Pub Date : 2025-11-25DOI: 10.1016/j.nmd.2025.106297
Eleonora Torchia , Werner Stenzel , Raphael Raspe , Hans-Hilmar Goebel , Udo Schneider , Martin Nielsen
We report the case of a 54-year-old male patient with Behçet Disease (BD) complicated by aseptic pyomyositis with features of medium vessel vasculitis. His clinical course was characterized by severe myalgia, a palpable mass in the left quadriceps, blistering and ulcerative skin lesions, and systemic inflammation. Laboratory tests revealed neutrophilic leukocytosis, markedly elevated C-reactive protein, and approximately 13-fold increased creatine kinase levels. MRI demonstrated diffuse and asymmetric skeletal muscle oedema in the lower limbs, suggestive of multifocal abscess-like lesions. Muscle biopsy revealed sterile pyomyositis with granulocytic-necrotizing infiltrates and fibrinoid vascular necrosis with massive endomysial inflammatory infiltration. Muscle symptoms responded well to high-dose corticosteroid therapy, while cutaneous ulcers were initially refractory and improved only after multiple immunosuppressive treatments. This case highlights the complexity of diagnosing and managing severe muscular involvement and treatment-resistant skin manifestations in the context of BD.
{"title":"Aseptic pyomyositis in Behçet’s disease: a case report and narrative review of muscle involvement phenotypes","authors":"Eleonora Torchia , Werner Stenzel , Raphael Raspe , Hans-Hilmar Goebel , Udo Schneider , Martin Nielsen","doi":"10.1016/j.nmd.2025.106297","DOIUrl":"10.1016/j.nmd.2025.106297","url":null,"abstract":"<div><div>We report the case of a 54-year-old male patient with Behçet Disease (BD) complicated by aseptic pyomyositis with features of medium vessel vasculitis. His clinical course was characterized by severe myalgia, a palpable mass in the left quadriceps, blistering and ulcerative skin lesions, and systemic inflammation. Laboratory tests revealed neutrophilic leukocytosis, markedly elevated C-reactive protein, and approximately 13-fold increased creatine kinase levels. MRI demonstrated diffuse and asymmetric skeletal muscle oedema in the lower limbs, suggestive of multifocal abscess-like lesions. Muscle biopsy revealed sterile pyomyositis with granulocytic-necrotizing infiltrates and fibrinoid vascular necrosis with massive endomysial inflammatory infiltration. Muscle symptoms responded well to high-dose corticosteroid therapy, while cutaneous ulcers were initially refractory and improved only after multiple immunosuppressive treatments. This case highlights the complexity of diagnosing and managing severe muscular involvement and treatment-resistant skin manifestations in the context of BD.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"58 ","pages":"Article 106297"},"PeriodicalIF":2.8,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724993","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}
Pub Date : 2025-11-22DOI: 10.1016/j.nmd.2025.106283
Sharika V Raga , Gwendoline Q Kandawasvika , Alvin Ndondo , Michael G Hanna , Mary M Reilly , Christopher J Record , Amanda Krause , Fahmida Essop , Alina Esterhuizen , Jo M Wilmshurst
Genetic peripheral neuropathies have prevalence of 1:2500–1:10,000 in populations of European ancestry but are underreported in African populations. This retrospective cross-sectional study described 64 children with genetic peripheral neuropathy attending a neuromuscular disease centre in South Africa. Twenty-one children (21/64, 33 %) had confirmed molecular diagnoses, and 43/64 (67 %) were diagnosed via histology and neurophysiology. In seven children, next generation sequencing did not identify a causative variant. The identified genetic causes were PMP22 duplications (n = 11), and variants in ATL1 (n=1), IGHMBP2 (n = 2), MPZ (n = 1), MFN2 (n = 1), MTMR2 (n = 2), SH3TC2 (n = 1), SLC12A6 (n = 1), and SLC52A3 (n = 1). Axonal neuropathy was most common (47/64, 73 %), affecting 9/12 children with African, 17/26 Mixed, and 21/26 European ancestry. Only two of the 11 children with PMP22 duplication were of Indigenous Black African ancestry. Access to genetic closure for children in sub-Saharan Africa remains a challenge due limited access to genetic testing. In this study there was a predominance of unsolved axonal diseases. PMP22-related CMT1A, appeared rare in children of Indigenous Black African ancestry. More research is needed to elucidate the genetic underpinnings of neuropathies in Africa, for informed and relevant genetic and clinical diagnostic protocols for local patients.
