Diagnosis Of Ehlers-Danlos Syndrome Research Articles

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

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

Patient and Parent Knowledge, Understanding, and Concerns After a New Diagnosis of Ehlers Danlos Syndrome.

After diagnosis of Ehlers Danlos Syndrome (EDS), it is unclear what information patients and parents need and understand about EDS. The objective of this study is to characterize patient and parent knowledge and concerns about EDS after a diagnosis of EDS is made to determine patient and parent concerns and identify barriers that cause discomfort with the diagnosis. A convenience sample of patient and parent dyads were recruited after new diagnosis of EDS. Patients and parents completed questionnaires that assessed knowledge, comfort, and barriers of EDS before and after diagnosis, EDS education materials accessed, and additional clinical needs and concerns. Seventy-two dyads completed the survey. Many respondents actively seek information on the diagnosis and management of EDS. Parents and patients look for information about EDS differently. Parents have more concerns after diagnosis and both want well-constructed, empirically supported educational materials delivered via multiple modalities, which makes clinical guidelines more essential.

Outcomes of primary total hip arthroplasty in patients with Ehlers Danlos Syndromes.

The Ehlers Danlos Syndromes (EDS) are inherited in an autosomal dominant pattern and patients classically present with hypermobility, skin hyper-elasticity, blood vessel fragility and atrophic scarring. Due to hypermobility, disorders such as joint pain and early arthritis are common. The aim of this study was to assess clinical and radiological outcomes of total hip arthroplasty (THA) in patients with EDS treated in a high volume orthopaedic centre. A search was performed of the electronic patient record system at our institution from 1998 - 2019 using the search terms 'EDS' or 'Danlos' and 'arthroplasty'. Over the 22-year study period, there were approximately 32,000 primary THAs performed at our institution. We collated demographic information including age, gender, BMI, smoking history and medical comorbidities. Implant type, bearing surfaces and size was also documented, with clinical and radiological assessment at last known follow up. A total of n=5 primary THAs were identified in n=4 patients at a median follow-up of 3 years. All patients were female with a median age of 68 (SD 18.9) years and a median BMI of 30.7 (SD 4.5). The majority of patients were smokers, and had a chronic history of low back pain (n=3, 75%). Uncemented implants were used on n=3 occasions with the remainder being hybrid (n=2). Femoral head size ranged from 28mm to 44mm. One patient had a post-operative surgical wound erythema that resolved within 48 hours of onset, otherwise there were no significant wound complications. To date, there have been no documented dislocations, with all patients having satisfactory clinical and radiological outcome at last known follow up. This study demonstrates that total hip arthroplasty can be safely performed in patients with a diagnosis of EDS, with no significant complications in the intermediate term.

Outcomes of Total Knee Arthroplasty in Patients Who Have Ehlers-Danlos Syndrome: A Matched Cohort Study

BackgroundTotal knee arthroplasty (TKA) is an excellent surgical option for patients who have end-stage knee osteoarthritis. While rates of major postoperative complications have steadily decreased with modern implants and operative techniques, contemporary outcome data for patients who have Ehlers-Danlos syndrome (EDS) are scarce. The goal of this study was to compare complication rates after primary TKA in patients who have EDS versus matched controls. MethodsA large administrative database was used to identify patients who underwent primary TKA from 2009 to 2020. Patients who had a diagnosis of EDS were identified by International Classification of Diseases Coding. Propensity scores were utilized to match these patients with controls at a 1:4 ratio based on age, sex, and various comorbidities. Multivariable logistic regression analysis was used to compare the rates of medical and surgical complications at 90 days and 2 years. A total of 188 patients who had EDS and 752 controls were included in this study. ResultsAfter univariate analysis, Ehlers-Danlos patients exhibited significantly higher rates of wound complications (4.8 versus 0.9%, P = .001) at 90 days. When adjusted for comorbidities, Ehlers-Danlos patients still exhibited significantly increased odds of developing wound complications (odds ratio: 7.06; P < .001). ConclusionsPatients who have EDS undergoing TKA exhibited significantly higher rates of wound complications within 90 days postoperatively compared to matched controls. Rates of instability, manipulation under anesthesia, periprosthetic joint infection, aseptic loosening, and aseptic revision arthroplasty did not significantly differ between the cohorts. This study found generally favorable short-term outcomes of TKA in this population; however, the inability to control for implant type and other confounding variables may have influenced the lack of difference in complication rates at 2 years. Surgeons should monitor for the potentially increased risk of wound complications and consider the possible need for increased constraint in this population during preoperative planning.

