Chronic Pain and Joint Hypermobility: A Brief Diagnostic Review for Clinicians and the Potential Application of Infrared Thermography in Screening Hypermobile Inflamed Joints.

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.

Hybridized deep learning goniometry for improved precision in Ehlers-Danlos Syndrome (EDS) evaluation.

BACKGROUND: Generalized Joint Hyper-mobility (GJH) can aid in the diagnosis of Ehlers-Danlos Syndrome (EDS), a complex genetic connective tissue disorder with clinical features that can mimic other disease processes. Our study focuses on developing a unique image-based goniometry system, the HybridPoseNet, which utilizes a hybrid deep learning model. OBJECTIVE: The proposed model is designed to provide the most accurate joint angle measurements in EDS appraisals. Using a hybrid of CNNs and HyperLSTMs in the pose estimation module of HybridPoseNet offers superior generalization and time consistency properties, setting it apart from existing complex libraries. METHODOLOGY: HybridPoseNet integrates the spatial pattern recognition prowess of MobileNet-V2 with the sequential data processing capability of HyperLSTM units. The system captures the dynamic nature of joint motion by creating a model that learns from individual frames and the sequence of movements. The CNN module of HybridPoseNet was trained on a large and diverse data set before the fine-tuning of video data involving 50 individuals visiting the EDS clinic, focusing on joints that can hyperextend. HyperLSTMs have been incorporated in video frames to avoid any time breakage in joint angle estimation in consecutive frames. The model performance was evaluated using Spearman's coefficient correlation versus manual goniometry measurements, as well as by the human labeling of joint position, the second validation step. OUTCOME: Preliminary findings demonstrate HybridPoseNet achieving a remarkable correlation with manual Goniometric measurements: thumb (rho = 0.847), elbows (rho = 0.822), knees (rho = 0.839), and fifth fingers (rho = 0.896), indicating that the newest model is considerably better. The model manifested a consistent performance in all joint assessments, hence not requiring selecting a variety of pose-measuring libraries for every joint. The presentation of HybridPoseNet contributes to achieving a combined and normalized approach to reviewing the mobility of joints, which has an overall enhancement of approximately 20% in accuracy compared to the regular pose estimation libraries. This innovation is very valuable to the field of medical diagnostics of connective tissue diseases and a vast improvement to its understanding.

Risk factors associated with symptoms of temporomandibular disorders among women with hypermobile Ehlers-Danlos syndrome: Questionnaire-based study in Finland and Sweden.

BACKGROUND: Generalized joint hypermobility as a characteristic feature of Ehlers-Danlos syndromes (EDS) is among the factors contributing to temporomandibular disorders (TMD). OBJECTIVE: To evaluate the prevalence of TMD symptoms and their risk factors among women born in Sweden or Finland who were 27- to 78-year-olds with diagnosed hypermobile EDS (hEDS). METHODS: A cohort of women with confirmed hEDS (n = 185) was constructed from the members of the National EDS Associations in both countries. Based on questionnaire data, frequency of independent variables in terms of socio-demographic, general health and oral health-related factors, comorbid symptoms and psychological distress for self-reported TMD symptoms as the dependent variables, were calculated first. Prevalence ratios (PR) and their 95% confidence interval (95% CI) were estimated for the association between independent and dependent variables. RESULTS: Nearly all participants reported TMD symptoms (98%) with TMD pain (95%), TMJ clicking (90%) and jaw fatigue (80%) as the most common symptoms and TMJ crepitation (63%) and luxation (44%) as the least common symptoms. Risk factors for TMD among 27- to 50-year-olds participants were Finland as a country of birth, living alone and self-reported worst pain in the body (not the joints). The respective risk factors among the 51- to 78-year-olds were Finland as a country of birth, family history of EDS, tinnitus and regularly taking contraceptives. CONCLUSIONS: Among adult women with confirmed hEDS, socio-demographic and health-related factors and comorbid symptoms were significantly associated with TMD but with differences regarding age group. Therefore, management of TMD requires a multidisciplinary approach among the affected.

