-
Fetal Diagnosis and Therapy 2021The majority of arthrogryposis multiplex congenita (AMC) and lethal forms of AMC such as foetal akinesia deformation sequence (FADS) cases are missed prenatally. We have...
INTRODUCTION
The majority of arthrogryposis multiplex congenita (AMC) and lethal forms of AMC such as foetal akinesia deformation sequence (FADS) cases are missed prenatally. We have demonstrated the additional value of foetal motor assessment and evaluation in a multidisciplinary team for the period 2007-2016. An applied care pathway was developed for foetuses presenting with joint contracture(s) in one anatomic region (e.g., talipes equinovarus [TEV]), more than one body part with non-progressive contractures and motility (AMC) and with deterioration over time (FADS).
METHODS
The multidisciplinary team of Amsterdam University Medical Centre Expertise Centre FADS and AMC developed the care pathway. Additional tools are provided including a motor assessment by ultrasound examination and a post-mortem assessment form.
RESULTS
An eight-step care pathway is presented with a proposed timing for prenatal sonographic examination, genetic examinations, multidisciplinary meetings, prenatal and postnatal counselling of the parents by a specialist also treating after birth, and the follow-up of prenatal and postnatal findings with counselling for future pregnancies.
DISCUSSION/CONCLUSION
The scheduled serial structural and motor sonograpahic assessment together with follow-up examinations and genetic analysis should be tailored per prenatal centre per available resources. The multidisciplinary care pathway may pave the way to increase the detection rate and diagnosis of isolated contracture(s), TEV with underlying genetic causes, and the rare phenotypes AMC/FADS and prompt treatment after birth within expertise teams.
Topics: Arthrogryposis; Contracture; Critical Pathways; Female; Fetus; Humans; Pregnancy
PubMed: 34775380
DOI: 10.1159/000520869 -
Journal of Orthopaedic Research :... Sep 2017The purpose of this study was to examine the time-dependent changes in the development of joint capsule fibrosis and in the number of myofibroblasts in the joint capsule...
The purpose of this study was to examine the time-dependent changes in the development of joint capsule fibrosis and in the number of myofibroblasts in the joint capsule after immobilization, using a rat knee contracture model. Both knee joints were fixed in full flexion for 1, 2, and 4 weeks (immobilization group). Untreated rats were bred for each immobilization period (control group). Histological analysis was performed to evaluate changes in the amount and density of collagen in the joint capsule. The changes in type I and III collagen mRNA were examined by in situ hybridization. The number of myofibroblasts in the joint capsule was assessed by immunohistochemical methods. In the immobilization group, the amount of collagen increased within 1 week and the density of collagen increased within 2 weeks, as compared with that in the control group. Type I collagen mRNA-positive cell numbers in the immobilization group increased at all time points. However, type III collagen mRNA-positive cell numbers did not increase. Myofibroblasts in the immobilization group significantly increased compared with those in the control group at all time points, and they increased significantly with the period of immobilization. These results suggest that joint capsule fibrosis with overexpression of type I collagen occurs and progresses within 1 week after immobilization, and an increase in myofibroblasts is related to the mechanism of joint capsule fibrosis. The findings suggest the need for a treatment targeting accumulation of type I collagen associated with an increase in myofibroblasts. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1998-2006, 2017.
Topics: Animals; Collagen; Contracture; Disease Models, Animal; Fibrosis; Immobilization; Joint Capsule; Male; Myofibroblasts; Range of Motion, Articular; Rats, Wistar
PubMed: 27918117
DOI: 10.1002/jor.23498 -
Medicine Mar 2021Contractures frequently occur in the finger joints after immobilization. This report describes the effect of acupotomy treatment in patients with joint contracture due...
INTRODUCTION
Contractures frequently occur in the finger joints after immobilization. This report describes the effect of acupotomy treatment in patients with joint contracture due to immobilization of the finger joints.
PATIENT CONCERNS AND CLINICAL FINDINGS
Case 1 was of a 39-year-old male patient who had flexion limitation of the left thumb and difficulty in grasping. Case 2 was of a 41-year-old female patient who had flexion limitation of the right index finger and difficulty in typing. Stiffness occurred after tendon repair surgery and cast immobilization in both cases. In Case 1, the patient had limited flexion movement of the first metacarpophalangeal and interphalangeal joints after 5 weeks of immobilization of the left thumb in a cast. In Case 2, the patient had limited flexion movement after 3 weeks of immobilization of the second proximal interphalangeal joint of the left hand in a cast.
