Contracture Research Articles

Clinical characterization of Collagen XII-related disease caused by biallelic COL12A1 variants.

While there have been several reports of patients with dominantly acting COL12A1 variants, few cases of the more severe recessive Collagen XII-related disorders have previously been documented. We present detailed clinical, immunocytochemical, and imaging data on eight additional patients from seven families with biallelic pathogenic variants in COL12A1. All patients presented with a consistent constellation of congenital onset clinical features: hypotonia, dysmorphic features, most notably gingival hypertrophy, prominent distal joint hyperlaxity, with co-occurring contractures of large joints, and variable muscle involvement, evident both clinically and on muscle imaging. Five patients presented with a severe congenital phenotype manifesting with profound weakness, significantly delayed or minimal attainment of motor milestones, respiratory insufficiency, and feeding difficulties. Three patients presented with mild-to-moderate muscle weakness and delayed milestones but were able to achieve independent ambulation. Patients were found to have biallelic loss-of-function COL12A1 variants, except for one family (p.I1393Ffs*11/p.A1110D). Consistent with the variable clinical spectrum, in vitro immunocytochemistry analysis in fibroblasts ranged from complete absence of Collagen XII expression in a patient with severe disease, to a mild reduction in a patient with milder disease. Here we characterize the clinical presentation, muscle imaging, and dermal fibroblast immunostaining findings associated with biallelic variants in COL12A1, further establishing COL12A1 as a recessive myopathic Ehlers-Danlos syndrome (mEDS) gene, and expanding the clinical spectrum to include a milder EDS phenotype.

Considerations for Anthropometry Specific to People with Disproportionate Short Stature.

In the clinical care of people with disproportionate short stature, healthcare practitioners need to accurately collect anthropometric measurements over time, including height, weight, head circumference, and lengths of affected limb and body segments. Accurate anthropometric measurements are important for diagnostic evaluation, tracking growth, measuring response to pharmacologic therapies or surgeries, and monitoring for potential complications. However, for this clinical population, anthropometric measurements may need to be adjusted or modified to accommodate characteristics such as body disproportions, joint contractures, long bone deformities, spinal deformities, or muscle hypotonia. This article provides guidance for key anthropometric measurements in children and adults with disproportionate short stature, with a focus on people with achondroplasia. The measurements described in this article and illustrated in the infographics can be performed without expensive specialized equipment and are suitable for a variety of clinical settings.

ECEL1 mutation in distal arthrogryposis type 5D: A case report.

Arthrogryposis multiplex congenita involves joint contractures across various body parts. Distal arthrogryposis type 5D (DA5D) is a rare, autosomal recessive subtype affecting distal extremities, with symptoms like knee extension contractures, camptodactyly, overriding fingers, ulnar wrist deviation, and scoliosis. A 24-year-old pregnant woman with a second-degree relative partner had a fetus showing increased nuchal translucency (3.4mm) and high Down syndrome risk in the first-trimester screen. Both parents were healthy and had no known family history of hereditary diseases. Genetic counselling and amniocentesis at 16weeks revealed a segmental gain on chromosome 1p31.1 of uncertain significance, ruling out aneuploidies of chromosomes 21, 18, and 13. Later scans suggested fetal akinesia deformation sequence (FADS) with limited limb movement. Whole exome sequencing confirmed DA5D due to a novel ECEL1 5' splice site variant (c.2151+2T>A) inherited autosomally recessive. The couple chose pregnancy termination, with an autopsy confirming DA5D. This case expands the mutational spectrum of prenatal ECEL1 gene using whole exome sequencing (WES) for fetal joint disorders, potentially helping in parental counselling and clinical decision-making.

