Hereditary Connective Tissue Disorder Research Articles

Autosomal Dominant Weill-Marchesani-Like Syndrome in a Chinese Family due to Novel Haplotypic Mutations in LTBP2.

Weill-Marchesani syndrome (WMS) is a hereditary connective tissue disorder with substantial heterogeneity in clinical features and genetic etiology, so it is essential to define the full mutation spectrum for earlier diagnosis. In this study, we report Weill-Marchesani-like syndrome (WMS-like) change to autosomal dominance inheritance caused by novel haplotypic mutations in latent transforming growth factor beta-binding protein 2 (LTBP2). Twenty-five members from a 4-generation Chinese family were recruited from Guangzhou, of whom nine were diagnosed with WMS-like disease, nine were healthy, and seven were of "uncertain" clinical status because of their young age. All members received detailed physical and ocular examinations. Whole-exome sequencing, Sanger sequencing, and real-time PCR were used to identify and verify the causative mutations in family members. Genetic sequencing revealed novel haplotypic mutations on the same LTBP2 chromosome associated with WMS-like, c. 2657C>A/p.T886K in exon 16 and deletion of exons 25-36. Real-time PCR and Sanger sequencing verified both mutations in patients with clinically diagnosed WMS-like, and in one "uncertain" child. In these patients, the haplotypic mutations led to ectopia lentis, short stature, and obesity. Our study revealed that WMS-like may be associated with haplotypic LTBP2 mutations with autosomal dominant inheritance.

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.

Correlation between benign joint hypermobility syndrome and headache in children and adolescents

BackgroundBenign Joint Hypermobility Syndrome (BJHS) is a most common hereditary connective tissue disorders in children and adolescents. This study aimed to investigate the prevalence and subtypes of headache in children with BJHS.MethodsThis observational-analytical study was conducted in a case-control setting on school children aged 7 to 16 years in 2021–2023 in Isfahan, Iran. Students were examined for BJHS using Beighton criteria by a pediatric rheumatologist. Headache disorder was diagnosed according to the Child Headache-Attributed Restriction, Disability, and Social Handicap and Impaired Participation (HARDSHIP) questionnaires for child and adolescent and International Classification of Headache Disorders (ICHD-III).ResultsA total of 4,832 student (mean age 10.3 ± 3.1 years), 798 patients with BJHS and 912 healthy children were evaluated. The probability of headache in children aged 7–11 with hypermobility was 3.7 times lower than in children aged 12–16 with hypermobility (P = 0.001). The occurrence of headache in children with BJHS was more than the control group (P = 0.001), and the probability of headache in children with BJHS was 3.7 times higher than in healthy children (P = 0.001). Migraine was the most common headache type reported of total cases. The probability of migraine in children with BJHS was 4.5 times higher than healthy children ( P = 0.001).ConclusionThis study showed a significant correlation between BJHS and headache (especially migraine) in children and adolescents.

OA19 Self-reported prevalence and impact of clinical signs, symptoms and events in adults with osteogenesis imperfecta

OA19 Self-reported prevalence and impact of clinical signs, symptoms and events in adults with osteogenesis imperfecta

