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MedRxiv : the Preprint Server For... Mar 2024Collagen VI-related dystrophies (COL6-RDs) manifest with a spectrum of clinical phenotypes, ranging from Ullrich congenital muscular dystrophy (UCMD), presenting with...
The recurrent deep intronic pseudoexon-inducing variant c.930+189C>T results in a consistently severe phenotype of COL6-related dystrophy: Towards clinical trial readiness for splice-modulating therapy.
Collagen VI-related dystrophies (COL6-RDs) manifest with a spectrum of clinical phenotypes, ranging from Ullrich congenital muscular dystrophy (UCMD), presenting with prominent congenital symptoms and characterised by progressive muscle weakness, joint contractures and respiratory insufficiency, to Bethlem muscular dystrophy, with milder symptoms typically recognised later and at times resembling a limb girdle muscular dystrophy, and intermediate phenotypes falling between UCMD and Bethlem muscular dystrophy. Despite clinical and immunohistochemical features highly suggestive of COL6-RD, some patients had remained without an identified causative variant in , or . With combined muscle RNA-sequencing and whole-genome sequencing we uncovered a recurrent, deep intronic variant in intron 11 of (c.930+189C>T) that leads to a dominantly acting in-frame pseudoexon insertion. We subsequently identified and have characterised an international cohort of forty-four patients with this intron 11 causative variant, one of the most common recurrent causative variants in the collagen VI genes. Patients manifest a consistently severe phenotype characterised by a paucity of early symptoms followed by an accelerated progression to a severe form of UCMD, except for one patient with somatic mosaicism for this intron 11 variant who manifests a milder phenotype consistent with Bethlem muscular dystrophy. Characterisation of this individual provides a robust validation for the development of our pseudoexon skipping therapy. We have previously shown that splice-modulating antisense oligomers applied effectively decreased the abundance of the mutant pseudoexon-containing COL6A1 transcripts to levels comparable to the scenario of the somatic mosaicism shown here, indicating that this therapeutic approach carries significant translational promise for ameliorating the severe form of UCMD caused by this common recurrent causative variant to a Bethlem muscular dystrophy phenotype.
PubMed: 38585825
DOI: 10.1101/2024.03.29.24304673 -
Journal of Orthopaedic Case Reports Mar 2024Juvenile idiopathic arthritis ( JIA) is a persistent autoimmune-inflammatory disease that affects children younger than 16. Aggressive synovitis of the hip may cause...
INTRODUCTION
Juvenile idiopathic arthritis ( JIA) is a persistent autoimmune-inflammatory disease that affects children younger than 16. Aggressive synovitis of the hip may cause joint destruction, hip protrusion, erosion, pseudosubluxation, dysplasia, and osteoarthritis. Subluxation of the hip had been reported previously. However, dislocation of the hip in JIA is an extremely rare situation, and only two cases have been reported up to date. Reduction of the dislocated hip has to be performed in any way. However, there is no algorithm to be followed for the treatment of hip dislocations caused by JIA.
CASE PRESENTATION
In this study, we presented two cases of hip dislocation caused by JIA.: An 11-year-old boy had JIA and chronic recurrent multifocal osteomyelitis (CRMO). X-rays and computed tomography (CT) revealed a posterior dislocation of the left hip. An urgent operation was planned for the reduction of the hip. Avascular necrosis, dysplasia, or erosions were not evident at the last follow-up.: An 11-year-old girl was referred to the hospital with excessive left hip pain starting 24 h ago. A limited synovectomy with joint irrigation was performed. However, pathological examination of the synovium showed chronic inflammation consistent with JIA. On the post-operative 10th day, the patient was consulted for an increase in hip pain and deformity of the left hip. X-rays and MRI revealed posterior dislocation of the left hip with synovial hypertrophy. An urgent operation was planned. The hip could be reduced under anesthesia with mild traction, and a pelvipedal cast was applied only for 3 weeks. Avascular necrosis, dysplasia, destruction, or erosions were not evident at the last follow-up.
