RARE DISEASE
Ehlers-Danlos syndrome
Ehlers-Danlos syndrome
Ehlers-Danlos syndrome
Synonyms: EDS
Synonyms: EDS
Synonyms: EDS
Drug discovery
3
drugs
With orphan designations
Overview
Ehlers-Danlos syndrome (EDS) comprises 13 heritable connective tissue disorders characterized by collagen defects, leading to joint hypermobility, skin fragility, chronic pain, and multisystem involvement (e.g., cardiovascular, gastrointestinal, autonomic dysfunction). The hypermobile type (hEDS) is most common. Diagnosis relies on clinical criteria and genetic testing (except hEDS). Management focuses on symptom mitigation and musculoskeletal stabilization [1][6][15].
Burden
Therapies
Physical/occupational therapy: Joint stabilization, low-impact exercise, and adaptive devices [3][16].
Pain management: NSAIDs, neuromodulators (e.g., gabapentin), and non-pharmacological approaches (e.g., warm baths, TENS) [3][8][13].
Multidisciplinary care: Includes POTS/dysautonomia management, cognitive behavioral therapy, and genetic counseling [5][16].
Categories: rare developmental anomalies during embryogenesis, rare genetic diseases, rare skin diseases, rare systemic and rheumatological diseases
Research Papers
760 drug discovery papers about Ehlers-Danlos syndrome, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
760 drug discovery papers about Ehlers-Danlos syndrome, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-17 | Ciprofloxacin Exposure Promotes Aortic Dissection and Arterial Rupture in a Mouse Model of Vascular Ehlers-Danlos Syndrome.
We tested the hypothesis that ciprofloxacin exposure increases the incidence of aortic dissection and arterial rupture in vEDS mice. While data support that fluoroquinolones exacerbate lethal sequela in some types of aortic pathology, the potential danger of these drugs has not been studied in the context of vascular Ehlers-Danlos syndrome (vEDS). Eight-week-old male and female vEDS mice (Col3a1[G209S/WT]) and wild-type littermates (Col3a1[WT/WT]) were randomly assigned to receive either ciprofloxacin (n=25) or vehicle control (n=24) through daily gavage for 2 weeks and were monitored for 4 weeks. We compared groups based on survival, aortic dissection and rupture incidence, and aortic tissue levels of collagen, lysyl oxidase (LOX), matrix metalloproteinases (MMP), macrophages, and apoptosis. All vEDS mice that received vehicle and all littermate controls survived the 4-week study period. In contrast, 44% of vEDS mice that received ciprofloxacin died (P<0.001) due to aortic or arterial rupture manifesting as hemopericardium or hemothorax, most within 7 days of exposure. Findings were similar in male and female vEDS mice. Compared to aortic tissue from vehicle-treated vEDS mice, tissue from ciprofloxacin-treated vEDS mice exhibited decreased collagen content, decreased LOX, increased MMP 2 and 9 levels, increased macrophage infiltration, and increased apoptosis (all P<0.001). In a mouse model of vEDS, ciprofloxacin exposure resulted in aortic inflammation, collagen disruption, cell death, reduced LOX, and increased risk of fatal dissection and rupture of the aorta and branch arteries. These novel translational findings strongly support recommendations to avoid fluoroquinolones in patients with vEDS.
2026-05-26 | Too high and too loose: dysautonomia and the hypertensive paradox in hypermobility disorders.
Hypertension in hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) represents an increasingly recognized but poorly understood clinical phenomenon. This review addresses the unique pathophysiology, diagnostic considerations, and management challenges of hypertension occurring in the context of dysautonomia - a comorbidity affecting up to 70% of patients with hEDS/HSD. Emerging evidence identifies distinct hypertensive endotypes in hEDS/HSD, including hyperadrenergic dysautonomia, paroxysmal hypertension, cervicogenic hypertension, and nocturnal/supine hypertension. Pathophysiologic mechanisms involve connective tissue laxity, altered baroreflex function, small fiber neuropathy, and mast cell activation. Standard antihypertensive therapies may paradoxically worsen symptoms by exacerbating orthostatic intolerance, while targeted approaches using alpha-blockers and central sympatholytics show promise in hyperadrenergic phenotypes. Management of hypertension in hEDS/HSD requires adaptation of standard guidelines to accommodate dysautonomia-specific considerations, including withdrawal of provocative medications, avoidance of volume-depleting agents, and phenotype-directed pharmacotherapy. Long-term cardiovascular outcomes remain poorly defined, highlighting critical research gaps and the need for evidence-based consensus guidelines tailored to this unique patient population.
2026-04-28 | Outpatient buprenorphine micro-induction for an older adult with chronic pain and opioid use disorder: a case report.
Buprenorphine micro-induction enables a gradual transition from full opioid agonists without requiring abstinence, minimizing the risk of precipitated withdrawal. This approach is particularly beneficial for older adults with chronic pain who remain on long-term opioid therapy and may be reluctant or medically unfit to undergo traditional induction protocols. A 68-year-old woman with Ehlers-Danlos Syndrome, complex surgical history, and severe opioid use disorder who was taking 280 (Morphine Milligram Equivalents per Day), including prescribed morphine and illicit hydromorphone. She underwent an outpatient buprenorphine-naloxone micro-induction while continuing full agonist use until target dose was reached. Doses were titrated over seven days with minimal withdrawal symptoms. She successfully transitioned to buprenorphine-naloxone 4-1 mg QID (Four Times Per Day), reporting improved pain, mobility, and overall functioning. Outpatient micro-induction can be safely implemented in older adults with chronic opioid exposure, particularly those receiving prescription opioids from outside prescribers for chronic pain. This case underscores the utility of pharmacogenomics, trauma-informed care, and interdisciplinary coordination to facilitate successful transition to MOUD.
2026-04-28 | Steroid hormone antagonism affords vascular protection in a mouse model of vascular Ehlers-Danlos syndrome.
Aortic dissection or rupture is a leading cause of mortality in vascular Ehlers-Danlos syndrome (VEDS), a disorder caused by mutations in the COL3A1 gene. Col3a1G938D/+ mice recapitulate features of VEDS, including high risk of aortic rupture. As in people with VEDS, aortic risk in this model accelerates at the onset of puberty, especially in males. We identify developmentally regulated gene programs associated with this vulnerability and that are targeted by treatments that mitigate aortic risk. Both genetic and pharmacological inhibition of the androgen receptor (AR) eliminated survival differences between sexes, while treatment with a dual AR and mineralocorticoid receptor (MR) antagonist provided near-complete and durable protection in both sexes. Pathways targeted by dual AR/MR inhibition, including those related to extracellular matrix (ECM) organization and cell-ECM interactions, largely overlapped with those also modulated by isolated MR antagonism. Selective targeting of MR signaling emerged as an effective therapeutic strategy in both sexes that avoids sexual side effects in males.
2026-04-13 | 2-Chloroprocaine vs. Lidocaine in a Patient With Hypermobile Ehlers-Danlos Syndrome and a History of Local Anesthetic Resistance: A Case Report.
Patients with hypermobile Ehlers-Danlos syndrome (hEDS) have a higher reported prevalence of local anesthetic (LA) resistance and obstetric complications than the general population. We describe a 33-year-old G2P0010 ASA III parturient with a history of hEDS and lidocaine resistance who presented for an anesthesia consultation in anticipation of possible neuraxial anesthesia. We surmised that performing a neuraxial procedure would require effective skin infiltration of the patient's lumbar area. A skin infiltration test revealed that 3% 2-chloroprocaine provided a much greater numbing effect than 2% lidocaine. The patient desired an unmedicated birth and ultimately delivered in this fashion. Still, our findings highlight the potential benefit of testing multiple LAs in hEDS patients to guide anesthetic planning.
gene therapies
2025-03-20 | Genetic factors and management strategies in aortic health: a literature review of inherited aortopathy.
Inherited aortopathies, including Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome, are genetic disorders characterized by structural abnormalities of the aorta that predispose individuals to life-threatening complications like aneurysms and dissections. These conditions result from mutations in genes essential for maintaining aortic wall integrity, such as FBN1, TGFBR1, and COL3A1, affecting extracellular matrix components and the transforming growth factor-beta (TGF-β) pathway. Marfan syndrome has a prevalence of approximately 1 in 5000, while Loeys-Dietz syndrome and vascular Ehlers-Danlos syndrome are rarer, with estimated prevalences of 1 in 100 000 and 1 in 20 000, respectively. Familial thoracic aortic aneurysms and dissections (FTAAD), linked to mutations in genes like ACTA2 and MYH11, highlight the genetic heterogeneity of aortopathies. Management strategies focus on early diagnosis, risk stratification, regular imaging, lifestyle modifications, and timely surgical intervention. Advances in genetic testing and targeted therapies offer promise for personalized care. However, challenges such as genetic heterogeneity, incomplete penetrance, and variability in disease progression limit effective management. Limitations in current research include heterogeneity among studies, which complicates meta-analyses and consensus building. Future directions include exploring novel genetic interventions, optimizing treatment timing, and addressing psychosocial impacts to enhance patient outcomes. By addressing gaps in knowledge and integrating patient-reported outcomes, this study underscores the importance of a multidisciplinary approach to managing inherited aortopathies and improving the quality of life for affected individuals.
