month) and worse health -related quality of life. Altered sensory profile was found in the cEDS group with higher (p=0.04) detection thresholds for vibration stimuli at the lower limb indicating hypoesthesia, reduced thermal sensitivity with more (p<0.001) paradoxical thermal sensations, and hyperalgesia with lower pain thresholds to mechanical (p<0.001) stimuli at both the upper and lower limbs and to cold (p=0.005) stimulation at the lower limb. Using a parallel conditioned pain paradigm, the cEDS group showed significantly smaller antinociceptive responses (p-value between 0.005 and 0.046) suggestive of impaired endogenous central pain modulation. In conclusion, Individuals with cEDS report chronic pain and worse health-related quality of life, and present altered somatosensory perception. This study is the first to systematically investigate pain and somatosensory characteristics in a genetically defined HCTD and provides interesting insights on the possible role of the ECM in the development and persistence of pain.

Sensory Profiling in Classical Ehlers-Danlos Syndrome: A Case-Control Study Revealing Pain Characteristics, Somatosensory Changes, and Impaired Pain Modulation.

Pain is one of the most important yet poorly understood complaints in heritable connective tissue disorders (HCTDs) caused by monogenic defects in extracellular matrix molecules. This is particularly the case for the Ehlers-Danlos syndrome (EDS), paradigm collagen-related disorders. This study aimed to identify the pain signature and somatosensory characteristics in the rare classical type of EDS (cEDS) caused by defects in type V or rarely type I collagen. We used static and dynamic quantitative sensory testing and validated questionnaires in 19 individuals with cEDS and 19 matched controls. Individuals with cEDS reported clinically relevant pain/discomfort (Visual Analogue Scale ≥5/10 in 32% for average pain intensity the past month) and worse health-related quality of life. An altered somatosensory profile was found in the cEDS group with higher (P = .04) detection thresholds for vibration stimuli at the lower limb, indicating hypoesthesia, reduced thermal sensitivity with more (P < .001) paradoxical thermal sensations (PTSs), and hyperalgesia with lower pain thresholds to mechanical (P < .001) stimuli at both the upper and lower limbs and cold (P = .005) stimulation at the lower limb. Using a parallel conditioned pain modulation paradigm, the cEDS group showed significantly smaller antinociceptive responses (P-value .005-.046) suggestive of impaired endogenous pain modulation. In conclusion, individuals with cEDS report chronic pain and worse health-related quality of life and present altered somatosensory perception. This study is the first to systematically investigate pain and somatosensory characteristics in a genetically defined HCTD and provides interesting insights into the possible role of the ECM in the development and persistence of pain. PERSPECTIVE: Chronic pain compromises the quality of life in individuals with cEDS. Moreover, an altered somatosensory perception was found in the cEDS group with hypoesthesia for vibration stimuli, more PTSs, hyperalgesia for pressure stimuli, and impaired pain modulation.