Diagnosis and treatment of the Ehlers-Danlos syndromes in China: synopsis of the first guidelines

BackgroundThe Ehlers-Danlos syndromes (EDS) are a group of rare hereditary connective tissue disorders. EDS is clinically and genetically heterogeneous and usually involves multiple systems. There are 14 subtypes of EDS with hallmark features including joint hypermobility, skin hyperextensibility, and tissue fragility. The clinical manifestations and their severity differ among the subtypes, encompassing recurrent joint dislocations, scoliosis, arterial aneurysm and dissection, and organ rupture. Challenges in diagnosis and management arise from the complexity of the disease, which is further complicated by its rarity. The development of clinical guidelines and implementation of coordinated multi-disciplinary team (MDT) approaches have emerged as global priorities.Main bodyChinese Multi-Disciplinary Working Group on the Ehlers-Danlos Syndromes was therefore established. Healthcare professionals were recruited from 25 top hospitals across China. The experts are specialized in 24 fields, including genetics, vascular surgery, dermatology, and orthopedics, as well as nursing care, rehabilitation, psychology, and nutrition. Based on GRADE methodology, the Guidelines were written by the Group supervised by methodologists, following a systemic review of all 4453 articles in PubMed published before August 9, 2023, using the search term “Ehlers Danlos”. A coordinated MDT approach for the diagnosis and management of EDS is highly recommended by the Group, along with 29 specific recommendations addressing key clinical questions. In addition to the treatment plan, the Guidelines also emphasize integrating support from nursing care, rehabilitation, psychology, and nutrition. This integration not only facilitates recovery in hospital settings, but most importantly, the transition from an illness-defined life to a more “normalized” life.ConclusionThe first guidelines on EDS will shorten the diagnostic odyssey and solve the unmet medical needs of the patients. This article is a synopsis of the full guidelines.

Total hip arthroplasty outcomes in Ehlers-Danlos patients: data from the Statewide Planning and Research Cooperative System.

Ehlers-Danlos syndromes (EDS) are genetic connective tissue disorders affecting multiple organ systems that frequently result in connective tissue hyperlaxity and early osteoarthritis. Short- and long-term outcomes after primary total hip arthroplasty (THA) in this patient population remain poorly characterised. The primary purpose of this study is to compare postoperative outcomes and survivorship after primary THA in patients with and without EDS. The New York Statewide Planning and Research Cooperative System (SPARCS) database was queried for all patients undergoing primary elective THA between September 2009 and December 2020. Patients with EDS were identified using ICD9 and ICD10 diagnosis codes. Given the relatively low incidence of EDS in this patient population, the cohort was propensity-matched 1:10 to patients without diagnosis of EDS based on demographics characteristics and medical comorbidities as measured by the Elixhauser Comorbidity Index. A total of 66 THA patients with and 660 without EDS were included in each group after 1:10 propensity-matching. There were no significant differences in baseline characteristics or THA indications. Early postoperative outcomes such as length of hospital stay and discharge disposition were similar. Emergency Room visits and inpatient readmission rates at 3 months postoperatively did not significantly differ between groups. Patients with EDS had a higher overall revision rate compared to those without (15.0% vs. 3.2%, p < 0.001). Revision free survival after primary THA in patients with EDS was significantly lower than those without EDS at 9-year follow-up. Cox proportional hazard regression demonstrated EDS patients had 7-times higher risk of revision (hazard ratio [HR] 7.43; 95% CI, 3.46-16.00; p < 0.001). Lastly, revision due to instability insignificantly trended higher in the EDS cohort (HR 2.29; 95% CI, 0.95-5.49; p = 0.063). EDS patients undergoing primary THA have increased rate of all cause revision and demonstrate decreased revision free survival compared to non-EDS THA patients.