2024-04-12 | Possible involvement of zinc transporter ZIP13 in myogenic differentiation
Abstract Ehlers–Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissue disorder that is caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. We previously reported that patients with EDSSPD3 harboring a homozygous loss of function mutation (c.221G > A, p.G64D) in ZIP13 exon 2 ( ZIP13 G64D ) suffer from impaired development of bone and connective tissues, and muscular hypotonia. However, whether ZIP13 participates in the early differentiation of these cell types remains unclear. In the present study, we investigated the role of ZIP13 in myogenic differentiation using a murine myoblast cell line (C2C12) as well as patient-derived induced pluripotent stem cells (iPSCs). We found that ZIP13 gene expression was upregulated by myogenic stimulation in C2C12 cells, and its knockdown disrupted myotubular differentiation. Myocytes differentiated from iPSCs derived from patients with EDSSPD3 (EDSSPD3-iPSCs) also exhibited incomplete myogenic differentiation. Such phenotypic abnormalities of EDSSPD3-iPSC-derived myocytes were corrected by genomic editing of the pathogenic ZIP13 G64D mutation. Collectively, our findings suggest the possible involvement of ZIP13 in myogenic differentiation, and that EDSSPD3-iPSCs established herein may be a promising tool to study the molecular basis underlying the clinical features caused by loss of ZIP13 function.
2024-03-08 | P321: Atypical presentation of vascular Ehlers-Danlos syndrome (vEDS)
Vascular Ehlers-Danlos Syndrome (vEDS) is a heritable disorder of connective tissue caused by heterozygous pathogenic variants in COL3A1. vEDS is characterized by arterial, intestinal, and/or uterine fragility; easy bruising; thin, translucent skin; and characteristic physical features (prominent eyes, narrow nose, thin vermilion of lips, micrognathia, and an aged appearance of the extremities, especially the hands). Most individuals without a positive family history present in adulthood with acute vascular dissection or organ rupture. Unlike other connective tissue disorders, vEDS dissections may occur at any existing dimension, and not just in those with known vascular dilation. Genetics was consulted to the NICU for a 1-day old infant, born at 35 week gestational age, with multiple congenital anomalies including rocker-bottom feet, hallux varus, bilateral cryptorchidism, right femur fracture, significant bruising, and right brachial plexus injury. The pregnancy was complicated by oligohydramnios, gestational diabetes, chorioamniotic separation, and ultrasound findings concerning for a lemon-shaped cranium, usually associated with neural tube defects, and rocker-bottom feet. A chromosomal microarray (CMA) was nondiagnostic. He was followed by outpatient genetics and there was concern for specific connective tissue disorders, including osteogenesis imperfecta or classical Ehlers Danlos Syndrome (cEDS). Genetic sequencing of COL1A1, COL1A2, COL5A1, and COL5A2 was performed and was normal. He was lost to follow-up around 20 months of age. At 14 years of age, he presented acutely to the emergency department with a spontaneous sigmoid bowel perforation. Updated history revealed recurrent shoulder dislocation, patellar instability, joint laxity, and easy bruising. Physical examination revealed dysmorphic facial features (thin nose and prominent eyes), wide scars, a prominent venous pattern on the chest, and slightly hyperextensible skin. Screening echocardiogram was normal. Single gene sequencing of COL3A1 revealed a heterozygous, likely pathogenic, splice-site variant (c.1609-5_1615del), predicted to result in the deletion of 12 nucleotides and interfere with splicing. This variant has not been reported before. Subsequent parental testing revealed that this variant is likely de novo. He was evaluated by cardiology and currently does not have any cardiac manifestations. He will undergo comprehensive MR angiography to screen for abnormalities in the vasculature. This case highlights an atypical presentation of vascular Ehlers-Danlos Syndrome (vEDS) with a novel variant in the COL3A1 gene, associated with a serious outcome. After presenting with a right femur fracture and brachial plexus injury at birth, the proband was largely asymptomatic other than easy bruising, joint laxity, and joint instability. He subsequently presented with a serious feature of spontaneous sigmoid perforation. Evidence suggests improvement in survival for vEDS patients when an accurate diagnosis is made, with appropriate clinical management and long-term follow-up. There is significant overlap in symptoms between the Ehlers Danlos Syndrome subtypes. Thus, improvement in phenotyping and early diagnosis is crucial. The use of multi-gene panels or comprehensive genomic testing is emerging as a more efficient option when indistinguishable phenotypes cause delays in testing. Further review and study will enhance our ability for early detection of vEDS and appropriate follow-up to prevent undesirable outcomes.
2024-02-23 | Genetic complexity of diagnostically unresolved Ehlers-Danlos syndrome.
The Ehlers-Danlos syndromes (EDS) are heritable disorders of connective tissue (HDCT), reclassified in the 2017 nosology into 13 subtypes. The genetic basis for hypermobile Ehlers-Danlos syndrome (hEDS) remains unknown. Whole exome sequencing (WES) was undertaken on 174 EDS patients recruited from a national diagnostic service for complex EDS and a specialist clinic for hEDS. Patients had already undergone expert phenotyping, laboratory investigation and gene sequencing, but were without a genetic diagnosis. Filtered WES data were reviewed for genes underlying Mendelian disorders and loci reported in EDS linkage, transcriptome and genome-wide association studies (GWAS). A genetic burden analysis (Minor Allele Frequency (MAF) <0.05) incorporating 248 Avon Longitudinal Study of Parents and Children (ALSPAC) controls sequenced as part of the UK10K study was undertaken using TASER methodology. Heterozygous pathogenic (P) or likely pathogenic (LP) variants were identified in known EDS and Loeys-Dietz (LDS) genes. Multiple variants of uncertain significance where segregation and functional analysis may enable reclassification were found in genes associated with EDS, LDS, heritable thoracic aortic disease (HTAD), Mendelian disorders with EDS symptomatology and syndromes with EDS-like features. Genetic burden analysis revealed a number of novel loci, although none reached the threshold for genome-wide significance. Variants with biological plausibility were found in genes and pathways not currently associated with EDS or HTAD. We demonstrate the clinical utility of large panel-based sequencing and WES for patients with complex EDS in distinguishing rare EDS subtypes, LDS and related syndromes. Although many of the P and LP variants reported in this cohort would be identified with current panel testing, they were not at the time of this study, highlighting the use of extended panels and WES as a clinical tool for complex EDS. Our results are consistent with the complex genetic architecture of EDS and suggest a number of novel hEDS and HTAD candidate genes and pathways.
2023-03-16 | Pathophysiological Investigation of Skeletal Deformities of Musculocontractural Ehlers–Danlos Syndrome Using Induced Pluripotent Stem Cells
Musculocontractural Ehlers–Danlos syndrome caused by mutations in the carbohydrate sulfotransferase 14 gene (mcEDS-CHST14) is a heritable connective tissue disorder characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral, and ocular systems. Progressive skeletal deformities are among the most frequent and serious complications affecting the quality of life and activities of daily living in patients. After establishing induced pluripotent stem cells (iPSCs) from cultured skin fibroblasts of three patients with mcEDS-CHST14, we generated a patient iPSC-based human osteogenesis model and performed an in vitro assessment of the phenotype and pathophysiology of skeletal deformities. Patient-derived iPSCs presented with remarkable downregulation of osteogenic-specific gene expression, less alizarin red staining, and reduced calcium deposition compared with wild-type iPSCs at each stage of osteogenic differentiation, including osteoprogenitor cells, osteoblasts, and osteocytes. These findings indicated that osteogenesis was impaired in mcEDS-CHST14 iPSCs. Moreover, the decrease in decorin (DCN) expression and increase in collagen (COL12A1) expression in patient-derived iPSCs elucidated the contribution of CHST14 dysfunction to skeletal deformities in mcEDS-CHST14. In conclusion, this disease-in-a-dish model provides new insight into the pathophysiology of EDS and may have the potential for personalized gene or drug therapy.
cell therapies
2025-09-24 | Complex Wound Reconstruction in a Patient With Ehlers-Danlos Syndrome.
Ehlers-Danlos syndrome (EDS) is a hereditary condition marked by collagen defects leading to tissue fragility throughout various body systems. One notable challenge for patients with EDS is compromised wound healing due to connective tissue fragility. This study described the case of a 53-year-old man with classical type EDS, presenting with a significant wound over his left knee, following numerous complications after a patellar tendon rupture. Traditional healing methods, including a gastrocnemius flap, were of limited benefit due to the patient's EDS condition. A novel surgical approach, involving the use of a split-thickness skin graft combined with the Recell Autologous Skin Cell Harvesting Device, resulted in successful wound healing. Ten months postsurgery, the patient demonstrated excellent graft adherence without any complications. This case indicates the potential benefits of the split-thickness skin graft and Recell method for patients with EDS, offering an effective treatment modality for significant wound healing challenges in this population.
2025-08-26 | B3GALT6 mutations lead to compromised connective tissue biomechanics in Ehlers-Danlos syndrome.
Ehlers-Danlos syndromes (EDS) comprise a genetically and clinically heterogenous group of rare diseases that cause severe, often fatal, damage to connective tissue. The molecular basis of EDS implicates defects in extracellular matrix components, including various fibrillar collagens and glycosaminoglycans (GAGs). However, the precise pathogenic mechanisms behind EDS remain elusive. Here, we have implemented a multi-tiered approach to demonstrate the functional impact of B3GALT6 mutations on biochemical and developmental processes, ultimately leading to the spondylodysplastic subtype of EDS (spEDS), characterized by severe musculoskeletal symptoms. We show that the loss of function of β1,3-galactosyltransferase 6 (β3GalT6) is partially compensated by β1,3-glucuronosyltransferase 3 (GlcAT-I), the next enzyme in the GAG biosynthetic pathway. In addition, results from transcriptomics, collagen analysis, and biophysical experiments revealed that impaired collagen maturation, including defective glycosylation of collagen XII, contributes to altered tissue structure and biomechanics, the hallmarks of spEDS. Our findings unravel a new pathogenic mechanism of spEDS and bring us one step closer to therapeutic strategies, including cell and tissue engineering.