Features of the genetic diagnosis of merosin-deficient muscular dystrophy (a clinical case)

Merosin-deficient muscular dystrophy is a rare neuromuscular disease characterized by diffuse muscular and epileptic seizures. The disease is inherited in an autosomal recessive type and occurs as a result of biallelic variants in the LAMA2 gene. In this gene there are described all types of violations of the normal nucleotide sequence (single nucleotide variants, variations in the number of DNA copies) which can lead to difficulties in genetic search. The combination of phenotype features (hypomimia, elongated face, ophthalmoparesis, muscle hypotonia, and weakness, spinal rigidity, contractures of large joints), laboratory and instrumental research results (increased activity of creatinephosphokinase in the blood, leukopathy on brain MRI) will help you choose the right diagnostic search tactics. In this article, we present a clinical case of a patient with three identified variants in the LAMA2 gene: two point substitutions (c.4048C>T and c.4860+75G>C) and deletion of exons 2 and 3. The use of several methods of genetic testing (high-throughput sequencing, chromosomal microarray analysis, Sanger sequencing) allowed the establishing of the diagnosis, which subsequently led to successful prenatal diagnosis and the birth of healthy siblings.

Pediatric eosinophilic fasciitis: similarities and differences with adult forms.

The purpose of this study was to identify pediatric eosinophilic fasciitis, which is an extremely rare condition, in order to describe their clinical, paraclinical, and therapeutic characteristics. We made a call for observations via societies for pediatric rheumatology in France and surrounding countries and collected clinical and paraclinical data of the cases fulfilling the diagnostic criteria. Eight patients under 18years of age with confirmed eosinophilic fasciitis followed between April 2004 and July 2022 in France, Germany, Italy, and Spain were included. The median age of onset of symptoms was 8.7years (range 3 to 12.6). All patients had skin and joint involvement at diagnosis. Eosinophilia was present at diagnosis in 5/8 patients and 5/7 patients presented hypergammaglobulinemia. All the patients had an MRI, and in 6, we observed thickened fascia with a T2 hypersignal. Five patients had undergone a full-thickness biopsy showing a polymorphic lymphoplasmacytic infiltrate of the fascia in all and the presence of eosinophils in 4 of them. All the patients were treated with corticosteroids with variable regimens and all received at least an immunosuppressant. Conclusion: To our knowledge, this is the largest pediatric series of eosinophilic fasciitis. The clinical and paraclinical presentation seems similar to that of adults except for a form that appears to be distinguished with isolated joint contractures, and hypergammaglobulinemia which appears to be more frequent in children. Dermatological and pathological expertise and MRI are key elements of the diagnosis. The most consensual treatment includes physiotherapy, prolonged corticosteroid therapy, and methotrexate as first-line therapy. What is Known •Eosinophilic fasciitis is a rare condition, especially in children with approximately 60 reportedpediatric cases. •Some pediatric specificities tend to emerge from somereports. What is New •Possible isolated joints contractures andmore frequent hypergammaglobulinemia seem to characterize pediatric eosinophilic fasciitis incomparison with adult forms. •The most frequently used first-line therapy combinesphysiotherapy, corticosteroids and methrotrexate.

Factors Reducing Pressure Ulcer Risk and the Importance of Care in ALS Patients: A Comprehensive Review

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by muscle atrophy, weakness, and loss of motor function. ALS patients are often bedridden for extended periods, increasing their risk of pressure ulcers. However, clinical data suggests that the incidence of pressure ulcers in ALS patients is lower compared to other bedridden patients. This review analyzes the factors contributing to reduced pressure ulcer risk in ALS patients, focusing on "pressure redistribution due to muscle atrophy," "stabilized postures caused by joint contractures," and "comprehensive care provided by caregivers." Additionally, this paper discusses a comprehensive approach to pressure ulcer prevention, including nutritional management, skincare, pressure redistribution techniques, and advanced technologies. Challenges in pressure ulcer prevention and the importance of ALS-specific care are also emphasized.

Combined ADAMTS10 and ADAMTS17 inactivation exacerbates bone shortening and compromises extracellular matrix formation.