{"title":"Expression of genetic peripheral neuropathies in South African children","authors":"Sharika V Raga , Gwendoline Q Kandawasvika , Alvin Ndondo , Michael G Hanna , Mary M Reilly , Christopher J Record , Amanda Krause , Fahmida Essop , Alina Esterhuizen , Jo M Wilmshurst","doi":"10.1016/j.nmd.2025.106283","DOIUrl":"10.1016/j.nmd.2025.106283","url":null,"abstract":"<div><div>Genetic peripheral neuropathies have prevalence of 1:2500–1:10,000 in populations of European ancestry but are underreported in African populations. This retrospective cross-sectional study described 64 children with genetic peripheral neuropathy attending a neuromuscular disease centre in South Africa. Twenty-one children (21/64, 33 %) had confirmed molecular diagnoses, and 43/64 (67 %) were diagnosed via histology and neurophysiology. In seven children, next generation sequencing did not identify a causative variant. The identified genetic causes were <em>PMP22</em> duplications (<em>n</em> = 11), and variants in <em>ATL1 (n</em> <em>=</em> <em>1), IGHMBP2</em> (<em>n</em> = 2), <em>MPZ</em> (<em>n</em> = 1), <em>MFN2</em> (<em>n</em> = 1), <em>MTMR2</em> (<em>n</em> = 2), <em>SH3TC2</em> (<em>n</em> = 1), <em>SLC12A6</em> (<em>n</em> = 1), and <em>SLC52A3</em> (<em>n</em> = 1). Axonal neuropathy was most common (47/64, 73 %), affecting 9/12 children with African, 17/26 Mixed, and 21/26 European ancestry. Only two of the 11 children with <em>PMP22</em> duplication were of Indigenous Black African ancestry. Access to genetic closure for children in sub-Saharan Africa remains a challenge due limited access to genetic testing. In this study there was a predominance of unsolved axonal diseases. <em>PMP22-related</em> CMT1A, appeared rare in children of Indigenous Black African ancestry. More research is needed to elucidate the genetic underpinnings of neuropathies in Africa, for informed and relevant genetic and clinical diagnostic protocols for local patients.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"59 ","pages":"Article 106283"},"PeriodicalIF":2.8,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145842443","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}
Pub Date : 2025-11-20DOI: 10.1016/j.nmd.2025.106284
A Vesperinas , J Rocaspana-Codana , D Reyes-Leiva , M Caballero-Ávila , Á Carbayo , R Collet-Vidiella , L Llansó , E Gallardo , J Turon-Sans , R Rojas-García , E Cortés-Vicente
Diagnosis of MG can be complicated and consequent delays in diagnosis can lead to potentially life-threatening situations. We designed a retrospective, observational study to review the diagnostic process of patients with suspicion of MG in real-world practice, identifying pitfalls and the most common mimic entities. Of the 561 patients referred with suspected MG, it was ruled out in 167 (29 %). An alternative diagnosis was reached in 53.9 %, showing high heterogeneity among these entities. During the diagnostic process, the cornerstone was the clinical picture, and in 30 % of the mimic group no further studies were needed. Regarding antibodies, 7.9 % of patients in MG mimic group had a previous, positive anti-AChR determination, later confirmed as a false positive result. Up to 19 % of patients in the mimic group showed abnormalities in the single fiber electromyography. This study highlights the diagnostic challenge in patients with suspected MG, especially in seronegative cases. In these patients, it took a mean of >2 years to rule out MG, and up to 23 % of these patients received immunosuppressants during this process.
