Pub Date : 2026-03-01Epub Date: 2025-12-30DOI: 10.1016/j.nmd.2025.106331
David Gómez-Andrés , Michelle A Farrar , Mireia Alvarez-Molinero , Rocío Garcia-Uzquiano , Chiara Brusa , Giovanni Baranello , Susana Quijano-Roy , 285th ENMC Workshop participants
Recent advances in spinal muscular atrophy (SMA) early diagnosis and treatment have significantly improved survival and motor outcomes, particularly for those with severe phenotypes. However, clinicians have observed unexpected cognitive, social, communication, and behavioural differences in a proportion of children. The 285th ENMC workshop convened 28 experts from 13 countries to address these neurodevelopmental concerns. Key outcomes included confirming the presence of challenges in neurodevelopment in a substantial proportion of treated SMA type 1 children, identifying higher-risk subgroups, and emphasizing the need for early identification, timely referrals, and family support. Participants agreed on a core screening strategy and highlighted the importance of international collaboration to develop specific diagnostic and intervention guidelines. Future steps involve launching an online survey to assess the prevalence of neurodevelopmental disorders and study their characteristics and trajectories, developing care guidelines, and promoting research working groups to further understand brain development in SMA and improve patient care.
{"title":"285th ENMC international workshop: SMN-associated neurodevelopmental disorder: type 1 spinal muscular atrophy and the brain, 31st January - 2nd February 2025, Hoofddorp, The Netherlands","authors":"David Gómez-Andrés , Michelle A Farrar , Mireia Alvarez-Molinero , Rocío Garcia-Uzquiano , Chiara Brusa , Giovanni Baranello , Susana Quijano-Roy , 285th ENMC Workshop participants","doi":"10.1016/j.nmd.2025.106331","DOIUrl":"10.1016/j.nmd.2025.106331","url":null,"abstract":"<div><div>Recent advances in spinal muscular atrophy (SMA) early diagnosis and treatment have significantly improved survival and motor outcomes, particularly for those with severe phenotypes. However, clinicians have observed unexpected cognitive, social, communication, and behavioural differences in a proportion of children. The 285th ENMC workshop convened 28 experts from 13 countries to address these neurodevelopmental concerns. Key outcomes included confirming the presence of challenges in neurodevelopment in a substantial proportion of treated SMA type 1 children, identifying higher-risk subgroups, and emphasizing the need for early identification, timely referrals, and family support. Participants agreed on a core screening strategy and highlighted the importance of international collaboration to develop specific diagnostic and intervention guidelines. Future steps involve launching an online survey to assess the prevalence of neurodevelopmental disorders and study their characteristics and trajectories, developing care guidelines, and promoting research working groups to further understand brain development in SMA and improve patient care.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106331"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024494","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 : 2026-03-01Epub Date: 2026-01-20DOI: 10.1016/j.nmd.2026.106354
Stefan Verlohren , Christof Dame , Beate Mayer , Iris Dressler-Steinbach , Claus-Eric Ott , Inga Koneczny , Marlene Wolfsgruber , Sarah Hoffmann , Andreas Meisel
Maternal antibodies against the fetal acetylcholine receptor (fAChR) can cause fetal acetylcholine receptor antibody-related disorders (FARAD), a rare but important cause of arthrogryposis multiplex congenita (AMC) and Fetal Akinesia Deformation Sequence (FADS), with recurrence rates up to 100%. Unlike genetic causes, FARAD may respond to maternal immunotherapy, yet standardized treatment protocols are lacking. We report four pregnancies in an asymptomatic mother with confirmed fAChR antibodies. After three fetal losses due to FARAD and two unsuccessful treatment attempts initiated only after sonographic abnormalities, a healthy infant was delivered in the fourth pregnancy following a pre-planned preemptive approach. Treatment, initiated at week 10 of gestation, consisted of plasmapheresis (PLEX) and subsequent weekly high-dose intravenous immunoglobulin (IVIg). Fetal serum after birth confirmed fAChR antibodies on cell-based assays (live and fixed). This case series underscores the importance of recognizing fAChR antibodies as differential diagnosis of AMC in asymptomatic mothers and of early, consistent antibody-reducing therapy to prevent FARAD-related pregnancy losses.