Otolaryngologic sequelae of Ehlers Danlos Syndrome in pediatric patients

ObjectiveAs outlined by the NIH, Ehlers Danlos Syndrome (EDS) is a group of hereditary connective tissue disorders characterized by skin hyperelasticity, joint hypermobility, atrophic scarring, and blood vessel fragility, with no otolaryngological criteria for diagnosis. We aimed to compare otolaryngological disorders between children with EDS and those not affected by EDS. MethodsA retrospective chart review was conducted using the US collaborative network within TriNetX. The EDS group was defined by ICD-10 code G47.33, while the non-EDS group excluded any patients with an EDS diagnosis. Cohorts were matched by age, sex, and race using propensity score matching. Pathologies analyzed included hearing loss (ICD-10H90, H91), otitis media (ICD-10H66, H65), allergic rhinitis, acute tonsillitis (ICD-10 J03), sinusitis (ICD-10 J32, J01), and obstructive sleep apnea (OSA) (ICD-10 G47.33). Chi-square and relative risk within a 95 % confidence interval were calculated. ResultsPropensity score matching yielded 6440 patients (male: N = 2,523, 39.2 %; female: N = 3,893, 60.5 %; unknown: N = 24, 0.37 %) with a mean age of 9.28 years (SD = 4.38). Children with EDS were 2.04 times more likely to be diagnosed with hearing loss, occurring in 286 (4.4 %) EDS children versus 140 (2.1 %) controls (P < 0.001). Children with EDS were 1.6 times more likely to be diagnosed with allergic rhinitis, occurring in 436 (6.8 %) EDS children versus 274 (4.2 %) controls (P < 0.001). Children with EDS were also 1.52 times (EDS: N = 350, 5.4 %; control: N = 231, 3.6 %) and 4.24 times (EDS: N = 335, 5.2 %; control: N = 79, 1.2 %) more likely to develop sinusitis and be diagnosed with OSA, respectively, compared to children without EDS (P < 0.001). However, children with EDS were only 0.71 times as likely to develop acute tonsillitis, with 101 (1.6 %) of EDS children compared to 142 (2.2 %) of control children being diagnosed (P = 0.009). No statistical difference was found in risk of developing otitis media. ConclusionsChildren with EDS are at higher risk of developing hearing loss, allergic rhinitis, acute sinusitis, and OSA, possibly due to underlying immune dysfunction. Pediatric otolaryngologists should be vigilant about these otolaryngologic sequela in EDS patients.

Demographics and medical burden of osteogenesis imperfecta: a nationwide database analysis.

This study examines osteogenesis imperfecta, a hereditary connective tissue disorder causing pediatric fractures and limb deformities, using a nationwide database from Taiwan to analyze clinical features and medical burden. The study identified validated OI patients from the Catastrophic Illness Registry in the National Health Insurance Research Database from 2008 to 2019. Demographic data and medical resource utilization were analyzed. A multivariate Cox model assessed the influence of sex, validation age, and comorbidities. 319 OI patients (M/F = 153/166) were identified, with 58% validated before age 20. Prevalence and incidence were 0.8-1.3/100,000 and 0.02-0.09/100,000, respectively, with higher rates in the pediatric demographic. In the study period, 69.6% of the patients had admission history, primarily to pediatric and orthopedic wards. The median admission number was 3, with a median length of stay of 12days and a median inpatient cost of approximately 3,163 USD during the period. Lower limb fractures were the main reason for hospitalization. 57% of OI patients received bisphosphonate treatment. The leading causes of mortality were OI-related deaths, neurovascular disease, and cardiovascular disease. The median age of validation in the non-survival group was significantly higher compared to the survival group (33 vs. 14years), and patients validated during childhood required more inpatient fracture surgeries than those validated during adulthood. This study provides comprehensive real-world evidence on the clinical characteristics and high medical resource utilization of OI patients in a low prevalence region like Taiwan. Early diagnosis is crucial for improving care quality and enhancing health outcomes.

Prevalence of endometriosis and pelvic pain in patients with hereditary connective tissue disorders

Prevalence of endometriosis and pelvic pain in patients with hereditary connective tissue disorders

Visual evoked potential in generalized joint hypermobility: A case-control study.

Generalized joint hypermobility (GJH) can be the result of several hereditary connective tissue disorders, especially Ehlers-Danlos syndrome. Cerebrovascular manifestations are among the most common complications in this disorder, and understanding their extent can help better diagnosis and prevention of hazardous events. We investigated visual evoked potential (VEP) changes in patients with GJH and compared them with healthy individuals. Our case-control study included 90 patients who fulfilled the Beighton score (B score) for joint hypermobility and other 90 healthy participants. All of them went under VEP study, and the amplitude and latency of the evoked potential (P100) were compared to each other. The Case group had significantly higher B score (7.18±0.967 vs. 1.18±0.712), P100 latency (110.23±6.64ms vs. 100.18±4.273ms), and amplitude (6.54±1.26mv vs. 6.50±1.29mv) compared with the Control group, but the difference was only significant regarding B score, and P100 latency (p-value <.0001). Moreover, both latency and amplitude of P100 had significantly positive correlations with the B score in the Case group (p-value <.0001), but such correlations were not found in the Control group (p-value=.059). Our study could reveal VEP changes, especially significant P100 latency in GJH patients without previous neurologic or musculoskeletal disorders. Whether these changes are due to GJH itself or are predictive of inevitable neurologic disease or visual pathway involvement, particularly Multiple Sclerosis needs further investigation with longer follow-up periods.