{"title":"Challenges in myasthenia gravis diagnosis: an analysis of the diagnostic process of myasthenia gravis in a specialized clinic","authors":"A Vesperinas , J Rocaspana-Codana , D Reyes-Leiva , M Caballero-Ávila , Á Carbayo , R Collet-Vidiella , L Llansó , E Gallardo , J Turon-Sans , R Rojas-García , E Cortés-Vicente","doi":"10.1016/j.nmd.2025.106284","DOIUrl":"10.1016/j.nmd.2025.106284","url":null,"abstract":"<div><div>Diagnosis of MG can be complicated and consequent delays in diagnosis can lead to potentially life-threatening situations. We designed a retrospective, observational study to review the diagnostic process of patients with suspicion of MG in real-world practice, identifying pitfalls and the most common mimic entities. Of the 561 patients referred with suspected MG, it was ruled out in 167 (29 %). An alternative diagnosis was reached in 53.9 %, showing high heterogeneity among these entities. During the diagnostic process, the cornerstone was the clinical picture, and in 30 % of the mimic group no further studies were needed. Regarding antibodies, 7.9 % of patients in MG mimic group had a previous, positive anti-AChR determination, later confirmed as a false positive result. Up to 19 % of patients in the mimic group showed abnormalities in the single fiber electromyography. This study highlights the diagnostic challenge in patients with suspected MG, especially in seronegative cases. In these patients, it took a mean of >2 years to rule out MG, and up to 23 % of these patients received immunosuppressants during this process.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"59 ","pages":"Article 106284"},"PeriodicalIF":2.8,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808335","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}
Pub Date : 2025-11-13DOI: 10.1016/j.nmd.2025.106281
Wolfram Kress , Ute Hehr , Berthold Schalke , Clemens R. Mueller , Tiemo Grimm
Becker muscular dystrophy, BMD (#300,324) was first described by Becker and Kiener in 1955 and later recognised as a clinically milder allelic form of Duchenne muscular dystrophy (DMD). In muscle biopsies, BMD is characterized by the residual expression of dystrophin protein resulting in an apparently partial function. The mutations underlying BMD belong to the milder end of the wide spectrum of dystrophin mutations. We had the opportunity to study the mutation in a recent offspring of the original family of Becker and Kiener and identified a single amino acid substitution in exon 3 of the dystrophin gene: c.136G>T, p.(Asp46Tyr), a missense mutation which has already been described in another BMD family from Italy.
{"title":"Becker muscular dystrophy (BMD) is caused by a dystrophin missense mutation in the original family of Becker and Kiener","authors":"Wolfram Kress , Ute Hehr , Berthold Schalke , Clemens R. Mueller , Tiemo Grimm","doi":"10.1016/j.nmd.2025.106281","DOIUrl":"10.1016/j.nmd.2025.106281","url":null,"abstract":"<div><div>Becker muscular dystrophy, BMD (#300,324) was first described by Becker and Kiener in 1955 and later recognised as a clinically milder allelic form of Duchenne muscular dystrophy (DMD). In muscle biopsies, BMD is characterized by the residual expression of dystrophin protein resulting in an apparently partial function. The mutations underlying BMD belong to the milder end of the wide spectrum of <em>dystrophin</em> mutations. We had the opportunity to study the mutation in a recent offspring of the original family of Becker and Kiener and identified a single amino acid substitution in exon 3 of the dystrophin gene: c.136G><em>T</em>, p.(Asp46Tyr), a missense mutation which has already been described in another BMD family from Italy.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"59 ","pages":"Article 106281"},"PeriodicalIF":2.8,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808334","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}
The late-onset axonal Charcot–Marie–Tooth type 2T (CMT2T) is a form of sensorimotor peripheral polyneuropathy caused by mutations in the membrane metalloendopeptidase (MME) gene and inherited either as an autosomal recessive (AR) or as an autosomal dominant (AD) manner with incomplete penetrance. Here, we describe the clinical presentations and genetic profiles of 11 unrelated Iranian families (15 cases) diagnosed with CMT2T. Whole exome sequencing (WES) was utilized to detect genetic variants, and Sanger sequencing was subsequently performed to validate the identified variants. Among our patients, 13 exhibited AR-CMT2T, whereas two presented AD-CMT2T. Altogether, six variants in MME were detected, four of which were novel. The known c.499T>A, the most prevalent, and c.1861T>C variants in total occurred in 7/11 families. Interestingly, in one patient, an additional likely-pathogenic variant was identified alongside the MME variant within the DNA2 gene. His muscle biopsy revealed mixed neurogenic and rimmed vacuole myopathic changes. Our findings highlight the clinical and genetic heterogeneity among CMT2T patients. The presence of both c.499T>A and c.1861T>C variants in multiple Iranian families suggests potential founder mutations. Furthermore, the evidence presented in our study underscores the importance of WES as a crucial diagnostic tool for detecting concomitant genetic disorders.