{"title":"Preemptive immunotherapy for fetal acetylcholine receptor antibody disorder (FARAD): from recurrent pregnancy losses to a healthy infant - a case report","authors":"Stefan Verlohren , Christof Dame , Beate Mayer , Iris Dressler-Steinbach , Claus-Eric Ott , Inga Koneczny , Marlene Wolfsgruber , Sarah Hoffmann , Andreas Meisel","doi":"10.1016/j.nmd.2026.106354","DOIUrl":"10.1016/j.nmd.2026.106354","url":null,"abstract":"<div><div>Maternal antibodies against the fetal acetylcholine receptor (fAChR) can cause fetal acetylcholine receptor antibody-related disorders (FARAD), a rare but important cause of arthrogryposis multiplex congenita (AMC) and Fetal Akinesia Deformation Sequence (FADS), with recurrence rates up to 100%. Unlike genetic causes, FARAD may respond to maternal immunotherapy, yet standardized treatment protocols are lacking. We report four pregnancies in an asymptomatic mother with confirmed fAChR antibodies. After three fetal losses due to FARAD and two unsuccessful treatment attempts initiated only after sonographic abnormalities, a healthy infant was delivered in the fourth pregnancy following a pre-planned preemptive approach. Treatment, initiated at week 10 of gestation, consisted of plasmapheresis (PLEX) and subsequent weekly high-dose intravenous immunoglobulin (IVIg). Fetal serum after birth confirmed fAChR antibodies on cell-based assays (live and fixed). This case series underscores the importance of recognizing fAChR antibodies as differential diagnosis of AMC in asymptomatic mothers and of early, consistent antibody-reducing therapy to prevent FARAD-related pregnancy losses.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106354"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132521","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 : 2026-03-01Epub Date: 2026-01-30DOI: 10.1016/j.nmd.2026.106364
Rishi Sharma , Lisa A. Schimmenti , Benn Smith , Filippo Pinto e Vairo , Duygu Selcen , Radhika Dhamija
We report clinical and genetic features in four patients from 3 independent families with an ultra-rare autosomal recessive myopathy associated with biallelic pathogenic or likely pathogenic variants in MSTO1. Exome or genome sequencing was used to identify genetic variants in patients with suspected hereditary myopathy who had negative results on targeted genetic panels. Age at diagnosis ranged from 13 to 30 years. All patients exhibited myopathy of variable severity. Two had congenital hypotonia and global developmental delay, while the remaining two developed muscle weakness at ages 2 and 5. Magnetic resonance imaging evidence of cerebellar atrophy was noted in Patient 3. The most common non-neurologic abnormality noted in our cases was skeletal abnormalities. MSTO1-related disease presents primarily as an early-onset myopathy, occasionally accompanied by cerebellar atrophy and skeletal abnormalities. As genome-wide sequencing is increasingly becoming a first line test for unexplained myopathy, further characterization of the phenotypic spectrum is likely.
{"title":"MSTO1-related mitochondrial myopathy and ataxia syndrome: Case series and literature review","authors":"Rishi Sharma , Lisa A. Schimmenti , Benn Smith , Filippo Pinto e Vairo , Duygu Selcen , Radhika Dhamija","doi":"10.1016/j.nmd.2026.106364","DOIUrl":"10.1016/j.nmd.2026.106364","url":null,"abstract":"<div><div>We report clinical and genetic features in four patients from 3 independent families with an ultra-rare autosomal recessive myopathy associated with biallelic pathogenic or likely pathogenic variants in <em>MSTO1</em>. Exome or genome sequencing was used to identify genetic variants in patients with suspected hereditary myopathy who had negative results on targeted genetic panels. Age at diagnosis ranged from 13 to 30 years. All patients exhibited myopathy of variable severity. Two had congenital hypotonia and global developmental delay, while the remaining two developed muscle weakness at ages 2 and 5. Magnetic resonance imaging evidence of cerebellar atrophy was noted in Patient 3. The most common non-neurologic abnormality noted in our cases was skeletal abnormalities. <em>MSTO1</em>-related disease presents primarily as an early-onset myopathy, occasionally accompanied by cerebellar atrophy and skeletal abnormalities. As genome-wide sequencing is increasingly becoming a first line test for unexplained myopathy, further characterization of the phenotypic spectrum is likely.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106364"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137745","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":"2026-03-01","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 : 2026-03-01Epub Date: 2026-01-09DOI: 10.1016/j.nmd.2026.106334
Tahereh Neyaz , Kristin M Conway , Yining Yang , Russell J Butterfield , Swamy Venkatesh , Paul A Romitti , Katherine D Mathews , the Muscular Dystrophy Surveillance, Tracking and Research Network (MD STARnet)
Reports of clinical characteristics of FSHD in childhood have often focused on the most severely affected. To include children in clinical trials, it is important to understand the full pediatric spectrum. The Muscular Dystrophy Surveillance, Tracking, and Research Network provides a population-based, cross-sectional cohort of children diagnosed with FSHD. Children diagnosed before 19 years of age during 2008–2019 were included (n = 93). Clinical characteristics abstracted from the medical record included motor symptoms, genetic test results, and family history. Of those with known FSHD type (n = 73 of 93, 78.8 %), 72 (98.6 %) had FSHD1. Among those with FSHD1, the most frequent D4Z4 repeat category was 1–3 repeats (n = 33, 45.8 %) and few had 7–10 repeats (n = 7, 9.7 %). Among those with FSHD1 and known symptom onset age (n = 70), 22 (31.4 %) had early onset disease. Overall, most (88.2 %) were ambulatory at last visit. The number of children diagnosed increased steadily across childhood, suggesting a continuous spectrum of age at onset. The most common co-morbidity was hearing loss (n = 19 of 93, 20.4 %); most commonly among children with FSHD1 and 1–3 D4Z4 repeats (n = 13 of 33, 39.4 %). Our series provides data to support the design of pediatric FSHD trials, critical to ensure timely access to future effective treatments.
