Striated muscles are fundamental components of the human body, playing a central role in motor function. Since antiquity, muscle structure and function have been subjects of inquiry, initially grounded in descriptive anatomical observations. Only with scientific progress and the development of new investigative tools—particularly microscopy—did the histological study of muscle begin to evolve into its current form. The histological examination of normal striated muscle has been instrumental in identifying key pathological features of neuromuscular disorders. Beginning with pivotal discoveries in the 19th century, followed by significant advances throughout the 20th century, our present understanding of myopathology has been shaped by this cumulative progress. Notably, muscle biopsy—now a routine diagnostic procedure in suspected myopathies—has played a critical role in these developments. This review presents a systematic approach that effectively illustrates the key steps in the histological analysis of normal and pathological striated muscle.
{"title":"A historical perspective on the morphology of normal and pathological striated muscle","authors":"Mégane Le Quang , Jean-Michel Vallat , Marie-Laure Martin-Négrier , Stéphane Mathis","doi":"10.1016/j.nmd.2025.106301","DOIUrl":"10.1016/j.nmd.2025.106301","url":null,"abstract":"<div><div>Striated muscles are fundamental components of the human body, playing a central role in motor function. Since antiquity, muscle structure and function have been subjects of inquiry, initially grounded in descriptive anatomical observations. Only with scientific progress and the development of new investigative tools—particularly microscopy—did the histological study of muscle begin to evolve into its current form. The histological examination of normal striated muscle has been instrumental in identifying key pathological features of neuromuscular disorders. Beginning with pivotal discoveries in the 19th century, followed by significant advances throughout the 20th century, our present understanding of myopathology has been shaped by this cumulative progress. Notably, muscle biopsy—now a routine diagnostic procedure in suspected myopathies—has played a critical role in these developments. This review presents a systematic approach that effectively illustrates the key steps in the histological analysis of normal and pathological striated muscle.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"58 ","pages":"Article 106301"},"PeriodicalIF":2.8,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734002","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 : 2025-11-27DOI: 10.1016/j.nmd.2025.106300
Samna Haider , Ahmed Daud Siddiqui , Muhammad Asad , Marium Amjad , Nidal Bin Kamran , Hoor Ul Ain , Ayesha Khan , Hussain Haider Shah , Shahreena Athar Siddiqui , Amama Anis , Elsa Khan , Radeyah Waseem
Primary periodic paralysis (PPP) comprises inherited ion channelopathies, marked by episodic or sustained muscle weakness. Dichlorphenamide has been investigated as a treatment option, however existing studies report inconsistent and variable findings regarding its efficacy. To clarify these inconsistencies, we conducted a meta-analysis and systematic review evaluating its effectiveness in managing PPP. A comprehensive literature exploration was undertaken across multiple databases encompassing studies disseminated up to July 2025, assessing efficacy of dichlorphenamide in PPP. Primary outcomes encompassed mean changes in weekly attack frequency and severity-weighted scores. Meta-analysis was performed using RevMan, reporting mean differences (MD), statistical significance was ascribed to p-values < 0.05. Evidence certainty was evaluated using the GRADE framework. Clinically significant reductions in the frequency of weekly periodic paralytic attacks were observed in both the hyperkalemic and hypokalemic subgroups (MD -1.72, P-value: 0.01), as well as across the age subgroups, adolescents and adults (MD -0.95, P-value: <0.00001). Analysis of severity-weighted attack scores also revealed significant improvements across both etiological hyperkalemic and hypokalemic categories (MD -1.37, P-value: 0.002), and age-based subgroups (MD -1.28, P-value: <0.00001). Along with therapeutic benefits, some adverse effects were also associated with dichlorphenamide, such as paresthesias (p < 0.00001), cognitive disturbances (p: 0.008), dysgeusia (p: 0.01), and rash (p: 0.006). The GRADE analysis confirmed high-certainty evidence for primary outcomes, supporting dichlorphenamide’s consistent efficacy across etiologies and ages, though its side effects necessitate careful monitoring and counseling.