2025-04-26 | The Successful Treatment of a Patient with Ehlers-Danlos Syndrome (EDS) After an Extensive Burn Injury: A Case Report.
Introduction: Ehlers-Danlos Syndromes (EDSs) are a heterogeneous group of monogenic connective tissue disorders (e.g., joint hypermobility and dislocation, skin hyperelasticity and fragility, chronic pain, delayed wound healing process,, etc.). The primary objective of this study was to present a specialized therapeutic wound management process for a burn-injured female patient diagnosed with EDS. Case Presentation: A 34-year-old female patient presented with extensive thermal burns (biofireplace explosion). The patient had a family history of diagnosed EDS. Additionally, the patient was in a poor mental condition and, since 2020, had been undergoing pharmacotherapy with antidepressant and anti-anxiety medication. This might be the first such clinical observation in the world, but a correlation has been observed between psychiatric medication use and EDS wound healing impairment. During the hospitalization process, the patient underwent a series of surgeries aimed at the fastest and most effective closure of wounds. The patient, after 182 days of hospitalization in our facility, was discharged home. Materials and Methods: During the patient's hospital stay, the patient underwent multiple procedures involving debridement of necrotic tissues. Additionally, allogeneic acellular dermal matrix (ADM) grafting was performed on the wounds, and a procedure was conducted in which skin was grafted using the MEEK technique. The in vitro cultured skin cells, as the advanced therapy medicinal products (ATMPs), were used. During the patient's stay in the hospital, images were taken using low-energy laser speckle contrast analysis (LASCA) to asses microperfusion or lack thereof. The measurements were taken at intervals of several days. Conclusions: The treatment of burn wounds in patients with EDS requires a long hospitalization period. It also may require a multi-stage approach utilizing innovative preparations (e.g., ADMs and ATMPs). The assessment of wound healing progress can be performed using advanced equipment, such as laser speckle contrast analysis (LASCA).
2025-01-01 | Management of Tongue Ulcer and Temporomandibular Joint Subluxation in Ehler-Danlos Syndrome Versus Non-Syndromic Patients
Objective: In our study we were focusing on treatment of ulcers in the lateral border of the tongue caused by repeated trauma and Temporomandibular joints (TMJ) subluxation. Moreover, we compared the results among non-syndromic patients (normal patients) versus syndromic patients (Ehlers-Danlos syndrome (EDS)).Methods: This clinical, interventional, prospective, and randomized controlled study was carried out on individual chosen from the outpatient clinic. The study has been performed on 20 patients divided into two groups equally, Group I (control group) consisted of 10 normal patients had tongue ulceration and TMJ subluxation (4 males and 6 females). Group II (study group) consisted of 10 patients had tongue ulceration and TMJ subluxation with Ehler-Danlos syndrome (4 males and 6 females).Results: After one day, group I showed a significant reduced pain score contrasted to group II (P-value = 0.015). After two days, group I revealed a significantly reduced pain score contrasted to group II (P-value = 0.012). After seven days, group I revealed a statistically significantly reduced pain score contrasted to group II (P-value = 0.071). A significant reduction in the diameter in group I in a shorter period contrasted to group II (P-value = 0.005).Conclusion: low level laser therapy is an effective tool for management of tongue ulcer and intrarticular injection of auotologous blood is a magic choice for management of temporomandibular joint subluxation. However, non- syndromic normal patients showed marked and rapid improvement more than patients with Ehler-Danols syndrome.
2024-11-15 | Hippotherapy in the management of hypermobile Ehlers-Danlos syndrome.
Hypermobile Ehlers-Danlos syndrome (EDS) is an inherited condition marked by joint hypermobility, instability, chronic pain and fatigue, significantly impacting quality of life and autonomy. Management focuses solely on symptom alleviation. After experiencing a rapid decline in functional abilities, a patient in late adolescence with hypermobile EDS underwent hippotherapy rehabilitation (30 hours). She saw substantial improvements in fatigue, chronic pain and regained walking abilities. Hippotherapy played a crucial role in refining her postural balance, motor skills, proprioception, muscle function and endurance. It also positively affected her cognitive and emotional regulation by stimulating sensory inputs that activate neural pathways, providing relief from pain and fatigue. Notably, the patient transitioned from wheelchair reliance to walking with crutches, and then greatly enhanced both gait quality and speed. These findings demonstrate the relevance of hippotherapy for the rehabilitation of hypermobile EDS, reducing the need for pharmacological interventions and fostering a proactive approach to future challenges.
proteins
2026-08-08 | Excessive Hypocapnic Cerebral Vasoconstriction in Hypermobile Ehlers-Danlos Syndrome Assessed With Real-Time Magnetic Resonance Imaging During Lower-Body Negative Pressure.
Orthostatic intolerance is common in hypermobile Ehlers-Danlos syndrome (hEDS) with one third of patients fulfilling postural orthostatic tachycardia syndrome criteria. Our aim was to assess cerebral blood flow in patients with hEDS and postural orthostatic tachycardia syndrome during orthostasis, which may be responsible for orthostatic intolerance. In 18 individuals with hEDS and postural orthostatic tachycardia syndrome and 20 healthy controls, we conducted real-time phase contrast magnetic resonance imaging of the middle cerebral artery with and without an orthostatic challenge through 30 mm Hg lower-body negative pressure. During lower-body negative pressure, heart rate increased more in hEDS than in controls (15.0±8.3 bpm versus 7.8±7.7 bpm, P=0.009); blood pressure remained unchanged; middle cerebral artery flow per heartbeat decreased more in hEDS (-28%±16% versus -15%±13% in controls, P=0.013) with decreased mean volumetric flow in hEDS (-12%±17%, P<0.001 versus -6%±8% in controls, P=0.102); average middle cerebral artery peak blood flow velocity decreased in both groups (hEDS: 44.6±8.1 cm/s to 37.6±8.4 cm/s, P<0.001; controls: 40.3±10.9 cm/s to 36.9±11.1 cm/s, P=0.018); respiration rate increased in hEDS (14.3±5.1/min to 17.4±5.3/min, P=0.002) leading to a decrease in end-tidal CO2 (39.2±4.2 mm Hg to 35.6±6.4 mm Hg, P=0.025), and cerebrovascular resistance increased more in hEDS (50.8%±48.4%, P<0.001) versus (20.3%±20.6%, P=0.005) in controls. Individuals with hEDS and postural orthostatic tachycardia syndrome maintain cerebral perfusion primarily through tachycardic compensation during orthostatic stress despite hypocapnic vasoconstriction. URL: https://drks.de/search/en; Unique Identifier: DRKS00028279.
2026-03-18 | Spontaneous coronary artery dissection and vascular Ehlers-Danlos syndrome: a systematic review and case series.
Spontaneous coronary artery dissection (SCAD) is a cause of acute myocardial infarction predominantly affecting adult women. A proportion of SCAD cases are associated with rare heritable connective tissue disorders. Vascular EDS (vEDS), due to deleterious variants in COL3A1, is one of the most common of these. Our aim was to identify specific features of SCAD in vEDS which may aid patient selection for genetic testing. A systematic review of published cases of individuals with SCAD and vEDS was conducted. Additionally, patients with SCAD and genetically confirmed vEDS (SCAD-vEDS) were identified through the UK national EDS service and UK SCAD registry. Data were collected on presentation, management and extra-cardiac findings. Angiography was compared with an age and sex-matched, exome sequenced, control cohort with SCAD but without vEDS (SCAD-nonvEDS). Data from ten SCAD-vEDS patients were identified. There was a lower average age of SCAD and higher proportion of males in individuals with SCAD-vEDS, however differences should be interpreted carefully given cohort size. Fifty-six cases of SCAD-vEDS were identified through systematic review. Systemic features were present in most but not all cases. This report presents a new, angiographically characterised case-control cohort along with a systematic review of the current literature. Whilst clinical differences appear between the SCAD-vEDS and SCAD-nonvEDS groups, these are insufficient to accurately distinguish SCAD-vEDS from the general SCAD population. All individuals with SCAD should be evaluated for underlying vEDS but clinical assessment will miss some cases. Wider genetic testing in some SCAD patients may be merited to enable appropriate management. Systematic review registration: https://www.crd.york.ac.uk/prospero/536751 Identifier: 536751.
2026-01-27 | Health-Related Quality of Life in Midlife and Older Women With Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders.
To identify factors associated with health-related quality of life (HRQOL) in midlife and older women with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders (hEDS/HSD). Online, cross-sectional survey. Online survey was administered to participants in Ehlers-Danlos syndrome Facebook groups. Women ages 40 years and older with a diagnosis of hEDS/HSD. Online survey including demographic and health history; 36-Item Short-Form Health Survey (SF-36) to measure HRQOL; and free-text questions related to things that reduced and improved well-being. Sixty-six women (mean age, 55 years) participated in the survey. Symptom onset was in childhood, but treatment was not sought until their late 20s. The mean age at diagnosis was the mid-40s; thus, the diagnosis was delayed by more than 18 years from the time participants first sought treatment. Comorbidities were common, with 62% of participants reporting seven or more comorbid diagnoses. The SF-36 scores indicated a high symptom burden and poor HRQOL, with worse mean scores in the physical domains compared to the mental domains. Symptom severity, treatment restrictions, environmental factors, comorbidities, and interactions with health care providers influenced HRQOL. Nursing has an emerging role in research and education related to genetic syndromes and heritable connective tissue disorders, including hEDS/HSD, in midlife and older women. Future research should address the complex relationships among physical, social, personal, and environmental factors to maximize HRQOL in this population.