{"title":"Facioscapulohumeral muscular dystrophy diagnosed in childhood: a muscular dystrophy surveillance, tracking and research network cohort","authors":"Tahereh Neyaz , Kristin M Conway , Yining Yang , Russell J Butterfield , Swamy Venkatesh , Paul A Romitti , Katherine D Mathews , the Muscular Dystrophy Surveillance, Tracking and Research Network (MD STARnet)","doi":"10.1016/j.nmd.2026.106334","DOIUrl":"10.1016/j.nmd.2026.106334","url":null,"abstract":"<div><div>Reports of clinical characteristics of FSHD in childhood have often focused on the most severely affected. To include children in clinical trials, it is important to understand the full pediatric spectrum. The Muscular Dystrophy Surveillance, Tracking, and Research Network provides a population-based, cross-sectional cohort of children diagnosed with FSHD. Children diagnosed before 19 years of age during 2008–2019 were included (<em>n</em> = 93). Clinical characteristics abstracted from the medical record included motor symptoms, genetic test results, and family history. Of those with known FSHD type (<em>n</em> = 73 of 93, 78.8 %), 72 (98.6 %) had FSHD1. Among those with FSHD1, the most frequent D4Z4 repeat category was 1–3 repeats (<em>n</em> = 33, 45.8 %) and few had 7–10 repeats (<em>n</em> = 7, 9.7 %). Among those with FSHD1 and known symptom onset age (<em>n</em> = 70), 22 (31.4 %) had early onset disease. Overall, most (88.2 %) were ambulatory at last visit. The number of children diagnosed increased steadily across childhood, suggesting a continuous spectrum of age at onset. The most common co-morbidity was hearing loss (<em>n</em> = 19 of 93, 20.4 %); most commonly among children with FSHD1 and 1–3 D4Z4 repeats (<em>n</em> = 13 of 33, 39.4 %). Our series provides data to support the design of pediatric FSHD trials, critical to ensure timely access to future effective treatments.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106334"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145982040","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 : 2026-03-01Epub Date: 2026-02-03DOI: 10.1016/j.nmd.2026.106367
Agata A. Mossakowski , Daniel Pascale , Yves Allenbach , Olivier Benveniste , Jeffrey Magaziner , Andrew Mammen , Felix Kleefeld , Werner Stenzel
Immune-mediated necrotizing myopathy (IMNM) associated with antibodies against 3‑hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is typically a severe autoimmune myopathy requiring immunosuppressive therapy. Rare spontaneous remissions after discontinuation of statins have been reported, suggesting that the disease course may be more heterogeneous than previously assumed. We retrospectively identified four patients with anti-HMGCR–positive IMNM who experienced full recovery without immunosuppressive treatment. All had developed proximal muscle weakness and markedly elevated creatine kinase levels (8–80 times the upper limit of normal) during statin therapy, and they fulfilled the histopathological criteria of IMNM, except for the p62-pattern. After statin withdrawal, all patients recovered within 6–12 months without specific treatment. Two later relapsed after statin re-exposure and again improved after statin discontinuation. One patient relapsed after a flu-like illness. During long-term follow-up of up to ten years, three patients remained asymptomatic, two despite persistently elevated antibody titers, and one patient was started on intravenous immunoglobulins. These findings indicate that a subset of anti-HMGCR IMNM may follow a self-limited or relapsing–remitting course. While these cases broaden the clinical spectrum of anti-HMGCR IMNM, their implications for management remain uncertain and warrant further investigation.
