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BMC Medical Genomics Jan 2024ALS2-related disorder involves retrograde degeneration of the upper motor neurons of the pyramidal tracts, among which autosomal recessive Infantile-onset ascending...
Clinical features and molecular genetic investigation of infantile-onset ascending hereditary spastic paralysis (IAHSP) in two Chinese siblings caused by a novel splice site ALS2 variation.
OBJECTIVE
ALS2-related disorder involves retrograde degeneration of the upper motor neurons of the pyramidal tracts, among which autosomal recessive Infantile-onset ascending hereditary spastic paralysis (IAHSP) is a rare phenotype. In this study, we gathered clinical data from two Chinese siblings who were affected by IAHSP. Our aim was to assess the potential pathogenicity of the identified variants and analyze their clinical and genetic characteristics.
METHOD
Here, Whole-exome sequencing (WES) was performed on proband to identify the candidate variants. Subsequently, Sanger sequencing was used to verify identified candidate variants and to assess co-segregation among available family members. Utilizing both silico prediction and 3D protein modeling, an analysis was conducted to evaluate the potential functional implications of the variants on the encoded protein, and minigene assays were performed to unravel the effect of the variants on the cleavage of pre-mRNA.
RESULTS
Both patients were characterized by slurred speech, astasia, inability to walk, scoliosis, lower limb hypertonia, ankle clonus, contracture of joint, foot pronation and no psychomotor retardation was found. Genetic analysis revealed a novel homozygous variant of ALS2, c.1815G > T(p.Lys605Asn) in two Chinese siblings. To our knowledge, it is the first confirmed case of a likely pathogenic variant leading to IAHSP in a Chinese patient.
CONCLUSION
This study broadens the range of ALS2 variants and has practical implications for prenatal and postnatal screening of IAHSR. Symptom-based diagnosis of IAHSP is frequently difficult for medical practitioners. WES can be a beneficial resource to identify a particular disorder when the diagnosis cannot be determined from the symptoms alone.
Topics: Female; Pregnancy; Humans; Mutation; Siblings; Guanine Nucleotide Exchange Factors; DNA Mutational Analysis; Molecular Biology; China; Pedigree; Amyotrophic Lateral Sclerosis; Spastic Paraplegia, Hereditary
PubMed: 38297306
DOI: 10.1186/s12920-024-01805-x -
Dermatology and Therapy Feb 2024Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive disorder characterized by typical facial dysmorphism, generalized muscle stiffness, joint contracture, and...
Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive disorder characterized by typical facial dysmorphism, generalized muscle stiffness, joint contracture, and skeletal abnormalities. This condition is caused by mutations in the heparan sulfate proteoglycan 2 (HSPG2) gene, which encodes perlecan, a component of the basement membrane. The management of patients with SJS primarily aims to alleviate symptoms related to muscle stiffness. In this report, we describe a male patient with SJS type 1A. Trio whole-exome sequencing identified a pathogenic mutation (NM_001291860.1: c.10897C>T; p.Arg3633Ter) and variants of unknown significance (NM_001291860.2: c.413+10G>T). The patient experienced difficulty in opening his eyes and mouth, which significantly limited his daily activities. Botulinum toxin A injection was administered and demonstrated significant clinical improvement after the treatment.
PubMed: 38285320
DOI: 10.1007/s13555-023-01088-7 -
Journal of Hand Therapy : Official... Jan 2024Limitations to proximal interphalangeal joint (PIPJ) motion can result in significant functional impairment for people with hand injuries and conditions. The role of...
BACKGROUND
Limitations to proximal interphalangeal joint (PIPJ) motion can result in significant functional impairment for people with hand injuries and conditions. The role of orthotic intervention to improve PIPJ motion has been studied; however, high-quality systematic reviews and meta-analyses are lacking.
PURPOSE
This study aimed to determine the effectiveness of orthotic intervention for restoring PIPJ extension/flexion following hand injuries or conditions.
STUDY DESIGN
Systematic review.