Patient interest in the development of a center for Ehlers-Danlos syndrome/hypermobility spectrum disorder in the Chicagoland region

BackgroundThe Ehlers-Danlos Syndromes (EDS) are a group of connective tissue disorders that are hereditary in nature and characterized by joint hypermobility and tissue fragility. The complex nature of this unique patient population requires multidisciplinary care, but appropriate centers for such care do not exist in large portions of the country. Need for more integrated services has been identified in Chicagoland, or Chicago and its suburbs. In order to explore and begin to address barriers to seeking appropriate care facing EDS patients in this region, we developed an online survey which we circulated through EDS social media groups for Chicagoland patients.ResultsThree hundred and nine unique respondents participated. We found that there exists a strong medical need for and interest in the development of a center in the region, and participants reported that, if made available to them, they would make extensive and regular use of such a facility.ConclusionsWe conclude that the establishment of a collaborative medical center specializing in the diagnosis and treatment of EDS, Hypermobility Spectrum Disorder, and related disorders in the Chicagoland area would greatly benefit patients by providing comprehensive care, alleviate the burden on overworked healthcare providers, and contribute to the sustainability of medical facilities.

Diagnosis of Ehlers-Danlos Syndrome in an Adolescent Who Presents with Recurrent Pneumothoraces and Hemoptysis

Diagnosis of Ehlers-Danlos Syndrome in an Adolescent Who Presents with Recurrent Pneumothoraces and Hemoptysis

An exploration of the journey to diagnosis of Ehlers-Danlos Syndrome (EDS) for women living in Australia.

Ehlers-Danlos syndromes (EDS) is an umbrella term for a group of hereditary connective tissue disorders usually featuring hyperextensible skin, easy bruising, poor healing, and joint hypermobility. According to international Ehlers-Danlos support groups, the average time to diagnosis of this rare genetic condition is 10-12 years. Consequently, the journey to diagnosis can potentially be traumatic. This pilot study aims to explore female patients' journey to a diagnosis of EDS while living in Australia. Over six weeks, from January to February 2023, a survey was distributed on EDS social media platforms including Facebook and LinkedIn. Ethical approval was obtained through the Ulster University Institute of Nursing and Health Research Ethics Filter Committee (FCNUR). Thematic and statistical analysis of the anonymous data was completed during March 2023. 152 women completed the survey. More than half of the respondents first noticed symptoms of EDS more than 15 years prior to diagnosis and more than three quarters of respondents received other diagnoses prior to their EDS diagnosis. Most respondents saw their general practitioner, a physiotherapist and/or a rheumatologist prior to being correctly diagnosed with the condition. While some respondents had positive experiences with these health professionals, many felt that they were not listened to and, after doing their own research, had to educate their health professional/s about EDS. This pilot survey demonstrated that the journey to diagnosis of EDS for women in Australia is frequently long and traumatic. Participants indicated that more EDS education and training is needed for health professionals, especially GPs, to improve the diagnostic process. Participants called for their self-reported symptoms to be listened to by health professionals and to be met with empathy and an open mind instead of being dismissed. Additional education and training to health professionals about connective tissue disorders including EDS may aid earlier diagnosis in Australia.

Some Patients with Suspected Thrombocytopathy Actually Have Ehlers-Danlos Syndrome; Clinical and Prognostic Implications