The use and effectiveness of exercise for managing postural orthostatic tachycardia syndrome in young adults with joint hypermobility and related conditions: A scoping review.

PURPOSE: 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. CONCLUSION: 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.

Are patients with hypermobile Ehlers-Danlos syndrome or hypermobility spectrum disorder so different?

Diagnosing hypermobile Ehlers-Danlos syndrome (hEDS) remains challenging, despite new 2017 criteria. Patients not fulfilling these criteria are considered to have hypermobile spectrum disorder (HSD). Our first aim was to evaluate whether patients hEDS were more severely affected and had higher prevalence of extra-articular manifestations than HSD. Second aim was to compare their outcome after coordinated physical therapy. Patients fulfilling hEDS/HSD criteria were included in this real-life prospective cohort (November 2017/April 2019). They completed a 16-item Clinical Severity Score (CSS-16). We recorded bone involvement, neuropathic pain (DN4) and symptoms of mast cell disorders (MCAS) as extra-articular manifestations. After a standardized initial evaluation (T0), all patients were offered the same coordinated physical therapy, were followed-up at 6 months (T1) and at least 1 year later (T2), and were asked whether or not their condition had subjectively improved at T2. We included 97 patients (61 hEDS, 36 HSD). Median age was 40 (range 18-73); 92.7% were females. Three items from CSS-16 (pain, motricity problems, and bleeding) were significantly more severe with hEDS than HSD. Bone fragility, neuropathic pain and MCAS were equally prevalent. At T2 (20 months [range 18-26]) 54% of patients reported improvement (no difference between groups). On multivariable analysis, only family history of hypermobility predicted (favorable) outcome (p = 0.01). hEDS and HDS patients showed similar disease severity score except for pain, motricity problems and bleeding, and similar spectrum of extra-articular manifestations. Long-term improvement was observed in > 50% of patients in both groups. These results add weight to a clinical pragmatic proposition to consider hEDS/HSD as a single entity that requires the same treatments.

Dysautonomia in hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders is associated with exercise intolerance and cardiac atrophy.

Dysautonomia is a recognized manifestation in patients with joint hypermobility (JH) disorders. Symptoms can be highly debilitating and commonly include physical deconditioning and poor aerobic fitness. In this study, the prevalence of dysautonomia, range of associated symptoms, patient-reported physical activity levels, and echocardiographic features were assessed retrospectively in a cohort of 144 patients (94% female) with hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSD). Echocardiographic parameters of left ventricular size and function were compared between patients with and without dysautonomia as well as to reported values from healthy controls. Dysautonomia was identified in 65% of female and 44% of male subjects and was associated with a high burden of symptomatology, most commonly exercise intolerance (78%). Exercise capacity was limited by dysautonomia, often postural symptoms, in half of all patients. We observed a reduction in physical activity following the onset or significant flare of hEDS/HSD, most strikingly noting the proportion of dysautonomic patients with sedentary lifestyle, which increased from 44% to 85%. JH-related dysautonomia was associated with smaller cardiac chamber sizes, consistent with the previous reports in positional orthostatic tachycardia syndrome. Dysautonomia is prevalent in patients with hEDS/HSD, and exercise intolerance is a key feature and leads to drastic decline in physical activity. Unfavorable cardiac geometry may underlie dysautonomia symptoms and may be due to cardiac atrophy in the setting of aerobic deconditioning.

Pain Management through Neurocognitive Therapeutic Exercises in Hypermobile Ehlers-Danlos Syndrome Patients with Chronic Low Back Pain.

