Journal of neuromuscular diseases最新文献

{"title":"Expanding the spectrum of <i>TNNC2</i> variants in neonatal hypotonia - a family report of a homozygous loss of function.","authors":"Anthony Maino, Marie Chevallier, Diane Giovannini, Mandy Leger, Anne-Laure Coston, Nathalie Roux-Buisson, Hervé Testard, Julien Thevenon, Isabelle Marty, Julien Fauré, Klaus Dieterich, John Rendu","doi":"10.1177/22143602251341413","DOIUrl":"https://doi.org/10.1177/22143602251341413","url":null,"abstract":"<p><p>The <i>TNNC2</i> gene is crucial for skeletal muscle function, and pathogenic variants have been linked to congenital myopathies characterized by hypotonia, muscle weakness, and respiratory insufficiency. To date, <i>TNNC2</i>-related myopathies have been associated only with autosomal dominant missense variants. We report here the first family case of a recessive form of myopathy related to <i>TNNC2</i>. We identified the homozygous splice variant <i>TNNC2</i>(NM_003279.3):c.314 + 1G > C p.(?) in two siblings with a severe clinical presentation, resulting in one neonatal death and one medical termination of pregnancy. This variant induces a splicing defect that leads to a complete loss of the <i>TNNC2</i> physiological transcript<i>.</i> This case expands the spectrum of <i>TNNC2</i> variants with a late-onset fetal loss. To the best of our knowledge, this is the first case reporting a recessive form of severe neonatal hypotonia due to <i>TNNC2</i> variant.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251341413"},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the road to blood biomarkers in myasthenia gravis (MG): Beyond clinical scales.","authors":"Amol K Bhandage, Yu-Fang Huang, Tanel Punga, Anna Rostedt Punga","doi":"10.1177/22143602251348753","DOIUrl":"https://doi.org/10.1177/22143602251348753","url":null,"abstract":"<p><p>Myasthenia Gravis (MG) is a heterogeneous neuromuscular autoimmune disorder characterized by fluctuating skeletal muscle weakness and a highly variable disease course. MG subgroups are defined by antibody type, age at onset, clinical phenotype, and thymus pathology. Given the unpredictable disease course, disease-specific objective biomarkers are needed to enable personalized treatment strategies and improve clinical trial outcomes beyond conventional clinical scales. Biomarkers are measurable indicators of physiological processes, disease states, and therapy responses. Despite significant advances in MG diagnostics and therapeutics, predictive biomarkers for personalized treatment remain underdeveloped. This review explores the progress and challenges in identifying blood-based biomarkers for MG, highlighting their potential applications in diagnosis and disease monitoring. Established diagnostic blood biomarkers include autoantibodies against acetylcholine receptors (AChR) and muscle-specific tyrosine kinase (MuSK), which confirm MG diagnosis and guide initial treatment decisions. Prognostic biomarkers, such as microRNAs (miR-150-5p and miR-30e-5p), show promise in predicting disease progression. Pharmacodynamic biomarkers, including CD20+ B cell counts, may enhance treatment precision for therapies like Rituximab. Furthermore, emerging research on metabolites, T and B-cell markers, complement factors, and proteomics offer new avenues to refine MG subtyping and identify molecular signatures predictive of treatment response to novel immunosuppressants. While the journey toward clinically useful blood biomarkers in MG remains complex, ongoing collaborative efforts within the MG research community hold the potential to revolutionize disease management. Future studies integrating multi-omics approaches, large-scale longitudinal cohorts, and disease controls will be critical to translating these biomarkers from research into routine clinical practice.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251348753"},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telemedicine and remote monitoring in neuromuscular diseases: Challenges and opportunities.","authors":"Francesca Torri, Erika Schirinzi, Lorenzo Fontanelli, Giulia Ricci, Michelangelo Mancuso, Mario Bochicchio, Gabriele Siciliano","doi":"10.1177/22143602251330436","DOIUrl":"https://doi.org/10.1177/22143602251330436","url":null,"abstract":"<p><strong>Background: </strong>Telemedicine, the application of those information technologies to remotely provide health services either for synchronously catching or asynchronous monitoring patient medical data, has shown a growing and widespread application in several chronic diseases, and, especially during and after COVID-19 pandemics, also in neuromuscular diseases.