2025-11-29 | Human Proteoglycan Linkage Region Glycosyltransferases are Dimeric and Show Unexpected Specificities.
We selected the N,O-glycosylated proteoglycan bikunin as a model to establish a chemoenzymatic approach to defined proteoglycans using native chemical ligation. Overexpression of the human linkage region glycosyltransferases B4GalT7, B3GalT6 and B3GlcAT-1 as N-terminal SUMO-fusions gave high yields of soluble and active enzymes in E. coli. When starting with xylosylated bikunin peptides the transferases performed well in enzymatic cascade reactions and provided the desired linkage region tetrasaccharide glycopeptides. B3GalT6 and B3GlcAT-1 led to side products with N,O-glycosylated bikunin peptides revealing unexpected promiscuity of both enzymes towards complex type N-glycans. Additionally, B3GalT6 was found to synthesize short poly-β3 Gal structures. B3GlcAT-1 can slowly convert the biosynthetic intermediate Gal-Xyl to the non-canonical trisaccharide GlcA-Gal-Xyl. This reaction independently confirmed the recently detected biosynthetic bypass to GAGs in the case of dysfunctional B3GalT6 (spondylodysplastic Ehlers-Danlos-syndrome). The three linkage region glycosyltransferases B4GalT7, B3GalT6 and B3GlcAT-1 were dimeric in solution and the crystal structure of B3GalT6 was solved showing a covalent dimer linked by a disulfide in the center of the large dimerization domain. This motif appears to be conserved in higher organisms and reinforces the concept of dimeric glycosyltransferases lining the Golgi.
2025-11-12 | A visual guide for emergency radiologists navigating the complexity of abdominal vasculitis: part 2 - the mimickers.
Part 2 of this pictorial essay focuses on conditions that mimic abdominal vasculitis, examining their distinct imaging characteristics using 2D and advanced 3D CT techniques, including volume rendering (VR) and cinematic rendering (CR). These mimickers include fibromuscular dysplasia (FMD), segmental arterial mediolysis (SAM), IgG4-related disease, median arcuate ligament syndrome, infections, genetic conditions such as vascular Ehlers-Danlos syndrome, Marfan syndrome, and Loeys-Dietz syndrome, as well as non-Langerhans cell histiocytic disorders like Erdheim-Chester disease and Rosai-Dorfman disease. This article features illustrative case examples that emphasize the imaging hallmarks of these conditions, aiding radiologists in differentiating them from true vasculitis. This is particularly useful in acute scenarios like abdominal pain, where timely recognition is crucial for informing treatment decisions and improving patient outcomes.
other
2025-11-17 | Challenging Orthognathic Surgery in Ehlers-Danlos Syndrome: A Successful Case with Denosumab Therapy : a case report
Background: Ehlers-Danlos Syndrome (EDS) is a heterogeneous disorder characterized by defects in collagen maturation. Patients with EDS commonly exhibit joint hypermobility, skin hyperextensibility, and tissue fragility. The syndrome can affect oral health, the vascular system, bones, teeth, periodontium, as well as the neuromuscular and joint systems. Due to reduced bone density, some EDS patients may receive antiresorptive medications, which can increase the risk of medication-related osteonecrosis of the jaw (MRONJ). Case Presentation : We report a case of a 25-year-old Iranian female with EDS and a history of denosumab therapy. She underwent bimaxillary orthognathic surgery to correct skeletal malocclusion. The procedure presented multiple challenges, including inherent bone abnormalities, prior denosumab use, and altered collagen structure, all contributing to unpredictable bone healing. Conclusion: Despite these challenges, the patient was successfully treated with bimaxillary orthognathic surgery, achieving a highly satisfactory outcome in terms of both functional rehabilitation and aesthetic improvement.
2025-11-01 | Hypermobile Ehlers-Danlos syndrome (hEDS) and the complement system: A new perspective on pathophysiology 9152
Abstract Description Hypermobile Ehlers-Danlos Syndrome (hEDS) is a heritable connective tissue disorder of unknown origin. Our studies show that hEDS extends beyond a connective tissue disease, broadly affecting gastrointestinal function, autonomic regulation, pain, and the immune system. Using an unbiased proteomics approach, we identified 25 differentially expressed serum proteins in hEDS (N = 38) compared to age- and sex-matched controls (N = 8). Half of these proteins were linked to complement and mast cell pathways. Validation via ELISAs confirmed significantly reduced levels of C1QA, C3, C8a, C8b, and C9 in hEDS patients compared to controls (165.5 vs. 125.1 µg/mL, p < 0.01; 1.976 vs. 1.847 mg/mL, p < 0.001; 77.32 vs. 58.80 µg/mL, p < 0.001; 90.78 vs. 67.13 µg/mL, p < 0.0001; 53.02 vs. 44.15 µg/mL, p < 0.05, respectively). Levels of C4B were also reduced, albeit not significantly (109.7 vs. 93.91 µg/mL). These findings persisted after controlling for known autoimmune conditions, suggesting these immune changes may be intrinsic to hEDS. Our findings reveal a previously unrecognized connection between hEDS and complement system dysregulation, challenging its classification as solely a connective tissue disorder and instead pointing to immune dysregulation as a central factor in hEDS pathophysiology. These findings warrant further research into complement dysfunction and mast cell activation in hEDS, and the development of immune-targeted therapies to mitigate symptoms. Funding Sources Supported by EDS Society; Maltz Fndn. Topic Categories Immune Mechanisms of Human Disease (HUM)
2025-01-08 | Integrative Multi-Omics Approach in Vascular Ehlers-Danlos Syndrome: Further Insights into the Disease Mechanisms by Proteomic Analysis of Patient Dermal Fibroblasts.
Background: Dominant mutations in COL3A1 are known to cause vascular Ehlers-Danlos syndrome (vEDS) by impairing extracellular matrix (ECM) homeostasis. This disruption leads to the fragility of soft connective tissues and a significantly increased risk of life-threatening arterial and organ ruptures. Currently, treatments for vEDS are primarily symptomatic, largely due to a limited understanding of its underlying pathobiology and molecular mechanisms. Methods: In this study, we conducted a comprehensive analysis of the intracellular proteome of vEDS fibroblasts, integrating these findings with our previous transcriptome results to identify key molecular pathways that drive the disease. Additionally, we explored the therapeutic potential of inhibiting miR-29b-3p as a proof of concept. Results: Our integrative multi-omics analysis revealed complex pathological networks, emphasizing the critical role of miRNAs, particularly miR-29b-3p, in impairing ECM organization, autophagy, and cellular stress responses, all of which contribute to the pathogenesis of vEDS. Notably, the inhibition of miR-29b-3p in vEDS fibroblasts resulted in the upregulation of several differentially expressed target genes involved in these critical processes, as well as increased protein expression of essential ECM components, such as collagen types V and I. These changes suggest potential therapeutic benefits aimed at improving ECM integrity and restoring intracellular homeostasis. Conclusions: Overall, our findings advance our understanding of the complex biological mechanisms driving vEDS and lay a solid foundation for future research focused on developing targeted and effective treatment strategies for this life-threatening disorder.
2024-08-29 | Is Exon Skipping a Viable Therapeutic Approach for Vascular Ehlers-Danlos Syndrome with Mutations in COL3A1 Exon 10 or 15?
Vascular Ehlers-Danlos syndrome or Ehlers-Danlos syndrome type IV (vEDS) is a connective tissue disorder characterised by skin hyperextensibility, joint hypermobility and fatal vascular rupture caused by COL3A1 mutations that affect collagen III expression, homo-trimer assembly and secretion. Along with collagens I, II, V and XI, collagen III plays an important role in the extracellular matrix, particularly in the inner organs. To date, only symptomatic treatment for vEDS patients is available. Fibroblasts derived from vEDS patients carrying dominant negative and/or haploinsufficiency mutations in COL3A1 deposit reduced collagen III in the extracellular matrix. This study explored the potential of an antisense oligonucleotide (ASO)-mediated splice modulating strategy to bypass disease-causing COL3A1 mutations reported in the in-frame exons 10 and 15. Antisense oligonucleotides designed to redirect COL3A1 pre-mRNA processing and excise exons 10 or 15 were transfected into dermal fibroblasts derived from vEDS patients and a healthy control subject. Efficient exon 10 or 15 excision from the mature COL3A1 mRNA was achieved and intracellular collagen III expression was increased after treatment with ASOs; however, collagen III deposition into the extracellular matrix was reduced in patient cells. The region encoded by exon 10 includes a glycosylation site, and exon 15 encodes hydroxyproline and hydroxylysine-containing triplet repeats, predicted to be crucial for collagen III assembly. These results emphasize the importance of post-translational modification for collagen III homo-trimer assembly. In conclusion, while efficient skipping of target COL3A1 exons was achieved, the induced collagen III isoforms generated showed defects in extracellular matrix formation. While therapeutic ASO-mediated exon skipping is not indicated for the patients in this study, the observations are restricted to exons 10 and 15 and may not be applicable to other collagen III in-frame exons.