METHODS
A comprehensive literature search was completed in MEDLINE, CINAHL, Embase, Cochrane Central, and PEDro using terms related to orthoses, finger PIPJ range of motion, and randomized controlled trial design. Methodological quality was assessed using the PEDro score, study outcomes were pooled wherever possible using random effects meta-analysis, and certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation.
RESULTS
Twelve trials were included (PEDro score: 4-7/10). The addition of orthotic intervention was not more effective than hand therapy alone following Dupuytren's release for improving total active extension (mean difference [MD] -2.8°, 95% confidence interval [CI]: -9.6° to 4.0°, p = 0.84), total active flexion (MD -5.8°, 95% CI: -12.7° to 1.2°, p = 0.70), Disability of the Arm, Shoulder and Hand scores (MD 0.4, 95% CI: -2.7 to 3.6, p = 0.79), or patient satisfaction (standardized MD 0.20, 95% CI: -0.49 to 0.09, p = 0.17). Orthotic intervention was more effective than hand therapy alone for improving PIPJ extension for fixed flexion deformities following traumatic finger injury or surgery (MD -16.7°, 95% CI: -20.1° to -13.3°, p < 0.001). No studies evaluated orthotic intervention to improve PIPJ flexion.
CONCLUSION
The addition of an extension orthosis following procedures to manage Dupuytren's contracture is no better than hand therapy alone for improving PIPJ extension. In contrast, the addition of a PIPJ extension orthosis in the presence of traumatic PIPJ fixed flexion deformities is more effective for improving PIPJ extension than hand therapy alone. Future studies are needed to evaluate the role of orthotic intervention for improving PIPJ flexion.
PubMed: 38278697
DOI: 10.1016/j.jht.2023.12.018 -
Genes Jan 2024A disease associated with malfunction of the MYH3 gene is characterised by scoliosis, contractures of the V fingers, knees and elbows, dysplasia of the calf muscles,...
A disease associated with malfunction of the MYH3 gene is characterised by scoliosis, contractures of the V fingers, knees and elbows, dysplasia of the calf muscles, foot deformity and limb length asymmetry. The aim of this study was to identify the cause of musculoskeletal deformities in a three-generation Polish family by exome sequencing. The segregation of the newly described c.866A>C variant of the MYH3 gene in the family indicates an autosomal dominant model of inheritance. The detected MYH3 variant segregates the disease within the family. The presented results expand the MYH3 disease spectrum and emphasize the clinical diagnostic challenge in syndromes harbouring congenital spine defects and joint contractures.
Topics: Humans; Contracture; Mutation; Phenotype; Poland; Scoliosis
PubMed: 38275606
DOI: 10.3390/genes15010125 -
JBJS Essential Surgical Techniques 2023First described by Soule in 1910, arthrodesis of the proximal interphalangeal joint is a common operative method of treatment of hammer toe, or fixed-flexion deformity...
BACKGROUND
First described by Soule in 1910, arthrodesis of the proximal interphalangeal joint is a common operative method of treatment of hammer toe, or fixed-flexion deformity of the proximal interphalangeal joint of the lesser toes. The deformity is often caused by imbalance in intrinsic and extrinsic muscle function across the interphalangeal joint and metatarsophalangeal joint, which can be effectively addressed through proximal interphalangeal joint straightening and arthrodesis in conjunction with soft-tissue balancing of the metatarsophalangeal joint.