Thrombocytopathy is the most likely diagnosis for patients with easy bruising and/or mucous bleeding and normal platelet counts. However, in a small proportion of these patients, all hemostatic tests are normal and the right diagnosis is actually Ehlers-Danlos syndrome (EDS). EDS is a heterogeneous group of genetic connective tissue disorders, characterized by joint hypermobility, skin and vascular fragility, and tissue friability; the most recent classification describes 13 clinical subtypes of EDS with mutations in 19 different genes (Malfait et al. Am J Med Genet C Semin Med Genet. 2017;175:8). Besides joint hypermobility, cutaneous-mucosal bleeding of variable intensity is observed in the majority of patients. In the vascular subtype of EDS, arterial aneurysms, dissections and ruptures of arteries and arteriovenous fistulas are detected as manifestations of vascular fragility; less frequently, such vascular pathologies can also appear in other types of EDS (Malfait. Matrix Biol 2018;71-72:380). Based on our experience on patients with suspected thrombocytopathy but finally diagnosed of EDS, our objective is to attract the attention of hematologists to the possible diagnosis of EDS for patients with cutaneous-mucosal bleeding without any platelet or coagulation abnormality. This will lead to the adoption of the necessary measures to confirm diagnosis and to prevent complications, sometimes serious, of EDS. We studied 8 patients, all women, with cutaneous-mucosal bleeding referred to our consultation as suspected thrombocytopathies. The main characteristics of the patients are shown in Table 1. Platelet counts, platelet function, and coagulation tests were normal in all cases. However, the evaluation of their articular mobility showed generalized hypermobility with the Beighton score (Beighton. Ann Rheum Dis 1973;32:413). Two of the patients (cases 3 and 4) presented carotid-cavernous fistulas that led to loss of vision on the corresponding side. Case 3 was a 6-year-old girl with mild cutaneous bleeding and no other clinical manifestations. His mother, with a mild hemorrhagic tendency and no other symptoms, had died at the age of 35 from a massive peritoneal hemorrhage secondary to spontaneous rupture of the spleen; the observation of marked tissue fragility, at surgery and at necropsy, established the diagnosis of EDS. The girl's clinical bleeding, together with normal hemostatic tests and family history, suggested the diagnosis of EDS. This patient developed well, but, at the age of 18, a right carotid-cavernous fistula was diagnosed. Case 4 was a 51-year-old woman with a history of bronchial asthma, duodenal ulcer, gallstones, shoulder dislocations and bleeding tendency. At the age of 45, she had suffered a left carotid-cavernous fistula. Because the results of all hemostasis tests were normal, an exploration of her joint mobility was performed resulting in a positive Beighton score. This suggested the diagnosis of EDS. At the age of 55, we were informed that the patient had died, in another center, from massive bleeding in a surgical intervention for colon diverticula. Although it is not frequent, there is the possibility that a patient with bleeding and without hemostatic abnormalities suffers from EDS which, in our experience, can lead to serious vascular complications, even in patients with mild symptomatology. We recommend in these patients to perform a test as simple as the Beighton score. If the result indicates a possible EDS, we suggest referring the patient to all the necessary specialists to confirm the diagnosis and carry out proper patient care and prevention of complications. Moreover, bearing in mind the frequency of carotid-cavernous fistulas with orbital involvement in our case series, we suggest the patient should be informed about the ophthalmologic symptoms of this vascular complication (Fay et al. Clin Neuroradiol 2021;31:165). The most characteristic symptom is the anteroposterior displacement of the eyeball with each heartbeat. Other findings are proptosis, difficulty in making eye movements, chemosis, and conjunctival-scleral hyperemia with vascular tortuosity (Fig. 1). The ophthalmologist may also find venous tortuosity in the fundus, intraocular hypertension, with or without associated glaucoma, and enlargement of the superior ophthalmic vein on imaging tests. The recommended treatment is embolization of the fistula.

Ethnicity, hypermobility syndrome and Ehlers-Danlos syndrome: A study based on hospital admissions

The purpose of the study was to identify any evidence of different patterns of disease for Ehlers Danlos Syndrome (EDS) and Hypermobility Syndrome (JHS) in the White British and South Asian communities in England. The numbers of hospital in-patients in ten NHS Trusts, between 2016 and 2020, in whom a diagnosis of EDS or JHS had been recorded were identified through Freedom of Information (FOI) requests. The condition was either the primary diagnosis or a secondary one, incidental to the reason for admission. The ten Trusts were selected because they served areas with a significant South Asian population and had been involved in previous studies of discrimination in the delivery of care. The study also assessed whether there was evidence of any of the Trusts underserving their South Asian community with lesser levels of recognition of EDS and JHS. Overall South Asian patients were almost four times more likely to have been diagnosed as having JHS. This proportion was statistically significant (z = -11.69, p &lt;0.00001). In Burton and Derby, Cambridge and Leicester the proportion of South Asian patients diagnosed as having EDS was significantly lower than in other Trusts (z = 9.4, p &lt;0.00001). This was also the case for JHS (z = 8.09, p &lt; 0.00001). This would indicate that in these three Trusts both conditions are underdiagnosed in the South Asian community. The significance of these findings is discussed.