{"title":"Spontaneous remission in statin-associated HMGCR-positive immune-mediated necrotizing myopathy after statin withdrawal","authors":"Agata A. Mossakowski , Daniel Pascale , Yves Allenbach , Olivier Benveniste , Jeffrey Magaziner , Andrew Mammen , Felix Kleefeld , Werner Stenzel","doi":"10.1016/j.nmd.2026.106367","DOIUrl":"10.1016/j.nmd.2026.106367","url":null,"abstract":"<div><div>Immune-mediated necrotizing myopathy (IMNM) associated with antibodies against 3‑hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is typically a severe autoimmune myopathy requiring immunosuppressive therapy. Rare spontaneous remissions after discontinuation of statins have been reported, suggesting that the disease course may be more heterogeneous than previously assumed. We retrospectively identified four patients with anti-HMGCR–positive IMNM who experienced full recovery without immunosuppressive treatment. All had developed proximal muscle weakness and markedly elevated creatine kinase levels (8–80 times the upper limit of normal) during statin therapy, and they fulfilled the histopathological criteria of IMNM, except for the p62-pattern. After statin withdrawal, all patients recovered within 6–12 months without specific treatment. Two later relapsed after statin re-exposure and again improved after statin discontinuation. One patient relapsed after a flu-like illness. During long-term follow-up of up to ten years, three patients remained asymptomatic, two despite persistently elevated antibody titers, and one patient was started on intravenous immunoglobulins. These findings indicate that a subset of anti-HMGCR IMNM may follow a self-limited or relapsing–remitting course. While these cases broaden the clinical spectrum of anti-HMGCR IMNM, their implications for management remain uncertain and warrant further investigation.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106367"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132526","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 : 2026-03-01Epub Date: 2026-01-30DOI: 10.1016/j.nmd.2026.106365
Kevin Renz Ambrocio , Rohit Aggarwal , James L. Coyle , Anna Miles , Lea Sayce , David Lacomis , Xingyu Zhang , Kendrea L. (Focht) Garand
Dysphagia often threatens the health of individuals with inclusion body myositis (IBM), significantly contributing to premature mortality. Quality evidence defining IBM-associated dysphagia remains scant and restricted to reports of limited utility. To address this gap, our group recently published a preliminary dysphagia profile for IBM using semi-quantitative impression-based kinematic analysis. In the current study, we offer updated evidence that combines our prior approach with quantitative pharyngeal kinematic analysis to better delineate swallowing features associated with dysphagia in IBM. This prospective, cross-sectional study leveraged the Modified Barium Swallow Impairment Profile (MBSImP) and the Analysis of Swallowing Physiology: Events, Kinematics & Timing (ASPEKT) method to perform videofluoroscopic kinematic analysis. We analyzed data from 15 individuals with IBM-associated dysphagia (9 males; mean age = 72.7 years [SD = 5.9]), compared their performance against normative data, and identified measures of clinical concern. A constellation of kinematic disruptions emerged across the swallowing continuum, but pharyngeal impairments were most pervasive and diffuse. Both MBSImP and ASPEKT findings suggest that bolus clearance mechanics were the primary or early culprit. Nonetheless, we identified subclinical airway response deficiencies that warrant clinical monitoring. This evidence provides new quantitative insights into better understanding IBM-associated dysphagia that can meaningfully guide targeted treatment.