DESCRIPTION
Following longitudinal skin incision over the joint, a transverse extensor tenotomy and capsulotomy reveal the proximal interphalangeal joint and provide appropriate exposure of the head of the proximal phalanx. With the soft tissues protected, the proximal and middle phalanges undergo resection of the articular surfaces to allow osseous apposition. This step can be performed with a rongeur sagittal saw or with osteotomes. The head of the proximal phalanx is resected proximal to the head-neck junction, and the proximal portion of the middle phalanx is removed to expose the subchondral bone. Often, there is a dorsal contracture of the metatarsophalangeal joint that is elevating the toe, which is addressed with use of a longitudinal incision over the metatarsophalangeal joint, a Z-lengthening of the long extensor tendon to the toe, and a subsequent capsulectomy. If there is an angular component to the deformity, the collateral ligaments are released from the metatarsal neck, and the toe can be balanced. If there is residual subluxation of the joint that is incompletely corrected by soft-tissue procedures, a metatarsal osteotomy should be considered. Fixation is then performed with use of a smooth Kirschner wire. The wire is inserted from the middle phalanx out the tip of the toe and subsequently inserted retrograde across the proximal interphalangeal joint, often into the metatarsal head and neck, holding the metatarsophalangeal joint in appropriate position. This step can also be completed with use of novel methods including screws, bioabsorbable pins, or intramedullary implants.
ALTERNATIVES
Nonoperative treatments for hammer toe deformity are generally pursued prior to surgery and include shoe modifications such as a wide toe-box, soft uppers, and padding of osseous prominences. Alternative surgical treatments include proximal interphalangeal arthroplasty, soft-tissue capsulotomy, extensor tendon lengthening, and amputation.
RATIONALE
Although nonoperative treatment can alleviate symptoms temporarily, surgical treatment is often necessary for definitive treatment of hammer toe. Soft-tissue procedures such as tendon lengthening can provide a stabilizing benefit, but the degenerative bone changes associated with hammer toe are better addressed with use of resection of the proximal interphalangeal joint. Arthroplasty allows for some retained motion; however, this motion may lead to deformity and pain over time. Arthrodesis provides less painful and more reliable fixation as well as equal outcomes compared with other operative techniques. Patient satisfaction rates after this procedure are high, with pain relief in up to 92% of patients and rare complications.
EXPECTED OUTCOMES
Outcomes of this procedure are favorable, with rates of osseous fusion ranging from 83% to 98%. Patient satisfaction rates range from 83% to 100%. Historically, patients have expressed dissatisfaction with pain and the appearance of exposed hardware, but novel internal fixative devices provide a more natural appearance to the toe without the need for secondary surgical procedures for pin removal. Patients are often able to return to regular activity at 6 weeks postoperatively; however, there may be persistent pain or swelling in the toe. Wide shoes and activity modifications are frequently continued for several more weeks postoperatively, and some patients may benefit from formal physical therapy and at-home rehabilitation.
IMPORTANT TIPS
Avoid vascular compromise by ensuring adequate resection of bone at the proximal interphalangeal joint.A longitudinal incision across the joint provides greater exposure but can lead to scar contracture that elevates the toe. One alternative is the use of an elliptically shaped incision over the proximal interphalangeal joint, which can improve cosmesis but does restrict exposure.Excessive osseous resection can lead to a cosmetically undesirable short toe.If using an implant for the arthrodesis, ensure the implant is not too big for the toe. Most implants are too big for fifth-toe arthrodesis.In toes with severe deformity, fixation with a Kirschner wire is often preferred because excessive stretching of the neurovascular bundle can lead to toe compromise and if Kirschner wire is used the pin can easily be removed at bedside.For flexible deformities, a nonoperative approach is recommended, such as stretching exercises, shoe-wear modifications, and metatarsal pads. A tenotomy of the flexor digitorum brevis is a soft-tissue procedure that can be considered if nonoperative treatment is insufficient to correct the deformity. If flexor digitorum brevis tenotomy does not adequately treat proximal interphalangeal joint deformity, a proximal interphalangeal joint arthrodesis should be the next step.
ACRONYMS AND ABBREVIATIONS
MTP = metatarsophalangealPIP = proximal interphalangeal.
PubMed: 38274283
DOI: 10.2106/JBJS.ST.21.00046 -
International Journal of Surgery Case... Feb 2024The elbow is one of the most mobile joints, and its movement is very important. Bony ankylosed elbow is an uncommon condition leading to complete loss of activity of...
