Journal of neuromuscular diseases最新文献

{"title":"Monomethylation of cytosolic 5'-nucleotidase 1A affects its recognition by inclusion body myositis autoantibodies.","authors":"Fleur Brinkman, Marian Barandica Graciani, Amrah Weijn, Filine Swets, Seher Al Bana, Chien-Yun Lee, Ger J M Pruijn","doi":"10.1177/22143602261487219","DOIUrl":"10.1177/22143602261487219","url":null,"abstract":"<p><p>The progressive muscle disease inclusion body myositis (IBM) is characterized, amongst others, by inflammatory features and protein accumulation in skeletal muscle fibers. One of the proteins that accumulates in perinuclear and peripheral regions of muscle fibers is cytosolic 5'-nucleotidase 1A (cN1A), the target of anti-cN1A autoantibodies, which are found in many IBM patients. To shed more light on potential pathogenic aspects of IBM, we identified post-translational modifications of cN1A in human skeletal muscle. Immunoaffinity-purification followed by mass spectrometry resulted in the identification of three monomethylation sites, K178, R223, and K243. Single amino acid substitutions of each of these methylation sites did not detectably affect the accumulation of cN1A in perinuclear regions of cultured human cell lines. Two of these monomethylation sites, R223 and K243, are located within one of the previously identified major linear epitope regions of cN1A. Synthetic peptides, corresponding to aa 219 - aa 247, were used to investigate the effect of monomethylation on the antigenicity of this epitope by ELISA. The results showed that the simultaneous monomethylation of R223 and K243 may enhance its recognition by IgG autoantibodies. We conclude that cN1A contains at least three amino acids that can be monomethylated and that monomethylation may affect its autoantigenicity.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602261487219"},"PeriodicalIF":3.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pembrolizumab-associated myasthenia gravis in thymic tumors: A single-center case series and comparative analysis.","authors":"Soonwook Kwon, Soo Ryun Park, Hyunjin Ju, Yeon Hak Chung, Eun Kyoung Kim, Se-Hoon Lee, Ju-Hong Min","doi":"10.1177/22143602261486591","DOIUrl":"10.1177/22143602261486591","url":null,"abstract":"<p><p>BackgroundMyasthenia gravis (MG) is commonly associated with thymic tumors and may be triggered or worsened by immune checkpoint inhibitors (ICIs). Although pembrolizumab (PEM) has shown efficacy in relapsed/refractory thymic tumors, its relationship with MG in thymic tumor patients is unclear.MethodsWe retrospectively reviewed patients with thymic tumors treated with PEM at a tertiary center (2016-2021) to assess the prevalence, timing, and clinical features of new-onset or exacerbated MG, along with immune-related adverse events (irAEs). Outcomes were compared with 714 thymic tumor patients not treated with ICIs (1993-2021), stratified by tumor type.ResultsAmong 60 PEM-treated patients (mean age 50.4 years; 33% female), six (10%) developed new-onset (3/60) or relapsed (3/60) generalized MG which worsened after PEM administration. MG occurred in 42% of thymoma (5/12) versus 2% of thymic carcinoma patients (1/43; p = 0.001). All MG cases had other irAEs, most frequently myositis (n = 5) and myocarditis/cardiomyopathy (n = 3). Despite improvement of MG with immunotherapy, three patients died from tumor progression or irAEs. Compared with non-PEM-treated thymoma patients, MG incidence was numerically higher but not statistically significant.ConclusionPEM-treated thymic tumor patients may develop or experience worsening MG, typically with severe symptoms and concurrent irAEs that affect prognosis. While a direct causal link between PEM and MG remains uncertain, careful monitoring is warranted.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602261486591"},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical evaluation of ThecaFlex DRx, a novel implantable catheter-port for intrathecal nusinersen delivery in spinal muscular atrophy: Initial results from the PIERRE-IDE study.","authors":"Ignacio Mesina-Estarrón, Michael Abruzzo, Fernando Cotrim Gomes, Melina Thaxton, Aaron Yengo-Kahn, Scellig Stone, Weston Northam, Brian Snyder, Patrick Cahill, David Bauer, Michael Muhonen","doi":"10.1177/22143602261432303","DOIUrl":"10.1177/22143602261432303","url":null,"abstract":"<p><strong>Background: </strong>Administration of Nusinersen requires repeated lumbar intrathecal access, posing challenges for patients with Spinal Muscular Atrophy (SMA). A purpose-built system may streamline drug delivery.