</p><p><strong>Objective: </strong>this review aims at providing an updated overview on the application of telemedicine and telemonitoring tools in neuromuscular diseases, in clinical practice, research and trials.</p><p><strong>Methods: </strong>a literature search was conducted on PubMed using keywords regarding telemedicine applications and several neuromuscular diseases, including papers up to May 2024.</p><p><strong>Conclusions: </strong>several tools have been developed and tested in myopathies, motoneuron diseases, myasthenia gravis and peripheral neuropathies, providing monitoring, assistance, and rehabilitation protocols for such frail population, for which obtaining real life data remotely can represent a concrete advantage in clinical trials and clinical practice. Although several barriers in the implementation of telemedicine in NMD still need to be overcome, there is evidence for both clinicians and patients showing positive acceptance and satisfaction on the use of remote supports, regarding them as confident outcome measures of quality of life in view of a more general concept of e-health solutions in routine medical care.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251330436"},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modelling mitochondrial diseases in neurons <i>In Vitro</i>: A systematic review.","authors":"Mariana Zarate-Mendez, Nihal A Basha, Oliver Podmanicky, Natalia Malig, Denisa Hathazi, Rita Horvath","doi":"10.1177/22143602241307198","DOIUrl":"https://doi.org/10.1177/22143602241307198","url":null,"abstract":"<p><p>Mitochondrial diseases, characterized by disruptions in cellular energy production, manifest diverse clinical phenotypes despite a shared molecular aetiology. Of note is the frequent involvement of the brain in these pathologies. Given the inherent challenges associated with accessing human tissue and the limitations of mouse models, especially concerning mitochondrial DNA (mtDNA), in vitro modelling is crucial in elucidating brain-related manifestations of mitochondrial diseases.In this review we recapitulate the current available in vitro models used to study neuronal cell types and advance our understanding of mitochondrial brain disease. This inquiry is especially pertinent considering the scarcity of suitable animal models, necessitating reliance on in vitro models to elucidate underlying molecular mechanisms. We found fifty papers modelling neuronal mechanisms of mitochondrial diseases in-vitro. While there was an even split between nuclear and mtDNA mutations, MELAS was the most commonly modelled syndrome. The emerging technologies in the stem cell field have revolutionized our approach to investigate cellular specificity in mitochondrial diseases, and we found a clear shift from neuroblastoma cell lines to iPSC-derived models. Interestingly, most of these studies reported impaired neuronal differentiation in mutant cells independent of the syndrome being modelled. The generation of appropriate in vitro models and subsequent mechanistic insights will be central for the development of novel therapeutic avenues in the mitochondrial field.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602241307198"},"PeriodicalIF":3.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult-onset distal myopathy with predominant hand involvement as a rare phenotype of plectinopathy.","authors":"Laura Llansó, David Reyes-Leiva, Alba Segarra-Casas, Tomàs Xuclà-Ferrarons, Eduard Gallardo, Rosa Blanco, Pia Gallano, Montse Olivé, Lidia González-Quereda","doi":"10.1177/22143602251350849","DOIUrl":"https://doi.org/10.1177/22143602251350849","url":null,"abstract":"<p><p>Classic phenotypes of plectinopathies include epidermolysis bullosa simplex and muscular dystrophy with proximal distribution, associated or not with skin blistering. However, in recent years, patients manifesting new muscular phenotypes including lower-limb distal weakness have been described. We aim to expand the phenotypic spectrum of plectinopathies by reporting a case presenting with a pure skeletal myopathy with predominant upper-limb distal weakness. We describe this distal myopathy phenotype providing comprehensive clinical, genetic, myopathological and radiological data. Genetic studies identified two truncating variants in <i>PLEC.</i></p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251350849"},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Some functional improvements in placebo and Delandistrogene moxeparvovec-treated trial participants explained by increased corticosteroid dosing.","authors":"Eric P Hoffman, Paula R Clemens, Laura Hagerty, Utkarsh J Dang","doi":"10.1177/22143602251346660","DOIUrl":"https://doi.org/10.1177/22143602251346660","url":null,"abstract":"","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251346660"},"PeriodicalIF":3.