BACKGROUND: Patients with uncommon genetic conditions often face limited in-person resources for social and informational support. Hypermobile Ehlers-Danlos syndrome (hEDS) is a rare or underdiagnosed hereditary disorder of the connective tissue, and like those with similar diseases, patients with hEDS have begun to turn to social media in search of care and community. The aims of our study were to understand the usage habits and perceptions of utility of social media use for patients with hEDS in order to formulate suggestions for how clinicians may best engage these and similar patient populations about this topic.
METHODS: We conducted both a quantitative survey and qualitative interviews with patients who had received a robust clinical diagnosis of hEDS.
RESULTS: Twenty-four individuals completed the initial survey, and a subset of 21 of those participants completed an interview. Through thematic analysis, we identified four primary themes related to their experience with social media: (1) befriending others with their disease, (2) seeking and vetting information, (3) the risks and downsides of social media use, and (4) the desire for clinicians to discuss this topic with them.
CONCLUSIONS: We conclude by proposing five suggestions that emerge empirically from our data. These proposals will help clinicians engage their patients regarding social media use in order to promote its potential benefits and circumvent its potential harms as they pursue support for their hereditary condition.

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.

UNASSIGNED: Chronic pain is a common feature of hypermobile Ehlers-Danlos Syndrome (hEDS), yet how patients assess and communicate their pain remains poorly understood. The objective of the present study was to explore the use of numeric pain assessment in individuals with hEDS, from a patient-centered perspective.
UNASSIGNED: Our analysis is based on in-depth qualitative interviews. The interviews were conducted over the phone. Our participants were patients living with hEDS (N = 35). Interviews were recorded, transcribed, and analyzed to identify factors related to their use of these pain assessment instruments.
UNASSIGNED: Three primary themes emerged from these data, namely, (1) confusion around the quantification of multidimensional pain, (2) the subjectivity of pain experience, and (3) a strategic use of assessments for practical purposes beyond the accurate representation of pain.
These results demonstrate the need for caution in relying exclusively on numeric pain assessment instruments. We conclude with a brief proposal for a clinical communication strategy that may help to address the limitations of numeric pain assessment that were identified in our interviews.
Chronic pain is a common feature of hypermobile Ehlers–Danlos Syndrome (hEDS), yet how patients assess and communicate their pain remains poorly understood.Clinicians should be aware that patients have difficulties with the Numeric Rating Scale (NRS) for at least three reasons: (1) confusion around the quantification of multidimensional pain, (2) the subjectivity of pain experience, and (3) a strategic use of assessments for practical purposes beyond the accurate representation of pain.Clinicians should use caution in relying exclusively on NRS instruments.Clinicians may benefit from using clinical communication strategies outlined in our paper, which may help to address the limitations of the NRS that were identified in our interviews.

Ehlers-Danlos syndromes (EDS) are a group of disorders characterized by abnormal connective tissue affecting several organ systems. Patients with the hypermobile type of EDS (hEDS) commonly experience chronic pain which can present as musculoskeletal pain, fibromyalgia, neuropathic pain or abdominal pain. The effective management of chronic pain in hEDS patients is a challenge. This study reviews two cases of chronic pain in hEDS patients and the multimodal treatment regimen used along with peripheral nerve stimulation for shoulder and knee pains, never before reported in hEDS patients. Since hEDS associated chronic pain is multifactorial in origin, treatment requires a multidisciplinary approach which includes physical therapy, psychotherapy, pharmacotherapy and interventional pain procedures such as trigger point injections, peripheral nerve block, radiofrequency ablation and peripheral nerve stimulation.
Ehlers–Danlos Syndromes (EDS) are a group of disorders that affects the connective tissues that supports skin, muscles and organs. Patients with the hypermobile subtype of EDS (hEDS) often experience chronic pain of multiple locations including the muscles, joints, nerves, abdomen, head or generalized pain. Treating chronic pain in patients with hEDS is challenging. In this study, we review the treatment of chronic pain in two patients with hEDS using multiple therapies including the novel use of peripheral nerve stimulation in this patient population. Chronic pain in hEDS patients is caused by multiple different mechanisms and therefore, the treatment of this pain requires multiple different therapeutic interventions such as medications, physical therapy, psychotherapy and minimally invasive procedures such as peripheral nerve stimulation.