Pain in Ehlers–Danlos Syndrome: A Non-Diagnostic Disabling Symptom?

Ehlers-Danlos syndrome (EDS) is a phenotypically and genetically heterogeneous group of connective tissue disorders. Currently, diagnosis of EDS is based on a series of clinical and genetic tools. On the other hand, the hypermobile form has not yet been characterized from a genetic point of view: it is considered a part of a continuous spectrum of phenotypes, ranging from isolated non syndromic joint hypermobility, through to the recently defined hypermobility spectrum disorders (HSD). The aim of this study is to characterize the pain symptom that is not considered among the diagnostic criteria but is relevant to what concerns the quality of life of patients with EDS. (2) Methods: A review of the literature was performed on two medical electronic databases (PubMed and Embase) on 20 December 2022. Study selection and data extraction were achieved independently by two authors and the following inclusion criteria were determined a priori: published in the English language and published between 2000 and 2022. (3) Results: There were fifty eligible studies obtained at the end of the search and screen process. Pain is one of the most common symptoms found in Ehlers-Danlos (ED) patients. Different causes seem to be recognized in different phases of the syndrome. (4) Conclusions: Pain is a nonspecific symptom and cannot be considered among the diagnostic criteria, but it is a negative predictive factor in the quality of life of patients with EDS. Therefore, proper evaluation and treatment is mandatory.

COL1A1 and COL1A2 variants in Ehlers-Danlos syndrome phenotypes and COL1-related overlap disorder.

Pathogenic variants in COL1A1 and COL1A2 are involved in osteogenesis imperfecta (OI) and, rarely, Ehlers-Danlos syndrome (EDS) subtypes and OI-EDS overlap syndromes (OIEDS1 and OIEDS2, respectively). Here we describe a cohort of 34 individuals with likely pathogenic and pathogenic variants in COL1A1 and COL1A2, 15 of whom have potential OIEDS1 (n= 5) or OIEDS2 (n= 10). A predominant OI phenotype and COL1A1 frameshift variants are present in 4/5 cases with potential OIEDS1. On the other hand, 9/10 potential OIEDS2 cases have a predominant EDS phenotype, including four with an initial diagnosis of hypermobile EDS (hEDS). An additional case with a predominant EDS phenotype had a COL1A1 arginine-to-cysteine variant that was originally misclassified as a variant of uncertain significance despite this type of variant being associated with classical EDS with vascular fragility. Vascular/arterial fragility was observed in 4/15 individuals (including one individual with an original diagnosis of hEDS), which underscores the unique clinical surveillance and management needs in these patients. In comparison to previously described OIEDS1/2, we observed differentiating features that should be considered to refine currently proposed criteria for genetic testing in OIEDS, which will be beneficial for diagnosis and management. Additionally, these results highlight the importance of gene-specific knowledge for informed variant classification and point to a potential genetic resolution (COL1A2) for some cases of clinically diagnosed hEDS.

Multistage surgical treatment of early-onset scoliosis in patients with Ehlers-Danlos syndrome: A series of observations