CONCLUSION
For early diagnosed patient reduction under anesthesia and medial soft-tissue contracture release; for late diagnosed patient medial soft-tissue contracture release, capsulotomy and synovectomy were effective to prevent destruction and early degenerative changes of the hip joint for treatment of dislocation caused by JIA.
PubMed: 38560299
DOI: 10.13107/jocr.2024.v14.i03.4288 -
Journal of Orthopaedic Case Reports Mar 2024Bilateral Sprengel deformities, mirror movements synkinesis, and arthrogryposis are described in different combinations in various syndromes but never together.
INTRODUCTION
Bilateral Sprengel deformities, mirror movements synkinesis, and arthrogryposis are described in different combinations in various syndromes but never together.
CASE REPORT
We present a 12-year-old girl who presented with bilateral shoulder deformities and difficulty in coordination while writing. On examination, she was noted to have bilateral Sprengel deformities with flexion contractures of upper-limb joints and mirror movements of both upper and lower-limb joints.
CONCLUSION
In the light of relevant literature, we may speculate that these three have a causal relation and even a genetic basis but further studies are needed to prove the same.
PubMed: 38560296
DOI: 10.13107/jocr.2024.v14.i03.4270 -
Cureus Feb 2024Tuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis (TB) characterized by the invasion of into the meninges surrounding the brain and spinal...
Tuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis (TB) characterized by the invasion of into the meninges surrounding the brain and spinal cord. It triggers an intense inflammatory response, leading to neurological complications if not promptly and adequately managed. TBM often precipitates muscle weakness, neurological deficits, respiratory challenges, swallowing difficulties, joint contractures, and pain. Physiotherapy intervention is essential in treating these problems by personalized treatment strategies and treatment plans to enhance muscle strength, motor control, coordination, and overall mobility. This case report aims to highlight the significant role of physiotherapy in improving the quality of life (QOL) and functional abilities of patients with TBM. The current case report reviews the case of a 73-year-old male who presented with complaints of generalized weakness and difficulty in swallowing. The patient had a history of fever for the last six months. Magnetic resonance imaging (MRI) and high-resolution computed tomography (HRCT) diagnosed the case as TBM with miliary TB. Six weeks of targeted intensive rehabilitation program was designed according to the patient's impairments initiated from the intensive care unit (ICU) phase. The main goals of physiotherapy were to start early bed mobility, maintain joint integrity, improve postural strength and swallowing, and make the patient independent in transfer and activities of daily living (ADLs). After a six-week intensive physiotherapy (TIP-6) program, the patient exhibited significant improvements in muscle strength and independence in ADLs. This case highlights the critical role of physiotherapy in enhancing the QOL and functional abilities of patients with severe TB-related conditions.
PubMed: 38558619
DOI: 10.7759/cureus.55214 -
The Pan African Medical Journal 2024During the 1970s, scientists first used botulinum toxin to treat strabismus. While testing on monkeys, they noticed that the toxin could also reduce wrinkles in the... (Review)
Review
During the 1970s, scientists first used botulinum toxin to treat strabismus. While testing on monkeys, they noticed that the toxin could also reduce wrinkles in the glabella area. This led to its widespread use in both medical and cosmetic fields. The objective of the study was to evaluate the potential use of Botox in managing post-operative contracture after below-knee amputation. We conducted a systematic review In Pubmed, Cochrane Library, Embase, and Google Scholar using the MESH terms Botox, botulinum toxin, post-operative contracture, amputation, and below knee amputation. Our goal was to evaluate the potential use of Botox to manage post-operative contracture in patients who have undergone below-knee amputation. Our findings show evidence in the literature that Botox can effectively manage stump hyperhidrosis, phantom pain, and jumping stump, but no clinical trial has been found that discusses the use of Botox for post-operative contracture. Botox has been used in different ways to manage spasticity. Further studies and clinical trials are needed to support the use of Botox to manage this complication.
