Neuromuscular Disorders最新文献_第4页

Expression of genetic peripheral neuropathies in South African children 遗传性周围神经病变在南非儿童中的表达

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2026-02-01 Epub Date: 2025-11-22 DOI: 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.

遗传周围神经病变在欧洲血统人群中的患病率为1:2500 - 1:10 000，但在非洲人群中报道不足。这项回顾性横断面研究描述了64名参加南非神经肌肉疾病中心的遗传性周围神经病变儿童。21例患儿（21/ 64,33 %）经分子诊断，43/64（67 %）经组织学和神经生理学诊断。在7名儿童中，下一代测序没有发现致病变异。确定的遗传原因为PMP22重复（n = 11），以及ATL1 （n = 1）、IGHMBP2 （n = 2）、MPZ （n = 1）、MFN2 （n = 1）、MTMR2 （n = 2）、SH3TC2 （n = 1）、SLC12A6 （n = 1）和SLC52A3 （n = 1）的变异。轴突神经病变最常见（47/64,73%），影响9/12的非洲、17/26混血和21/26欧洲血统的儿童。在11名携带PMP22重复基因的儿童中，只有2名是非洲土著黑人血统。由于获得基因检测的机会有限，撒哈拉以南非洲儿童获得基因封闭仍然是一项挑战。在这项研究中，未解决的轴突疾病占主导地位。pmp22相关的CMT1A在土著非洲黑人血统的儿童中很少见。需要更多的研究来阐明非洲神经病的遗传基础，为当地患者制定知情和相关的遗传和临床诊断方案。

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引用次数: 0

WMS Congress 2026 Hiroshima WMS大会2026广岛

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2026-02-01 Epub Date: 2026-01-31 DOI: 10.1016/S0960-8966(26)00010-6

引用次数: 0

Challenges in myasthenia gravis diagnosis: an analysis of the diagnostic process of myasthenia gravis in a specialized clinic 重症肌无力诊断的挑战：重症肌无力专科诊断过程分析

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2026-02-01 Epub Date: 2025-11-20 DOI: 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.

MG的诊断可能很复杂，随后的诊断延误可能导致潜在的危及生命的情况。我们设计了一项回顾性观察性研究，以回顾现实世界中疑似MG患者的诊断过程，确定陷阱和最常见的模拟实体。在561例疑似MG的患者中，167例（29% %）被排除。替代诊断达到53.9% %，显示这些实体之间的高度异质性。在诊断过程中，临床图像是基础，30% %的模拟组不需要进一步的研究。关于抗体，7.9 %的MG模拟组患者先前有抗achr检测阳性，后来证实为假阳性结果。高达19. %的模拟组患者显示单纤维肌电图异常。这项研究强调了对疑似MG患者的诊断挑战，特别是在血清阴性的病例中。在这些患者中，排除MG的平均时间为2年，在此过程中，高达23% %的患者接受了免疫抑制剂治疗。

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引用次数: 0

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2026-02-01 Epub Date: 2025-12-16 DOI: 10.1016/j.nmd.2025.106312

Jonas Gillenstrand , Malin Broberg , Anna-Karin Kroksmark , Jennifer Strand , Mar Tulinius , Anne-Berit Ekström

This study investigated age-related differences in hot (affective-motivational) and cold (cognitive) executive functions (EF) in boys with Duchenne Muscular Dystrophy (DMD) across childhood and adolescence. In a cross-sectional design, 70 boys with DMD aged 5, 8, 11, and 14 years completed performance-based EF assessments, accompanied by parent-reported EF ratings. Longitudinal data were also collected from a subsample of 13 boys over a three-year period, with repeated assessments at the age intervals of 5–8, 8–11, and 11–14 years. At age 5, no significant EF impairments were observed. By age 8, however, significant deficits in hot EF tasks emerged, followed by impairments in cold EF at age 11. Cold EF performance indicated developmental delay rather than decline, as reflected in logits-based data. Longitudinal analyses using the Reliable Change Index revealed heterogeneous developmental patterns. Findings suggest that boys with DMD exhibit disrupted EF development, with increasing impairment through middle childhood and a potential positive trend from 11 to 14 years. These results underscore the importance of monitoring EF across a wider age range in this population.