Giant aortic aneurysm repair in a child due to arterial tortuosity syndrome.

Arterial tortuosity syndrome is an extremely rare hereditary connective tissue disorder. We present a case of an incidentally diagnosed aneurysm of the aortic root and the ascending aorta caused by arterial tortuosity syndrome, which was confirmed genetically. The aneurysm was repaired surgically. One year after the procedure, there was no further dilation of the aorta or formation of new aneurysms.

Aortic Dissection: Classification, Etiology, Pathogenesis and Clinical Picture

Aortic dissection is a pathological process in which the aortic wall is divided into inner and outer layers under the action of hemodynamic forces. The process can be localized in various parts of the aorta, and also can be cause of blood supply disorders not only of organs which are located along the vessel (orthograde), but also organs which are located retrogradely. Risk factors for aortic dissection may include age, gender, atherosclerosis, inflammatory diseases, chest injuries, heart surgery, hereditary predisposition, congenital defects of the cardiovascular system and hereditary connective tissue disorders. The most often complication of aortic dissection is malperfusion syndrome, which can manifest itself as symptoms of upper and lower limb ischemia, syncope, ischemic stroke, prerenal azotemia (with decreased renal perfusion), abdominal ischemia syndrome (with occlusion of mesenteric arteries), spinal ischemic stroke. Knowledge of the totality of etiological factors, risk factors, pathogenesis, various manifestations and complications of aortic dissection allows you not to miss the beginning of the pathological process and provide timely assistance.

Co-prevalence of arterial aneurysm location - a correlation analysis based on a retrospective cross-sectional observational study.

Background: The aim of this retrospective single-centre cross-sectional observational study was to investigate co-prevalence of arterial aneurysm location systematically. Patients and methods: Patients with the diagnosis of any arterial aneurysm from January 2006 to January 2016 were investigated in a single centre. Patients with hereditary disorders of connective tissue, systemic inflammatory disease, or arterial pathologies other than true aneurysms were excluded. Aneurysm locations were assessed for every patient included. For patients with at least two co-existing aneurysms, co-prevalence of aneurysm location was investigated by calculating correlation coefficients and applying Fisher's exact test. This study report is prepared according to the STROBE statement. Results: Of 3107 identified patients with arterial aneurysms, 918 were excluded. Of the remaining 2189 patients, 951 patients with at least two aneurysms were included in the study. Bilateral aneurysm combinations of paired iliac, femoral and popliteal arteries showed the highest correlation (ϕ=0.35 to 0.67), followed by bilateral combinations of subclavian (ϕ=0.36) and internal carotid (ϕ=0.38) arteries. Abdominal aortic aneurysms in combination with visceral artery aneurysms (ϕ=-0.24 to -0.12), popliteal arteries (ϕ=-0.22) and the ascending aorta (ϕ=-0.19) showed the lowest correlation, followed by the descending aorta in combination with the common iliac arteries (ϕ=-0.12 to -0.13). Conclusions: In our study sample, aneurysm co-prevalence was highly non-random. This should be considered in the context of aneurysm screening programs.

A new conceptual model for anorexia nervosa: A role for connective tissue?