{"title":"Kinematic features of dysphagia in inclusion body myositis","authors":"Kevin Renz Ambrocio , Rohit Aggarwal , James L. Coyle , Anna Miles , Lea Sayce , David Lacomis , Xingyu Zhang , Kendrea L. (Focht) Garand","doi":"10.1016/j.nmd.2026.106365","DOIUrl":"10.1016/j.nmd.2026.106365","url":null,"abstract":"<div><div>Dysphagia often threatens the health of individuals with inclusion body myositis (IBM), significantly contributing to premature mortality. Quality evidence defining IBM-associated dysphagia remains scant and restricted to reports of limited utility. To address this gap, our group recently published a preliminary dysphagia profile for IBM using semi-quantitative impression-based kinematic analysis. In the current study, we offer updated evidence that combines our prior approach with quantitative pharyngeal kinematic analysis to better delineate swallowing features associated with dysphagia in IBM. This prospective, cross-sectional study leveraged the Modified Barium Swallow Impairment Profile (MBSImP) and the Analysis of Swallowing Physiology: Events, Kinematics & Timing (ASPEKT) method to perform videofluoroscopic kinematic analysis. We analyzed data from 15 individuals with IBM-associated dysphagia (9 males; mean age = 72.7 years [SD = 5.9]), compared their performance against normative data, and identified measures of clinical concern. A constellation of kinematic disruptions emerged across the swallowing continuum, but pharyngeal impairments were most pervasive and diffuse. Both MBSImP and ASPEKT findings suggest that bolus clearance mechanics were the primary or early culprit. Nonetheless, we identified subclinical airway response deficiencies that warrant clinical monitoring. This evidence provides new quantitative insights into better understanding IBM-associated dysphagia that can meaningfully guide targeted treatment.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106365"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132513","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 : 2026-03-01Epub Date: 2026-01-09DOI: 10.1016/j.nmd.2026.106335
Elizabeth Ulm Seiwert , Xinrui Shi , Alyxis Coyan , Sarah Crawford , Ammar Husami , Cuixia Tian , Alex Zygmunt , Hani Kushlaf , Jie Liu , Chinmayee B Nagaraj
Pathogenic copy number and sequence variants in the dystrophin (DMD) gene cause X-linked dystrophinopathies. Predicting the clinical consequences of intragenic DMD duplications is challenging because their functional impact depends on the physical location of the duplicated material, which cannot be determined through conventional testing. Optical genome mapping is a method of structural variant analysis that can identify both the quantity and location of rearranged segments. We report three male patients with intragenic DMD duplications whose significance was revised using clinical optical genome mapping. Two were inserted outside of the DMD gene and reclassified as likely benign. The third was situated in tandem with the original sequence and reclassified as pathogenic. These cases emphasize the importance of evaluating the genomic location of DMD duplications, particularly when the patient’s phenotype does not align with their genotype classification, and highlight the implications for clinical management and genetic counseling.
{"title":"Reclassification of intragenic DMD gene duplications by optical genome mapping resolves uncertainty and improves clinical management","authors":"Elizabeth Ulm Seiwert , Xinrui Shi , Alyxis Coyan , Sarah Crawford , Ammar Husami , Cuixia Tian , Alex Zygmunt , Hani Kushlaf , Jie Liu , Chinmayee B Nagaraj","doi":"10.1016/j.nmd.2026.106335","DOIUrl":"10.1016/j.nmd.2026.106335","url":null,"abstract":"<div><div>Pathogenic copy number and sequence variants in the dystrophin (<em>DMD</em>) gene cause X-linked dystrophinopathies. Predicting the clinical consequences of intragenic <em>DMD</em> duplications is challenging because their functional impact depends on the physical location of the duplicated material, which cannot be determined through conventional testing. Optical genome mapping is a method of structural variant analysis that can identify both the quantity and location of rearranged segments. We report three male patients with intragenic <em>DMD</em> duplications whose significance was revised using clinical optical genome mapping. Two were inserted outside of the <em>DMD</em> gene and reclassified as likely benign. The third was situated in tandem with the original sequence and reclassified as pathogenic. These cases emphasize the importance of evaluating the genomic location of <em>DMD</em> duplications, particularly when the patient’s phenotype does not align with their genotype classification, and highlight the implications for clinical management and genetic counseling.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106335"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145982079","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 : 2026-03-01Epub Date: 2026-01-09DOI: 10.1016/j.nmd.2026.106333
Dhruv Nandakumar , Salman Bhai
Rhabdomyolysis is a poorly understood condition characterized by the rapid breakdown of skeletal muscle tissue. Recurrent episodes are very debilitating, and these patients often undergo extensive workup with no etiology identified. Maximal cycle exercise testing (CPX) provides numerical markers which when elevated can provide evidence of a peripheral limitation to exercise. Twenty-three patients with recurrent rhabdomyolysis episodes performed ramp cycle testing where they pedaled between 60-70 rpm at 2 sub-maximal and one maximal exercise state. Data collected included heart rate, blood pressure, oxygen saturation, oxygen consumption, and cardiac output. These patients’ files were also queried for EMG, DNA, or biopsy testing. Only 2 of 10 EMG studies showed myopathic studies, 1 of which was associated with an underlying myopathy. 20 muscle biopsies showed normal non-specific changes with only 1 indicating a possible underlying myopathy. Nuclear DNA testing only identified a definitive cause in 1 of 20 cases with an additional 12 showing variants of unknown significance in rhabdomyolysis associated genes. 4 patients had an elevated ratio of cardiac output to maximal oxygen consumption, all of which had positive mitochondrial DNA testing. CPX shows potential as a non-invasive method of identifying people at risk of recurrent rhabdomyolysis episodes before further testing. Further studies exploring the role of polygenic mutations in rhabdomyolysis would be beneficial.
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