The Ehlers-Danlos syndromes are a group of multisystemic heritable connective tissue disorders with clinical presentations that range from multiple congenital malformations, over adolescent-onset debilitating or even life-threatening complications of connective tissue fragility, to mild conditions that remain undiagnosed in adulthood. To date, thirteen different EDS types have been recognized, stemming from genetic defects in 20 different genes. While initial biochemical and molecular analyses mainly discovered defects in genes coding for the fibrillar collagens type I, III and V or their modifying enzymes, recent discoveries have linked EDS to defects in non-collagenous matrix glycoproteins, in proteoglycan biosynthesis and in the complement pathway. This genetic heterogeneity explains the important clinical heterogeneity among and within the different EDS types. Generalized joint hypermobility and skin hyperextensibility with cutaneous fragility, atrophic scarring and easy bruising are defining manifestations of EDS; however, other signs and symptoms of connective tissue fragility, such as complications of vascular and internal organ fragility, orocraniofacial abnormalities, neuromuscular involvement and ophthalmological complications are variably present in the different types of EDS. These features may help to differentiate between the different EDS types but also evoke a wide differential diagnosis, including different inborn errors of metabolism. In this narrative review, we will discuss the clinical presentation of EDS within the context of inborn errors of metabolism, give a brief overview of their underlying genetic defects and pathophysiological mechanisms and provide a guide for the diagnostic approach.

The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissues disorders mainly characterized by skin hyperextensibility, joint hypermobility and generalized tissue fragility. Currently, 14 EDS subtypes each with particular phenotypic features are recognized and are caused by genetic defects in 20 different genes. All of these genes are involved in the biosynthesis and/or fibrillogenesis of collagens at some level. Although great progress has been made in elucidating the molecular basis of different EDS subtypes, the pathogenic mechanisms underlying the observed phenotypes remain poorly understood, and consequentially, adequate treatment and management options for these conditions remain scarce. To date, several animal models, mainly mice and zebrafish, have been described with defects in 14 of the 20 hitherto known EDS-associated genes. These models have been instrumental in discerning the functions and roles of the corresponding proteins during development, maturation and repair and in portraying their roles during collagen biosynthesis and/or fibrillogenesis, for some even before their contribution to an EDS phenotype was elucidated. Additionally, extensive phenotypical characterization of these models has shown that they largely phenocopy their human counterparts, with recapitulation of several clinical hallmarks of the corresponding EDS subtype, including dermatological, cardiovascular, musculoskeletal and ocular features, as well as biomechanical and ultrastructural similarities in tissues. In this narrative review, we provide a comprehensive overview of animal models manifesting phenotypes that mimic EDS with a focus on engineered mouse and zebrafish models, and their relevance in past and future EDS research. Additionally, we briefly discuss domestic animals with naturally occurring EDS phenotypes. Collectively, these animal models have only started to reveal glimpses into the pathophysiological aspects associated with EDS and will undoubtably continue to play critical roles in EDS research due to their tremendous potential for pinpointing (common) signaling pathways, unveiling possible therapeutic targets and providing opportunities for preclinical therapeutic interventions.

High rates of comorbid chronic pain, anxiety, and mood disorders among individuals with the Ehlers-Danlos syndromes (EDS+) are becoming increasingly recognized, though this complex symptomology remains poorly understood and undertreated. The current project examined whether interoceptive attention regulation is protective against depressive and anxiety symptoms in individuals with suspected EDS+. Data were collected from individuals participating in a transdisciplinary diagnostic visit within an EDS+ specialty consultation clinic. Participants were included in the current analyses (n = 49) if they had complete data on the following measures: the PHQ-8, the GAD-7, the Pain Severity subscale from the West Haven-Yale Multidimensional Pain Inventory, and the Attention Regulation subscale from the Multidimensional Assessment of Interoceptive Awareness. Consistent with expectations, the sample showed high levels of clinically significant anxiety and depressive symptoms. Pain severity ratings were significantly correlated with depressive but not anxiety severity. Moreover, higher levels of perceived interoceptive attention regulation abilities were significantly associated with less severe anxiety and depressive symptoms; however, attention regulation did not moderate the associations of pain with anxiety and depressive symptom severity.
CONCLUSIONS: The current project replicated recent findings that pain, anxiety, and depression are common in individuals with EDS+. The ability to focus and control somatic attention appears to be protective and a potential target for interventions in EDS+.