Weill-Marchesani syndrome (WMS) is characterized by severe short stature, short hands and feet (brachydactyly), joint contractures, tight skin, and heart valve, eye, and skin anomalies. Whereas recessive WMS is caused by mutations in ADAMTS10 , ADAMTS17 , or LTBP2 , dominant WMS is caused by mutations in FBN1 (encoding fibrillin-1). Since bone growth is driven by chondrocyte proliferation and hypertrophy in the growth plates, the genetics of WMS suggests that the affected ECM proteins act within the same pathway to regulate chondrocyte and growth plate function. Here, we investigated the role of the secreted ADAMTS proteases ADAMTS10 and ADAMTS17 in growth plate function and ECM formation. We generated Adamts10 ; Adamts17 double knockout (DKO) mice, which showed significant postnatal lethality compared to single Adamts10 or Adamts17 KO mice. Importantly, we observed severe bone shortening DKO mice, which correlated with a narrower hypertrophic zone in their growth plates. ADAMTS17 substrates identified by N-terminomics and yeast two-hybrid screening identified the ECM proteins fibronectin and collagen VI (COL6). However, validation experiments did not reveal direct proteolysis of either fibronectin or COL6 by ADAMTS17. We then investigated ECM formation in primary ADAMTS10- and ADAMTS17-deficient skin fibroblasts and observed compromised fibronectin deposition concomitant with aberrant intracellular accumulation of fibrillin-1. These findings support a role for ADAMTS17 in ECM protein secretion and assembly. Collectively, our data suggest that ADAMTS10 and ADAMTS17 regulate bone growth by regulating chondrocyte hypertrophy or hypertrophic chondrocyte turnover. Mechanistically, ADAMTS17 appears to be a critical regulator of ECM protein secretion or pericellular matrix assembly, whereas ADAMTS10 likely modulates ECM formation at later stages, possibly regulating the spatio-temporal deposition of fibrillin isoforms.

NUBP2 deficiency disrupts the centrosome-check point in the brain and causes primary microcephaly.

Microcephaly affects 1 in 2,500 babies per year. Primary microcephaly results from aberrant neurogenesis leading to a small brain at birth. This is due to altered patterns of proliferation and/or early differentiation of neurons. Premature differentiation of neurons is associated with defects in the centrosome and/or primary cilia. In this study, we report on the first patients identified with NUBP2 -deficiency and utilize a conditional mouse model to ascertain the molecular mechanisms associated with NUBP2 -deficient primary microcephaly. We identified homozygous NUBP2 variants in these patients who displayed profound primary microcephaly in addition to intrauterine growth restriction, cervical kyphosis, severe contractures of joints, and facial dysmorphia. We then generated a mouse model using Emx1-Cre to ablate Nubp2 from the forebrain. The mice presented with severe microcephaly starting at E18.5. Neurospheres generated from the forebrain of Emx1-Cre; Nubp2 flox/flox conditional deletion mice were used to support the pathogenicity of the patient variants. We show that loss of Nubp2 increases both canonical and non-canonical cell death, but that loss of p53 fails to rescue microcephaly in the mouse model. Examination of neurogenesis in Emx1-Cre; Nubp2 flox/flox mice revealed distinct alterations in proliferation and cellular migration accompanied by supernumerary centrosomes and cilia. We therefore propose that NUBP2 is a novel primary microcephaly-related gene and that the role of Nubp2 in centrosome and cilia regulation is crucial for proper neurogenesis.

Application of minimally invasive debridement for deep second-degree facial burns in the early postburn phase

ObjectiveThis study aimed to evaluate the therapeutic efficacy of minimally invasive dermabrasion for deep second-degree facial burn wounds during the early postburn phase.MethodsA total of 35 patients with deep second-degree facial burns underwent minimally invasive debridement using a hydrosurgery system within 2–4 days post-injury. Subsequently, the wounds were covered with human biological dressings. The wound infection rate, healing time, and overall healing quality following debridement were monitored.ResultIn this cohort of 35 patients, no infections were reported after debridement. The average healing time for these wounds was significantly shorter than that of those treated with standard surgical excision. Clinical observations indicated that minimally invasive dermabrasion was associated with a lower infection rate and reduced healing time. After 6 months, scar assessment using the Vancouver Scar Scale showed that the average score for wounds treated with minimally invasive techniques was lower than those treated with standard surgical excisional technique.ConclusionsThis research indicates that minimally invasive debridement during the early postburn stage can effectively reduce wound infection rates, shorten healing times, and minimize the occurrence of scar hyperplasia and contracture deformities. Therefore, minimally invasive dermabrasion is valuable in treating deep second-degree facial burn wounds.