</p><p><strong>Objective: </strong>To assess the feasibility and safety of ThecaFlex DRx for intrathecal Nusinersen dosing.</p><p><strong>Methods: </strong>We present initial results of a prospective, multicenter investigational device exemption (IDE) study. Patients with SMA who had an indication for intrathecal Nusinersen were enrolled. Primary outcomes were successful system implantation and postoperative infusion. Prespecified safety outcomes consisted of adverse events adjudicated for severity and device or procedure relatedness.</p><p><strong>Results: </strong>Twenty-five subjects underwent device implantation. Median age at implantation was 13.8 years (IQR 10.0-18.0), and 52% were female. Subjects included individuals with SMA types I (16%), II (64%), and III (20%). Implantation was successful in all cases. At the interim data cutoff, median follow-up was 230 days (IQR 76.0-369.0) at which point 23 subjects (92%) had successfully received Nusinersen infusions. Ten patients reached one year of follow-up, and all of them maintained a functional device at this visit. Sixty adverse events occurred in 19 subjects, with 12 events (20%) adjudicated as serious adverse events that were most commonly wound-related or respiratory. At one year, the estimated probability of remaining free from device action was 86.2% (95% CI 0.73-1.00), with two devices requiring explantation due to wound dehiscence and access difficulties, respectively.</p><p><strong>Conclusions: </strong>This interim report supports the feasibility of ThecaFlex DRx for Nusinersen administration, with long-term durability and effectiveness to be defined with longer follow-up.For more information about the PIERRE study (NCT05866419), visit: https://www.</p><p><strong>Clinicaltrials: </strong>gov/study/NCT05866419.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"1107-1114"},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147458072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired renal function in patients with spinal muscular atrophy: A longitudinal cohort study.","authors":"Fay-Lynn Asselman, Sabine Ca Meijvis, Renske I Wadman, Inge Cuppen, Robin Wm Vernooij, Lina M Vermeer, Leonard H van den Berg, Ewout Jn Groen, W Ludo van der Pol","doi":"10.1177/22143602251377240","DOIUrl":"10.1177/22143602251377240","url":null,"abstract":"<p><p>BackgroundSpinal muscular atrophy (SMA) is caused by loss-of-function of the survival motor neuron 1 (<i>SMN1</i>) gene and deficiency of the ubiquitously expressed SMN protein. Genetic therapies can partially rescue motor units and improve prognosis of SMA, but effects of SMN shortage in other tissues has not been studied in detail.MethodsWe longitudinally assessed renal function in a cohort of patients with SMA before and after the start of genetic therapies.ResultsWe enrolled 263 patients with SMA types 1c-4. Median age was 33 years (IQR: 22-49). Fifty (19%) patients had serum cystatin C based eGFR rates <90 ml/min/1.73m², indicating increased risk of developing chronic kidney failure, 9 (3.5%) patients had eGFR compatible with chronic kidney failure (eGFR <60 ml/min/1.73m²) and 2 patients showed end-stage renal failure based on eGFR <15 ml/min/1.73m². Symptoms of tubular dysfunction (abnormal low serum potassium levels (<3.8 mmol/L) and proteinuria) were present in 134 (51.7%) and 53 patients (22%), respectively. Forty-two (16%) patients had a history of kidney stones or nephrocalcinosis. Treatment with nusinersen or risdiplam resulted in reduction of the number of patients with hypokalaemia, but not of those with proteinuria. Cystatin C eGFR continued to decline during treatment.ConclusionsPatients with SMA are at risk of impaired renal clearance, which does not improve after treatment with <i>SMN2</i>-splicing modifying therapies. Tubular function may improve partially following the start of treatment. These data indicate that SMN protein deficiency affects kidneys and that this will probably cause health problems in later life.