Multisystem Involvement in a Pediatric Patient With Hypermobile Ehlers-Danlos Syndrome: A Case Report of the Diagnostic Complexity and Management Challenges.

Ehlers-Danlos syndrome (EDS) is a collection of genetic disorders caused by abnormalities in collagen and typified by hyperflexible joints, hyperextensible skin, and a tendency for easy bruising and tissue injuries. Hypermobile Ehlers-Danlos syndrome (hEDS), the most common subtype, presents a diagnostic challenge due to the lack of specific genetic markers. This case report describes a 13-year-old girl with hEDS, presenting with hypermobility, thoracolumbar scoliosis, constipation, glucosuria, microscopic hematuria, urticaria, and intermittent episodes of bilateral hand and feet swelling. Genetic testing revealed a variant of uncertain significance in the COL9A2 gene. An echocardiogram showed a mildly dilated aortic root. The complexity of her presentation underscores the challenges in diagnosing and managing hEDS with multisystem involvement.

The centrality of healthcare and education interactions - An Interpretive Phenomenological Analysis of experiences of parents of children with Ehlers-Danlos Syndrome.

BACKGROUND: Ehlers-Danlos Syndrome (EDS) is a rare group of connective tissue disorders and, as such, the diagnosis can often be delayed. While emerging research indicates that there may be adverse psychosocial consequences for the child, little is known about the processes behind such outcomes, including the psychosocial impact of this rare disease on family life. AIMS: To extend our understanding, we examined the lived experiences of parenting a child with EDS. METHODS: Four parents recruited from a specialist child development clinic participated in semi-structured interviews. Data were analysed using Interpretative Phenomenological Analysis RESULTS: Three superordinate themes were identified: (1) Challenges Associated with hEDS, (2) Interactions with Professionals and (3) "Pulling and Pacing": Life with EDS. DISCUSSION: This is one of the first qualitative studies to gain an insight into the lived experiences of parenting a child with EDS. Findings had systemic implications. Specifically, we demonstrate the need for raising awareness in health and educational professionals about how to better support families to support the child, as well as the importance of promoting effective advocacy skills in parents.

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

Introduction: 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. Methods: 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. Results: Seventy-two dyads completed the survey. Conclusion: 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.

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

Joint hypermobility syndromes, particularly chronic pain associated with this condition, including Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD), present diagnostic challenges due to their multifactorial origins and remain poorly understood from biomechanical and genomic-molecular perspectives. Recent diagnostic guidelines have differentiated hEDS, HSD, and benign joint hypermobility, providing a more objective diagnostic framework. However, incorrect diagnoses and underdiagnoses persist, leading to prolonged journeys for affected individuals. Musculoskeletal manifestations, chronic pain, dysautonomia, and gastrointestinal symptoms illustrate the multifactorial impact of these conditions, affecting both the physical and emotional well-being of affected individuals. Infrared thermography (IRT) emerges as a promising tool for joint assessment, especially in detecting inflammatory processes. Thermal distribution patterns offer valuable insights into joint dysfunctions, although the direct correlation between pain and inflammation remains challenging. The prevalence of neuropathies among hypermobile individuals accentuates the discordance between pain perception and thermographic findings, further complicating diagnosis and management. Despite its potential, the clinical integration of IRT faces challenges, with conflicting evidence hindering its adoption. However, studies demonstrate objective temperature disparities between healthy and diseased joints, especially under dynamic thermography, suggesting its potential utility in clinical practice. Future research focused on refining diagnostic criteria and elucidating the underlying mechanisms of hypermobility syndromes will be essential to improve diagnostic accuracy and enhance patient care in this complex and multidimensional context.

Variants in the Kallikrein Gene Family and Hypermobile Ehlers-Danlos Syndrome.

Hypermobile Ehlers-Danlos syndrome (hEDS) is a common heritable connective tissue disorder that lacks a known genetic etiology. To identify genetic contributions to hEDS, whole exome sequencing was performed on families and a cohort of sporadic hEDS patients. A missense variant in Kallikrein-15 (KLK15 p. Gly226Asp), segregated with disease in two families and genetic burden analyses of 197 sporadic hEDS patients revealed enrichment of variants within the Kallikrein gene family. To validate pathogenicity, the variant identified in familial studies was used to generate knock-in mice. Consistent with our clinical cohort, Klk15 G224D/+ mice displayed structural and functional connective tissue defects within multiple organ systems. These findings support Kallikrein gene variants in the pathogenesis of hEDS and represent an important step towards earlier diagnosis and better clinical outcomes.