It is a well-known fact that people with Ehlers-Danlos syndromes (EDS) report a worse oral health-related quality of life (OHRQoL) than the general population. The aim of this study was to examine whether there is a correlation between the subjective OHRQoL and the objectively measured oral health in people with EDS. To determine the subjective OHRQoL, the German version of the 14-item Oral Health Impact Profile (OHIP-14) questionnaire was used. Furthermore, all participants in the study were clinically examined, and the measured parameters were recorded using the Physical Oral Health Index (PhOX). Altogether, records of 46 participants were collected. The median (interquartile range (IQR)) of the OHIP-14 was 17 (23) points and the median of the PhOX was 73 (16) points. However, a statistically significant correlation could not be demonstrated (r = -0.240, p = 0.108). In the observed cohort, for participants who reported having pain often or very often, the OHIP score (median = 24, IQR = 18, p < 0.01) was higher than the score of the group given by participants who never or intermittently experienced pain (median = 8, IQR = 18). In conclusion, patients with EDS showed a reduced OHRQoL, although it was not possible to observe an association between the subjective OHRQoL and the objective oral health. However, participants who often or very often suffer from pain in their tooth, mouth, and jaw areas showed a reduced OHRQoL.

Background and objective: To date, there have only been a few studies on oral health-related quality of life (OHRQoL) of people with Ehlers-Danlos syndromes (EDS) and oral conditions. The aim of this study was, therefore, to analyze the OHRQoL of people with EDS from their own point of view as well as obtain information about their age at the time of the diagnosis, the period of time until diagnosis, and the presence of oral conditions (if any) and their association with oral health quality. Methods: The study was designed as an anonymous questionnaire-based cross-sectional study. We conducted a descriptive analysis of the Oral Health Impact Profile-14 (OHIP-14) scores, age of the participants, age at diagnosis, and the time-period between the first signs of the disease and the diagnosis of EDS. To verify the differences in OHIP-14 scores between patients with and without oral conditions, a Mann-Whitney U test was performed. A multivariate quantile (median) regression analysis was performed to evaluate the effect of different general characteristics (gender, age, and the presence of oral conditions) on the OHIP 14 scores. Furthermore, using a Mann-Whitney U test, the influence of different oral conditions was verified by testing the differences between patients without any oral conditions and patients with a specific diagnosis. Results: A total of 79 evaluable questionnaires from 66 female (83.5%) and 13 male (16.5%) participants were analyzed. On average, after the first condition, it takes 18.36 years before EDS are correctly diagnosed. Oral conditions were described by 69.6% of the participants. The median (interquartile range) OHIP-14 score was eight (ten) points for patients without oral conditions and 19 (15) for patients with oral conditions. The multivariable quantile regression shows a statistical notable association between OHIP-14 score and oral conditions (p < 0.001). OHIP-14 scores for dysgnathia, periodontitis, TMD (Temporomandibular dysfunction), a high-arched palate, malocclusion, and the anomaly of tooth formation were statistical notably different between the participants with and the participants without oral conditions. Conclusions: Long diagnostic pathways seem to be a typical problem in patients with EDS. Oral conditions associated with the underlying disease occurred regularly and showed a negative correlation with OHRQoL.

The αvβ3 integrin, an endothelial cells\' receptor-binding fibronectin (FN) in the extracellular matrix (ECM) of blood vessels, regulates ECM remodeling during migration, invasion, angiogenesis, wound healing and inflammation, and is also involved in the epithelial mesenchymal transition. In vitro-grown human control fibroblasts organize a fibrillar network of FN, which is preferentially bound on the entire cell surface to its canonical α5β1 integrin receptor, whereas the αvβ3 integrin is present only in rare patches in focal contacts. We report on the preferential recruitment of the αvβ3 integrin, due to the lack of FN-ECM and its canonical integrin receptor, in dermal fibroblasts from Ehlers-Danlos syndromes (EDS) and arterial tortuosity syndrome (ATS), which are rare multisystem connective tissue disorders. We review our previous findings that unraveled different biological mechanisms elicited by the αvβ3 integrin in fibroblasts derived from patients affected with classical (cEDS), vascular (vEDS), hypermobile EDS (hEDS), hypermobility spectrum disorders (HSD), and ATS. In cEDS and vEDS, respectively, due to defective type V and type III collagens, αvβ3 rescues patients\' fibroblasts from anoikis through a paxillin-p60Src-mediated cross-talk with the EGF receptor. In hEDS and HSD, without a defined molecular basis, the αvβ3 integrin transduces to the ILK-Snail1-axis inducing a fibroblast-to-myofibroblast-transition. In ATS cells, the deficiency of the dehydroascorbic acid transporter GLUT10 leads to redox imbalance, ECM disarray together with the activation of a non-canonical αvβ3 integrin-TGFBRII signaling, involving p125FAK/p60Src/p38MAPK. The characterization of these different biological functions triggered by αvβ3 provides insights into the multifaced nature of this integrin, at least in cultured dermal fibroblasts, offering future perspectives for research in this field.