Motor function and compound muscle action potential amplitude in children with spinal muscular atrophy treated with nusinersen.

Disease-modifying therapies can improve motor function in patients with spinal muscular atrophy (SMA), but efficacy varies between individuals. The aim was to evaluate the efficacy and safety of nusinersen treatment in children with SMA and to investigate prognostic factors. Motor function, compound muscle action potential (CMAP), and other indicators were prospectively collected before and 14months after nusinersen treatment. A total of 55 children were included in our study to assess safety. 41 patients (with at least 6months of nusinersen treatment) were included in the final efficacy analyses, with a median age at first treatment of 4.2years. After 14months of treatment with nusinersen, motor function improved, with increases in CHOP INTEND (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders), HINE-2 (Hammersmith Infant Neurological Exam-Part 2), HFMSE (Hammersmith Functional Motor Scale-Expanded) and RULM (Revised Upper Limb Module) of 5.5 (95% CI -2.4-13.4), 0.8 (95% CI -0.2-1.9), 5.0 (95% CI 2.5-7.4) and 2.4 (95% CI 0.7-4.1) points, respectively. The CMAP amplitudes of the bilateral tibial, median and ulnar nerves increased, with greatest improvements of 0.87±1.41mV, 1.08±1.71mV and 0.59±1.01mV, respectively. Spearman correlation analysis showed that age at first treatment, disease duration, joint contractures and scoliosis were associated with treatment efficacy (r=-0.4-0.7, P<0.05). Subgroup analyses showed that the mean HFMSE and RULM scores improved in the Physical therapy group (P<0.05). Early treatment, mild bone and joint complications, and regular rehabilitation training were associated with better outcomes. The other motor-related functions, such as respiratory and bullar function, and prognostic factors should be studied in the future.

Acellular Dermal Matrices in Reconstructive Pediatric Complex Lower Limb Trauma: An Observational Study.

Contemporary research has shown that acellular dermal matrices can benefit adult lower extremity traumatic injuries; however, its use in children has not been explored. This study aims to explore the use of acellular dermal matrices in pediatric complex lower extremity trauma. This single-center retrospective observational cohort study of children with complex lower extremity trauma treated with Pelnac™, commercial acellular dermal matrices, was conducted at a tertiary hospital in South Africa from 2010 to 2017. Demographic and clinical data were collected from medical records. The primary outcome was the rate and type of acellular dermal matrices-related complications. Secondary outcomes included the usage of negative pressure wound therapy. A total of 54 children were studied; 30 (55%) were male, and the median age was six. Forty-five children healed without complications, while nine experienced complications - four acute and five chronic. Four patients had complete loss of acellular dermal matrices, and three developed acute infections. More than 30days post-acellular dermal matrices application, five patients had hypertrophic scarring, four had joint contractures, and two had non-healing wounds. All patients who healed without complication received negative pressure wound therapy (n =45), while those who did not (n =5) developed complications. Three of the five patients without negative pressure wound therapy had acute acellular dermal matrices loss, compared to only one of the 49 patients who received negative pressure wound therapy. Our findings suggest that acellular dermal matrices may be an effective and safe reconstructive adjunct or alternative when used with negative pressure wound therapy.

Lateral Polydactyly of the Foot: Surgical Outcomes Based on a New Classification.