Generation of two iPSC lines from vascular Ehlers-Danlos Syndrome (vEDS) patients carrying a missense mutation in COL3A1 gene.

Vascular Ehlers-Danlos Syndrome (vEDS) is an inherited connective tissue disorder caused by COL3A1 gene, mutations that encodes type III collagen, a crucial component of blood vessels. vEDS can be life-threatening as these patients can have severe internal bleeding due to arterial rupture. Here, we generated induced pluripotent stem cell (iPSC) lines from two vEDS patients carrying a missense mutation in the COL3A1 (c.226A > G, p.Asn76Asp) gene. These lines exhibited typical iPSC characteristics including morphology, expression of pluripotency markers, and could differentiate to all three germ layer. These iPSC lines can serve as valuable tools for elucidating the pathophysiology underlying vEDS.

Hereditary Aortic Aneurysms and Dissections: Clinical Diagnosis and Genetic Testing.

Hereditary aortic aneurysms and dissections, such as Marfan syndrome, differ in that they occur in younger patients without generally recognized risk factors, have a predilection for the thoracic rather than the abdominal aorta, and are at risk for dissection even at smaller aortic diameters. Early diagnosis, careful follow-up, and early intervention, such as medication to reduce aortic root growth and prophylactic aortic replacement to prevent fatal aortic dissection, are essential for a better prognosis. Molecular genetic testing is extremely useful for early diagnosis. However, in actual clinical practice, the question often arises as to when and to which patient genetic testing should be offered since the outcome of the tests can have important implications for the patient and the relatives. Pre- and post-test genetic counseling is essential for early intervention to be effective. (This article is a secondary translation of Jpn J Vasc Surg 2023; 32: 261-267.).

Evaluating the effects of two different kinesiology taping techniques on shoulder range of motion and proprioception in patients with hypermobile Ehlers-Danlos syndrome: a randomized controlled trial.

Background: Ehlers-Danlos syndrome (EDS) is a common group of inherited connective tissue disorders with a prevalence as high as 0.75%-2% of the population. Physical manifestations include pain and decreased proprioception, especially in more mobile joints, such as the shoulder. The kinesiology tape (K-Tape) is often used to treat patients with shoulder dysfunction. The effectiveness of the K-Tape is uncertain, and there is a lack of studies specifically studying the K-Tape in an EDS population. Purpose: The purpose of this study was to compare the short-term effects of two different K-Tape procedures on shoulder active joint reposition (AJR) and active range of motion (AROM) in patients with hypermobile EDS (hEDS) and shoulder pain. Methods: All participants were recruited from the EDS support groups and presented with shoulder pain. Baseline demographic information was obtained for each participant, after which AROM and AJR were assessed. The participants were randomized to receive one of two K-Tape procedures. Testing was repeated immediately post-taping and 48 h post-taping. Results: Significant improvements in shoulder external (F = 10.917, p < 0.001) and internal (F = 11.736, p < 0.001) rotations were seen from baseline to immediately post-taping and baseline to 48 h post-taping in the experimental K-Tape group. There were no significant differences in the shoulder rotation in the control K-Tape group and no significant differences in either group for shoulder flexion or AJR at any time point (p > 0.05). Conclusion: K-Tape may offer short-term improvements in shoulder rotation AROM in patients with hEDS and shoulder pain.

Traumatic False Passage During Nasogastric Tube Insertion and Spontaneous Small Bowel Perforation in a Patient With Vascular Ehlers-Danlos Syndrome: A Case Report.

Ehlers-Danlos Syndrome (EDS) is a rare connective tissue disorder characterized by mutation in genes that encode or modify collagen. Clinical findings in these patients include skin hyperextensibility, hypermobility of joints, and tissue fragility. Vascular EDS (vEDS) is an autosomal dominant disease typically caused by a mutation in COL3A1, which encodes type III collagen. Presenting signs in the majority of vEDS patients include arterial rupture, uterine rupture, and sigmoid colon perforation. In this case report, the author presents an unusual case of spontaneous small bowel perforation and the creation of a traumatic false passage in the parapharyngeal space during a complicated nasogastric tube insertion in a patient with vEDS.