BACKGROUND: The hypermobile type of Ehlers-Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue mainly characterized by joint hypermobility. Patients with hEDS suffer joint pain, in particular low back pain, commonly resistant to drug therapy. The aim of this research was to evaluate a neurocognitive rehabilitation approach based not only on the motion and function recovery but also on the pain management. METHODS: In this nonrandomized clinical trial, eighteen hEDS patients (4 males and 14 females) with mean age 21 years (range 13-55) were recruited and evaluated before and after three months of rehabilitation treatment. RESULTS: The outcome scores showed significant statistical results after treatment in reducing pain symptoms (numerical rating scale, P = 0.003; McGill (total score), P = 0.03), fatigue (fatigue severity scale, P = 0.03), fear of movement (Tampa scale, P = 0.003), and pain-associated disability (Oswestry disability index, P = 0.03). CONCLUSION: The clinical results observed in our study seem to confirm the role of a specific neurocognitive rehabilitation program in the chronic pain management in the Ehlers-Danlos syndrome; the rehabilitation treatment should be tailored on patient problems and focused not only in the recovery of movement but also on pain perception.

Physical therapy treatment of hypermobile Ehlers-Danlos syndrome: A systematic review.

Physiotherapy techniques are regularly prescribed in the hypermobile type Ehlers-Danlos syndrome (hEDS) and they are appreciated by the patients. The objective of this systematic review was to investigate the effect of the different physiotherapy techniques related to the children and adult patients with hEDS. PubMed, SPORTDiscus, Cochrane Library, PEDro, Scopus, and Embase databases were analyzed from inception to April 2020. Characteristics of the studies (authors), patients (sample size, sex, age, Beighton score), and nonpharmacological treatment (length of the program, number of session, duration of the session, and type of intervention), and the results with the dropout rate were extracted. From the 1045 retrieved references, 6 randomized controlled trial with a sample size ranging from 20 to 57 patients were included in the systematic review. There was a huge heterogeneity in the interventions. The durations of the program were from 4 to 8 weeks. Pain or proprioception demonstrated significant improvements in the intervention group regardless of the type of intervention. A benefit of the inspiratory muscle training was observed on functional exercise capacity. The quality of life was systematically improved. Physiotherapy benefits on proprioception and pain in patients with hEDS even if robust randomized control studies are missing.

Mitral Valve Prolapse and Its Motley Crew-Syndromic Prevalence, Pathophysiology, and Progression of a Common Heart Condition.

Mitral valve prolapse (MVP) is a commonly occurring heart condition defined by enlargement and superior displacement of the mitral valve leaflet(s) during systole. Although commonly seen as a standalone disorder, MVP has also been described in case reports and small studies of patients with various genetic syndromes. In this review, we analyzed the prevalence of MVP within syndromes where an association to MVP has previously been reported. We further discussed the shared biological pathways that cause MVP in these syndromes, as well as how MVP in turn causes a diverse array of cardiac and noncardiac complications. We found 105 studies that identified patients with mitral valve anomalies within 18 different genetic, developmental, and connective tissue diseases. We show that some disorders previously believed to have an increased prevalence of MVP, including osteogenesis imperfecta, fragile X syndrome, Down syndrome, and Pseudoxanthoma elasticum, have few to no studies that use up-to-date diagnostic criteria for the disease and therefore may be overestimating the prevalence of MVP within the syndrome. Additionally, we highlight that in contrast to early studies describing MVP as a benign entity, the clinical course experienced by patients can be heterogeneous and may cause significant cardiovascular morbidity and mortality. Currently only surgical correction of MVP is curative, but it is reserved for severe cases in which irreversible complications of MVP may already be established; therefore, a review of clinical guidelines to allow for earlier surgical intervention may be warranted to lower cardiovascular risk in patients with MVP.

Vascular Ehlers-Danlos Syndrome: Treatment of a Complex Abdominal Wound with Vitamin C and Mesenchymal Stromal Cells.

ABSTRACT: Vascular Ehlers-Danlos syndrome (EDSv) can present with life-threatening surgical complications. The article describes the case of a patient with EDSv who developed total abdominal wound dehiscence and multiple enterocutaneous fistulas. Treatment with IV allogeneic mesenchymal stromal cells (MSCs) and high-dose vitamin C was trialed with success. Near-complete wound healing of the abdominal dehiscence with a 94% reduction in the size of the wound bed occurred. Maturation of the enterocutaneous fistulas also ensued.There is no current consensus on the management of large cutaneous wounds in EDSv. This article discusses the pathophysiology of wound healing with regard to nutrition requirements and growth factors with special reference to collagen deficits in EDSv. A potential therapy with IV vitamin C supplementation and MSCs is proposed following the patient's positive outcome. Medium-dose MSCs and high-dose IV vitamin C may offer significant benefits to complex and problematic wounds.