2024-01-12 | Systemic pain relief after omalizumab injection in patient with hypermobile Ehlers–Danlos syndrome: A case report
Key Clinical Message Omalizumab may be a beneficial adjunct treatment option for hEDS patients require to improve pain control, ability to perform ADLs and functionality and social engagement, and most importantly, quality of life.
small molecules
2026-06-17 | Ciprofloxacin Exposure Promotes Aortic Dissection and Arterial Rupture in a Mouse Model of Vascular Ehlers-Danlos Syndrome.
We tested the hypothesis that ciprofloxacin exposure increases the incidence of aortic dissection and arterial rupture in vEDS mice. While data support that fluoroquinolones exacerbate lethal sequela in some types of aortic pathology, the potential danger of these drugs has not been studied in the context of vascular Ehlers-Danlos syndrome (vEDS). Eight-week-old male and female vEDS mice (Col3a1[G209S/WT]) and wild-type littermates (Col3a1[WT/WT]) were randomly assigned to receive either ciprofloxacin (n=25) or vehicle control (n=24) through daily gavage for 2 weeks and were monitored for 4 weeks. We compared groups based on survival, aortic dissection and rupture incidence, and aortic tissue levels of collagen, lysyl oxidase (LOX), matrix metalloproteinases (MMP), macrophages, and apoptosis. All vEDS mice that received vehicle and all littermate controls survived the 4-week study period. In contrast, 44% of vEDS mice that received ciprofloxacin died (P<0.001) due to aortic or arterial rupture manifesting as hemopericardium or hemothorax, most within 7 days of exposure. Findings were similar in male and female vEDS mice. Compared to aortic tissue from vehicle-treated vEDS mice, tissue from ciprofloxacin-treated vEDS mice exhibited decreased collagen content, decreased LOX, increased MMP 2 and 9 levels, increased macrophage infiltration, and increased apoptosis (all P<0.001). In a mouse model of vEDS, ciprofloxacin exposure resulted in aortic inflammation, collagen disruption, cell death, reduced LOX, and increased risk of fatal dissection and rupture of the aorta and branch arteries. These novel translational findings strongly support recommendations to avoid fluoroquinolones in patients with vEDS.
2026-05-26 | Too high and too loose: dysautonomia and the hypertensive paradox in hypermobility disorders.
Hypertension in hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) represents an increasingly recognized but poorly understood clinical phenomenon. This review addresses the unique pathophysiology, diagnostic considerations, and management challenges of hypertension occurring in the context of dysautonomia - a comorbidity affecting up to 70% of patients with hEDS/HSD. Emerging evidence identifies distinct hypertensive endotypes in hEDS/HSD, including hyperadrenergic dysautonomia, paroxysmal hypertension, cervicogenic hypertension, and nocturnal/supine hypertension. Pathophysiologic mechanisms involve connective tissue laxity, altered baroreflex function, small fiber neuropathy, and mast cell activation. Standard antihypertensive therapies may paradoxically worsen symptoms by exacerbating orthostatic intolerance, while targeted approaches using alpha-blockers and central sympatholytics show promise in hyperadrenergic phenotypes. Management of hypertension in hEDS/HSD requires adaptation of standard guidelines to accommodate dysautonomia-specific considerations, including withdrawal of provocative medications, avoidance of volume-depleting agents, and phenotype-directed pharmacotherapy. Long-term cardiovascular outcomes remain poorly defined, highlighting critical research gaps and the need for evidence-based consensus guidelines tailored to this unique patient population.
2026-04-28 | Outpatient buprenorphine micro-induction for an older adult with chronic pain and opioid use disorder: a case report.
Buprenorphine micro-induction enables a gradual transition from full opioid agonists without requiring abstinence, minimizing the risk of precipitated withdrawal. This approach is particularly beneficial for older adults with chronic pain who remain on long-term opioid therapy and may be reluctant or medically unfit to undergo traditional induction protocols. A 68-year-old woman with Ehlers-Danlos Syndrome, complex surgical history, and severe opioid use disorder who was taking 280 (Morphine Milligram Equivalents per Day), including prescribed morphine and illicit hydromorphone. She underwent an outpatient buprenorphine-naloxone micro-induction while continuing full agonist use until target dose was reached. Doses were titrated over seven days with minimal withdrawal symptoms. She successfully transitioned to buprenorphine-naloxone 4-1 mg QID (Four Times Per Day), reporting improved pain, mobility, and overall functioning. Outpatient micro-induction can be safely implemented in older adults with chronic opioid exposure, particularly those receiving prescription opioids from outside prescribers for chronic pain. This case underscores the utility of pharmacogenomics, trauma-informed care, and interdisciplinary coordination to facilitate successful transition to MOUD.
2026-04-28 | Steroid hormone antagonism affords vascular protection in a mouse model of vascular Ehlers-Danlos syndrome.
Aortic dissection or rupture is a leading cause of mortality in vascular Ehlers-Danlos syndrome (VEDS), a disorder caused by mutations in the COL3A1 gene. Col3a1G938D/+ mice recapitulate features of VEDS, including high risk of aortic rupture. As in people with VEDS, aortic risk in this model accelerates at the onset of puberty, especially in males. We identify developmentally regulated gene programs associated with this vulnerability and that are targeted by treatments that mitigate aortic risk. Both genetic and pharmacological inhibition of the androgen receptor (AR) eliminated survival differences between sexes, while treatment with a dual AR and mineralocorticoid receptor (MR) antagonist provided near-complete and durable protection in both sexes. Pathways targeted by dual AR/MR inhibition, including those related to extracellular matrix (ECM) organization and cell-ECM interactions, largely overlapped with those also modulated by isolated MR antagonism. Selective targeting of MR signaling emerged as an effective therapeutic strategy in both sexes that avoids sexual side effects in males.
2026-04-13 | 2-Chloroprocaine vs. Lidocaine in a Patient With Hypermobile Ehlers-Danlos Syndrome and a History of Local Anesthetic Resistance: A Case Report.
Patients with hypermobile Ehlers-Danlos syndrome (hEDS) have a higher reported prevalence of local anesthetic (LA) resistance and obstetric complications than the general population. We describe a 33-year-old G2P0010 ASA III parturient with a history of hEDS and lidocaine resistance who presented for an anesthesia consultation in anticipation of possible neuraxial anesthesia. We surmised that performing a neuraxial procedure would require effective skin infiltration of the patient's lumbar area. A skin infiltration test revealed that 3% 2-chloroprocaine provided a much greater numbing effect than 2% lidocaine. The patient desired an unmedicated birth and ultimately delivered in this fashion. Still, our findings highlight the potential benefit of testing multiple LAs in hEDS patients to guide anesthetic planning.
gene therapies
2025-03-20 | Genetic factors and management strategies in aortic health: a literature review of inherited aortopathy.
Inherited aortopathies, including Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome, are genetic disorders characterized by structural abnormalities of the aorta that predispose individuals to life-threatening complications like aneurysms and dissections. These conditions result from mutations in genes essential for maintaining aortic wall integrity, such as FBN1, TGFBR1, and COL3A1, affecting extracellular matrix components and the transforming growth factor-beta (TGF-β) pathway. Marfan syndrome has a prevalence of approximately 1 in 5000, while Loeys-Dietz syndrome and vascular Ehlers-Danlos syndrome are rarer, with estimated prevalences of 1 in 100 000 and 1 in 20 000, respectively. Familial thoracic aortic aneurysms and dissections (FTAAD), linked to mutations in genes like ACTA2 and MYH11, highlight the genetic heterogeneity of aortopathies. Management strategies focus on early diagnosis, risk stratification, regular imaging, lifestyle modifications, and timely surgical intervention. Advances in genetic testing and targeted therapies offer promise for personalized care. However, challenges such as genetic heterogeneity, incomplete penetrance, and variability in disease progression limit effective management. Limitations in current research include heterogeneity among studies, which complicates meta-analyses and consensus building. Future directions include exploring novel genetic interventions, optimizing treatment timing, and addressing psychosocial impacts to enhance patient outcomes. By addressing gaps in knowledge and integrating patient-reported outcomes, this study underscores the importance of a multidisciplinary approach to managing inherited aortopathies and improving the quality of life for affected individuals.
2024-04-12 | Possible involvement of zinc transporter ZIP13 in myogenic differentiation
Abstract Ehlers–Danlos syndrome spondylodysplastic type 3 (EDSSPD3, OMIM 612350) is an inherited recessive connective tissue disorder that is caused by loss of function of SLC39A13/ZIP13, a zinc transporter belonging to the Slc39a/ZIP family. We previously reported that patients with EDSSPD3 harboring a homozygous loss of function mutation (c.221G > A, p.G64D) in ZIP13 exon 2 ( ZIP13 G64D ) suffer from impaired development of bone and connective tissues, and muscular hypotonia. However, whether ZIP13 participates in the early differentiation of these cell types remains unclear. In the present study, we investigated the role of ZIP13 in myogenic differentiation using a murine myoblast cell line (C2C12) as well as patient-derived induced pluripotent stem cells (iPSCs). We found that ZIP13 gene expression was upregulated by myogenic stimulation in C2C12 cells, and its knockdown disrupted myotubular differentiation. Myocytes differentiated from iPSCs derived from patients with EDSSPD3 (EDSSPD3-iPSCs) also exhibited incomplete myogenic differentiation. Such phenotypic abnormalities of EDSSPD3-iPSC-derived myocytes were corrected by genomic editing of the pathogenic ZIP13 G64D mutation. Collectively, our findings suggest the possible involvement of ZIP13 in myogenic differentiation, and that EDSSPD3-iPSCs established herein may be a promising tool to study the molecular basis underlying the clinical features caused by loss of ZIP13 function.