The etiology of anorexia nervosa (AN) remains to be fully elucidated, and current theories also fail to account for the direct effect of starvation on the health of the organs and tissues, specifically the connective tissue present in most organs of the body. Individuals with hereditary disorders of connective tissue manifest with clinical symptoms that overlap with AN, as the abnormal connective tissue also contributes to many of the other extra-articular manifestations of these hereditary disorders. This article hypothesizes that a similar pathophysiology may also contribute to the clinical presentation of AN. Therefore, a better understanding is needed to elucidate: (1) the relationship between abnormal connective tissue and AN, (2) the impact of starvation toward the development of abnormal connective tissue and how this manifests clinically, (3) the etiology of autonomic nervous system changes contributing to the dysautonomia in AN, and (4) how the sensory signals sent from potentially abnormal connective tissue to the central nervous system impact interoception in AN. A conceptual model incorporating abnormal connective tissue is provided. PUBLIC SIGNIFICANCE: The etiology of AN remains poorly understood and current theories fail to account for the direct impact of starvation on the health of the organs and tissues of the body. There is significant clinical overlap between AN and hereditary connective tissue disorders. This paper attempts to provide a new conceptual model for AN in which abnormal connective tissue contributes to the underlying pathogenesis.

An Analysis From a Tertiary Pediatric Hospital: Does Physical Activity Play a Role in the Management of Children and Young Adults With Osteogenesis Imperfecta?

Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder characterized by reduced bone density and increased proneness to fractures. It manifests across a varied clinical spectrum of expressions in children and young adults. It is crucial for children with OI to have a multidisciplinary follow-up, including orthopedics, pediatrics, and physical medicine and rehabilitation.Although exercise may have no effect on the disease itself, it might improve the autonomy, self-esteem, and fitness of these children. Methods: Retrospective cohort analysis of children and young adults aged three or more years old followed-up in a Level III Pediatric Hospital between 1995 and 2020. Demographic and clinical data were obtained from the hospital records and from the caregivers via phone calls. To our knowledge, this is the first national case series published assessing exercise habits in children with this condition. Among the 21 patients studied, the median age was 14 years, with no gender predominance. Eighteen (86%) practiced regular physical activity, while the remaining three (14%), all of whom were type III OI, were totally dependent. Of the aforementioned 18 children, 12 (67%) considered practicing the same level of physical activity compared to their healthy peers, although most of them needed adaptations. The most reported extracurricular activity was swimming, in 50% of the cases. About 39% engaged in physical activity two times or less per week, and 89% practiced for one hour or less per session. Over the years, it has become clear that physical activity is an important part of OI management. While awareness of the importance of exercise already exists, proper planning, follow-up, and monitoring are essential.

Craniocervical instability in patients with Ehlers-Danlos syndromes: outcomes analysis following occipito-cervical fusion

Craniocervical instability (CCI) is increasingly recognized in hereditary disorders of connective tissue and in some patients following suboccipital decompression for Chiari malformation (CMI) or low-lying cerebellar tonsils (LLCT). CCI is characterized by severe headache and neck pain, cervical medullary syndrome, lower cranial nerve deficits, myelopathy, and radiological metrics, for which occipital cervical fusion (OCF) has been advocated. We conducted a retrospective analysis of patients with CCI and Ehlers-Danlos syndrome (EDS) to determine whether the surgical outcomes supported the criteria by which patients were selected for OCF. Fifty-three consecutive subjects diagnosed with EDS, who presented with severe head and neck pain, lower cranial nerve deficits, cervical medullary syndrome, myelopathy, and radiologic findings of CCI, underwent open reduction, stabilization, and OCF. Thirty-two of these patients underwent suboccipital decompression for obstruction of cerebral spinal fluid flow. Questionnaire data and clinical findings were abstracted by a research nurse. Follow-up questionnaires were administered at 5–28 months (mean 15.1). The study group demonstrated significant improvement in headache and neck pain (p < 0.001), decreased use of pain medication (p < 0.0001), and improved Karnofsky Performance Status score (p < 0.001). Statistically significant improvement was also demonstrated for nausea, syncope (p < 0.001), speech difficulties, concentration, vertigo, dizziness, numbness, arm weakness, and fatigue (p = 0.001). The mental fatigue score and orthostatic grading score were improved (p < 0.01). There was no difference in pain improvement between patients with CMI/LLCT and those without. This outcomes analysis of patients with disabling CCI in the setting of EDS demonstrated significant benefits of OCF. The results support the reasonableness of the selection criteria for OCF. We advocate for a multi-center, prospective clinical trial of OCF in this population.