Copper Toxicity Associated With an ATP7A-Related Complex Phenotype.

BACKGROUND: The ATP7A gene encodes a copper transporter whose mutations cause Menkes disease, occipital horn syndrome (OHS), and, less frequently, ATP7A-related distal hereditary motor neuropathy (dHMN). Here we describe a family with OHS caused by a novel mutation in the ATP7A gene, including a patient with a comorbid dHMN that worsened markedly after being treated with copper histidinate. METHODS: We studied in detail the clinical features of the patients and performed a genomic analysis by using TruSight One Expanded Sequencing Panel. Subsequently, we determined the ATP7A and ATP7B expression levels, mitochondrial membrane potential, and redox balance in cultured fibroblasts of Patient 1. RESULTS: We found a novel ATP7A late truncated mutation p.Lys1412AsnfsX15 in the two affected members of this family. The co-occurrence of OHS and dHMN in Patient 1 reveals the variable phenotypic expressivity of the variant. A severe clinical and neurophysiologic worsening was observed in the dHMN of Patient 1 when he was treated with copper replacement therapy, with a subsequent fast recovery after the copper histidinate was withdrawn. Functional studies revealed that the patient had low levels of both ATP7A and ATP7B, the other copper transporter, and high levels of superoxide ion in the mitochondria. CONCLUSIONS: Our findings broaden the clinical spectrum of ATP7A-related disorders and demonstrate that two clinical phenotypes can occur in the same patient. The copper-induced toxicity and low levels of both ATP7A and ATP7B in our patient suggest that copper accumulation in motor neurons is the pathogenic mechanism in ATP7A-related dHMN.

Spontaneous Cervical Artery Dissection in Vascular Ehlers-Danlos Syndrome: A Cohort Study.

BACKGROUND AND PURPOSE: Vascular Ehlers-Danlos syndrome is a rare inherited connective tissue disorder because of pathogenic variants in the COL3A1 gene. Arterial complications can affect all anatomic areas and about 25% involve supra-aortic trunks (SATs) but no systematic assessment of cervical artery lesions has been made. The primary objective was to determine an accurate prevalence of spontaneous SAT lesions in a large series of patients with vascular Ehlers-Danlos syndrome at diagnosis and during follow-up. Secondary objectives were to study their neurological consequences (transient ischemic attack or stroke) and the possible relationships with sex, genotype, ascertainment status. METHODS: A retrospective review of a monocentric cohort of patients with molecularly proven vascular Ehlers-Danlos syndrome followed in a tertiary referral center from 2000 to 2017. RESULTS: One hundred forty-four patients were analyzed, 56.9% (n=82) had SAT lesions: 64.6% females, 74.4% index-case patients. Most lesions were identified in early arterial assessment (48% at first work-up, mean age of 35.7±13.0 years). Cumulative incidence of a first identification of a SAT lesion was 41.7% at 40 years old. On the complete period of survey, 183 SAT lesions (with 132 dissections and 33 aneurysms) were identified, mainly in internal carotid arteries (56.3%) and vertebral arteries (28.9%), more rarely in patients with COL3A1 null mutations (P=0.008). Transient ischemic attack or stroke were reported in n=16 (19.5%) of the 82 patients with SAT lesions without relation with age, sex, treatment, or hypertension. CONCLUSIONS: Cervical artery lesions are frequent and mostly asymptomatic in patients with vascular Ehlers-Danlos syndrome. Local dissections and aneurysms are the most frequent type of lesions, but transient ischemic attack or stroke seem rare.

Prepubertal Periodontitis in a Patient with Combined Classical and Periodontal Ehlers-Danlos Syndrome.