BACKGROUND: EhlersDanlos syndrome (EDS) is a group of hereditary pathological conditions caused by various disorders of collagen biosynthesis. The study analyzed the results of multistage surgical treatment of early scoliosis in patients with severe spinal deformities due to EDS. No similar observations have been found in the literature.&#x0D; CLINICAL CASES: Four patients with a verified diagnosis of EDS and progressive spinal deformities were subjected to multistage surgical treatment using the VEPTRII instrumentation, which included periodic distractions and final spinal fusion with segmental instrumentation. Stage-by-stage surgical treatment was initiated from the age of 3 to 6 years. In 3 of 4 cases, the kyphotic component prevailed over the scoliotic one (86140 vs. 21110). The number of staged distractions ranged from 6 to 10. The age of the final stage (correction and dorsal fusion) was 914 years (surgery was performed in three of four cases). The primary correction was 3056, the loss of correction before the final stage was 1435, and the correction during the final stage was 2240. A significant correction of the frontal and sagittal imbalances of the spine was noted. Blood loss during the final fusion was 540750 mL, and the operation time was 310350 min. Ten complications occurred, of which 9 were associated with implants and disappeared during staged distractions. No neurological and vascular complications occurred.&#x0D; DISCUSSION: Scoliosis occurring in the first decade of life in patients with EDS is characterized by early-onset, rapid progression, and tendency to form a significant kyphotic component of spinal deformity.&#x0D; CONCLUSIONS: Multistage treatment of early scoliosis in patients with EDS using VEPTRII tools allows for obtaining quite satisfactory results and has not severe complications. The final fusion gives a significant corrective effect; however, new research and accumulation of data are needed to optimize the treatment process.

Resource utilization and multidisciplinary care needs for patients with Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) represents a family of heritable connective tissue disorders with overlapping phenotypic features, frequently including joint hypermobility, tissue fragility, and skin hyperextensibility. Comorbid symptoms are common for patients with EDS and include multiple body systems marked by neurologic, cardiovascular, gastrointestinal, musculoskeletal issues, chronic pain, headaches, and anxiety and depression. The many comorbidities lead to high disease burden, which requires greater healthcare utilization. This survey of families examines healthcare utilization, of adults and minors, through evaluation of subspecialty care appointments across many healthcare systems in one region. There were 155 adults and 83 minors with a diagnosis of EDS with a total of 693 unique visits across 27 different specialties at over 20 different hospitals or clinics in the surveyed area. Cardiology, neurology, and gastroenterology were the most utilized subspecialties for adults, while rheumatology, cardiology, and neurology were most utilized by minors. Many respondents (67%) reported their medical care needs are not being met, and 87% reported interest in a multidisciplinary clinic for EDS with the most interest in pain management, physical and occupational therapy, and rheumatology. Understanding healthcare utilization and needs of those with EDS can provide the foundation for improved care for those with EDS through a coordinated multidisciplinary care model.

Hypermobile Ehlers-Danlos Syndrome: A Prodromal Subtype of Functional Movement Disorders?

The phenotypic diversity of functional movement disorders (FMD) is considered a reflection of its many etiological subtypes. Ehlers-Danlos syndrome (EDS), a joint hypermobility syndrome, also has variable phenotypes, which may include functional symptoms. To determine the prevalence of combined diagnoses of FMD and EDS. We searched our Electronic Medical Records for patients carrying diagnostic codes for EDS and FMD. Further data extraction was done through chart review. Of 11,621 patients evaluated from January 1, 2016 to May 1, 2022, 16 carried a diagnosis of EDS, of which 9 (56.3%) were also diagnosed with FMD. Conversely, a diagnosis of FMD was documented in 190 (1.6%), of whom 16 (8.4%) were diagnosed with EDS. In all EDS-FMD cases, the diagnosis of EDS preceded the onset and diagnosis of FMD. The co-occurrence of FMD and EDS is beyond chance, suggesting association. EDS may represent a prodromal subtype of, and share common pathophysiologic features with, FMD.

P43. Single-level posterior lumbar fusions in patients with Ehlers Danlos syndrome not found to be associated with increased postoperative adverse events or five-year reoperations