本研究探讨了男孩杜氏肌营养不良症（DMD）在儿童期和青春期热（情感动机）和冷（认知）执行功能（EF）的年龄相关差异。在横断面设计中，70名年龄分别为5岁、8岁、11岁和14岁的DMD男孩完成了基于表现的EF评估，并附有父母报告的EF评分。纵向数据也从13个男孩的子样本中收集了三年的时间，并在5-8岁、8-11岁和11-14岁之间进行了重复评估。在5岁时，没有观察到明显的EF损伤。然而，到8岁时，在热英语任务中出现显著缺陷，随后在11岁时在冷英语任务中出现损伤。正如基于物流的数据所反映的那样，冷EF表现表明发育延迟而不是下降。使用可靠变化指数的纵向分析揭示了异质性的发展模式。研究结果表明，患有DMD的男孩表现出EF发育中断，在儿童中期损伤增加，11至14岁有潜在的积极趋势。这些结果强调了在更大的年龄范围内监测EF的重要性。

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引用次数: 0

Expanded spectrum of MEGF10 related myopathies: late-onset myofibrillar myopathy-like phenotype with novel variants MEGF10相关肌病的扩展谱：迟发性肌纤维样肌病表型与新变体

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2026-02-01 Epub Date: 2025-12-12 DOI: 10.1016/j.nmd.2025.106307

Bochen Zhu , Kexin Jiao , Darrel Sou Li , Jialong Zhang , Ning Zhu , Xingyu Xia , Lingchun Liu , Mingshi Gao , Nachuan Cheng , Ningning Wang , Sushan Luo , Jianying Xi , Chongbo Zhao , Shengqing Li , Wenhua Zhu

Early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD) is a muscular dystrophy associated with pathogenic variants in MEGF10, with previous studies suggesting a potential genotype-phenotype correlation. In this report, we present three patients from two unrelated families finally diagnosed with a milder phenotype of EMARDD. All patients presented with adulthood-onset disease, featuring progressive limb weakness, dysphagia, and severe respiratory difficulties. Muscle pathology was characterized by rimmed vacuoles, and abnormal protein aggregates rather than minicores. Four novel heterozygous variants in MEGF10 were identified: c.1A>T, p.(Met1?); c.370T>C, p.(Cys124Arg); c.2087G>T, p.(Gly696Val); and c.2484T>G, p.(Cys828Trp). This report enriches the genetic and phenotypic landscape of EMARDD and further advances our understanding of MEGF10-related myopathies.

早发性肌病、反射性松弛、呼吸窘迫和吞咽困难（EMARDD）是一种与MEGF10致病变异相关的肌肉营养不良，先前的研究表明存在潜在的基因型-表型相关性。在本报告中，我们介绍了来自两个不相关家庭的三名患者，最终被诊断为EMARDD的轻度表型。所有患者均表现为成年发病，表现为进行性肢体无力、吞咽困难和严重呼吸困难。肌肉病理表现为边缘空泡和异常蛋白聚集，而非微小颗粒。鉴定出4个新的MEGF10杂合变异体：c.1A>T, p.(Met1?)；c.370T > C、p。(Cys124Arg);c.2087G > T, p。(Gly696Val);p.（Cys828Trp）。该报告丰富了EMARDD的遗传和表型景观，并进一步推进了我们对megf10相关肌病的理解。

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引用次数: 0

Phenotypic continuum in IGHMBP2-related disorders: a portfolio of cases from typical to Guillain-Barré syndrome-like presentation ighmbp2相关疾病的表型连续体：从典型到格林-巴勒综合征样表现的病例组合

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2026-02-01 Epub Date: 2025-12-16 DOI: 10.1016/j.nmd.2025.106309

Hatice Bektaş , Nagihan Şener , Neslihan Bilgin , Gizem Ürel Demir , İbrahim Öncel , Ülkühan Öztoprak , Çağrı Mesut Temuçin , Pelin Özlem Şimşek Kiper , Gülen Eda Utine , Göknur Haliloğlu

IGHMBP2-related disorders comprise a clinical spectrum from spinal muscular atrophy with respiratory distress type 1 (SMARD1) to Charcot-Marie-Tooth disease type 2S, with increasingly recognized atypical and overlapping phenotypes. We report four pediatric cases from three unrelated families with biallelic pathogenic variants in IGHMBP2. Case 1, a premature infant represents SMARD1. Case 2 had infantile-onset neuropathy without respiratory symptoms. Case 3 and 4, two siblings, presented with a Guillain-Barré syndrome-like phenotype, cauda equina enhancement on spinal neuroimaging, elevated cerebrospinal fluid protein, and electromyography revealing acute motor and sensory axonal neuropathy. Despite an initial response to intravenous immunoglobulin, previous symptoms in Case 3 led to consideration of an immune-mediated neuropathy superimposed on a genetic background. Genetic analysis identified a homozygous nonsense variant in Cases 1 and 2, and novel compound heterozygous missense variants in Case 3 and 4. Thus, the list of overlapping genetic and acquired neuropathies now also includes IGHMBP2-related CMT2S.