{"title":"Clinical and molecular spectrum of an Iranian Charcot-Marie-Tooth 2T cohort, and the diagnostic importance of whole exome sequencing in identifying co-occurrence inherited disorders","authors":"Zahra Salami , Mahsa Mohammadi , Aida Ghasemi , Ali Asghar Okhovat , Yalda Nilipour , Marzieh Khani , Shahriar Nafissi , Afagh Alavi","doi":"10.1016/j.nmd.2025.106279","DOIUrl":"10.1016/j.nmd.2025.106279","url":null,"abstract":"<div><div>The late-onset axonal Charcot–Marie–Tooth type 2T (CMT2T) is a form of sensorimotor peripheral polyneuropathy caused by mutations in the membrane metalloendopeptidase (<em>MME)</em> gene and inherited either as an autosomal recessive (AR) or as an autosomal dominant (AD) manner with incomplete penetrance. Here, we describe the clinical presentations and genetic profiles of 11 unrelated Iranian families (15 cases) diagnosed with CMT2T. Whole exome sequencing (WES) was utilized to detect genetic variants, and Sanger sequencing was subsequently performed to validate the identified variants. Among our patients, 13 exhibited AR-CMT2T, whereas two presented AD-CMT2T. Altogether, six variants in <em>MME</em> were detected, four of which were novel. The known c.499T><em>A</em>, the most prevalent, and c.1861T><em>C</em> variants in total occurred in 7/11 families. Interestingly, in one patient, an additional likely-pathogenic variant was identified alongside the <em>MME</em> variant within the <em>DNA2</em> gene. His muscle biopsy revealed mixed neurogenic and rimmed vacuole myopathic changes. Our findings highlight the clinical and genetic heterogeneity among CMT2T patients. The presence of both c.499T><em>A</em> and c.1861T><em>C</em> variants in multiple Iranian families suggests potential founder mutations. Furthermore, the evidence presented in our study underscores the importance of WES as a crucial diagnostic tool for detecting concomitant genetic disorders.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106279"},"PeriodicalIF":2.8,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145982039","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}
Pub Date : 2025-11-08DOI: 10.1016/j.nmd.2025.106278
Emily A. Hayes , Chet R. Villa , Benjamin Kroslowitz , Deipanjan Nandi , Linda Cripe , Jonathan H. Soslow , Deepa Mokshagundam , Renata Shih , Bethany Wisotzkey , John J. Parent , Tyler Cunningham , Jennifer Conway , Paul Esteso , Brian F. Birnbaum , Svetlana B. Shugh , Frank J. Raucci , Beth D. Kaufman , Nelia Soares , Sonya Kirmani , Hugo R. Martinez , Carol A. Wittlieb-Weber
The Advanced Cardiac Therapies Improving Outcomes Network formed a dystrophinopathy registry to define cardiac diagnostics, management, and advanced therapies in the current era. Males with dystrophinopathy and one of the following: age ≥10 years, cardiomyopathy, or receipt of gene therapy, were eligible for enrollment. Data collection occurred at enrollment and every 6 months thereafter and includes demographics, neuromuscular, cardiac, and pulmonary endpoints, medications, advanced cardiac therapies, and outcomes. This analysis is of the first 500 males with a mean age of 18.1 years (± 5.38 years), the majority being white (81.2%) with Duchenne Muscular Dystrophy (91.4%), on glucocorticoids (80.2%), non-ambulatory (67.2%), and not requiring respiratory support (54.0%). In this cohort, 58.8% had evidence of cardiac involvement, 54.6% with evidence of ventricular dysfunction. The majority were on cardiac medication: 458 (91.6%) on angiotensin converting enzyme inhibitor or equivalent, 346 (69.2%) on mineralocorticoid receptor antagonist, and 264 (52.8%) on beta-blocker. One-hundred thirteen (22.6%) had an arrhythmia, 8 (1.6%) an implantable cardioverter defibrillator, 6 (1.2%) a ventricular assist device, and 3 (0.6%) underwent heart transplantation. Longitudinal data collection will establish a modern natural history of cardiomyopathy in dystrophinopathy, providing critical information to inform cardiac management and clinical trials.