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"983-991"},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of infections and malignancy risks among patients with myasthenia gravis compared with matched controls in a US real-world setting.","authors":"Jana Podhorna, Charlotte Ward, Kushal B Naik, Ikjae Lee, Yuebing Li, Tobias Ruck, Elizabeth Teperov, Jeffrey T Guptill","doi":"10.1177/22143602251403092","DOIUrl":"10.1177/22143602251403092","url":null,"abstract":"<p><p>IntroductionMyasthenia gravis (MG) is a rare, debilitating autoimmune disease associated with pathogenic immunoglobulin G autoantibodies directed against components of the neuromuscular junction. The autoimmune nature of the disease and long-term immunosuppressive treatment may increase susceptibility to infections and malignancies, but studies investigating the association between MG and infections or malignancies remain scarce.MethodsWe conducted a retrospective, observational study using Optum's deidentified Market Clarity Data (Market Clarity) to evaluate the incidence rate (IR) of infections and malignancies in US-based patients with MG in a real-world setting. Adults with ≥2 diagnosis claims of MG were identified over a 2-year period (2016-2019) and propensity score (PS) matched with controls from the general population without MG. Patients with malignancies in the 1-year look-back period were excluded.ResultsPatients with MG (N = 5002) were compared with the PS-matched general population (N = 20,008). The IR of serious infections (primary outcome) was higher in the MG cohort compared with the general population (52.81 vs 31.46 per 1000 person-years [PY], respectively). IRs of opportunistic infections (87.48 vs 57.01 per 1000 PY) and infection-related death (3.98 vs 1.94 per 1000 PY) were also higher in the MG cohort compared with the general population. The overall rate of malignancy was higher in the MG cohort compared with the general population (73.55 vs 50.01 per 1000 PY, respectively).ConclusionsIn this analysis, patients with MG were more susceptible to serious infections, infection-related death, and malignancies.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"898-908"},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of early-onset, rapidly progressive scoliosis in spinal muscular atrophy type I treated with disease-modifying therapy -a multicenter retrospective study conducted in Japan.","authors":"Tomokazu Kimizu, Reiko Arakawa, Mikiko Hasegawa, Tomoko Mizuno, Ryosuke Bou, Emiko Kobayashi, Toshio Saito, Kazuhiro Muramatsu, Yoshi-Ichiro Kamijo, Tamaki Kato, Kenji Inoue, Mitsuo Motobayashi, Yuichi Abe, Keisuke Oki, Saki Yokawa, Daisuke Tamura, Keiko Yanagihara","doi":"10.1177/22143602251414327","DOIUrl":"10.1177/22143602251414327","url":null,"abstract":"<p><p>In the era of disease-modifying therapy (DMT), almost all patients with spinal muscular atrophy (SMA) type I treated after onset, but before 6 months of age, develop early-onset, rapidly progressive scoliosis by 2 years of age, despite improvements in their motor function. Seven symptomatic patients with SMA type I who were treated before the age of 6 months were included in this retrospective observational study. Scoliosis had developed in all patients by 27 months of age. Among them, the patients who could stand with support or independently (standing patients; n = 3) tended to present with more progressive scoliosis than the sitters (n = 4). All standing patients demonstrated thoracic hyperkyphosis before or at the time of their scoliosis diagnosis. Despite receiving DMT, these patients continued to show residual key manifestations of SMA type I. Chronic difficulty maintaining posture due to trunk muscle weakness in the lying, sitting, or standing position was considered to be the main contributor to the development and progression of the scoliosis. The development and progression of such scoliosis, which begins in infancy, may be related to inappropriate postural management, which is not currently recognized as such by clinicians, caregivers, or guardians. In this population, it is important to closely monitor patients for such scoliosis from soon after the diagnosis of SMA. As this type of scoliosis progresses rapidly during the early developmental stage, when surgery is not possible, it is necessary to establish a proactive non-surgical management strategy for it.