ighmbp2相关疾病包括从脊髓性肌萎缩伴呼吸窘迫1型（SMARD1）到沙科-玛丽-图斯病2S型的临床谱，具有越来越多的非典型和重叠表型。我们报告了来自三个不相关家庭的四例儿童病例，他们患有IGHMBP2双等位基因致病性变异。病例1，早产儿代表SMARD1。病例2为婴儿发病的神经病变，无呼吸道症状。病例3和4，两个兄弟姐妹，表现为格林-巴勒综合征样表型，脊髓神经成像马尾增强，脑脊液蛋白升高，肌电图显示急性运动和感觉轴索神经病变。尽管最初对静脉注射免疫球蛋白有反应，但病例3的既往症状导致考虑免疫介导的神经病变叠加在遗传背景上。遗传分析在病例1和2中发现了纯合无义变异，在病例3和4中发现了新的复合杂合错义变异。因此，重叠的遗传性和获得性神经病变列表现在也包括了与ighmbp2相关的CMT2S。

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引用次数: 0

Monoclonal Gammopathy – the common denominator of sporadic late-onset nemaline myopathy and paraproteinemic neuropathy 单克隆伽玛病-散发性迟发性线状肌病和副蛋白血症性神经病的共同特征

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2026-02-01 Epub Date: 2025-12-18 DOI: 10.1016/j.nmd.2025.106313

Eleonora Torchia , Frauke Stascheit , Felix Kleefeld , Stephan J. Schreiber , Hans H. Goebel , Werner Stenzel

Sporadic late-onset nemaline myopathy (SLONM) is an acquired adult-onset myopathy characterized by subacute proximal weakness and nemaline rods in muscle. Although SLONM frequently occurs with monoclonal gammopathy of undetermined significance (MGUS), the coexistence with other MGUS-related disorders has not been reported. We describe three patients with SLONM and paraproteinemic neuropathy, showing sensory involvement and variable motor deficits, from mild non-progressive disease to a severe form with bulbar complications. Muscle histology revealed a significant number of fibres with nemaline rods and also frequent mitochondrial abnormalities, while nerve pathology demonstrated granular endoneurial deposits consistent with immune–complex–mediated neuropathy. One untreated patient remained stable, whereas the other two progressive, immunosuppressive-refractory cases improved with anti–plasma cell therapy. These cases illustrate a previously unreported co-occurrence of SLONM and MGUS-associated neuropathy. Despite differing clinical courses, shared pathology suggests common mechanisms, with mitochondrial abnormalities as a possibly under-recognized feature. Muscle and nerve biopsy including electronmicroscopic analysis is crucial for accurate diagnosis, and clone-directed therapy may provide benefit.

散发性迟发性线状肌病（SLONM）是一种获得性成年性肌病，其特征是亚急性近端无力和肌肉中的线状棒。虽然SLONM常与未确定意义的单克隆γ病（MGUS）一起发生，但与其他MGUS相关疾病的共存尚未见报道。我们描述了3例SLONM伴蛋白旁蛋白性神经病变的患者，表现为感觉受累和可变运动缺陷，从轻度非进行性疾病到严重的伴球并发症。肌肉组织学显示大量带有线状棒的纤维和频繁的线粒体异常，而神经病理学显示颗粒状神经内膜沉积与免疫复合物介导的神经病变一致。一名未经治疗的患者保持稳定，而另外两名进展性免疫抑制难治性病例通过抗浆细胞治疗得到改善。这些病例说明了以前未报道的SLONM和mgus相关神经病变的共同发生。尽管临床过程不同，但共同的病理表明了共同的机制，线粒体异常可能是一个未被认识到的特征。包括电子显微镜分析在内的肌肉和神经活检对于准确诊断至关重要，克隆定向治疗可能会带来好处。

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引用次数: 0

The complexity of dystrophin transcription and processing: implications of transcript imbalance on dystrophin gene targeting strategies 肌营养不良蛋白转录和加工的复杂性：转录不平衡对肌营养不良蛋白基因靶向策略的影响

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2026-02-01 Epub Date: 2025-12-13 DOI: 10.1016/j.nmd.2025.106306

Rachele Rossi , Annemieke Aartsma-Rus , Francesco Muntoni , Aurelie Goyenvalle , Pietro Spitali

Duchenne muscular dystrophy (DMD) is a rare genetic disorder affecting male children, characterized by progressive muscle wasting and weakness. It is a fatal disease, typically leading to death between the ages of 20 and 40, and currently, there is no effective cure. DMD is caused by mutations, most commonly large deletions, in the DMD gene, one of the largest genes in the human genome. This gene also exhibits a distinctive feature known as transcript imbalance, which refers to the unbalance expression of the transcript along its length, with the 5′ end being more abundantly expressed than the 3′ end. Although transcript imbalance was first described in 1995, it remains a poorly understood phenomenon with many unanswered questions. This review highlights the need for a deeper investigation into transcript imbalance, which has not yet received sufficient attention from the scientific community or from sponsors involved in DMD translational research. Understanding and addressing this phenomenon is critical not only for refining antisense oligonucleotide (AON) therapies and enhancing their therapeutic efficacy, but also for developing innovative strategies that improve DMD transcript targeting and muscle delivery.