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical validity of congenital myopathy genes determined by the ClinGen Congenital Myopathies Expert Panel.","authors":"Justyne E Ross, May Flowers, Shannon McNulty, Mayher Patel, Hui Yang, Brooke Palus, Marwa Abdelmoneim Elnagheeb, Lucy Eng, Emma Owens, Alan H Beggs, Enrico Bertini, Adele D'Amico, Sandra Donkervoort, James Dowling, Fabiana Fattori, Ana Ferreiro, Casie A Genetti, Hernan Gonorazky, Monkol Lek, Amanda Lindy, Livija Medne, Francesco Muntoni, Sander Pajusalu, Katarina Pelin, John Rendu, Anna Sarkozy, Matteo Vatta, Tom Winder, Grace Yoon, Carsten G Bönnemann, Ozge Ceyhan-Birsoy","doi":"10.1177/22143602251339369","DOIUrl":"https://doi.org/10.1177/22143602251339369","url":null,"abstract":"<p><strong>Background: </strong>Congenital myopathies are a group of neuromuscular disorders that typically present at birth or early childhood with hypotonia and non-progressive or slowly progressive muscle weakness. They are classically subclassified by characteristic structural changes and histopathological findings in skeletal muscle. Variants in over 40 genes have been described to date in patients with various forms of congenital myopathy with overlapping phenotypic and histological features, which poses a challenge for laboratories and clinicians in interpreting genetic findings.</p><p><strong>Objective: </strong>The purpose of this study was to evaluate the evidence supporting each gene-disease relationship and provide an expert-reviewed classification for the clinical validity of genes involved in congenital myopathies.</p><p><strong>Methods: </strong>The ClinGen Neurological Disorders Clinical Domain Working Group assembled the Congenital Myopathies Gene Curation Expert Panel (CongenMyopathy-GCEP), a group of clinicians and geneticists with expertise in congenital myopathies tasked to perform evidence-based curation of 50 gene-disease relationships using the ClinGen semiquantitative framework to assign clinical validity.</p><p><strong>Results: </strong>Our curation effort resulted in 35 (70%) Definitive, eight (16%) Moderate, six (12%) Limited, and one (2%) Disputed disease relationship classifications. The summary of each curation is made publicly available on the ClinGen website.</p><p><strong>Conclusions: </strong>Expert-reviewed assignment of gene-disease relationships by the CongenMyopathy-GCEP facilitates accurate molecular diagnoses for congenital myopathies and can allow genetic testing to focus on genes with a validated role in disease.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251339369"},"PeriodicalIF":3.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calpainopathy (limb-girdle muscular dystrophy type R1): clinical features, diagnostic approaches, and biotechnological treatment methods.","authors":"Sergey N Bardakov, Irina Sorochanu, Lilit A Mkrtchyan, Yana S Slesarenko, Vadim A Tsargush, Igor S Limaev, Artur A Isaev, Ivan A Yakovlev, Roman V Deev","doi":"10.1177/22143602251345967","DOIUrl":"https://doi.org/10.1177/22143602251345967","url":null,"abstract":"<p><p>Calpainopathy, or limb-girdle muscular dystrophy type R1/2A (LGMDR1/2A), is the most prevalent form of LGMD, comprising about 32% of all cases. The disease is caused by mutations in the <i>CAPN3</i> gene, leading to dysfunction of the corresponding protein-an enzyme critical for muscle fiber cytoskeleton remodeling and protein signaling regulation through selective proteolysis. Clinical manifestations demonstrate significant phenotypic polymorphisms, ranging from oligosymptomatic forms to severe early-onset cases, with the loss of ambulation occurring 10-25 years after disease onset. A characteristic feature is predominantly symmetrical involvement of limb and trunk muscles, leading to early mobility loss, disability, and reduced work capacity. Noninvasive imaging can suggest dystrophic muscle disease but requires differentiation from other myopathies. Confirming the diagnosis involves histological, immunological, and molecular genetic studies to identify calpain-3 activity or <i>CAPN3</i> gene expression alterations. Currently, no targeted or etiological therapies are available for calpainopathy. Treatment focuses on symptom management, complication prevention, and slowing disease progression. Preclinical research demands the development of an appropriate animal model that displays disease phenotypes mirroring those observed in humans. Preclinical and clinical research are also investigating therapeutic options, including the use of drugs that have proven effective in other myopathies and genome editing via transgenic <i>CAPN3</i> delivery to restore protein activity. Gene therapy has shown promise in murine models, but safety concerns, particularly systemic toxicity affecting the heart and other organs, remain significant. This review comprehensively analyzes the clinical features, diagnostic approaches, and advancements in modeling and therapeutic development for calpainopathy.