Musculocontractural type of Ehlers-Danlos syndrome with novel CHST14 pathogenic variant in two siblings.

Musculocontractural Ehlers-Danlos syndrome (MC-EDS) is a rare entity worldwide with underlying pathogenic variant in the carbohydrate sulfotransferase 14 (CHST14) gene. Previous reports of the same entity from India were of two unrelated cases. Ours is the first report of two siblings in an Indian family with craniofacial dysmorphism and distal arthrogryposis with a clinical diagnosis of EDS, where an underlying pathogenic variant in CHST14 was detected by exome sequencing.

Corrigendum: Assessment of a novel Ehlers-Danlos syndromes disability index.

[This corrects the article DOI: 10.3389/fresc.2024.1280582.].

Psychometric properties of the Mini-Balance Evaluation Systems Test and physical function measures in patients with Ehlers-Danlos syndrome/hypermobility spectrum disorders.

PURPOSE: Ehlers-Danlos syndrome (EDS) and hypermobility spectrum disorders (HSD) are associated with impairments in balance and physical function. However, the psychometric properties of relevant outcome measures remain largely unexplored. The objectives of this study were to evaluate the construct validity of the Mini-Balance Evaluation Systems Test (Mini-BESTest) alongside the test-retest reliability of the Mini-BESTest, Six Minute Walk Test (6MWT), and Lower Extremity Functional Scale (LEFS) in patients with the hypermobility subtype of EDS (hEDS) and HSD. MATERIALS AND METHODS: Participants with hEDS/HSD (n = 20) attended two visits scheduled one to two weeks apart. The construct validity of the Mini-BESTest was determined through Pearson correlations between force plate balance measures, 6MWT, and LEFS. Test-retest reliability of the measures was evaluated through intraclass correlation coefficients (ICC). Minimal detectable change values with 95% confidence (MDC95) were also calculated. RESULTS: Mini-BESTest demonstrated significant correlations with force plate measures, 6MWT, and LEFS (r = -0.41 to 0.66). Test-retest reliability was excellent for the Mini-BESTest, 6MWT, and LEFS (ICC = 0.91 to 0.96). MDC95 was 4 for the Mini-BESTest, 77 m for the 6MWT, and 11 for the LEFS. CONCLUSION: The Mini-BESTest is valid and reliable for assessing balance and mobility in patients with hEDS/HSD.IMPLICATIONS FOR REHABILITATIONThe Mini Balance Evaluation Systems Test (Mini-BESTest) is valid in capturing aspects of balance and physical function in patients with hypermobile Ehlers-Danlos syndrome or hypermobility spectrum disorders.However, the Mini-BESTest may show a potential ceiling effect for high functioning patients in this population.The Mini-BESTest, 6 Minute Walk Test, and the Lower Extremity Functional Scale also show excellent test-retest reliability in this population.The Minimal Detectable Change with 95% confidence intervals is 4 for the Mini-BESTest, 77 m for the 6 Minute Walk Test, and 11 for the Lower Extremity Functional Scale in this population.

Intraocular lens calcification in a patient with Ehlers-Danlos syndrome.

Introduction: Calcification of hydrophilic intraocular lenses (IOL) is a rare complication following cataract surgery. Secondary calcification is described as due to host factors or changes in the IOL environment and uveitis, proliferative diabetic retinopathy and sequelae of ocular surgery are recognised potentiators. The impact of systemic connective tissue disease on IOL opacification is yet to described. Purpose: To describe the clinical presentation and management of a young patient, with a rare subtype of Ehlers-Danlos syndrome, who presented with secondary IOL calcification 14 years after primary IOL insertion. Observations: Floret-like lesions were observed on the IOL surface. Positive staining for calcification was observed with Alizarin red and von Kossa method on laboratory analysis. Conclusions and importance: Patients with systemic connective tissue disease, such as a subtype of Ehlers-Danlos, may present with secondary IOL calcification many years after primary lens insertion. This poses an additional consideration when implanting IOLs in these patients.Good visual acuity can be achieved with IOL exchange.

Midterm Outcomes of Isolated Medial Patellofemoral Ligament Reconstruction for Patellar Instability in Ehlers-Danlos Syndrome.