DIAGNOSIS, INTERVENTIONS, AND OUTCOMES
We diagnosed both patients with finger joint contracture due to immobilization. Conservative treatment for approximately 4 weeks did not lead to improvement in either patient. Acupotomy is the key treatment for improving movement in Korean Medicine. Therefore, acupotomy was performed, and joint stiffness markedly improved without adverse events. Both patients reported that the daily use of the damaged fingers became comfortable.
CONCLUSION
We found that acupotomy may be effective for finger joint contracture due to improper immobilization. We suggest it as a simple and safe treatment for joint contracture.
Topics: Acupuncture Therapy; Adult; Casts, Surgical; Contracture; Female; Finger Injuries; Finger Joint; Humans; Joint Capsule; Male; Postoperative Complications; Range of Motion, Articular; Tendon Injuries; Treatment Outcome
PubMed: 33725871
DOI: 10.1097/MD.0000000000024988 -
Proceedings of the National Academy of... Jun 2021Osteogenesis imperfecta (OI) is a genetic disorder that features wide-ranging defects in both skeletal and nonskeletal tissues. Previously, we and others reported that...
Osteogenesis imperfecta (OI) is a genetic disorder that features wide-ranging defects in both skeletal and nonskeletal tissues. Previously, we and others reported that loss-of-function mutations in FK506 Binding Protein 10 () lead to skeletal deformities in conjunction with joint contractures. However, the pathogenic mechanisms underlying joint dysfunction in OI are poorly understood. In this study, we have generated a mouse model in which is conditionally deleted in tendons and ligaments. removal substantially reduced telopeptide lysyl hydroxylation of type I procollagen and collagen cross-linking in tendons. These biochemical alterations resulting from ablation were associated with a site-specific induction of fibrosis, inflammation, and ectopic chondrogenesis followed by joint deformities in postnatal mice. We found that the ectopic chondrogenesis coincided with enhanced Gli1 expression, indicating dysregulated Hedgehog (Hh) signaling. Importantly, genetic inhibition of the Hh pathway attenuated ectopic chondrogenesis and joint deformities in mutants. Furthermore, Hh inhibition restored alterations in gait parameters caused by loss. Taken together, we identified a previously unappreciated role of in tendons and ligaments and pathogenic mechanisms driving OI joint dysfunction.
Topics: Animals; Animals, Newborn; Chondrocytes; Chondrogenesis; Collagen Type I; Disease Models, Animal; Fibrosis; Gait; Gene Deletion; Gene Expression Regulation; Hedgehog Proteins; Hydroxylation; Inflammation; Joints; Ligaments; Lysine; Mice; Models, Biological; Motor Activity; Ossification, Heterotopic; Osteogenesis; Osteogenesis Imperfecta; Peptides; Sequence Analysis, RNA; Signal Transduction; Tacrolimus Binding Proteins; Tendons
PubMed: 34161280
DOI: 10.1073/pnas.2100690118 -
Journal of Orthopaedic Research :... Nov 2019Fetal movements are essential for normal development of the human skeleton. When fetal movements are reduced or restricted, infants are at higher risk of developmental...
Fetal movements are essential for normal development of the human skeleton. When fetal movements are reduced or restricted, infants are at higher risk of developmental dysplasia of the hip and arthrogryposis (multiple joint contractures). Joint shape abnormalities have been reported in mouse models with abnormal or absent musculature, but the effects on joint shape in such models have not been quantified or characterized in detail. In this study, embryonic mouse forelimbs and hindlimbs at a single developmental stage (Theiler Stage 23) with normal, reduced, or absent muscle were imaged in three-dimensions. Skeletal rudiments were virtually segmented and rigid image registration was used to reliably align rudiments with each other, enabling repeatable assessment and measurement of joint shape differences between normal, reduced-muscle and absent-muscle groups. We demonstrate qualitatively and quantitatively that joint shapes are differentially affected by a lack of, or reduction in, skeletal muscle, with the elbow joint being the most affected of the major limb joints. Surprisingly, the effects of reduced muscle were often more pronounced than those of absent skeletal muscle, indicating a complex relationship between muscle mass and joint morphogenesis. These findings have relevance for human developmental disorders of the skeleton in which abnormal fetal movements are implicated, particularly developmental dysplasia of the hip and arthrogryposis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2287-2296, 2019.