The objective of this study was to propose a novel classification for lateral polydactyly of the foot that integrates both visual appearance and radiographic findings and to delineate surgical techniques and their outcomes based on this classification. This study enrolled 148 feet from 126 patients who underwent initial surgery at our hospital between January 2009 and July 2021. The new classification system was derived from visual appearance according to the Hirase classification and radiological bifurcation level (D: distal or middle phalanx, P: proximal phalanx, and M: metatarsal). Incidence rates, surgical procedures, and surgical outcomes were compared across each type. Morphologically, 25 cases were classified as type A, 43 cases as type B1, and 80 cases as type B2. The branching level was categorized as D in 81 feet, P in 41 feet, and M in 26 feet, with 68 feet (46%) classified as B2-D type. Excision of the sixth toes was performed in all type A cases, whereas the majority of type B cases required excision of the fifth toes. Revision procedures were conducted on 8 feet. Three patients with type A-P classification developed painful hammer toe deformities as a late sequela that necessitated extensor tenolysis and metatarsophalangeal joint contracture release during their school-age years. The classification system based on the combination of visual appearance and radiological branching level was both straightforward and beneficial for surgical planning and for predicting surgical outcomes and late sequelae.

Process evaluation of an individually tailored complex intervention to improve activities and participation of older nursing home residents with joint contractures (JointConEval): a mixed-methods study

BackgroundOlder people with joint contractures in nursing homes often experience severe restrictions in their activities and participation. The effectiveness of an individually tailored complex intervention to improve residents’ activities and participation by incorporating the biopsychosocial perspective into nursing care using a structured facilitator approach could not be established in the JointConEval cluster-randomised controlled trial. This process evaluation aimed to systematically identify factors influencing implementation and effectiveness.MethodsThe mixed-methods process evaluation analysed recruitment, implementation, mechanisms of impact, and context. Qualitative data was generated in semi-structured focus groups and in individual interviews with facilitators, nursing and social care staff, residents, relatives and guardians. Quantitative data was recorded with facilitators and 20% of nursing and social care staff using standardised documentation forms and questionnaires. Qualitative data was analysed using qualitative thematic content analysis, while the quantitative data was analysed descriptively. An interpretation was performed by combining and comparing the qualitative and quantitative results after the separate analyses.ResultsThe implementation was realised as planned, but the intervention did not always reach the nursing home staff, which hindered the planned change in attitude and behaviour. The attitude of the facilitators was mainly in line with the intervention. However, the intervention reached only half the residents. We identified various key influencing factors related to the context, setting and implementation agents. Nursing homes lacking facilitator support from staff or management or experiencing staff shortages and facing organisational weaknesses had difficulties in achieving the desired behavioural changes and positive primary outcomes.ConclusionsThe complex intervention was delivered as planned with several factors affecting the implementation. A key influencing factor was the organisational structure and leadership of the nursing homes, which had an impact on the behaviour and motivation of the implementation agents. The findings highlight challenges in achieving behavioural changes among nursing staff in the context of long-term care in Germany. We recommend a systematic organisational context analysis for similar complex interventions in long-term care, involving stakeholders and improving leadership participation for more effective implementation.Trial registrationDRKS (German Clinical Trials Register), number DRKS00015185. Registered on 1 August 2018, https://drks.de/search/en/trial/DRKS00015185. Universal Trial Number U1111-1218–1555.

Post-traumatic patellar tendon ossification in children: a case series

Background. Fractures of the bones that form the knee joint in children are quite rare, accounting for up to 6% of all bone fractures. These include avulsion fractures of the patellar apex as well as tibial tuberosity avulsion fractures, which may result in patellar tendon ossification. Based on literature, the ossification may also occur in cases of primary or chronic (complete or partial) patellar tendon tears. Such a complication is quite rare in pediatric traumatology; it requires differential diagnosis and various surgical tactics. The aim of the study is to present a clinical and radiological picture of post-traumatic patellar tendon ossification in children and its surgical treatment outcomes using a case series as an example. Methods. We present a monocenter retrospective series of 4 male patients. Anamnestic, clinical, radiological and histological data were analyzed. Results. The patients’ mean age was 14 (range, 11-16) years. In all cases, there was a history of trauma. Initially, after getting injured, the patients were treated for a knee injury. In one patient, as a result of his falling on 2 limbs, a bilateral pathology was observed; in other three cases, the pathology was unilateral. Flexion contracture and pain syndrome prevailed in the clinical picture. All patients underwent surgery ranging from excision of ossifications to excision of ossifications with reconstruction of tendon defects and refixation of the tibial tuberosity with osteosynthesis. In all cases, knee joint contracture was eliminated and the volume of movement was fully restored. Histology showed fragments of mature bone tissue represented by thinned bone beams with focal osteoclastic reaction and areas of endochondral ossification. Conclusions. The clinical picture of pediatric patients with patellar tendon ossification manifests in the form of a chronic cascade of symptoms and functional and topographic disorders: patellar tendon ossification, patella alta, anterior knee pain, flexion contracture and rectus femoris muscle hypotrophy. X-ray and MRI data determine a formation of bone density with uneven clear contours in the projection of the patellar tendon, along with patella alta and the Caton-Deschamps index increasing more than 1.3. The primary treatment method of the developed complication is the surgical one, which leads to the restoration of the full amplitude of movements in the knee joint.