We report an extremely rare case of combined classical and periodontal Ehlers-Danlos syndrome (EDS) with early severe periodontitis and a generalized lack of attached gingiva. A German family with classical EDS was investigated by physical and dental evaluation and exome and Sanger sequencing. Due to the specific periodontal phenotype in the affected child, an additional diagnosis of periodontal EDS was suspected. Physical and genetic examination of two affected and three unaffected family members revealed a family diagnosis of classical EDS with a heterozygous mutation in COL5A1 (c.1502del; p.Pro501Leufs*57). Additional to the major clinical criteria for classical EDS-generalized joint hypermobility, hyperelastic skin, and atrophic scarring -the child aged four years presented with generalized alveolar bone loss up to 80%, early loss of two lower incisors, severe gingival recession, and generalized lack of attached gingiva. Due to these clinical findings, an additional diagnosis of periodontal EDS was suspected. Further genetic analysis revealed the novel missense mutation c.658T>G (p.Cys220Gly) in C1R in a heterozygous state. Early severe periodontitis in association with generalized lack of attached gingiva is pathognomonic for periodontal EDS and led to the right clinical and genetic diagnosis in the present case.

Does Muscle Strength Change Over Time in Patients With Hypermobile Ehlers-Danlos Syndrome/Hypermobility Spectrum Disorder? An Eight-Year Follow-Up Study.

OBJECTIVE: Reduced maximal muscle strength and strength endurance have been found in patients with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorder (hEDS/HSD) and are recognized as common associated features of the disorder. However, the extent to which these parameters change over time is currently not documented. Therefore, the purpose of this 8-year follow-up study was to investigate this evolution. METHODS: Thirty female patients (mean age 41 years) with hEDS/HSD and 17 controls participated at baseline and 8 years later. Maximal muscle strength and strength endurance tests of the knee flexors and extensors, and 2 lower-extremity posture maintenance tests were performed to evaluate static strength endurance. In addition, muscle mass and density were evaluated by dual-energy x-ray absorptiometry and peripheral quantitative computed tomography. RESULTS: Maximal muscle strength and strength endurance were significantly lower at both baseline and follow-up in the hEDS/HSD group compared to the control group (P ≤ 0.007). Maximal muscle strength of the knee flexors (decreased in the control group: pɳ2 = 0.139), strength endurance of the knee extensors (decreased in the hEDS/HSD group and increased in the control group: pɳ2 = 0.244), and muscle density (decreased in the hEDS/HSD group: pɳ2 = 0.263) showed a significantly different evolution over 8 years. No other significant differences in evolution were found. CONCLUSION: Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.

Mechanisms and management of gastrointestinal symptoms in postural orthostatic tachycardia syndrome.

Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance associated with many GI manifestations that can be broadly classified into two different categories: those present all the time (non-positional) and those that occur with orthostatic position change. There are also many conditions that can co-exist with POTS such as mast cell activation syndrome and the hypermobile form of Ehlers-Danlos syndrome (hEDS) that are also oftentimes associated with GI symptoms. In the current issue of Neurogastroenterology and Motility, Tai et al. explored the relationship between functional GI disorders among hEDS patients with and without concomitant POTS and showed that the hEDS-POTS cohort was more likely to have more than one GI organ involved compared to the cohort with hEDS alone, and certain GI symptoms were also more common in the hEDS-POTS cohort. In this review article, we will briefly review the literature surrounding putative mechanisms responsible for GI symptoms in POTS with an emphasis on the contributory role of concomitant hEDS and then discuss management strategies for GI symptoms in POTS.

Biallelic mutations in Tenascin-X cause classical-like Ehlers-Danlos syndrome with slowly progressive muscular weakness.