{"title":"Dystrophinopathy in ACTION: The first 500 males enrolled in the Advanced Cardiac Therapies Improving Outcomes Network prospective dystrophinopathy registry","authors":"Emily A. Hayes , Chet R. Villa , Benjamin Kroslowitz , Deipanjan Nandi , Linda Cripe , Jonathan H. Soslow , Deepa Mokshagundam , Renata Shih , Bethany Wisotzkey , John J. Parent , Tyler Cunningham , Jennifer Conway , Paul Esteso , Brian F. Birnbaum , Svetlana B. Shugh , Frank J. Raucci , Beth D. Kaufman , Nelia Soares , Sonya Kirmani , Hugo R. Martinez , Carol A. Wittlieb-Weber","doi":"10.1016/j.nmd.2025.106278","DOIUrl":"10.1016/j.nmd.2025.106278","url":null,"abstract":"<div><div>The Advanced Cardiac Therapies Improving Outcomes Network formed a dystrophinopathy registry to define cardiac diagnostics, management, and advanced therapies in the current era. Males with dystrophinopathy and one of the following: age ≥10 years, cardiomyopathy, or receipt of gene therapy, were eligible for enrollment. Data collection occurred at enrollment and every 6 months thereafter and includes demographics, neuromuscular, cardiac, and pulmonary endpoints, medications, advanced cardiac therapies, and outcomes. This analysis is of the first 500 males with a mean age of 18.1 years (± 5.38 years), the majority being white (81.2%) with Duchenne Muscular Dystrophy (91.4%), on glucocorticoids (80.2%), non-ambulatory (67.2%), and not requiring respiratory support (54.0%). In this cohort, 58.8% had evidence of cardiac involvement, 54.6% with evidence of ventricular dysfunction. The majority were on cardiac medication: 458 (91.6%) on angiotensin converting enzyme inhibitor or equivalent, 346 (69.2%) on mineralocorticoid receptor antagonist, and 264 (52.8%) on beta-blocker. One-hundred thirteen (22.6%) had an arrhythmia, 8 (1.6%) an implantable cardioverter defibrillator, 6 (1.2%) a ventricular assist device, and 3 (0.6%) underwent heart transplantation. Longitudinal data collection will establish a modern natural history of cardiomyopathy in dystrophinopathy, providing critical information to inform cardiac management and clinical trials.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"58 ","pages":"Article 106278"},"PeriodicalIF":2.8,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145584384","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}
Pub Date : 2025-11-06DOI: 10.1016/j.nmd.2025.106262
Lucienne Ronco , Stephen Tapscott , Nicol C. Voermans , Program Committee
Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder marked by progressive muscle weakness and disability throughout life. Affecting about one million people worldwide, FSHD is among the most common forms of muscular dystrophy. To advance global collaboration, the FSHD Society hosted the 32nd International Research Congress (IRC) on June 12–13, 2025, in Amsterdam, the Netherlands. More than 250 researchers, clinicians, patients, and industry representatives attended, highlighting key developments in FSHD research. The Congress comprised six scientific sessions: (1) Population Genetics & Modifiers, (2) Measures of Disease Activity & Progression, (3) Novel Clinical Outcome Measures, (4) Mechanisms of Disease & Interventional Strategies, (5) Clinical Care & Related Issues, and (6) Clinical Studies & Trial Design. Keynote presentations were delivered by Leendert Trouw (Leiden University Medical Center, Netherlands) and Karen Chen (SMA Foundation, USA), who shared perspectives from their respective research domains. Preceding the IRC, the Industry Collaborative (IC) for Therapeutic Development united experts in clinical science, biomarkers, and industry to identify knowledge gaps and strengthen strategies for developing effective FSHD therapies. Following the IRC, the inaugural FSHD Connect Europe meeting brought together patients and families from across Europe to exchange experiences and gain updates on emerging clinical and scientific advances. The FSHD Society continues to foster research and community engagement to accelerate treatment breakthroughs. The next International Research Congress will be held in Chicago, Illinois, on June 25–26, 2026.