Topics: Animals; Fetal Movement; Imaging, Three-Dimensional; Joints; Mice; Models, Biological; Muscles
PubMed: 31297860
DOI: 10.1002/jor.24415 -
BMJ Case Reports Feb 2018Disabling pansclerotic morphoea (DPM) of childhood is a severe and often fatal variant of deep morphoea. It usually starts in childhood and rarely seen in adults. The...
Disabling pansclerotic morphoea (DPM) of childhood is a severe and often fatal variant of deep morphoea. It usually starts in childhood and rarely seen in adults. The course of the disease is progressive with lifelong morbidity in the form of joint contractures and immobility. The causes of mortality include complications such as sepsis, gangrene and cardiopulmonary involvement. Herein, we discuss the case of a 15-year-old girl with limb deformity and finger contractures, that is, bone involvement. The diagnosis of DPM of childhood was fortuitously made after the correction of limb deformity, when the patient was seen in the dermatology department for evaluation of skin discolouration on the thighs.
Topics: Adolescent; Biopsy; Contracture; Disease Progression; Elastic Tissue; Extremities; Female; Fingers; Humans; Scleroderma, Localized; Skin
PubMed: 29455178
DOI: 10.1136/bcr-2017-222132 -
Scientific Reports Sep 2021Joint contracture leads to major patient discomfort. Metformin, one of the most extensively used oral drugs against type 2 diabetes has recently been found to suppress...
Joint contracture leads to major patient discomfort. Metformin, one of the most extensively used oral drugs against type 2 diabetes has recently been found to suppress tissue fibrosis as well. However, its role in suppressing tissue fibrosis in joint contractures remains unknown. In this study, we examined the role of metformin treatment in suppressing joint capsular fibrosis and the most effective time of its administration. Joint capsular fibrosis was induced by immobilizing the knee joints of mice using splints and tapes. Metformin was administered intraperitoneally every alternate day after immobilization. Histological and immunohistochemical changes and expression of fibrosis-related genes were evaluated. Metformin treatment significantly suppressed fibrosis in joint capsules based on histological and immunohistochemical evaluation. Joint capsular tissue from metformin-treated mice also showed decreased expression of fibrosis-related genes. Early, but not late, metformin administration showed the same effect on fibrosis suppression in joint capsule as the whole treatment period. The expression of fibrosis-related genes was most suppressed in mice administered with metformin early. These studies demonstrated that metformin treatment can suppress joint capsular fibrosis and the most effective time to administer it is early after joint immobilization; a delay of more than 2 weeks of administration is less effective.
Topics: Animals; Contracture; Disease Models, Animal; Fibrosis; Gene Expression; Immobilization; Immunohistochemistry; Injections, Intraperitoneal; Joint Capsule; Knee Joint; Male; Metformin; Mice; Mice, Inbred C57BL; Range of Motion, Articular; Time Factors; Transforming Growth Factor beta1; Treatment Outcome
PubMed: 34504209
DOI: 10.1038/s41598-021-97445-7 -
Journal of Nippon Medical School =... Mar 2022Knees with severe varus osteoarthritis can develop medial structure contracture. However, there is no report on the relationship between severity of varus deformity and...
BACKGROUND
Knees with severe varus osteoarthritis can develop medial structure contracture. However, there is no report on the relationship between severity of varus deformity and contracture of the medial structure. We aimed to determine the threshold angle that could be corrected in proportion to the width of medial osteophyte removal and to examine correction differences between angles larger and smaller than the threshold angle in total knee arthroplasty.
METHODS
This study included 27 varus osteoarthritic knees scheduled for total knee arthroplasty (TKA). A navigation system was used to measure hip-knee-ankle angle (HKA) in all knees at maximum extension and 30˚ and 60˚ flexion, before and after osteophyte removal and with and without external 10 N-m valgus torque loads. Subsequently, resected osteophyte widths were measured. Mean correction angle per 1 mm of osteophyte removal was calculated, and the threshold angle was calculated with the receiver operating characteristic curve. HKA differences were compared against deformities larger and smaller than the threshold angle.