Tenascin-X, is an extracellular matrix glycoprotein expressed in skin, muscle, tendons, and blood vessels with an anti-adhesive function. Biallelic Tenascin-X mutations cause classical-like Ehlers-Danlos syndrome. We report a 46-year-old woman with slowly progressive weakness of the lower limbs and myalgia from age 28 years. In the past she had Raynaud's phenomenon, multiple sprains and joint dislocations, conjunctival haemorrhages and a colonic perforation during colonoscopy. Neurologic examination showed moderate asymmetric proximal and axial muscular weakness, distal amyotrophy of 4 limbs, moderate skin hyperextensibility, and hypermobility of distal joints of fingers. Whole body Magnetic Resonance Imaging showed symmetric fatty infiltration of thigh and leg muscles, with predominant atrophy of thighs. Next Generation Sequencing revealed two pathogenic TNXB variants, g.32024681C>G, c.7826-1G>C, and g.32016181dup, c.9998dupA, p.(Asn3333Lysfs*35). Western Blot and immunofluorescence studies confirmed a marked Tenascin-X reduction in both patient's serum and muscle. Here we further detail the clinical and genetic spectrum of a patient with classical-like Ehlers-Danlos syndrome and prominent muscle involvement.

Increased augmentation index in patients with Ehlers-Danlos syndrome.

BACKGROUND: Ehlers-Danlos Syndrome (EDS) comprises a heterogeneous group of diseases characterized by joint hypermobility, connective tissue friability, and vascular fragility. Reliable prognostic factors predicting vascular disease progression (e.g. arterial aneurysms, dissections, and ruptures) in EDS patients are still missing. Recently, applanation tonometry derived augmentation index (AIx), an indirect marker of arterial stiffness, has shown to be positively associated with progression of aortic disease in Marfan syndrome. In this study, we assessed aortic AIx in patients with EDS and matched healthy controls. METHODS: We performed noninvasive applanation tonometry in 61 adults with EDS (43 women and 18 men aged 39.3 ± 14.6 years) and 61 age-, gender-, height-, and weight-matched healthy controls. Radial artery pulse waveforms were recorded and analyzed using the SphygmoCor System (AtCor Medical, Sydney, NSW, Australia). Calculated AIx was adjusted to a heart rate of 75/min. Groups were compared and association between AIx and EDS was determined by univariate and multivariate regression analysis. RESULTS: EDS patients were categorized in classical type EDS (34%), hypermobile type EDS (43%), vascular type EDS (5%), or remained unassignable (18%) due to overlapping features. EDS patients showed a significantly increased aortic AIx compared to healthy controls (22.8% ± 10.1 vs 14.8% ± 14.0, p < 0.001). EDS showed a positive association with AIx; independent of age, sex, height, blood pressure, medication, and pack years of smoking. CONCLUSIONS: Patients with EDS showed elevated AIx, indicating increased arterial stiffness when compared to healthy controls. Further investigations are needed in order to assess the prognostic value of increased AIx for cardiovascular outcomes in patients with EDS.

The Ehlers-Danlos syndromes.

The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of hereditary disorders of connective tissue, with common features including joint hypermobility, soft and hyperextensible skin, abnormal wound healing and easy bruising. Fourteen different types of EDS are recognized, of which the molecular cause is known for 13 types. These types are caused by variants in 20 different genes, the majority of which encode the fibrillar collagen types I, III and V, modifying or processing enzymes for those proteins, and enzymes that can modify glycosaminoglycan chains of proteoglycans. For the hypermobile type of EDS, the molecular underpinnings remain unknown. As connective tissue is ubiquitously distributed throughout the body, manifestations of the different types of EDS are present, to varying degrees, in virtually every organ system. This can make these disorders particularly challenging to diagnose and manage. Management consists of a care team responsible for surveillance of major and organ-specific complications (for example, arterial aneurysm and dissection), integrated physical medicine and rehabilitation. No specific medical or genetic therapies are available for any type of EDS.

The management of adult patients with severe chronic small intestinal dysmotility.

Adult patients with severe chronic small intestinal dysmotility are not uncommon and can be difficult to manage. This guideline gives an outline of how to make the diagnosis. It discusses factors which contribute to or cause a picture of severe chronic intestinal dysmotility (eg, obstruction, functional gastrointestinal disorders, drugs, psychosocial issues and malnutrition). It gives management guidelines for patients with an enteric myopathy or neuropathy including the use of enteral and parenteral nutrition.