Angiopoietin-2: A Therapeutic Target for Vascular Protection in Hutchinson-Gilford Progeria Syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a pediatric condition characterized by clinical features that resemble accelerated aging. The abnormal accumulation of a toxic form of the lamin A protein known as progerin disrupts cellular functions, leading to various complications, including growth retardation, loss of subcutaneous fat, abnormal skin, alopecia, osteoporosis, and progressive joint contractures. Death primarily occurs as the result of complications from progressive atherosclerosis, especially from cardiac disease, such as myocardial infarction or heart failure, or cerebrovascular disease like stroke. Despite the availability of lonafarnib, the only US Food and Drug Administration-approved treatment for HGPS, cardiovascular complications remain the leading cause of morbidity and mortality in affected patients. Defective angiogenesis-the process of forming new blood vessels from existing ones-plays a crucial role in the development of cardiovascular disease. A recent study suggests that Angiopoietin-2 (Ang2), a pro-angiogenic growth factor that regulates angiogenesis and vascular stability, may offer therapeutic potential for the treatment of HGPS. In this review, we describe the clinical features and key cellular processes impacted by progerin and discuss the therapeutic potential of Ang2 in addressing these challenges.

Isolated Right Atrial Enhancement with Atrial Standstill: An Uncommon Presentation of Emery–Dreifuss Muscular Dystrophy

AbstractEmery–Dreifuss muscular dystrophy (EDMD) is a rare inherited syndrome that affects muscles, joints, and the heart. The classic clinical triad includes early joint contractures, slowly progressive muscle weakness, and cardiac abnormalities. The common cardiac manifestations include conduction disturbances, systolic dysfunction, and dilated cardiomyopathy and may be associated with left ventricular noncompaction with an increased risk of thromboembolic events. Conduction disturbances include atrial arrhythmias, atrial standstill, complete heart block, or ventricular tachyarrhythmia. Cardiac magnetic resonance imaging (CMR) can help in the diagnosis of this condition by identifying chamber dilatation, systolic dysfunction, and late gadolinium enhancement of the atrium. Additional MRI finding of paraspinal muscle atrophy, an important finding in this muscular dystrophy, helped in reaching a confident imaging diagnosis. Our case in this article highlights the clinical and CMR findings of this rare condition.

The proton RBE and the distal edge effect for acute and late normal tissue damage in vivo.

In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used toreach an isoeffective biological response between photon and proton doses. However, the RBE varies with biological endpoints and linear energy transfer (LET), two key parameters in radiotherapy. Few in vivo studies have investigated the increasing RBE with increasing LET. This study aims to test the hypothesis that the RBE varies between endpoints and has a distal edge effect in vivo. Unanesthetized micewere restrainedin jigs where their right hind legs were irradiated with a single dose of protons at the center (LET, all=5.3keV/μm) and distal edge (LET, all=7.6keV/μm) of a spread-out Bragg peak (SOBP). 6 MV photons were used as reference. The acute damage and skin toxicity were scored daily until day 30, and the late damage was evaluated using a joint contracture assay for one year after treatment. An acute damage RBE of 1.06±0.02(1.02-1.10) and late damage RBE of 1.16±0.08(1.00-1.32) were found, displaying an enhanced RBE for late damage in the center SOBP. The distal edge RBE for acute and late damage was 1.15±0.02(1.10-1.19) and 1.26±0.09(1.07-1.43), showing a similar center-to-distal edge RBE enhancement of 8% and 9% for acute and late damage. The findings demonstrate an increased RBE for late damage than acute damage and the distal edge effect is evident with increased RBE at the distal end of the proton SOBP in vivo.