{"title":"Safety and efficacy of dichlorphenamide in patients with periodic paralysis: A systematic review and meta-analysis","authors":"Samna Haider , Ahmed Daud Siddiqui , Muhammad Asad , Marium Amjad , Nidal Bin Kamran , Hoor Ul Ain , Ayesha Khan , Hussain Haider Shah , Shahreena Athar Siddiqui , Amama Anis , Elsa Khan , Radeyah Waseem","doi":"10.1016/j.nmd.2025.106300","DOIUrl":"10.1016/j.nmd.2025.106300","url":null,"abstract":"<div><div>Primary periodic paralysis (PPP) comprises inherited ion channelopathies, marked by episodic or sustained muscle weakness. Dichlorphenamide has been investigated as a treatment option, however existing studies report inconsistent and variable findings regarding its efficacy. To clarify these inconsistencies, we conducted a meta-analysis and systematic review evaluating its effectiveness in managing PPP. A comprehensive literature exploration was undertaken across multiple databases encompassing studies disseminated up to July 2025, assessing efficacy of dichlorphenamide in PPP. Primary outcomes encompassed mean changes in weekly attack frequency and severity-weighted scores. Meta-analysis was performed using RevMan, reporting mean differences (MD), statistical significance was ascribed to p-values < 0.05. Evidence certainty was evaluated using the GRADE framework. Clinically significant reductions in the frequency of weekly periodic paralytic attacks were observed in both the hyperkalemic and hypokalemic subgroups (MD -1.72, P-value: 0.01), as well as across the age subgroups, adolescents and adults (MD -0.95, P-value: <0.00001). Analysis of severity-weighted attack scores also revealed significant improvements across both etiological hyperkalemic and hypokalemic categories (MD -1.37, P-value: 0.002), and age-based subgroups (MD -1.28, P-value: <0.00001). Along with therapeutic benefits, some adverse effects were also associated with dichlorphenamide, such as paresthesias (<em>p</em> < 0.00001), cognitive disturbances (p: 0.008), dysgeusia (p: 0.01), and rash (p: 0.006). The GRADE analysis confirmed high-certainty evidence for primary outcomes, supporting dichlorphenamide’s consistent efficacy across etiologies and ages, though its side effects necessitate careful monitoring and counseling.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"58 ","pages":"Article 106300"},"PeriodicalIF":2.8,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724898","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}
We report a case of HMGCR-related limb-girdle muscular dystrophy (LGMD) with neonatal onset and early lethality. The patient, homozygous for the p.Arg641Cys variant in HMGCR, presented with profound hypotonia, respiratory failure by 5 months, and markedly elevated creatine kinase (CK). This case stands out among the 17 previously reported patients for its extremely early onset and rapid clinical deterioration. Functional studies confirmed the pathogenicity of the variant: in vitro assays showed severely impaired HMGCR enzymatic activity, and in vivo modeling using homozygous knock-in mice resulted in embryonic lethality, underscoring its deleterious effect on essential metabolic processes. The patient’s early death highlights the urgent need for targeted therapies and early diagnosis. This case expands the clinical and molecular spectrum of HMGCR-related LGMD and supports refining phenotype classification based on genotype–phenotype correlations and age of onset to improve diagnostic precision.