RESULTS
Mean osteophyte width was 7.1±2.20 mm. Osteophyte removal produced a mean 3.1° correction, which equaled a 0.4° correction per 1 mm of osteophyte width removal. The varus deformity threshold angle was 9.5°. However, when comparing groups with angles larger and smaller than the threshold angle, there was no significant difference in HKA difference between each step and flexion angle.
CONCLUSIONS
The threshold angle for expected correction with medial osteophyte removal was 9.5˚. However, because there were no differences in correction between those with angles larger or smaller than this, medial structure contracture seemed to be unrelated to the severity of deformity.
Topics: Arthroplasty, Replacement, Knee; Contracture; Humans; Knee Joint; Osteoarthritis, Knee; Range of Motion, Articular
PubMed: 34526449
DOI: 10.1272/jnms.JNMS.2022_89-113 -
Frontiers in Physiology 2020Distal arthrogryposis (DA) is a skeletal muscle disorder which can be classified under a broader term as Arthrogryposis multiplex contractures. DA is characterized by... (Review)
Review
Distal arthrogryposis (DA) is a skeletal muscle disorder which can be classified under a broader term as Arthrogryposis multiplex contractures. DA is characterized by the presence of joint contractures at various parts of the body, particularly in distal extremities. It is identified as an autosomal dominant and a rare X-linked recessive disorder associated with increased connective tissue formation around joints in such way that immobilizes muscle movement causing deformities. DA is again classified into various types since it manifests as a range of conditions representing different etiologies. Myopathy is one of the most commonly listed etiologies of DA. The mutations in sarcomeric protein-encoding genes lead to decreased sarcomere integrity, which is often associated with this disorder. Also, skeletal disorders are often associated with cardiac disorders. Some studies mention the presence of cardiomyopathy in patients with skeletal dysfunction. Therefore, it is hypothesized that the congenitally mutated protein that causes DA can also lead to cardiomyopathy. In this review, we will summarize the different forms of DA and their clinical features, along with gene mutations responsible for causing DA in its different forms. We will also examine reports that list mutations also known to cause heart disorders in the presence of DA.
PubMed: 32670090
DOI: 10.3389/fphys.2020.00689 -
Frontiers in Immunology 2023H syndrome is a rare autosomal recessive genetic disorder characterized by the following clinical features: cutaneous hyperpigmentation, hypertrichosis,... (Review)
Review
H syndrome is a rare autosomal recessive genetic disorder characterized by the following clinical features: cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, short stature, hallux valgus, hyperglycemia, fixed flexion contractures of the toe joints, and the proximal interphalangeal joints. In rare cases, autoinflammatory and lymphoproliferative manifestations have also been reported. This disorder is due to loss-of-function mutations in gene, which encode the equilibrative nucleoside transporter ENT3. This deficiency leads to abnormal function and proliferation of histiocytes. H syndrome is part of the R-group of histiocytosis. We report two different cases, one was diagnosed in adulthood and the other in childhood. The first case reported is a 37-year-old woman suffering from H syndrome with an autoinflammatory systemic disease that begins in adulthood (fever and diffuse organ's infiltration) and with cutaneous, articular, auditory, and endocrinological manifestations since childhood. The second case reported is a 2-year-old girl with autoinflammatory, endocrine, and cutaneous symptoms (fever, lymphadenopathy, organomegaly, growth delay, and cutaneous hyperpigmentation). Homozygous mutations in confirmed the diagnosis of H syndrome in both cases. Each patient was treated with Tocilizumab with a significant improvement for lymphoproliferative, autoinflammatory, and cutaneous manifestations. Both cases were reported to show the multiple characteristics of this rare syndrome, which can be diagnosed either in childhood or in adulthood. In addition, an overview of the literature suggested Tocilizumab efficiency.
Topics: Female; Humans; Adult; Child, Preschool; Hearing Loss, Sensorineural; Contracture; Histiocytosis; Fever; Nucleoside Transport Proteins
PubMed: 37638031
DOI: 10.3389/fimmu.2023.1061182