2024-03-08 | P321: Atypical presentation of vascular Ehlers-Danlos syndrome (vEDS)
Vascular Ehlers-Danlos Syndrome (vEDS) is a heritable disorder of connective tissue caused by heterozygous pathogenic variants in COL3A1. vEDS is characterized by arterial, intestinal, and/or uterine fragility; easy bruising; thin, translucent skin; and characteristic physical features (prominent eyes, narrow nose, thin vermilion of lips, micrognathia, and an aged appearance of the extremities, especially the hands). Most individuals without a positive family history present in adulthood with acute vascular dissection or organ rupture. Unlike other connective tissue disorders, vEDS dissections may occur at any existing dimension, and not just in those with known vascular dilation. Genetics was consulted to the NICU for a 1-day old infant, born at 35 week gestational age, with multiple congenital anomalies including rocker-bottom feet, hallux varus, bilateral cryptorchidism, right femur fracture, significant bruising, and right brachial plexus injury. The pregnancy was complicated by oligohydramnios, gestational diabetes, chorioamniotic separation, and ultrasound findings concerning for a lemon-shaped cranium, usually associated with neural tube defects, and rocker-bottom feet. A chromosomal microarray (CMA) was nondiagnostic. He was followed by outpatient genetics and there was concern for specific connective tissue disorders, including osteogenesis imperfecta or classical Ehlers Danlos Syndrome (cEDS). Genetic sequencing of COL1A1, COL1A2, COL5A1, and COL5A2 was performed and was normal. He was lost to follow-up around 20 months of age. At 14 years of age, he presented acutely to the emergency department with a spontaneous sigmoid bowel perforation. Updated history revealed recurrent shoulder dislocation, patellar instability, joint laxity, and easy bruising. Physical examination revealed dysmorphic facial features (thin nose and prominent eyes), wide scars, a prominent venous pattern on the chest, and slightly hyperextensible skin. Screening echocardiogram was normal. Single gene sequencing of COL3A1 revealed a heterozygous, likely pathogenic, splice-site variant (c.1609-5_1615del), predicted to result in the deletion of 12 nucleotides and interfere with splicing. This variant has not been reported before. Subsequent parental testing revealed that this variant is likely de novo. He was evaluated by cardiology and currently does not have any cardiac manifestations. He will undergo comprehensive MR angiography to screen for abnormalities in the vasculature. This case highlights an atypical presentation of vascular Ehlers-Danlos Syndrome (vEDS) with a novel variant in the COL3A1 gene, associated with a serious outcome. After presenting with a right femur fracture and brachial plexus injury at birth, the proband was largely asymptomatic other than easy bruising, joint laxity, and joint instability. He subsequently presented with a serious feature of spontaneous sigmoid perforation. Evidence suggests improvement in survival for vEDS patients when an accurate diagnosis is made, with appropriate clinical management and long-term follow-up. There is significant overlap in symptoms between the Ehlers Danlos Syndrome subtypes. Thus, improvement in phenotyping and early diagnosis is crucial. The use of multi-gene panels or comprehensive genomic testing is emerging as a more efficient option when indistinguishable phenotypes cause delays in testing. Further review and study will enhance our ability for early detection of vEDS and appropriate follow-up to prevent undesirable outcomes.
2024-02-23 | Genetic complexity of diagnostically unresolved Ehlers-Danlos syndrome.
The Ehlers-Danlos syndromes (EDS) are heritable disorders of connective tissue (HDCT), reclassified in the 2017 nosology into 13 subtypes. The genetic basis for hypermobile Ehlers-Danlos syndrome (hEDS) remains unknown. Whole exome sequencing (WES) was undertaken on 174 EDS patients recruited from a national diagnostic service for complex EDS and a specialist clinic for hEDS. Patients had already undergone expert phenotyping, laboratory investigation and gene sequencing, but were without a genetic diagnosis. Filtered WES data were reviewed for genes underlying Mendelian disorders and loci reported in EDS linkage, transcriptome and genome-wide association studies (GWAS). A genetic burden analysis (Minor Allele Frequency (MAF) <0.05) incorporating 248 Avon Longitudinal Study of Parents and Children (ALSPAC) controls sequenced as part of the UK10K study was undertaken using TASER methodology. Heterozygous pathogenic (P) or likely pathogenic (LP) variants were identified in known EDS and Loeys-Dietz (LDS) genes. Multiple variants of uncertain significance where segregation and functional analysis may enable reclassification were found in genes associated with EDS, LDS, heritable thoracic aortic disease (HTAD), Mendelian disorders with EDS symptomatology and syndromes with EDS-like features. Genetic burden analysis revealed a number of novel loci, although none reached the threshold for genome-wide significance. Variants with biological plausibility were found in genes and pathways not currently associated with EDS or HTAD. We demonstrate the clinical utility of large panel-based sequencing and WES for patients with complex EDS in distinguishing rare EDS subtypes, LDS and related syndromes. Although many of the P and LP variants reported in this cohort would be identified with current panel testing, they were not at the time of this study, highlighting the use of extended panels and WES as a clinical tool for complex EDS. Our results are consistent with the complex genetic architecture of EDS and suggest a number of novel hEDS and HTAD candidate genes and pathways.
2023-03-16 | Pathophysiological Investigation of Skeletal Deformities of Musculocontractural Ehlers–Danlos Syndrome Using Induced Pluripotent Stem Cells
Musculocontractural Ehlers–Danlos syndrome caused by mutations in the carbohydrate sulfotransferase 14 gene (mcEDS-CHST14) is a heritable connective tissue disorder characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral, and ocular systems. Progressive skeletal deformities are among the most frequent and serious complications affecting the quality of life and activities of daily living in patients. After establishing induced pluripotent stem cells (iPSCs) from cultured skin fibroblasts of three patients with mcEDS-CHST14, we generated a patient iPSC-based human osteogenesis model and performed an in vitro assessment of the phenotype and pathophysiology of skeletal deformities. Patient-derived iPSCs presented with remarkable downregulation of osteogenic-specific gene expression, less alizarin red staining, and reduced calcium deposition compared with wild-type iPSCs at each stage of osteogenic differentiation, including osteoprogenitor cells, osteoblasts, and osteocytes. These findings indicated that osteogenesis was impaired in mcEDS-CHST14 iPSCs. Moreover, the decrease in decorin (DCN) expression and increase in collagen (COL12A1) expression in patient-derived iPSCs elucidated the contribution of CHST14 dysfunction to skeletal deformities in mcEDS-CHST14. In conclusion, this disease-in-a-dish model provides new insight into the pathophysiology of EDS and may have the potential for personalized gene or drug therapy.
cell therapies
2025-09-24 | Complex Wound Reconstruction in a Patient With Ehlers-Danlos Syndrome.
Ehlers-Danlos syndrome (EDS) is a hereditary condition marked by collagen defects leading to tissue fragility throughout various body systems. One notable challenge for patients with EDS is compromised wound healing due to connective tissue fragility. This study described the case of a 53-year-old man with classical type EDS, presenting with a significant wound over his left knee, following numerous complications after a patellar tendon rupture. Traditional healing methods, including a gastrocnemius flap, were of limited benefit due to the patient's EDS condition. A novel surgical approach, involving the use of a split-thickness skin graft combined with the Recell Autologous Skin Cell Harvesting Device, resulted in successful wound healing. Ten months postsurgery, the patient demonstrated excellent graft adherence without any complications. This case indicates the potential benefits of the split-thickness skin graft and Recell method for patients with EDS, offering an effective treatment modality for significant wound healing challenges in this population.
2025-08-26 | B3GALT6 mutations lead to compromised connective tissue biomechanics in Ehlers-Danlos syndrome.
Ehlers-Danlos syndromes (EDS) comprise a genetically and clinically heterogenous group of rare diseases that cause severe, often fatal, damage to connective tissue. The molecular basis of EDS implicates defects in extracellular matrix components, including various fibrillar collagens and glycosaminoglycans (GAGs). However, the precise pathogenic mechanisms behind EDS remain elusive. Here, we have implemented a multi-tiered approach to demonstrate the functional impact of B3GALT6 mutations on biochemical and developmental processes, ultimately leading to the spondylodysplastic subtype of EDS (spEDS), characterized by severe musculoskeletal symptoms. We show that the loss of function of β1,3-galactosyltransferase 6 (β3GalT6) is partially compensated by β1,3-glucuronosyltransferase 3 (GlcAT-I), the next enzyme in the GAG biosynthetic pathway. In addition, results from transcriptomics, collagen analysis, and biophysical experiments revealed that impaired collagen maturation, including defective glycosylation of collagen XII, contributes to altered tissue structure and biomechanics, the hallmarks of spEDS. Our findings unravel a new pathogenic mechanism of spEDS and bring us one step closer to therapeutic strategies, including cell and tissue engineering.
2025-04-26 | The Successful Treatment of a Patient with Ehlers-Danlos Syndrome (EDS) After an Extensive Burn Injury: A Case Report.