BACKGROUND CONTEXT Ehlers Danlos Syndrome (EDS) is a rare connective tissue disorder that results from mutations in collagen genes. Potentially related to laxity and resultant degenerative changes, adult EDS patients may require posterior lumbar fusion (PLF). However, with low numbers, adequately powered outcome studies have been limited. PURPOSE To investigate the effect of Ehlers Danlos Syndrome on postoperative outcomes and reoperations following PLF. STUDY DESIGN/SETTING Retrospective cohort study using the 2010 - 2020 MSpine Pearldiver dataset. PATIENT SAMPLE Patients with a diagnosis of EDS (any type) were identified using International Classification of Diseases (ICD) codes. Patients over 18 years of age undergoing PLF with or without laminectomy were identified using Current Procedural Terminology (CPT) codes. Patients who had a primary diagnosis code of fractures, infection, neoplasm or were not in the database for at least 90 days following the surgery were excluded. Further, patients who had multilevel fusions or had concurrent anterior fusion were excluded. OUTCOME MEASURES Ninety-day any, severe, and minor adverse events as well as readmissions and five-year reoperations. METHODS Adult patients undergoing single-level PLF (excluding any with anterior procedures) with and without EDS for which at least 90-day follow up was available were identified. Any cases performed for trauma, tumor, or infection were excluded. Single-level PLF EDS patients were then matched 1:4 with PLF non-EDS patients based on age, sex and Elixhauser Comorbidity Index (ECI). Rates of 90-day any, severe, and minor adverse events as well as readmissions were tabulated and compared with chi-square tests. Multivariate logistical regression was then performed (controlling for age, and ECI). Reoperation surgeries over five years were assessed, Kaplan-Meier survival curves generated, and curves of those with and without EDS were compared with log rank test. RESULTS In total, there were 170,100 single-level PLF case identified, of which 242 (0.14%) had EDS. After matching, there were 957 without EDS and 239 with EDS. On multivariate regression, there were no significant differences in 90-day any, severe, or minor adverse events, or readmissions (p>0.05 for each). Over five years, there were also not significant differences in rates of reoperation (p> 0.05). CONCLUSIONS For EDS patients undergoing PLF, the current study identified similar 90-day adverse events and five-year reoperation rates compared to those without EDS. These findings may be useful for patient counseling and surgical planning for those with this rare condition. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs. Ehlers Danlos Syndrome (EDS) is a rare connective tissue disorder that results from mutations in collagen genes. Potentially related to laxity and resultant degenerative changes, adult EDS patients may require posterior lumbar fusion (PLF). However, with low numbers, adequately powered outcome studies have been limited. To investigate the effect of Ehlers Danlos Syndrome on postoperative outcomes and reoperations following PLF. Retrospective cohort study using the 2010 - 2020 MSpine Pearldiver dataset. Patients with a diagnosis of EDS (any type) were identified using International Classification of Diseases (ICD) codes. Patients over 18 years of age undergoing PLF with or without laminectomy were identified using Current Procedural Terminology (CPT) codes. Patients who had a primary diagnosis code of fractures, infection, neoplasm or were not in the database for at least 90 days following the surgery were excluded. Further, patients who had multilevel fusions or had concurrent anterior fusion were excluded. Ninety-day any, severe, and minor adverse events as well as readmissions and five-year reoperations. Adult patients undergoing single-level PLF (excluding any with anterior procedures) with and without EDS for which at least 90-day follow up was available were identified. Any cases performed for trauma, tumor, or infection were excluded. Single-level PLF EDS patients were then matched 1:4 with PLF non-EDS patients based on age, sex and Elixhauser Comorbidity Index (ECI). Rates of 90-day any, severe, and minor adverse events as well as readmissions were tabulated and compared with chi-square tests. Multivariate logistical regression was then performed (controlling for age, and ECI). Reoperation surgeries over five years were assessed, Kaplan-Meier survival curves generated, and curves of those with and without EDS were compared with log rank test. In total, there were 170,100 single-level PLF case identified, of which 242 (0.14%) had EDS. After matching, there were 957 without EDS and 239 with EDS. On multivariate regression, there were no significant differences in 90-day any, severe, or minor adverse events, or readmissions (p>0.05 for each). Over five years, there were also not significant differences in rates of reoperation (p> 0.05). For EDS patients undergoing PLF, the current study identified similar 90-day adverse events and five-year reoperation rates compared to those without EDS. These findings may be useful for patient counseling and surgical planning for those with this rare condition.

A COL5A2 In-Frame Deletion in a Chihuahua with Ehlers-Danlos Syndrome.