{"title":"HMGCR-related muscular dystrophy: a case of severe neonatal-onset form","authors":"Jariya Upadia , Yuwen Li , Yoshinori Osaki , Seiya Mizuno , Satoru Takahashi , Hitoshi Shimano","doi":"10.1016/j.nmd.2025.106299","DOIUrl":"10.1016/j.nmd.2025.106299","url":null,"abstract":"<div><div>We report a case of <em>HMGCR</em>-related limb-girdle muscular dystrophy (LGMD) with neonatal onset and early lethality. The patient, homozygous for the p.Arg641Cys variant in <em>HMGCR</em>, presented with profound hypotonia, respiratory failure by 5 months, and markedly elevated creatine kinase (CK). This case stands out among the 17 previously reported patients for its extremely early onset and rapid clinical deterioration. Functional studies confirmed the pathogenicity of the variant: <em>in vitro</em> assays showed severely impaired HMGCR enzymatic activity, and <em>in vivo</em> modeling using homozygous knock-in mice resulted in embryonic lethality, underscoring its deleterious effect on essential metabolic processes. The patient’s early death highlights the urgent need for targeted therapies and early diagnosis. This case expands the clinical and molecular spectrum of <em>HMGCR</em>-related LGMD and supports refining phenotype classification based on genotype–phenotype correlations and age of onset to improve diagnostic precision.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"58 ","pages":"Article 106299"},"PeriodicalIF":2.8,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678250","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}
Malignant Hyperthermia Susceptibility (MHS) is a pharmacogenetic disorder triggered by volatile anesthetics and muscle relaxants, leading to a hypermetabolic reaction in skeletal muscle that can be fatal if untreated. Diagnosis relies on an in vitro contracture test (IVCT) on muscle biopsy and/or genetic testing for pathogenic variants in the RYR1 gene, which accounts for most cases; less frequently, variants are found in CACNA1S and STAC3. However, unlike the IVCT, genetic testing is limited by the large number of RYR1 variants classified as of uncertain significance (VUS), preventing it from fully replacing the IVCT.
We report data from 250 MHS individuals followed over 20 years, in whom 100 RYR1 and 3 CACNA1S variants were identified. Among the RYR1 variants, 81 were previously reported and 19 were novel, all classified as VUS according to European Malignant Hyperthermia Group (EMHG) and Variant Curation Expert Panel (VCEP) criteria. Similarly, of the 3 CACNA1S variants, 1 was previously reported and 2 were classified as VUS.
The reporting of novel variants is crucial for improving the accuracy and consistency of variant classification, thereby supporting a more precise interpretation of their clinical significance.
{"title":"Identification of novel potentially causative RYR1 variants in individuals with malignant hyperthermia susceptibility","authors":"Daniela Rossi , Carlotta Pranzo , Sara Roccabianca , Lucia Galli , Alfredo Orrico , Giovanna Sorbello , Vincenzo Tegazzin , Pasquale D’Onofrio , Armando Fucci , Salvatore Quarta , Stefano Perni , Egidio Maria Rubino , Matteo Serano , Gianna Berti , Diego Lopergolo , Alessandro Malandrini , Filip Van Petegem , Vincenzo Sorrentino","doi":"10.1016/j.nmd.2025.106296","DOIUrl":"10.1016/j.nmd.2025.106296","url":null,"abstract":"<div><div>Malignant Hyperthermia Susceptibility (MHS) is a pharmacogenetic disorder triggered by volatile anesthetics and muscle relaxants, leading to a hypermetabolic reaction in skeletal muscle that can be fatal if untreated. Diagnosis relies on an <em>in vitro</em> contracture test (IVCT) on muscle biopsy and/or genetic testing for pathogenic variants in the <em>RYR1</em> gene, which accounts for most cases; less frequently, variants are found in <em>CACNA1S</em> and <em>STAC3</em>. However, unlike the IVCT, genetic testing is limited by the large number of <em>RYR1</em> variants classified as of uncertain significance (VUS), preventing it from fully replacing the IVCT.</div><div>We report data from 250 MHS individuals followed over 20 years, in whom 100 <em>RYR1</em> and 3 <em>CACNA1S</em> variants were identified. Among the <em>RYR1</em> variants, 81 were previously reported and 19 were novel, all classified as VUS according to European Malignant Hyperthermia Group (EMHG) and Variant Curation Expert Panel (VCEP) criteria. Similarly, of the 3 <em>CACNA1S</em> variants, 1 was previously reported and 2 were classified as VUS.</div><div>The reporting of novel variants is crucial for improving the accuracy and consistency of variant classification, thereby supporting a more precise interpretation of their clinical significance.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"58 ","pages":"Article 106296"},"PeriodicalIF":2.8,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786660","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 : 2025-11-25DOI: 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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号