Neuromuscular Disorders最新文献

{"title":"VMA21-X-linked myopathy in Peru: characterization of three families","authors":"Peggy Martínez-Esteban ,&nbsp;Milagros Sotelo-Muñoz ,&nbsp;Gianmarco Severa ,&nbsp;Luis Cortez-Salazar ,&nbsp;Denise Cassandrini ,&nbsp;Jon Andoni Urtizberea ,&nbsp;Claudia Castiglioni ,&nbsp;Edoardo Malfatti","doi":"10.1016/j.nmd.2025.105311","DOIUrl":"10.1016/j.nmd.2025.105311","url":null,"abstract":"<div><div><em>VMA21-</em>X-Linked related myopathy is a rare neuromuscular disease characterized by a wide phenotypic spectrum ranging from neonatal forms with severe muscular weakness and respiratory failure, to mild childhood or adult-onset forms with slowly progressive muscular weakness and variably elevated serum creatine kinases. This condition is also called X-linked myopathy with excessive autophagy (XMEA) due to the presence of autophagic vacuoles with sarcolemmal proteins. Here we describe the clinical, muscle imaging, and genetic findings of six <em>VMA21-</em>X-Linked related myopathy patients belonging to three unrelated Peruvian families. Lower limb proximal muscle weakness and extraocular muscles involvement leading to upward ophtalmoparesis are the main clinical features in our cohort. Lower limb muscle MRI showed a typical pattern with major involvement of antero-medial compartment of thigh, and relative sparing of <em>rectus femoris, gracilis, adductor longus</em>. This is the first report of the <em>VMA21-</em>X-Linked related myopathy in Peru.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"48 ","pages":"Article 105311"},"PeriodicalIF":2.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurogenic arthrogryposis, hypotonia, dysmorphic features plus malformation of cortical development further expands the ARL6IP1 loss-of-function phenotype","authors":"Göknur Haliloğlu ,&nbsp;Sandra Donkervoort ,&nbsp;Ülkühan Öztoprak ,&nbsp;Ikeoluwa A. Osei-Owusu ,&nbsp;Lynn Pais ,&nbsp;Fatma Dereli Devrez ,&nbsp;Beril Talim ,&nbsp;Rahşan Göçmen ,&nbsp;Serdar Ceylaner ,&nbsp;Carsten G. Bönnemann","doi":"10.1016/j.nmd.2025.105312","DOIUrl":"10.1016/j.nmd.2025.105312","url":null,"abstract":"<div><div>Biallelic variants in <em>ARL6IP1</em> are associated with a rare, complicated form of progressive hereditary spastic paraplegia. Among the few cases reported thus far, two distinct phenotypic clusters with upper and lower motor neuron pathology and varying severities have emerged. Here, we describe a proband who presented with decreased fetal movements, intrauterine growth retardation, arthrogryposis multiplex congenita (AMC), dysmorphic features, weakness and hypotonia. Course was complicated by extubation failure and feeding problems at age 3 months. Muscle biopsy demonstrated neurogenic changes. Magnetic resonance imaging revealed thin corpus callosum and simplified gyri most notable at the insula with incomplete opercularization. The proband developed tongue fasciculations at 5 months, and passed away at 15 months of age. A homozygous deletion of exon 1–3 of <em>ARL6IP1</em> was identified through exome sequencing. <em>ARL6IP1</em>-related phenotypes now include in utero involvement, neurogenic AMC, dysmorphic features, microcephaly and malformations of cortical development, in the absence of spastic paraplegia.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"48 ","pages":"Article 105312"},"PeriodicalIF":2.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420943","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}

{"title":"Bone mineral density changes in patients on drug therapy for spinal muscular atrophy","authors":"Abdelrahman Osman ,&nbsp;Halley Wasserman ,&nbsp;Paul S. Horn ,&nbsp;Eileen Broomall","doi":"10.1016/j.nmd.2025.105300","DOIUrl":"10.1016/j.nmd.2025.105300","url":null,"abstract":"<div><div>Patients with Spinal Muscular Atrophy (SMA) are at higher risk of diminished bone health due to decreased ambulation and mobility. With the advent of new FDA-approved therapies, we aimed to analyze the effects of SMA therapy on bone mineral density (BMD) using dual energy X-ray absorptiometry (DXA) scan data of 27 patients diagnosed with SMA Type 1, 2, or 3. Patients were divided into those with DXA scans both before and after treatment (older cohort), and patients with first DXA post-treatment (cohort treated in infancy). In patients with DXA both before and after treatment, SMA drug therapy did not normalize (Z-score &gt; -2) bone density in anyone with pre-established low bone mineral density. Patients with first DXA post-treatment initiation had a higher rate of normal bone mineral density compared to older cohort. Fractures were also tracked; frequency of fractures after therapy decreased from 52 % of patients to 14 % (<em>p</em> = 0.0584).</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"48 ","pages":"Article 105300"},"PeriodicalIF":2.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429166","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}