Cellular and Molecular Effects of the Bruck Syndrome-Associated Mutation in the PLOD2 Gene.

Bruck syndrome is a rare autosomal recessive disorder characterized by increased bone fragility and joint contractures similar to those in arthrogryposis and is known to be associated with mutations in the FKBP10 (FKBP prolyl isomerase 10) and PLOD2 (Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 2) genes. These genes encode endoplasmic reticulum proteins that play an important role in the biosynthesis of type I collagen, which in turn affects the structure and strength of connective tissues and bones in the body. Mutations are associated with disturbances in both the primary collagen chain and its post-translational formation, but the mechanism by which mutations lead to Bruck syndrome phenotypes has not been determined, not only because of the small number of patients who come to the attention of researchers but also because of the lack of disease models. In our work, we investigated the cellular effects of two forms of the wild-type PLOD2 gene, as well as the PLOD2 gene with homozygous mutation c.1885A>G (p.Thr629Ala). The synthesized genetic constructs were transfected into HEK293 cell line and human skin fibroblasts (DF2 line). The localization of PLOD2 protein in cells and the effects caused by the expression of different isoforms-long, short, and long with mutation-were analyzed. In addition, the results of the transcriptome analysis of a patient with Bruck syndrome, in whom this mutation was detected, are presented.

Bi-allelic MYMX variants cause a syndromic congenital myopathy with recognizable facial palsy, growth restriction, and dysmorphism.

Myogenic fusion, primarily regulated by the Myomaker and Myomixer proteins, is essential for skeletal muscle development, yet its mechanisms remain poorly understood. This study presents the clinical and molecular details of the third and fourth reported patients with biallelic variants in MYMX, the gene that encodes Myomixer. We identified a homozygous truncating variant [c.107 T > A (p.Leu36Ter)] and a homozygous stop-codon loss variant [c.255 A > G (p.Ter85TrpextTer41)] in MYMX, both associated with a complex neuromuscular syndrome characterized by generalized hypotonia, congenital myopathy, facial nerve palsy, growth restrictionand facial dysmorphism. Additional variable features includehearing loss (confirmed in one patient, suspected in the other), scoliosis, joint contractures, cleft palate, hypoglossia, potentially contributing to Pierre Robin sequence,and abnormalities on neuroimaging studies including cerebellar atrophy and Chiari 1 deformity. Comparative analysis of patients with pathogenic variants in MYMK and MYMX, including our cases, reveals largely overlapping phenotypes, underscoring their synergistic role in myofiber formation and implicating their involvement in the etiology of neuromuscular conditions.

Stretching after spinal cord injury: a call for evidence for this common clinical practice

Stretching is a ubiquitous rehabilitation intervention for individuals with spinal cord injury (SCI), intended to reduce spasticity, maintain or improve joint range of motion, and prevent joint contractures. Although people with SCI report that stretching is their preferred approach to reduce spasticity, limited evidence supports the use of stretching for people with SCI, including short-term (&amp;lt; one hour) effects on spasticity. Further, the long-term effects and the effects of stretching on motor function have yet to be examined in humans with SCI. Evidence from pre-clinical studies in rats with SCI demonstrates that stretching impairs motor output, reduces spinal cord excitability, and abolishes walking function. This perspective paper discusses evidence of static stretching in humans and rats with SCI regarding the effects on range of motion, joint contractures, and effects on voluntary and involuntary (i.e., spasticity) motor output. Additionally, we aim to challenge assumptions regarding the use of stretching and encourage research to advance the understanding of this common rehabilitation approach. Research is needed to investigate underlying mechanisms of stretch-induced effects and to advance stretching protocols to optimize the potential beneficial effects of stretching for people with SCI.