INTRODUCTION AND IMPORTANCE
The elbow is one of the most mobile joints, and its movement is very important. Bony ankylosed elbow is an uncommon condition leading to complete loss of activity of elbow, and then lead to severe disability and limitation in activities of daily living.
CASE PRESENTATION
A 63-year-old woman sustained comminuted fracture of left distal humerus. She underwent open reduction and internal fixation by plates. After the plates were removed in 2016,stiffness developed.The elbow was stable but fixed at 90°,there was no vascular injury or deficit in sensory and motor function of the ulnar nerve. She hopes to eliminate pain and restore normal mobility compatible with ADL.
CLINICAL DISCUSSION
Complete bony ankylosis of the elbow joint may be caused by trauma, rheumatic disease, burns, congenital stiffness and other conditions. Even with the compensation of shoulder and wrist, it will still have a great impact on upper limb function. Whether to treat mainly depends on whether the patient has the require to improve the functionality and return to daily activities. Treatment methods are very limited, including interposition arthroplasty and TEA. Defect of soft tissue appeared was seen in our case, Hernia Patch was innovatively applied to reconstruct the defect of soft tissue and maintain continuity of elbow extension mechanism.
CONCLUSION
Patients with post-traumatic elbow joint ankylosis were suffered from severe bony abnormalities, but also soft tissue contracture or defects due to multiple operations and trauma. We present a case of complete bony ankylosed elbow treated with total elbow arthroplasty and Hernia Patch.
PubMed: 38271866
DOI: 10.1016/j.ijscr.2023.109123 -
Pediatric Rheumatology Online Journal Jan 2024H Syndrome is a rare genetic condition caused by biallelic pathogenic variants in the SLC29A3 gene. It is characterized by a wide range of clinical manifestations, many...
BACKGROUND
H Syndrome is a rare genetic condition caused by biallelic pathogenic variants in the SLC29A3 gene. It is characterized by a wide range of clinical manifestations, many of which are related to the immune-rheumatological field. These include scleroderma-like skin changes, deforming arthritis, and enlarged lymph nodes. The condition also features cardiac and endocrine defects, as well as hearing loss, for which the immune pathogenesis appears less clear. Immunomodulatory medications have been shown to improve many symptoms in recent experiences.
CASE PRESENTATION
A 21-year-old girl was referred to our institute after being diagnosed with H syndrome. Her medical history was characterized by the development of finger and toe deformities, which developed since the first years of life and progressively worsened with clinodactyly. At 6 years of age, she was diagnosed with diabetes mellitus without typical autoantibodies and with bilateral sensorineural hearing loss. She also complained of frequent episodes of lymphadenopathy, sometimes with colliquation and growth retardation due to pancreatic insufficiency. It wasn't until the genetic diagnosis of H syndrome that the continual increase in acute phase reactants was noticed, suggesting that an immunological pathogenesis may be the source of her problems. During her visit to our institute, she reported serious pain in both feet and hands and difficulty walking due to knee arthritis and muscle contractures. Conventional therapy with steroid injection in affected joints and methotrexate only led to partial improvement. After a thorough assessment of her inflammatory profile showing a high interferon score, the girl received treatment with baricitinib. Furthermore, based on recent data showing that SLC29A3 deficiency results in interferon production because of Toll-like Receptor 7 activation in lysosomes, hydroxychloroquine was also added. The combination of the two drugs resulted for the first time in a rapid and persistent normalization of inflammatory markers, paralleled by a dramatic improvement in symptoms.
CONCLUSIONS
We describe the results of inhibiting IFN inflammation in H syndrome and discuss how JAK inhibitors and antimalarials might represent a mechanistically based treatment for this orphan drug disorder.
Topics: Female; Humans; Young Adult; Adult; Hearing Loss, Sensorineural; Contracture; Arthritis; Interferons; Rheumatic Diseases; Nucleoside Transport Proteins; Histiocytosis
PubMed: 38263041
DOI: 10.1186/s12969-023-00950-4 -
Cureus Dec 2023While definitions may vary, infected non-union is generally described as a condition where a fracture fails to heal due to infection, typically persisting for a duration...