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"909-918"},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13442909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substance use may be associated with non-adherence to non-invasive ventilation in adults with myotonic dystrophy type 1.","authors":"Jalal Moolji, Erika MacIntyre, Janice Richman-Eisenstat","doi":"10.1177/22143602261421680","DOIUrl":"10.1177/22143602261421680","url":null,"abstract":"<p><p>Adults with myotonic dystrophy type 1 who require non-invasive ventilation (NIV) often have difficulty with adherence. Few risk factors for non-adherence have been identified, and these are mostly unmodifiable. As part of a quality assurance initiative, we sought to identify psychosocial barriers to NIV adherence to improve supports around isolation and mental health. We found that substance use was associated with non-adherence to NIV in our cohort. Cognitive impairment, the receipt of provincial income support, presence of a psychiatric condition, living alone, and marital status were not associated with NIV adherence. Interventions that limit the impact of substance use may improve NIV in this population.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"1176-1178"},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Rasch-transformed gastrointestinal symptoms rating scale in myotonic dystrophy type 1 (RT-GSRS-DM1).","authors":"Leandre A la Fontaine, Basil Pap van Veen, Tatiana Hamadeh, José M Conchillo, Sander Mj van Kuijk, Ingemar Sj Merkies, Catharina G Faber","doi":"10.1177/22143602251412672","DOIUrl":"10.1177/22143602251412672","url":null,"abstract":"<p><strong>Background: </strong>Myotonic Dystrophy type 1 (DM1) is a multisystemic neuromuscular disorder. Gastrointestinal (GI) symptoms significantly impact quality of life, but remain under-assessed. Currently, no DM1 specific GI questionnaire is available. The Gastrointestinal Symptoms Rating Scale (GSRS) is widely used but lacks validation with modern clinimetric methods.</p><p><strong>Objectives: </strong>To evaluate the GSRS using Rasch analysis in DM1 patients and develop a disease-specific, interval-level GI symptom measure.</p><p><strong>Methods: </strong>Rasch analysis evaluated item fit, threshold ordering, differential item functioning (DIF), local dependency, and unidimensionality. Model fit was evaluated using chi-square statistics, item and person fit residuals, and the Person Separation Index (PSI).</p><p><strong>Results: </strong>Four hundred and three DM1 patients (206 women, mean age 48.3 years) completed the GSRS questionnaire. The GSRS initial data did not meet Rasch model expectations. Three items (hard stools, heartburn, diarrhea) were removed and the item nausea was split by age category. The item constipation had misfit exceeding the Bonferroni threshold, but was retained due to its clinical relevance. The final model did not fulfill Rasch requirements (item fit residuals: -0.23, SD 1.29; person fit residuals: mean -0.27, SD 1.15; item-trait Chi-square: p-value < 0.001; degrees of freedom: 60). Acceptable person separation index (0.76) was obtained.</p><p><strong>Conclusion: </strong>This study highlights the challenges of measuring GI symptoms in DM1. Although this research is an important first step, more research is needed for developing a questionnaire that reflects the patient experience whilst simultaneously considering measurement accuracy.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"946-954"},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145944630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized, double-blind, placebo-controlled study of losmapimod in patients with facioscapulohumeral muscular dystrophy: Results of the REACH study.","authors":"Nicol C Voermans, Jeffrey M Statland, Lawrence J Hayward, Angela Rosenbohm, Adolfo López de Munain, Sabrina Sacconi, Doris G Leung, Umesh A Badrising, John Vissing, Benedikt Schoser, Nuria Muelas, Hanns Lochmüller, Enrico Bugiardini, Leo H Wang, Lorenzo Maggi, Thomas Ragole, Alan Pestronk, Johanna I Hamel, Namita A Goyal, Lawrence Korngut, Elie Naddaf, Amy Harper, Perry B Shieh, Cornelia Kornblum, Valeria Sansone, Angela Genge, Giorgio Tasca, John Jiang, Marie-Helene Jouvin, Rabi Tawil","doi":"10.1177/22143602261419558","DOIUrl":"10.1177/22143602261419558","url":null,"abstract":"<p><strong>Background: </strong>Losmapimod is an orally administered small molecule and selective p38α/β mitogen-activated protein kinase (MAPK) inhibitor able to reduce aberrant expression of <i>DUX4 in vitro</i> and thereby potentially slowing disease progression in patients with facioscapulohumeral muscular dystrophy (FSHD).