杜氏肌营养不良症（DMD）是一种罕见的遗传性疾病，影响男性儿童，其特点是进行性肌肉萎缩和无力。这是一种致命的疾病，通常会导致20至40岁的人死亡，目前还没有有效的治疗方法。DMD是由突变引起的，最常见的是DMD基因的大缺失，DMD是人类基因组中最大的基因之一。该基因还表现出一个显著的特征，即转录不平衡，即转录物沿其长度表达不平衡，5 ‘端比3 ’端表达更丰富。虽然转录不平衡在1995年首次被描述，但它仍然是一个知之甚少的现象，有许多未解之谜。这篇综述强调了对转录不平衡进行更深入调查的必要性，这一问题尚未得到科学界或参与DMD转化研究的资助者的足够重视。理解和解决这一现象不仅对于完善反义寡核苷酸（AON）疗法和提高其治疗效果至关重要，而且对于开发改进DMD转录物靶向和肌肉递送的创新策略也至关重要。

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引用次数: 0

Learnings from a registry-based cohort study for spinal muscular atrophy disease 从一项基于登记的脊髓性肌萎缩病队列研究中获得的经验

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2026-02-01 Epub Date: 2025-12-30 DOI: 10.1016/j.nmd.2025.106332

Carla J. Jonker , Kelly Plueschke , Kieran C. Breen , Mencía de Lemus Belmonte , Patrice Verpillat , Alexandra Pacurariu

Spinal muscular atrophy is a rare recessive progressive neurodegenerative disorder. To better understand the progression of spinal muscular atrophy the European Medicines Agency launched a study based on registry data. This manuscript describes some lessons learnt and considerations how to improve future registry-based studies that aim to inform regulatory decision-making. The study started with a feasibility assessment to select appropriate registries from the TREAT-NMD network. The feasibility assessment is key to understand upfront the quality, capability and capacity of registries to address a research question, as well as the potential limitations. Several tools are available on how to assess and ultimately improve data quality. Data from a registry becomes more valuable if it can be linked to other data sources to supplement data. For regulatory decision-making on orphan drugs, it is crucial to collect comprehensive data from non-treated patients. Missing information for important variables in non-treated patients complicates comparison with data from treated patients, as this may introduce bias into the results. Collaboration with registries has demonstrated opportunities for access to registry data and the steps needed to improve data quality. This requires more support in the form of funding, resources and training to understand the legal requirements.

摘要脊髓性肌萎缩症是一种罕见的隐性进行性神经退行性疾病。为了更好地了解脊髓性肌萎缩症的进展，欧洲药品管理局启动了一项基于登记数据的研究。本文描述了一些经验教训和考虑如何改进未来的基于注册的研究，旨在为监管决策提供信息。这项研究首先进行了可行性评估，以便从《条约》- nmd网络中选择适当的登记处。可行性评估是预先了解登记处解决研究问题的质量、能力和能力以及潜在限制的关键。关于如何评估并最终提高数据质量，有几个工具可用。如果可以将来自注册中心的数据链接到其他数据源以补充数据，那么它将变得更有价值。对于孤儿药的监管决策，收集未治疗患者的全面数据至关重要。未治疗患者中重要变量信息的缺失使与治疗患者数据的比较复杂化，因为这可能会导致结果偏倚。与注册中心的协作证明了访问注册中心数据的机会以及提高数据质量所需的步骤。这需要以资金、资源和培训的形式提供更多支持，以了解法律要求。

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引用次数: 0

HMGCR-related muscular dystrophy: a case of severe neonatal-onset form hmgcr相关性肌营养不良：新生儿发病的严重形式1例。

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2026-01-01 Epub Date: 2025-11-26 DOI: 10.1016/j.nmd.2025.106299

Jariya Upadia , Yuwen Li , Yoshinori Osaki , Seiya Mizuno , Satoru Takahashi , Hitoshi Shimano

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.

我们报告一例hmgcr相关的四肢肌营养不良症（LGMD）与新生儿发病和早期死亡。该患者为HMGCR p.a g641cys变异纯合子，5个月后出现深度张力低下，呼吸衰竭，肌酸激酶（CK）明显升高。该病例在先前报道的17例患者中因其极早发病和快速临床恶化而突出。功能研究证实了该变异的致病性：体外实验显示HMGCR酶活性严重受损，使用纯合子敲入小鼠的体内模型导致胚胎致死，强调了其对基本代谢过程的有害影响。患者的早逝凸显了对靶向治疗和早期诊断的迫切需要。该病例扩展了hmgcr相关LGMD的临床和分子谱，并支持基于基因型-表型相关性和发病年龄的表型分类，以提高诊断精度。

引用次数: 0