While definitions may vary, infected non-union is generally described as a condition where a fracture fails to heal due to infection, typically persisting for a duration of six to eight months. Infected non-unions occurring in the shaft of the femur are infrequent and typically result from severe open fractures with deep fragmentation and segmental bone loss or following internal fixation of a severely fragmented closed fracture. Some associated factors contributing to non-union include positive bacterial cultures from deep wounds, histological evidence of bone necrosis, exposed bone without a vascularized periosteum for more than six weeks, and the presence of purulent discharge. Osteomyelitis, stiffness in adjacent joints, smoking, loss of soft tissue resulting in multiple sinus tracts, osteopenia, and deformities leading to limb length discrepancies are all complicating factors that impact treatment and prognosis. Infected non-union of bones, although rare, presents a significant challenge for physiotherapists striving to provide appropriate treatment. The level of stabilization at the fracture site is the most critical factor influencing whether a fracture progresses to non-union or successfully heals. Infection, such as osteomyelitis, also contributes to the development of non-union. Additionally, issues like tissue atrophy, joint stiffness, and muscle contractures can further complicate the non-union of a bone, posing a considerable challenge for physical therapists in helping patients achieve their recovery goals. Top of form this case report reviews the case of a 35-year-old male who was reported to Acharya Vinoba Bhave Rural Hospital (AVBRH) with an infective non-union of the shaft of the femur fracture after two months of repair. This case report highlights the recovery of patients from post-operative complications like non-union, stiffness, and reduced range of motion through tailored physiotherapy rehabilitation and improved quality of life.
PubMed: 38239531
DOI: 10.7759/cureus.50786 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Jan 2024To report the clinical characteristics and treatment analysis of 3 cases of congenital ulnar collateral flexor contracture of the forearm and take a reference for clinic.
OBJECTIVE
To report the clinical characteristics and treatment analysis of 3 cases of congenital ulnar collateral flexor contracture of the forearm and take a reference for clinic.
METHODS
A total of 3 patients with congenital ulnar collateral flexor contracture of the forearm were admitted between February 2019 and August 2021. Two patients were male and 1 was female, and their ages were 16, 20, and 16 years, respectively. The disease durations were 8, 20, and 15 years, respectively. They all presented with flexion deformity of the proximal and distal interphalangeal joints of the middle, ring, and little fingers in the neutral or extended wrist position, and the deformity worsened in the extended wrist position. The total action motion (TAM) scores of 3 patients were 1 and the gradings were poor. The Carroll's hand function evaluation scores were 48, 55, and 57, and the grip strength indexes were 72.8, 78.4, and 30.5. Preoperative CT of case 2 showed a bony protrusion of the flexor digitorum profundus tendon at the proximal end of the ulna; and MRI of case 3 showed that the ulnar flexor digitorum profundus presented as a uniform cord. After diagnosis, all patients were treated with operation to release the denatured tendon, and functional exercise was started early after operation.
RESULTS
The incisions of 3 patients healed by first intention. Three patients were followed up for 12, 35, and 12 months, respectively. The hand function and the movement range of the joints significantly improved, but the grip strength did not significantly improve. At last follow-up, TAM scores were 3, 4, and 4, respectively, among which 2 cases were excellent and 1 case was good. Carroll's hand function evaluation scores were 95, 90, and 94, and the grip strength indexes were 73.5, 81.3, and 34.2, respectively.
CONCLUSION
Congenital ulnar collateral flexor contracture is a rare clinical disease that should be distinguished from ischemic muscle contracture. The location of the contracture should be identified and appropriate surgical timing should be selected for surgical release. Active postoperative rehabilitation and functional exercise can achieve good hand function.
Topics: Humans; Male; Female; Forearm; Contracture; Muscle, Skeletal; Tendons; Ulna; Range of Motion, Articular
PubMed: 38225841
DOI: 10.7507/1002-1892.202309086