Introduction: Ehlers-Danlos Syndromes (EDSs) are a heterogeneous group of monogenic connective tissue disorders (e.g., joint hypermobility and dislocation, skin hyperelasticity and fragility, chronic pain, delayed wound healing process,, etc.). The primary objective of this study was to present a specialized therapeutic wound management process for a burn-injured female patient diagnosed with EDS. Case Presentation: A 34-year-old female patient presented with extensive thermal burns (biofireplace explosion). The patient had a family history of diagnosed EDS. Additionally, the patient was in a poor mental condition and, since 2020, had been undergoing pharmacotherapy with antidepressant and anti-anxiety medication. This might be the first such clinical observation in the world, but a correlation has been observed between psychiatric medication use and EDS wound healing impairment. During the hospitalization process, the patient underwent a series of surgeries aimed at the fastest and most effective closure of wounds. The patient, after 182 days of hospitalization in our facility, was discharged home. Materials and Methods: During the patient's hospital stay, the patient underwent multiple procedures involving debridement of necrotic tissues. Additionally, allogeneic acellular dermal matrix (ADM) grafting was performed on the wounds, and a procedure was conducted in which skin was grafted using the MEEK technique. The in vitro cultured skin cells, as the advanced therapy medicinal products (ATMPs), were used. During the patient's stay in the hospital, images were taken using low-energy laser speckle contrast analysis (LASCA) to asses microperfusion or lack thereof. The measurements were taken at intervals of several days. Conclusions: The treatment of burn wounds in patients with EDS requires a long hospitalization period. It also may require a multi-stage approach utilizing innovative preparations (e.g., ADMs and ATMPs). The assessment of wound healing progress can be performed using advanced equipment, such as laser speckle contrast analysis (LASCA).
2025-01-01 | Management of Tongue Ulcer and Temporomandibular Joint Subluxation in Ehler-Danlos Syndrome Versus Non-Syndromic Patients
Objective: In our study we were focusing on treatment of ulcers in the lateral border of the tongue caused by repeated trauma and Temporomandibular joints (TMJ) subluxation. Moreover, we compared the results among non-syndromic patients (normal patients) versus syndromic patients (Ehlers-Danlos syndrome (EDS)).Methods: This clinical, interventional, prospective, and randomized controlled study was carried out on individual chosen from the outpatient clinic. The study has been performed on 20 patients divided into two groups equally, Group I (control group) consisted of 10 normal patients had tongue ulceration and TMJ subluxation (4 males and 6 females). Group II (study group) consisted of 10 patients had tongue ulceration and TMJ subluxation with Ehler-Danlos syndrome (4 males and 6 females).Results: After one day, group I showed a significant reduced pain score contrasted to group II (P-value = 0.015). After two days, group I revealed a significantly reduced pain score contrasted to group II (P-value = 0.012). After seven days, group I revealed a statistically significantly reduced pain score contrasted to group II (P-value = 0.071). A significant reduction in the diameter in group I in a shorter period contrasted to group II (P-value = 0.005).Conclusion: low level laser therapy is an effective tool for management of tongue ulcer and intrarticular injection of auotologous blood is a magic choice for management of temporomandibular joint subluxation. However, non- syndromic normal patients showed marked and rapid improvement more than patients with Ehler-Danols syndrome.
2024-11-15 | Hippotherapy in the management of hypermobile Ehlers-Danlos syndrome.
Hypermobile Ehlers-Danlos syndrome (EDS) is an inherited condition marked by joint hypermobility, instability, chronic pain and fatigue, significantly impacting quality of life and autonomy. Management focuses solely on symptom alleviation. After experiencing a rapid decline in functional abilities, a patient in late adolescence with hypermobile EDS underwent hippotherapy rehabilitation (30 hours). She saw substantial improvements in fatigue, chronic pain and regained walking abilities. Hippotherapy played a crucial role in refining her postural balance, motor skills, proprioception, muscle function and endurance. It also positively affected her cognitive and emotional regulation by stimulating sensory inputs that activate neural pathways, providing relief from pain and fatigue. Notably, the patient transitioned from wheelchair reliance to walking with crutches, and then greatly enhanced both gait quality and speed. These findings demonstrate the relevance of hippotherapy for the rehabilitation of hypermobile EDS, reducing the need for pharmacological interventions and fostering a proactive approach to future challenges.
proteins
2026-08-08 | Excessive Hypocapnic Cerebral Vasoconstriction in Hypermobile Ehlers-Danlos Syndrome Assessed With Real-Time Magnetic Resonance Imaging During Lower-Body Negative Pressure.
Orthostatic intolerance is common in hypermobile Ehlers-Danlos syndrome (hEDS) with one third of patients fulfilling postural orthostatic tachycardia syndrome criteria. Our aim was to assess cerebral blood flow in patients with hEDS and postural orthostatic tachycardia syndrome during orthostasis, which may be responsible for orthostatic intolerance. In 18 individuals with hEDS and postural orthostatic tachycardia syndrome and 20 healthy controls, we conducted real-time phase contrast magnetic resonance imaging of the middle cerebral artery with and without an orthostatic challenge through 30 mm Hg lower-body negative pressure. During lower-body negative pressure, heart rate increased more in hEDS than in controls (15.0±8.3 bpm versus 7.8±7.7 bpm, P=0.009); blood pressure remained unchanged; middle cerebral artery flow per heartbeat decreased more in hEDS (-28%±16% versus -15%±13% in controls, P=0.013) with decreased mean volumetric flow in hEDS (-12%±17%, P<0.001 versus -6%±8% in controls, P=0.102); average middle cerebral artery peak blood flow velocity decreased in both groups (hEDS: 44.6±8.1 cm/s to 37.6±8.4 cm/s, P<0.001; controls: 40.3±10.9 cm/s to 36.9±11.1 cm/s, P=0.018); respiration rate increased in hEDS (14.3±5.1/min to 17.4±5.3/min, P=0.002) leading to a decrease in end-tidal CO2 (39.2±4.2 mm Hg to 35.6±6.4 mm Hg, P=0.025), and cerebrovascular resistance increased more in hEDS (50.8%±48.4%, P<0.001) versus (20.3%±20.6%, P=0.005) in controls. Individuals with hEDS and postural orthostatic tachycardia syndrome maintain cerebral perfusion primarily through tachycardic compensation during orthostatic stress despite hypocapnic vasoconstriction. URL: https://drks.de/search/en; Unique Identifier: DRKS00028279.
2026-03-18 | Spontaneous coronary artery dissection and vascular Ehlers-Danlos syndrome: a systematic review and case series.
Spontaneous coronary artery dissection (SCAD) is a cause of acute myocardial infarction predominantly affecting adult women. A proportion of SCAD cases are associated with rare heritable connective tissue disorders. Vascular EDS (vEDS), due to deleterious variants in COL3A1, is one of the most common of these. Our aim was to identify specific features of SCAD in vEDS which may aid patient selection for genetic testing. A systematic review of published cases of individuals with SCAD and vEDS was conducted. Additionally, patients with SCAD and genetically confirmed vEDS (SCAD-vEDS) were identified through the UK national EDS service and UK SCAD registry. Data were collected on presentation, management and extra-cardiac findings. Angiography was compared with an age and sex-matched, exome sequenced, control cohort with SCAD but without vEDS (SCAD-nonvEDS). Data from ten SCAD-vEDS patients were identified. There was a lower average age of SCAD and higher proportion of males in individuals with SCAD-vEDS, however differences should be interpreted carefully given cohort size. Fifty-six cases of SCAD-vEDS were identified through systematic review. Systemic features were present in most but not all cases. This report presents a new, angiographically characterised case-control cohort along with a systematic review of the current literature. Whilst clinical differences appear between the SCAD-vEDS and SCAD-nonvEDS groups, these are insufficient to accurately distinguish SCAD-vEDS from the general SCAD population. All individuals with SCAD should be evaluated for underlying vEDS but clinical assessment will miss some cases. Wider genetic testing in some SCAD patients may be merited to enable appropriate management. Systematic review registration: https://www.crd.york.ac.uk/prospero/536751 Identifier: 536751.
2026-01-27 | Health-Related Quality of Life in Midlife and Older Women With Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders.
To identify factors associated with health-related quality of life (HRQOL) in midlife and older women with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders (hEDS/HSD). Online, cross-sectional survey. Online survey was administered to participants in Ehlers-Danlos syndrome Facebook groups. Women ages 40 years and older with a diagnosis of hEDS/HSD. Online survey including demographic and health history; 36-Item Short-Form Health Survey (SF-36) to measure HRQOL; and free-text questions related to things that reduced and improved well-being. Sixty-six women (mean age, 55 years) participated in the survey. Symptom onset was in childhood, but treatment was not sought until their late 20s. The mean age at diagnosis was the mid-40s; thus, the diagnosis was delayed by more than 18 years from the time participants first sought treatment. Comorbidities were common, with 62% of participants reporting seven or more comorbid diagnoses. The SF-36 scores indicated a high symptom burden and poor HRQOL, with worse mean scores in the physical domains compared to the mental domains. Symptom severity, treatment restrictions, environmental factors, comorbidities, and interactions with health care providers influenced HRQOL. Nursing has an emerging role in research and education related to genetic syndromes and heritable connective tissue disorders, including hEDS/HSD, in midlife and older women. Future research should address the complex relationships among physical, social, personal, and environmental factors to maximize HRQOL in this population.
2025-11-29 | Human Proteoglycan Linkage Region Glycosyltransferases are Dimeric and Show Unexpected Specificities.