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251345967"},"PeriodicalIF":3.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic review for economic evaluations on newborn screening for spinal muscular atrophy.","authors":"Alexander C Pace, Corrina Poon, Pranesh Chakraborty, Maryam Oskoui, Hugh McMillan, Alex Mackenzie, Jeff Round","doi":"10.1177/22143602251336862","DOIUrl":"https://doi.org/10.1177/22143602251336862","url":null,"abstract":"<p><p>ObjectiveEvaluate the quality and cost-effectiveness of economic evaluations of newborn screening (NBS) for Spinal Muscular Atrophy (SMA).MethodsA systematic review was conducted following Cochrane Handbook guidelines and PRISMA-S checklist. From 146 identified papers, 22 were screened for full-text, and 5 were included. Studies were evaluated for quality of reporting and transparency using the CHEERs and QHES checklists. Data was extracted to inform the review.ResultsFour economic evaluations on NBS for SMA with high reporting quality were identified. Each study employed a cost-utility analysis with similar model structures, using a decision tree for screening and a Markov model for treatment outcomes. They each compared NBS with treatment vs clinical diagnosis (no screening) with treatment. Although treatment protocols of each study varied due to differences in the strategies considered and availability of treatment. All studies included a societal perspective in their analysis and considered a lifetime horizon ranging from 30 months to 100 years. Early NBS with treatment was found to be more cost-effective than late treatment in all studies with ICER values ranging from £-117,541 to $714,000 per QALY. The wide range of ICER values are due to assumptions of long-term outcomes which are still largely unknown.ConclusionNBS with treatment was found to be cost-effective by all studies when compared to no NBS and late treatment. Although there is uncertainty around long term outcomes. Future research should focus on collecting long-term efficacy and safety data and evaluating the cost-effectiveness of pre-symptomatic treatment.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251336862"},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered reversal and extinction learning in the DMSXL mouse model of type I myotonic dystrophy (DM1): An exploratory study.","authors":"Sylvia Nieuwenhuis, Denys Kozakov, Kasia Kapusta, Geneviève Gourdon, Jeffrey C Glennon","doi":"10.1177/22143602251339350","DOIUrl":"https://doi.org/10.1177/22143602251339350","url":null,"abstract":"<p><p>BackgroundCognitive changes in type 1 myotonic dystrophy (DM1) have a pronounced negative effect on quality of life measures. Despite this, the neural basis of these changes is poorly understood. DM1 patients demonstrate deficits in motivation and cognitive flexibility, reflective of apathy and obsessive-compulsive / autistic-like traits.ObjectiveThese traits can be readily assessed using reversal learning and appetitive extinction tasks. Reversal learning assesses the ability to learn following a change in a rule and can evaluate cognitive flexibility and habitual responding, while appetitive extinction assesses the ability to suppress a stimulus-action response following the change in the stimulus-reward relationship from rewarded to non-rewarded.MethodsIn this study we evaluated the performance of a mouse model of DM1, the DMSXL mouse in reversal learning and appetitive extinction tasks.ResultsSimilar to C57/BL6 wild type (WT) mice, DMSXL mice were able to learn stimulus reward relationships, however, in the late phase of reversal learning experiment DMSXL mice demonstrated increased habit-like behavior (increased number of correct responses). Following rule switching, DMSXL mice produced an increased number of errors compared to WT and showed increased latency to deliver correct responses. In the extinction task, DMSXL mice showed the ability to more rapidly extinguish a previously rewarded response than WT mice.ConclusionsThese findings constitute differences in cognitive flexibility, rule learning and motivation between DMSXL and WT mice which may inform our understanding of cognitive changes in DM1.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251339350"},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}