{"title":"Meeting report: The FSHD society 2025 international research congress","authors":"Lucienne Ronco , Stephen Tapscott , Nicol C. Voermans , Program Committee","doi":"10.1016/j.nmd.2025.106262","DOIUrl":"10.1016/j.nmd.2025.106262","url":null,"abstract":"<div><div>Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder marked by progressive muscle weakness and disability throughout life. Affecting about one million people worldwide, FSHD is among the most common forms of muscular dystrophy. To advance global collaboration, the FSHD Society hosted the 32nd International Research Congress (IRC) on June 12–13, 2025, in Amsterdam, the Netherlands. More than 250 researchers, clinicians, patients, and industry representatives attended, highlighting key developments in FSHD research. The Congress comprised six scientific sessions: (1) Population Genetics & Modifiers, (2) Measures of Disease Activity & Progression, (3) Novel Clinical Outcome Measures, (4) Mechanisms of Disease & Interventional Strategies, (5) Clinical Care & Related Issues, and (6) Clinical Studies & Trial Design. Keynote presentations were delivered by Leendert Trouw (Leiden University Medical Center, Netherlands) and Karen Chen (SMA Foundation, USA), who shared perspectives from their respective research domains. Preceding the IRC, the Industry Collaborative (IC) for Therapeutic Development united experts in clinical science, biomarkers, and industry to identify knowledge gaps and strengthen strategies for developing effective FSHD therapies. Following the IRC, the inaugural FSHD Connect Europe meeting brought together patients and families from across Europe to exchange experiences and gain updates on emerging clinical and scientific advances. The FSHD Society continues to foster research and community engagement to accelerate treatment breakthroughs. The next International Research Congress will be held in Chicago, Illinois, on June 25–26, 2026.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"58 ","pages":"Article 106262"},"PeriodicalIF":2.8,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145584387","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}
Pub Date : 2025-11-01DOI: 10.1016/j.nmd.2025.106255
Elizabeth M. van der Pijl , Svetlana Pasteuning-Vuhman , Johanna Boertje-van der Meulen , Erik H. Niks , Jan J.G.M. Verschuuren , Annemieke Aartsma-Rus , Jaap J. Plomp , Maaike van Putten
Duchenne muscular dystrophy is a muscle wasting disorder caused by lack of dystrophin protein. Dystrophin is present intracellularly at the sarcolemma and is enriched at the postsynaptic membrane of the neuromuscular junction. Morphological and functional neuromuscular junction deficits have been shown in mdx mice, a model lacking dystrophin. Antisense oligonucleotide-mediated exon skipping has been approved in several countries. It is however unclear whether the partial dystrophin restoration achieved is sufficient to rescue muscle functioning. Despite being well investigated at a myofiber level, it is unknown if the exon skipping therapy holds potential to ameliorate or restore neuromuscular junction deficits.
This study investigated the effects of exon skipping on the structure and function of the neuromuscular junction in the mdx mouse. On average, restoration of 16 % of wild type dystrophin protein level was achieved in diaphragm muscle following treatment with a 2′-O-methyl phosphorothioate antisense oligonucleotide. This partially improved neuromuscular junction functioning, evidenced by enhanced amplitudes of miniature endplate potentials and endplate potentials, and reduced sensitivity of neuromuscular transmission to the acetylcholine receptor blocker d-tubocurarine, indicating improved synaptic strength. Additionally, aberrant acetylcholine receptor cluster geometry improved.
杜氏肌营养不良症是一种由肌营养不良蛋白缺乏引起的肌肉萎缩症。肌营养不良蛋白存在于肌膜的细胞内，并在神经肌肉连接处的突触后膜富集。在mdx小鼠（一种缺乏肌营养不良蛋白的模型）中发现了形态学和功能性神经肌肉连接缺陷。反义寡核苷酸介导的外显子跳变已在多个国家得到批准。然而，目前尚不清楚所获得的部分肌营养不良蛋白恢复是否足以挽救肌肉功能。尽管在肌纤维水平上进行了很好的研究，但目前尚不清楚外显子跳跃疗法是否具有改善或恢复神经肌肉连接缺陷的潜力。本研究探讨了外显子跳变对mdx小鼠神经肌肉连接处结构和功能的影响。平均而言，用2 ' - o -甲基硫代磷酸酯反义寡核苷酸治疗膈肌后，恢复了野生型肌营养不良蛋白水平的16%。这部分改善了神经肌肉连接功能，证明了微型终板电位和终板电位的振幅增强，神经肌肉传递对乙酰胆碱受体阻滞剂d-管curarine的敏感性降低，表明突触强度得到改善。此外，异常乙酰胆碱受体簇的几何形状得到改善。
{"title":"Antisense-mediated exon skipping therapy improves neuromuscular junction deficits in a Duchenne muscular dystrophy mouse model","authors":"Elizabeth M. van der Pijl , Svetlana Pasteuning-Vuhman , Johanna Boertje-van der Meulen , Erik H. Niks , Jan J.G.M. Verschuuren , Annemieke Aartsma-Rus , Jaap J. Plomp , Maaike van Putten","doi":"10.1016/j.nmd.2025.106255","DOIUrl":"10.1016/j.nmd.2025.106255","url":null,"abstract":"<div><div>Duchenne muscular dystrophy is a muscle wasting disorder caused by lack of dystrophin protein. Dystrophin is present intracellularly at the sarcolemma and is enriched at the postsynaptic membrane of the neuromuscular junction. Morphological and functional neuromuscular junction deficits have been shown in <em>mdx</em> mice, a model lacking dystrophin. Antisense oligonucleotide-mediated exon skipping has been approved in several countries. It is however unclear whether the partial dystrophin restoration achieved is sufficient to rescue muscle functioning. Despite being well investigated at a myofiber level, it is unknown if the exon skipping therapy holds potential to ameliorate or restore neuromuscular junction deficits.