</p><p><strong>Objective: </strong>This global, randomized, placebo-controlled, double-blind phase 3 study in patients with FSHD1 and FSHD2 examined the efficacy and safety of losmapimod over a 48-week treatment period compared to placebo (NCT05397470, EUDRACT 2022-000389-16).</p><p><strong>Methods: </strong>The primary endpoint was change in quantification of reachable workspace (RWS) expressed as relative surface area (RSA). Other endpoints included measures of muscle composition (fat content and lean muscle) using magnetic resonance imaging (MRI), muscle strength using quantitative dynamometry, and quality of life measures.</p><p><strong>Results: </strong>130 participants received losmapimod and 130 participants received placebo, with 252 participants completing the 48-week treatment period. There were no statistically significant differences between groups in change in RSA and all secondary efficacy endpoints from baseline to Week 48. Losmapimod treatment was well-tolerated, and most adverse events were mild.</p><p><strong>Conclusions: </strong>Losmapimod was generally well tolerated with a favorable safety profile at a dose of 15 mg twice daily. Although none of the efficacy endpoints were met, study design and data from the study may inform future studies of FSHD therapies.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"1049-1064"},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13442687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The natural history of Becker muscular dystrophy: A systematic literature review.","authors":"Alexis T Mickle, Karissa M Johnston, Kristen L Ricchetti-Masterson, Andrew R Kennedy, Sarah Gc Korpach, Katherine L Gooch","doi":"10.1177/22143602261420045","DOIUrl":"10.1177/22143602261420045","url":null,"abstract":"<p><strong>Background: </strong>Becker muscular dystrophy (BMD) is caused primarily by in-frame mutations in the <i>DMD</i> gene. Phenotype varies from asymptomatic to severe; manifestations may include muscle weakness, scoliosis, cardiac involvement, loss of ambulation, respiratory impairment, cognitive dysfunction, and premature death. This study aimed to characterize the frequency and age at occurrence of these milestones.</p><p><strong>Methods: </strong>A systematic literature review (SLR) was refreshed in 2022 using MEDLINE and EMBASE to identify articles describing the natural history of BMD. The proportion of patients experiencing clinical milestones was reported by 'life-stage' age groups (0-17; 18-40; 41+ years) using patient-level data from the general BMD population; age at each milestone's occurrence as mean (standard deviation [SD]).</p><p><strong>Results: </strong>From 4948 abstracts screened, 121 publications were included. Among 36 general BMD population studies, by age 41+ years (lifetime-risk proxy), 93.6% experienced muscle weakness; 69.4% cardiac involvement; 55.6% scoliosis; 47.4% loss of ambulation; and 33.3% ventilation. Decreased cognitive function or cognitive dysfunction were reported in 41% across all ages. Among those experiencing milestones (79 studies), mean (SD) age at symptom onset was 12.5 (9.7); muscle weakness, 19.9 (11.7); scoliosis, 24.9 (3.1); cardiac involvement, 31.9 (13.4); loss of ambulation, 33.3 (13.5); ventilation, 35.7 (12.2); and death at 55.6 (19.4) years. Data availability ranged from three to 1079 patients/outcome.</p><p><strong>Conclusions: </strong>This SLR highlights the variability in disease presentation in BMD. Stratifying BMD populations into phenotype groups based on the full spectrum of clinical manifestations may better capture disease progression and enhance comparability across studies.Included clinical trials:ClinicalTrials.gov NCT01070511 (https://clinicaltrials.gov/study/NCT01070511), ClinicalTrials.gov NCT02147639 (https://clinicaltrials.gov/study/NCT02147639?term=Becker%20Muscular%20Dystrophy&intr=Sodium%20Nitrate&rank=3), ClinicalTrials.gov NCT01350154 and EudraCT number: 2010-024659-10 (https://clinicaltrials.gov/study/NCT01350154?term=NCT01350154&rank=1; https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-024659-10/results).</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"1140-1158"},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}