We selected the N,O-glycosylated proteoglycan bikunin as a model to establish a chemoenzymatic approach to defined proteoglycans using native chemical ligation. Overexpression of the human linkage region glycosyltransferases B4GalT7, B3GalT6 and B3GlcAT-1 as N-terminal SUMO-fusions gave high yields of soluble and active enzymes in E. coli. When starting with xylosylated bikunin peptides the transferases performed well in enzymatic cascade reactions and provided the desired linkage region tetrasaccharide glycopeptides. B3GalT6 and B3GlcAT-1 led to side products with N,O-glycosylated bikunin peptides revealing unexpected promiscuity of both enzymes towards complex type N-glycans. Additionally, B3GalT6 was found to synthesize short poly-β3 Gal structures. B3GlcAT-1 can slowly convert the biosynthetic intermediate Gal-Xyl to the non-canonical trisaccharide GlcA-Gal-Xyl. This reaction independently confirmed the recently detected biosynthetic bypass to GAGs in the case of dysfunctional B3GalT6 (spondylodysplastic Ehlers-Danlos-syndrome). The three linkage region glycosyltransferases B4GalT7, B3GalT6 and B3GlcAT-1 were dimeric in solution and the crystal structure of B3GalT6 was solved showing a covalent dimer linked by a disulfide in the center of the large dimerization domain. This motif appears to be conserved in higher organisms and reinforces the concept of dimeric glycosyltransferases lining the Golgi.
2025-11-12 | A visual guide for emergency radiologists navigating the complexity of abdominal vasculitis: part 2 - the mimickers.
Part 2 of this pictorial essay focuses on conditions that mimic abdominal vasculitis, examining their distinct imaging characteristics using 2D and advanced 3D CT techniques, including volume rendering (VR) and cinematic rendering (CR). These mimickers include fibromuscular dysplasia (FMD), segmental arterial mediolysis (SAM), IgG4-related disease, median arcuate ligament syndrome, infections, genetic conditions such as vascular Ehlers-Danlos syndrome, Marfan syndrome, and Loeys-Dietz syndrome, as well as non-Langerhans cell histiocytic disorders like Erdheim-Chester disease and Rosai-Dorfman disease. This article features illustrative case examples that emphasize the imaging hallmarks of these conditions, aiding radiologists in differentiating them from true vasculitis. This is particularly useful in acute scenarios like abdominal pain, where timely recognition is crucial for informing treatment decisions and improving patient outcomes.
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2025-11-17 | Challenging Orthognathic Surgery in Ehlers-Danlos Syndrome: A Successful Case with Denosumab Therapy : a case report
Background: Ehlers-Danlos Syndrome (EDS) is a heterogeneous disorder characterized by defects in collagen maturation. Patients with EDS commonly exhibit joint hypermobility, skin hyperextensibility, and tissue fragility. The syndrome can affect oral health, the vascular system, bones, teeth, periodontium, as well as the neuromuscular and joint systems. Due to reduced bone density, some EDS patients may receive antiresorptive medications, which can increase the risk of medication-related osteonecrosis of the jaw (MRONJ). Case Presentation : We report a case of a 25-year-old Iranian female with EDS and a history of denosumab therapy. She underwent bimaxillary orthognathic surgery to correct skeletal malocclusion. The procedure presented multiple challenges, including inherent bone abnormalities, prior denosumab use, and altered collagen structure, all contributing to unpredictable bone healing. Conclusion: Despite these challenges, the patient was successfully treated with bimaxillary orthognathic surgery, achieving a highly satisfactory outcome in terms of both functional rehabilitation and aesthetic improvement.
2025-11-01 | Hypermobile Ehlers-Danlos syndrome (hEDS) and the complement system: A new perspective on pathophysiology 9152
Abstract Description Hypermobile Ehlers-Danlos Syndrome (hEDS) is a heritable connective tissue disorder of unknown origin. Our studies show that hEDS extends beyond a connective tissue disease, broadly affecting gastrointestinal function, autonomic regulation, pain, and the immune system. Using an unbiased proteomics approach, we identified 25 differentially expressed serum proteins in hEDS (N = 38) compared to age- and sex-matched controls (N = 8). Half of these proteins were linked to complement and mast cell pathways. Validation via ELISAs confirmed significantly reduced levels of C1QA, C3, C8a, C8b, and C9 in hEDS patients compared to controls (165.5 vs. 125.1 µg/mL, p < 0.01; 1.976 vs. 1.847 mg/mL, p < 0.001; 77.32 vs. 58.80 µg/mL, p < 0.001; 90.78 vs. 67.13 µg/mL, p < 0.0001; 53.02 vs. 44.15 µg/mL, p < 0.05, respectively). Levels of C4B were also reduced, albeit not significantly (109.7 vs. 93.91 µg/mL). These findings persisted after controlling for known autoimmune conditions, suggesting these immune changes may be intrinsic to hEDS. Our findings reveal a previously unrecognized connection between hEDS and complement system dysregulation, challenging its classification as solely a connective tissue disorder and instead pointing to immune dysregulation as a central factor in hEDS pathophysiology. These findings warrant further research into complement dysfunction and mast cell activation in hEDS, and the development of immune-targeted therapies to mitigate symptoms. Funding Sources Supported by EDS Society; Maltz Fndn. Topic Categories Immune Mechanisms of Human Disease (HUM)
2025-01-08 | Integrative Multi-Omics Approach in Vascular Ehlers-Danlos Syndrome: Further Insights into the Disease Mechanisms by Proteomic Analysis of Patient Dermal Fibroblasts.
Background: Dominant mutations in COL3A1 are known to cause vascular Ehlers-Danlos syndrome (vEDS) by impairing extracellular matrix (ECM) homeostasis. This disruption leads to the fragility of soft connective tissues and a significantly increased risk of life-threatening arterial and organ ruptures. Currently, treatments for vEDS are primarily symptomatic, largely due to a limited understanding of its underlying pathobiology and molecular mechanisms. Methods: In this study, we conducted a comprehensive analysis of the intracellular proteome of vEDS fibroblasts, integrating these findings with our previous transcriptome results to identify key molecular pathways that drive the disease. Additionally, we explored the therapeutic potential of inhibiting miR-29b-3p as a proof of concept. Results: Our integrative multi-omics analysis revealed complex pathological networks, emphasizing the critical role of miRNAs, particularly miR-29b-3p, in impairing ECM organization, autophagy, and cellular stress responses, all of which contribute to the pathogenesis of vEDS. Notably, the inhibition of miR-29b-3p in vEDS fibroblasts resulted in the upregulation of several differentially expressed target genes involved in these critical processes, as well as increased protein expression of essential ECM components, such as collagen types V and I. These changes suggest potential therapeutic benefits aimed at improving ECM integrity and restoring intracellular homeostasis. Conclusions: Overall, our findings advance our understanding of the complex biological mechanisms driving vEDS and lay a solid foundation for future research focused on developing targeted and effective treatment strategies for this life-threatening disorder.
2024-08-29 | Is Exon Skipping a Viable Therapeutic Approach for Vascular Ehlers-Danlos Syndrome with Mutations in COL3A1 Exon 10 or 15?
Vascular Ehlers-Danlos syndrome or Ehlers-Danlos syndrome type IV (vEDS) is a connective tissue disorder characterised by skin hyperextensibility, joint hypermobility and fatal vascular rupture caused by COL3A1 mutations that affect collagen III expression, homo-trimer assembly and secretion. Along with collagens I, II, V and XI, collagen III plays an important role in the extracellular matrix, particularly in the inner organs. To date, only symptomatic treatment for vEDS patients is available. Fibroblasts derived from vEDS patients carrying dominant negative and/or haploinsufficiency mutations in COL3A1 deposit reduced collagen III in the extracellular matrix. This study explored the potential of an antisense oligonucleotide (ASO)-mediated splice modulating strategy to bypass disease-causing COL3A1 mutations reported in the in-frame exons 10 and 15. Antisense oligonucleotides designed to redirect COL3A1 pre-mRNA processing and excise exons 10 or 15 were transfected into dermal fibroblasts derived from vEDS patients and a healthy control subject. Efficient exon 10 or 15 excision from the mature COL3A1 mRNA was achieved and intracellular collagen III expression was increased after treatment with ASOs; however, collagen III deposition into the extracellular matrix was reduced in patient cells. The region encoded by exon 10 includes a glycosylation site, and exon 15 encodes hydroxyproline and hydroxylysine-containing triplet repeats, predicted to be crucial for collagen III assembly. These results emphasize the importance of post-translational modification for collagen III homo-trimer assembly. In conclusion, while efficient skipping of target COL3A1 exons was achieved, the induced collagen III isoforms generated showed defects in extracellular matrix formation. While therapeutic ASO-mediated exon skipping is not indicated for the patients in this study, the observations are restricted to exons 10 and 15 and may not be applicable to other collagen III in-frame exons.
2024-01-12 | Systemic pain relief after omalizumab injection in patient with hypermobile Ehlers–Danlos syndrome: A case report
Key Clinical Message Omalizumab may be a beneficial adjunct treatment option for hEDS patients require to improve pain control, ability to perform ADLs and functionality and social engagement, and most importantly, quality of life.
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Drug Discovery Landscape
3 orphan drug designations for Ehlers-Danlos syndrome.
3 orphan drug designations for Ehlers-Danlos syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Enzastaurin hydrochloride | small molecules | EMA | 2022-02-24 | — | Orphix Consulting GmbH |
enzastaurin | small molecules | FDA | 2021-12-07 | — | Aytu BioPharma, Inc. |
celiprolol | small molecules | FDA | 2015-01-05 | — | Acer Therapeutics, Inc. |
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