Background: Patellar instability is frequently encountered in patients with Ehlers-Danlos syndrome (EDS). The clinical outcomes of isolated medial patellofemoral ligament reconstruction (MPFLR) for patellar instability in patients with EDS are unknown. Purpose: To evaluate midterm clinical outcomes of isolated MPFLR for patellar instability in patients with EDS and factors affecting these outcomes. Study Design: Case series; Level of evidence, 4. Methods: In a retrospective study, 31 patients (n = 47 knees) with EDS and patellar instability who underwent isolated MPFLR for recurrent patellar instability between 2008 and 2017 and had a minimum 2-year follow-up were identified. Preoperative radiographic images were measured for anatomic risk factors. Clinical outcomes-including postoperative complications-were evaluated. Factors associated with MPFLR failure were identified. Postoperative patient-reported outcomes (PROs)-including the pediatric version of the International Knee Documentation Committee, the Kujala score, the Hospital for Special Surgery Pediatric Functional Activity Brief Scale, the Banff Patellofemoral Instability Instrument 2.0, and the Knee injury and Osteoarthritis Outcome Score-were collected, and factors affecting PRO scores were analyzed. Results: The mean age of the cohort was 14.9 ± 2 years. At a mean follow-up of 7.2 years, 18 of 47 (38.3%) knees required reoperations, of which 9 of 47 (19.1%) knees required revision stabilization for recurrent patellar instability. Also, 7 of 31 knees (22.6%) with autografts failed compared with 2 of 16 (12.5%) with allografts (P = .69). For autografts, 6 of 17 (35.3%) failures occurred with gracilis, but 0 of 13 (0%) occurred with semitendinosus (P = .02). Compared with patients without failures, patients with failed primary MPFLR were significantly younger (P = .0005) and were able to touch the palm to the floor with their knees extended (P = .03). For radiographic parameters, the patellar height and tilt were significantly higher in the failure group. The postoperative PROs were suboptimal at a mean follow-up of 5.2 years. All but 1 patient were satisfied with the final outcome. Conclusion: At the midterm follow-up, 38.3% of patients with EDS required further surgery after isolated MPFLR for patellar instability; half of these revisions (19.1%) were to address recurrent instability. Recurrent instability after isolated MPFLR was more likely in younger patients and those who could touch the palm to the floor with their knees extended. Postoperative PROs were inferior; nonetheless, patient satisfaction was high.

Creatine Monohydrate as an Effective Supplement for Muscular Fatigue in an Ehlers-Danlos Patient.

Patients with Ehlers-Danlos syndrome (EDS) frequently report symptoms such as chronic pain and muscular fatigue that can heavily impact their quality of life. The treatment for many of the physical symptoms of EDS is focused on supportive care, which may include physical therapy and exercise programs. However, many patients will experience difficulty in deriving benefits from these activities due to significant pain and fatigue from physical activity. We report a case of a 39-year-old female with a history of EDS whose physical capabilities were severely impacted by their chronic pain and fatigue symptoms. After little progress was made with their current treatment plan of analgesics, manual therapy, exercise, and physical therapy, the patient was supplemented with creatine monohydrate due to its studied benefits in muscular strength and endurance for athletes. Following supplementation, the patient reported significant benefits in their muscular fatigue symptoms, allowing them to engage in daily activities and exercises more effectively. This case demonstrates a potential addition to the treatment of EDS that can improve a patient's quality of life.

Vascular Ehlers-Danlos syndrome and pregnancy: A systematic review.

BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) is a hereditary connective tissue disorder associated with an elevated risk of vascular, uterine and digestive complications. Managing pregnancy in this context can be a challenge. OBJECTIVES: To systematically review the literature data on the complications in pregnancy associated with vEDS. SEARCH STRATEGY: We searched the Pubmed Medline and Embase databases for articles using the following terms "vascular Ehlers-Danlos syndrome" or "vEDS" AND "pregnancy". SELECTION CRITERIA: Women with vEDS. DATA COLLECTION AND ANALYSIS: We searched the PubMed® MEDLINE® database for publications evaluating obstetric outcomes in women with vEDS. MAIN RESULTS: A total of 121 publications were screened, with six (accounting for 412 pregnancies) included in our review. Of the women included in this sample, 30% were infertile. The miscarriage rate was 13.8% (57/412) and 8.8% of the live births were premature. Obstetric anal sphincter injuries occurred in 11.3% (23/203) of the deliveries. The maternal mortality rate per pregnancy was 5.7%. CONCLUSIONS: Women with vEDS present an elevated risk of uterine rupture, vascular events, digestive events and death during pregnancy. Women appear to be most at risk during the peripartum period; to avoid expulsive efforts, a caesarean section should be scheduled at 37 weeks of gestation.