</div><div>This study investigated the effects of exon skipping on the structure and function of the neuromuscular junction in the <em>mdx</em> mouse. On average, restoration of 16 % of wild type dystrophin protein level was achieved in diaphragm muscle following treatment with a 2′-<em>O</em>-methyl phosphorothioate antisense oligonucleotide. This partially improved neuromuscular junction functioning, evidenced by enhanced amplitudes of miniature endplate potentials and endplate potentials, and reduced sensitivity of neuromuscular transmission to the acetylcholine receptor blocker d-tubocurarine, indicating improved synaptic strength. Additionally, aberrant acetylcholine receptor cluster geometry improved.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"56 ","pages":"Article 106255"},"PeriodicalIF":2.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467718","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}
RYR1-related myopathies (RYR1-RMs) have been reported to exhibit distinct clinical manifestations and muscle pathology. Muscle imaging has gained increasing importance in the diagnosis and the imaging data have also been used in clinical trials for some diseases. This study aims to identify fat replacement patterns among RYR1-RMs and to investigate their relationship with clinical manifestations. A total of 36 patients with RYR1-RMs were examined by quantifying fat replacement in 47 skeletal muscles using the modified Mercuri score (mMS). Patients were classified into 6 diseases: central core disease (CCD), congenital neuromuscular disease with uniform type 1 fiber, central core disease with atypical core, multiminicore disease (MmD), dusty core disease, and myopathy with central nuclei. For data analyses, we employed dimensionality reduction using uniform manifold approximation and projection (UMAP), and hierarchical clustering. The patients with RYR1-RMs were positioned close together on UMAP. Violin plot analysis identified chronological patterns of fat replacement in whole body. Significant correlations were observed between imaging data and clinical symptoms, including respiratory failure, ambulation impairment and scoliosis, and muscle pathology. The patients with RYR1-RMs share a common pattern of fat replacement. Progressive fat replacement was identified, providing a foundation for establishing muscle imaging as a marker for disease progression and treatment efficacy.
{"title":"Muscle imaging of patients with RYR1-related myopathies and its significance to clinical features","authors":"Rui Shimazaki , Satoru Noguchi , Wakako Yoshioka , Hotake Takizawa , Yuji Takahashi , Shinichiro Hayashi , Ichizo Nishino","doi":"10.1016/j.nmd.2025.106275","DOIUrl":"10.1016/j.nmd.2025.106275","url":null,"abstract":"<div><div>RYR1-related myopathies (RYR1-RMs) have been reported to exhibit distinct clinical manifestations and muscle pathology. Muscle imaging has gained increasing importance in the diagnosis and the imaging data have also been used in clinical trials for some diseases. This study aims to identify fat replacement patterns among RYR1-RMs and to investigate their relationship with clinical manifestations. A total of 36 patients with RYR1-RMs were examined by quantifying fat replacement in 47 skeletal muscles using the modified Mercuri score (mMS). Patients were classified into 6 diseases: central core disease (CCD), congenital neuromuscular disease with uniform type 1 fiber, central core disease with atypical core, multiminicore disease (MmD), dusty core disease, and myopathy with central nuclei. For data analyses, we employed dimensionality reduction using uniform manifold approximation and projection (UMAP), and hierarchical clustering. The patients with RYR1-RMs were positioned close together on UMAP. Violin plot analysis identified chronological patterns of fat replacement in whole body. Significant correlations were observed between imaging data and clinical symptoms, including respiratory failure, ambulation impairment and scoliosis, and muscle pathology. The patients with RYR1-RMs share a common pattern of fat replacement. Progressive fat replacement was identified, providing a foundation for establishing muscle imaging as a marker for disease progression and treatment efficacy.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"56 ","pages":"Article 106275"},"PeriodicalIF":2.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574033","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}
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