Ehlers-Danlos syndrome (EDS) is a group of heterogeneous, rare diseases affecting the connective tissues. The main clinical signs of EDS are skin hyperextensibility, joint hypermobility, and skin fragility. Currently, the classification of EDS in humans distinguishes 13 clinical subtypes associated with variants in 20 different genes, reflecting the heterogeneity of this set of diseases. At present, variants in three of these genes have also been identified in dogs affected by EDS. The purpose of this study was to characterize the clinical and histopathological phenotype of an EDS-affected Chihuahua and to identify the causative genetic variant for the disease. The clinical examination suggested a diagnosis of classical EDS. Skin histopathology revealed an abnormally thin dermis, which is compatible with classical EDS. Whole-genome sequencing identified a heterozygous de novo 27 bp deletion in the COL5A2 gene, COL5A2:c.3388_3414del. The in-frame deletion is predicted to remove 9 amino acids in the triple-helical region of COL5A2. The molecular analysis and identification of a likely pathogenic variant in COL5A2 confirmed the subtype as a form of classical EDS. This is the first report of a COL5A2-related EDS in a dog.

Association of mast-cell-related conditions with hypermobile syndromes: a review of the literature.

Ehlers–Danlos syndrome (EDS) is a group of related connective tissue disorders consisting of 13 subtypes, each with its own unique phenotypic and genetic variation. The overlap of symptoms and multitude of EDS variations makes it difficult for patients to achieve a diagnosis early in the course of their disease. The most common form, hypermobile type EDS (hEDS) and its variant, hypermobile spectrum disorder (HSD), are correlated with rheumatologic and inflammatory conditions. Evidence is still needed to determine the pathophysiology of hEDS; however, the association among these conditions and their prevalence in hEDS/HSD may be explained through consideration of persistent chronic inflammation contributing to a disruption of the connective tissue. Aberrant mast cell activation has been shown to play a role in disruption of connective tissue integrity through activity of its mediators including histamine and tryptase which affects multiple organ systems resulting in mast cell activation disorders (MCAD). The overlap of findings associated with MCAD and the immune-mediated and rheumatologic conditions in patients with hEDS/HSD may provide an explanation for the relationship among these conditions and the presence of chronic inflammatory processes in these patients. It is clear that a multidisciplinary approach is required for the treatment of patients with EDS. However, it is also important for clinicians to consider the summarized symptoms and MCAD-associated characteristics in patients with multiple complaints as possible manifestations of connective tissue disorders, in order to potentially aid in establishing an early diagnosis of EDS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12026-022-09280-1.

Outcomes and Complications in Patients With Hypermobile Ehlers-Danlos Syndrome Who Have Undergone Laser In Situ Keratomileusis Surgery.

The purpose of this study was to determine the safety and outcomes of myopic laser in situ keratomileusis (LASIK) in patients who were secondarily diagnosed with hypermobile Ehlers-Danlos syndrome (EDS). We conducted a case series study on patients with hypermobile EDS who underwent myopic LASIK surgery. Visual acuity, manifest refraction, a full dilated eye examination, biometry measurements, and Scheimpflug imaging were performed in the Wilmer outpatient clinic. There were 24 eyes of 12 patients included in this study. All participants were White women with a mean age of 46.58 years (SD 8.91 years). Participants were seen at an average of 13.83 years (SD 4.3 years, range 6-21 years) after undergoing LASIK. None of the patients in the series had a diagnosis of hypermobile EDS before LASIK surgery. Overall, 92% of patients were happy they got LASIK. The uncorrected distance visual acuity was 20/20 or better in 68% of eyes, and the best-corrected visual acuity was 20/20 or better in 92% of eyes. Manifest refraction was within 1 diopter of plano in 79% of patients. Dry eye symptoms were present in 83% of patients, and 46% of eyes had either punctate epithelial erosions or decreased tear break-up time. One of the 12 patients developed corneal ectasia in both eyes. Patients with hypermobile EDS are generally satisfied with myopic LASIK correction, with good visual acuity outcomes and low rates of myopic regression. However, the risk of corneal ectasia may prevent laser vision correction from being a viable treatment option in these patients. Further studies are needed to make a definitive recommendation.