Case of a 33-Year-Old Woman With Hemoptysis and Migrant Nodular Cavitary Lesions.

We describe the case of a young 33-year-old woman that was referred to our clinic for evidence of migrant cavitary nodules at CT scan, dyspnea, and blood sputum. Her physical examination showed translucent and thin skin, evident venous vascular pattern, vermilion of the lip thin, micrognathia, thin nose, and occasional Raynaud phenomenon. We prescribed another CT scan that showed multiple pulmonary nodules in both lungs, some of which had evidence of cavitation. Because bronchoscopy was not diagnostic, we decided to perform surgical lung biopsy. At histologic examination, we found the presence of irregularly shaped, but mainly not dendritic, foci of ossification that often contained bone marrow and were embedded or surrounded by tendinous-like fibrous tissue. After incorporating data from the histologic examination, we decided to perform genetic counseling and genetic testing with the use of whole-exome sequencing. The genetic test revealed a heterozygous de novo missense mutation of COL3A1 gene, which encodes for type III collagen synthesis, and could cause vascular Ehlers-Danlos syndrome.

The relationship between joint hypermobility and patellar instability: A systematic review.

Introduction: Hypermobility describes the movement of joints beyond normal limits. Whether hypermobility predisposes to patellar instability is yet to be established. We aimed to determine if joint hypermobility leads to an increased risk of patellar instability, and to evaluate outcomes of treatment for patellar instability in those who exhibit hypermobility. Methods: Published and unpublished literature databases were searched to September 7, 2023. Studies comparing prevalence of patellar dislocation/differences in treatment outcomes in patients with and without hypermobility were included. Results: We identified 18 eligible studies (4,391 patients). The evidence was low in quality. A case series on 82 patients found that there was a relationship between generalised joint laxity and patellar instability. This was corroborated by a study comparing 104 patients with patellar dislocation to 110 patients without. Prevalence of generalised joint laxity was six time higher in the former (64.4% vs 10.9%, p < 0.001).Five studies found surgical intervention aimed at correcting patellar dislocation in patients with idiopathic hypermobility led to satisfactory outcomes. There was conflicting evidence regarding if hypermobile patients have worse outcomes than non-hypermobile patients following medial patellofemoral ligament reconstruction (MPFLR) in two studies. In addition, this procedure had a 19.1% failure rate in patients with Ehlers Danlos Syndrome (EDS), with hypermobility associated with a higher failure rate (p = 0.03). One study showed the type of graft used made no difference in outcome scores or re-dislocation rates (p > 0.5). Another study had 7/31 (22.6%) autografts which failed, compared to 2/16 allografts (12.5%) (p = 0.69). Conclusion: Joint hypermobility is a risk factor for patellar instability. Identification of at-risk groups may aid prevention of dislocations and allow for appropriate treatment. Patients with EDS experience poor outcomes following patellar stabilization surgery, with post-operative monitoring required.

Airway Complications in a Patient With Ehlers-Danlos Syndrome: A Case Report.

A female patient, known to have hypermobile Ehlers-Danlos syndrome (hEDS), underwent several elective gastroscopies under sedation in different hospitals. Except for a single incident of mild laryngospasm during emergence, all procedures were uneventful. On that occasion, following the procedure in the postanesthesia care unit, the patient suffered severe airway obstruction, and standard airway rescue techniques exacerbated adequate ventilation. After the removal of all stimuli and maintaining only an indirect oxygen supply via a mask in front of her face, her airway improved, and the patient fully recovered after 17 minutes. After the gastroscopy, physical examination revealed that the patient had an extremely flexible trachea that could be completely moved outside the midline to the extreme right and left. For the subsequent procedures, an airway plan was developed in conjunction with the patient and resulted in uncomplicated perianesthetic care. This case report serves to alert readers to the risk of adverse airway events in patients with EDS and suggests an alternative approach to avoid such complications. When patients receive care in different hospitals, adequate documentation is essential and adequate preoperative assessment is crucial. This case study demonstrates the value of patient-coproduction care plans.