Desmoid Fibromatosis Presenting with Gastrointestinal Manifestations in a Patient with Ehlers-Danlos Syndrome: A Case ReportDesmoid Fibromatosis Presenting with Gastrointestinal Manifestations in a Patient with Ehlers-Danlos Syndrome: A Case Report

Ehlers-Danlos syndrome comprises 13 hereditary connective tissue disorders associated with skin hyperelasticity, joint hypermobility, atrophic scarring, and blood vessel fragility. Hypermobile EDS, the most common subtype, has no clear genetic or molecular source. When presented with wide-ranging clinical symptoms, it requires effective clinical diagnosis. A 31-year-old female with hypermobile EDS underwent an abdominal Computed Tomography (CT) scan displaying a 2.9 cm soft-tissue mass possibly arising from the terminal ileum, which was revealed to be a desmoid fibromatosis. It is believed that Gastrointestinal (GI) manifestations may be associated with EDS, specifically the hypermobile subtype. The patient demonstrated manifestations commonly seen throughout the literature on hypermobile EDS, including abdominal pain, nausea, and diarrhoea. With symptoms worsening, a follow-up CT disclosed an enlargement of the ileocecal desmoid tumour, measuring 5.1 cm. Because all the subtypes of EDS share features such as tissue fragility, joint hypermobility, and skin hyperextensibility, and many of the manifestations are insufficient to establish a diagnosis, imaging modalities are essential for proper identification and patient management. Given the patient’s medical history and the involvement of EDS and desmoid tumours with connective tissue, there is a strong linkage between desmoid fibromatosis and the patient’s hypermobile Ehlers-Danlos diagnosis. The available literature does not clearly attribute such a tumour to the syndrome. This patient’s symptoms represent a possible association between hypermobile EDS and desmoid fibromatosis, warranting future research in this area. The patient is now stable and was recently discharged.

The spectrum of gastrointestinal functional bowel disorders in joint hypermobility syndrome and in an academic referral center.

Joint hypermobility syndrome (JHS) is a non-inflammatory hereditary disorder of connective tissue with varied clinical presentations, including frequent joint dislocations, hyperextensible skin, easy bruising, and abnormal paper-thin scar formation. Many of these patients have unexplained gastrointestinal (GI) symptoms. Our aim was to evaluate the prevalence of JHS in a tertiary gastroenterology motility clinic and the spectrum of functional bowel disorders in JHS patients. In this retrospective case series, we screened the medical records of 277 patients seen over 4 years at an academic GI Motility Center. The patients who met the criteria for JHS by Beighton hypermobility score were evaluated for the presence of functional GI disorders by Rome IV criteria. They also underwent gastric emptying study and glucose breath testing for small intestinal bacterial overgrowth. The prevalence of JHS in the study population was 9.7%. The mean age was 27 years, and 92.5% were female. The symptoms experienced by these patients include nausea/vomiting (89%), abdominal pain (70%), constipation (48%), and bloating (18.5%). The disorders associated with JHS include gastroparesis (52%), irritable bowel syndrome (55.5%), and gastroesophageal reflux disease (30%). Also, 10 patients (37%) were diagnosed with postural hypotension tachycardia syndrome secondary to autonomic dysfunction. Approximately 10% of patients with suspected functional bowel disorders have hypermobility syndrome. Hence, it is crucial to familiarize gastrointestinal practitioners with the criteria utilized to diagnose JHS and the methods to identify physical examination findings related to this condition.