Topics: Humans; Botulinum Toxins, Type A; Amputation, Surgical; Contracture; Amputation Stumps; Muscle Spasticity; Joint Dislocations; Neuromuscular Agents
PubMed: 38558551
DOI: 10.11604/pamj.2024.47.26.42249 -
Animals : An Open Access Journal From... Mar 2024Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration through animal... (Review)
Review
Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration through animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, from a One Health perspective. This review offers a hands-on vision of the non-invasive and conservative approaches to peripheral nerve injury, focusing on the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation of BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities (low-level laser therapy, ultrasounds, pulsed electromagnetic fields, electroacupuncture and others). In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoid situations of permanent monoplegic limbs that could lead to amputation.
PubMed: 38539981
DOI: 10.3390/ani14060884 -
The Turkish Journal of Pediatrics 2024Campotodactyly-artrhropathy-coxa vara-pericarditis (CACP) syndrome is a very rare autosomal recessive genetic disorder. It is characterized by flexion contracture of the...
BACKGROUND
Campotodactyly-artrhropathy-coxa vara-pericarditis (CACP) syndrome is a very rare autosomal recessive genetic disorder. It is characterized by flexion contracture of the fifth finger (camptodactyly); noninflammatory arthropathy; decreased angle between the shaft and the head of the femur (coxa vara) and pericarditis. Its association with mitral stenosis has not yet been reported. Hereby we report this unique association with CACP syndrome.
CASE
An eleven-year-old girl presented with non-productive cough, dyspnea, and orthopnea. She was diagnosed CACP syndrome at the age of seven and a biallelic frameshift mutation in the PRG4 gene was determined. The physical examination revealed pectus excavatum, camptodactyly, genu valgum, tachypnea and orthopnea. The functional capacity was NYHA III-IV. She had 2/6 soft pansystolic murmur at 4th left intercostal space and a rumbling diastolic murmur at apex. Echocardiography revealed an enlarged left atrium, severe stenotic mitral valve with a mean diastolic transmitral gradient of 22.5 mmHg, mild mitral regurgitation and mild apical pericardial effusion. The patient had mitral comissurotomy and partial pericardiectomy operation. Her post-operative transmitral gradient decreased to 6.9 mmHg and the pulmonary pressure was 30 mmHg. Her functional capacity increased to NYHA I-II.
CONCLUSIONS
The main defect is the proteoglycan 4 protein which acts like a lubricant in articular and visceral surfaces. Therefore, the leading clinical feature is arthropathy. Cardiac involvement other than clinically mild pericarditis is not usually expected. Three types of proteoglycans (decorin, biglycan, and versican) are present in the mitral valve. This could be the reason of mitral valve involvement in rare cases as like ours. It is important that these patients undergo echocardiographic examination regularly.
Topics: Female; Humans; Child; Coxa Vara; Mitral Valve Stenosis; Joint Diseases; Pericarditis; Dyspnea; Arthropathy, Neurogenic; Hand Deformities, Congenital; Synovitis
PubMed: 38523390
DOI: 10.24953/turkjped.2023.647 -
Wearable Technologies 2024Orthotic wrist supports will be beneficial for people with muscular weakness to keep their hand in a neutral rest position and prevent potential wrist contractures....
Orthotic wrist supports will be beneficial for people with muscular weakness to keep their hand in a neutral rest position and prevent potential wrist contractures. Compensating the weight of the hands is complex since the level of support depends on both wrist and forearm orientations. To explore simplified approaches, two different weight compensation strategies ( and ) were compared to the theoretical ideal profile and no compensation in eight healthy subjects using a mechanical wrist support system. All three compensation strategies showed a significant reduction of 47-53% surface electromyography activity in the anti-gravity m. extensor carpi radialis. However, for the higher palmar flexion region, a significant increase of 44-61% in the m. flexor carpi radialis was found for all compensation strategies. No significant differences were observed between the various compensation strategies. Two conclusions can be drawn: (1) a simplified torque profile (e.g., constant or linear) for weight compensation can be considered as equally effective as the theoretically ideal sinusoidal profile and (2) even the theoretically ideal profile provides no perfect support as other factors than weight, such as passive joint impedance, most likely influence the required compensation torque for the wrist joint.
PubMed: 38510986
DOI: 10.1017/wtc.2023.23