Abstract 14415: Aortic Strain and Stiffness in Patients With Turner and Marfan Syndrome: Non-Invasive Phenotyping of Aortic Biomechanical Properties

Introduction: Turner and Marfan Syndromes (TS and MFS) are hereditary connective tissue disorders with increased risk of aortic aneurysm and rates of dissection. Prior studies suggest that TS and MFS have increased aortic stiffness when compared to healthy controls but comparative phenotyping of central aortic stiffness between the two syndromes has not yet been performed. Hypothesis: Non-invasively derived aortic biomechanical properties will differ between MFS and TS patients. Methods: Patients underwent cardiac MRI to evaluate central aortic strain and stiffness. Circumferential strain was evaluated using relative area change (RAC) for both the ascending and descending aorta and longitudinal aortic strain (LAS) was measured in the ascending aorta. Stiffness was evaluated using pulse wave velocity (PWV) and by wave-intensity analysis derived backward compression wave (BCW) ratio measuring stiffness of arch and abdominal vessels. Results: Patients with TS (N=53, mean age: 17.2±5.4) and MFS (N = 22, mean age: 17.8±6.2) had similar ascending aortic size and z-score. When compared to TS, MFS patients had reduced RAC in both ascending (33 vs 16%, P &lt; 0.05) and descending aorta (24 vs 14%, P &lt; 0.01) (Figure). PWV was increased in MFS in both ascending (4.0 vs 3.0 m/s, P &lt; 0.01) and descending aorta (3.8 vs 4.7 m/s, P &lt; 0.01). LAC was reduced in MFS patients as well (14 vs 8%, P &lt; 0.01). Lastly, MFS had increased BCW ratio for arch vessel stiffness (0.11 vs 0.26, P &lt; 0.01) with no difference in abdominal vessels (0.35 vs 0.36, P = NS). Conclusion: In contrast to TS, MFS patients have comparably increased stiffness and reduced compliance throughout the central aorta including aortic arch vessels. These differences are in parallel with clinical observations describing higher rate of aortic events throughout the entire aorta in patients with MFS. Our results might also be critical given the increasingly dominant role of biomechanical indices in the risk assessment for aortic events.

The effects of joint hypermobility on pain and functional biomechanics in adolescents with juvenile fibromyalgia: secondary baseline analysis from a pilot randomized controlled trial

BackgroundJoint hypermobility is a common clinical finding amongst hereditary connective tissue disorders that is observed in pediatric rheumatological settings, and often associated with chronic pain. Joint hypermobility may also contribute to deficits in physical functioning and physical activity, but previous findings have been inconsistent. It is possible that physical activity impairment in joint hypermobility may be due to chronic aberrant movement patterns subsequent to increased joint laxity.MethodAs part of a larger randomized pilot trial of juvenile onset fibromyalgia (JFM), a secondary analysis was conducted to explore whether adolescents with JFM and joint hypermobility differed from non-joint hypermobility peers in terms of pain, daily functioning, and biomechanics (i.e., kinetics and kinematics) during a moderately vigorous functional task.ResultsFrom the larger sample of adolescents with JFM (N = 36), 13 adolescents (36.1%) met criteria for joint hypermobility and 23 did not have joint hypermobility. Those with joint hypermobility exhibited poorer overall functioning (Md = 20, Q1,Q3 [5.8, 7.6] vs. Md = 29, Q1,Q3 [5.1, 7.6]) but there were no differences in pain (Md = 6.9, Q1,Q3 [22, 33], vs. Md = 6.45, Q1,Q3 [15, 29.5]). Inspection of time-series plots suggests those with joint hypermobility exhibited decreased hip flexion and frontal plane hip moment (e.g., resistance to dynamic valgus) during the landing phase (early stance) and greater hip and knee transverse plane moments during the propulsion phase (late stance) of the drop vertical jump task (DVJ). No other differences in lower extremity biomechanics were observed between study groups.ConclusionsIn this exploratory study, there were small but notable differences in biomechanics between patients with JFM who also had joint hypermobility versus those without joint hypermobility during a landing and jumping task (e.g., DVJ). These differences may indicate decreased joint stiffness during landing, associated with increased joint laxity and decreased joint stability, which may put them at greater risk for injury. Further study with a larger sample size is warranted to examine whether these biomechanical differences in patients with JFM and joint hypermobility affect their response to typical physical therapy or exercise recommendations.

THU411 Fracture And Osteoporosis In Hereditary Connective Tissue Disorders: A Systematic Review And Meta-analysis

Abstract Disclosure: N. Charoenngam: None. T. Rittiphairoj: None. A. Jaroenlapnopparat: None. B. Ponvilawan: None. P. Waitayangkoon: None. P. Supakitjanusant: None. V. Prasitsumrit: None. C. Pongchaiyakul: None. M.F. Holick: None. Introduction: Hereditary connective tissue disorders (HCTDs) refer to a constellation of conditions caused by defects in the structure and synthesis of extracellular matrix. It is well-known that bone fragility is the hallmark feature of osteogenesis imperfecta. Interestingly, other HCTDs, including Ehlers-Danlos syndrome (EDS), Marfan’s syndrome (MFS) and Loeys-Dietz syndrome (LDS) are shown to be associated with bone fragility. However, most of the existing studies were small in sample sizes, thereby limiting validity and generalizability. Therefore, we aimed to identify all available data, using systematic review and meta-analysis, to determine the risks of fracture and osteoporosis in patients with HCTDs, including EDS, MFS and LDS. Methods: From inception to June 2022, potentially eligible studies were identified in the Medline and EMBASE databases using search strategy that included terms for “HCTD”, “Fracture” and “Osteoporosis”. Eligible studies must consist of a group of patients with HCTD and report prevalence/incidence of fracture/osteoporosis in their participants, with or without comparison with healthy individuals. Point estimates with standard errors were obtained from each study and combined using the generic inverse variance method. Results: Among the 4,206 articles that were identified, 19 studies fulfilled the eligibility criteria. The pooled prevalence of fracture in patients with EDS, MFS and LDS were 44% (95%CI, 25 - 65%, I2 88%), 17% (95%CI, 11 - 26%, I2 68%), 69% (95%CI, 47 - 85%, I2 83%), respectively. The pooled prevalence of osteoporosis among patients with EDS was 17% (95%CI, 8 - 34%, I2 96%). EDS was associated with fracture [pooled odds ratio 4.90 (95%CI, 1.49 - 16.08, I2 86%)], but not osteoporosis [pooled odds ratio 1.34 (95%CI, 0.28 - 6.36, I2 87%). One study reported a 5% (95%CI, 3 - 8%) prevalence of osteoporosis in MFS, and MFS was associated with fracture [incidence rate ratio 1.35 (95%CI, 1.18 - 1.55)] and osteoporosis [subhazard ratio 3.97 (95%CI, 2.53 - 6.25)]. Conclusion: EDS was associated with fracture, which could be independent of osteoporosis status. MFS had a milder degree of increased risk of fracture and osteoporosis. Despite the lack of data from cohort studies, there was a significantly higher rate of fracture in LDS. Presentation: Thursday, June 15, 2023

Marfan’s Syndrome and associated pathologies: An integrative systematic review of randomised controlled trials

Background Marfan’s syndrome (MFS) is an autosomal dominant hereditary connective tissue disorder associated with numerous skeletal, ocular, cardiovascular, and respiratory pathologies which advance with age. Following multiple system involvement of body, the clinical presentation and management of MFS with associated pathologies are an area of cautious focus. Therefore, this review focused on highlighting various management options that are currently being supported for the MFS patients. Methodology The search methodology involved randomized controlled trials (RCTs) published between 2018 to 2022 from PubMed and Google Scholar databases. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) were followed for reviewing the data extracted following the inclusion and exclusion criteria using the keywords “Marfan’s Syndrome”, “Irbesartan”, “Aortic Dilatation”, “Atenolol”, and “Lens Subluxation.” Results A total of eight articles were reviewed for the preferred distribution of population and the management options followed in the studies consisting of medical, psychological, and surgical interventions. Also, the associated pathologies related to MFS patients were analysed and found to have significant impact on health-related quality of life of MFS patients. Conclusions The review concluded that a combination of drugs atenolol, a β-blocker, and losartan which is an angiotensin receptor blocker, is beneficial in case of aortic root dilatation and higher aortic root stiffness. Additionally, ADRB1 testing may determine patients that are more likely to respond therapeutically to atenolol in comparison to losartan. Cionni modified capsular tension rings (MCTR) have been acknowledged as an effective device for delivering good capsular bag stabilization in cases of lens subluxation in MFS patients.