{"title":"ENMC Themed Workshop announcement","authors":"","doi":"10.1016/j.nmd.2025.105305","DOIUrl":"10.1016/j.nmd.2025.105305","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105305"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Desmoid tumour: a rare cause of congenital unilateral calf enlargement mimicking calf hypertrophy","authors":"Maha Elseed ,&nbsp;James N Sampson ,&nbsp;Tuomo Polvikoski ,&nbsp;Matthew Henderson ,&nbsp;Yolande Parkhurst ,&nbsp;Marta Bertoli ,&nbsp;Marianela Schiava ,&nbsp;Robert Muni Lofra ,&nbsp;Dionne Moat ,&nbsp;Karen Wong ,&nbsp;Jassi Michell-Sodhi ,&nbsp;Michela Guglieri ,&nbsp;Volker Straub ,&nbsp;Elizabeth Harris ,&nbsp;Chiara Marini-Bettolo","doi":"10.1016/j.nmd.2024.105258","DOIUrl":"10.1016/j.nmd.2024.105258","url":null,"abstract":"<div><div>Desmoid tumours, also known as aggressive fibromatosis, are rare tumours derived from mesenchymal stem cells, accounting for only 0.03 % of all tumours. While 85–90 % of cases are sporadic, desmoid tumours can occasionally be associated with Gardner syndrome (or Familial Adenomatous Polyposis), which is linked to variants in the tumour suppressor gene, <em>APC</em> (adenomatous polyposis coli) gene on chromosome 5. We describe a paediatric patient with congenital unilateral calf enlargement who was diagnosed as fibromatosis confirmed by muscle biopsy. Genetic workup was unrevealing, and muscle biopsy confirmed the diagnosis of fibromatosis. <em>APC</em> gene mutations were negative in this patient. Fibromatosis is a rare diagnosis which may have implications for the whole family and may present with congenital calf enlargement.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105258"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877428","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}

{"title":"The influence of genotype on the natural history of types 1 - 3 spinal muscular atrophy","authors":"C. Simone Sutherland ,&nbsp;Sophie Schneider ,&nbsp;Valerie Aponte Ribero ,&nbsp;Alex Simpson ,&nbsp;Christos Kokaliaris ,&nbsp;Renata S. Scalco ,&nbsp;Carol Jean Guittari ,&nbsp;Ksenija Gorni ,&nbsp;Darryl C. De Vivo ,&nbsp;William B. Martens ,&nbsp;Teresa M. Karrer","doi":"10.1016/j.nmd.2024.105270","DOIUrl":"10.1016/j.nmd.2024.105270","url":null,"abstract":"<div><div>The severity of spinal muscular atrophy (SMA) is inversely correlated with the number of survival of motor neuron 2 (<em>SMN2</em>) copies an individual has. This observational, retrospective analysis of natural history data included untreated individuals with a genetic diagnosis of types 1–3 SMA and stratified disease-related characteristics by <em>SMN2</em> copy number. The outcomes investigated were time to: death, permanent ventilation, respiratory support, feeding support, scoliosis surgery, and achievement and loss of motor milestones. Of 134 individuals; 33 had two <em>SMN2</em> copies and 101 had 3 or more copies. Survival was linked to increasing <em>SMN2</em> copy number: mean age at death for individuals with two <em>SMN2</em> copies was 8 months (standard deviation [SD]: 4 months) and 10 years (SD: 5 months) for individuals with three copies, and no deaths were reported in individuals with ≥4 <em>SMN2</em> copies. Increasing <em>SMN2</em> copy number was linked to a longer time to permanent ventilation, respiratory support, feeding support, and scoliosis, as well as loss of motor milestones. SMA disease-related endpoints showed distinct patterns between groups with differing <em>SMN2</em> copy numbers. Prediction and assessment of disease progression may be stratified by <em>SMN2</em> copy number, which will be important for evaluating the impact of treatment.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105270"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel c.221+1dup pathogenic variant in AGK gene linked to Sengers syndrome","authors":"Mercedes Galloway ,&nbsp;Lizbeth Mellin ,&nbsp;Violeta Alvarez Retamales ,&nbsp;Charles W. Heilig","doi":"10.1016/j.nmd.2024.105271","DOIUrl":"10.1016/j.nmd.2024.105271","url":null,"abstract":"<div><div>Sengers Syndrome (SS) is a rare autosomal recessive mitochondrial disorder caused by mutations in the acylglycerol kinase <em>(AGK)</em> gene on chromosome 7, also known as cardiomyopathic mitochondrial DNA depletion syndrome (<em>MTDPS10</em>). This disorder disrupts mitochondrial DNA function and energy metabolism, presenting with symptoms such as congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Previous research has shown SS affects oxidative phosphorylation and mitochondrial respiration, implicating the TIM22 complex and carrier import. We report a 32-year-old Palestinian female with a novel homozygous pathogenic variant<em>, c.221+1dup</em>, in the <em>AGK gene</em>. Her clinical presentation included chronic lactic acidosis, congenital cataracts, exercise intolerance, mild hypertrophic cardiomyopathy, and persistent muscle fatigue. Genetic testing was essential for confirming the diagnosis of Sengers Syndrome, revealing this previously undocumented variant. Family history indicated a hereditary pattern with a brother exhibiting similar symptoms. Typically diagnosed in infancy, SS's diverse and rare clinical manifestations can sometimes delay diagnosis. This case emphasizes the importance of considering SS in differential diagnoses when patients present with ocular lesions, lactic acidosis, muscle weakness, and cardiomyopathy. The novel <em>AGK</em> gene variant, with its rarity, highlights the need for heightened clinical suspicion and genetic evaluation, while suggesting further investigation into its pathogenic role and potential founder effects to enhance understanding of the genetic diversity of Sengers Syndrome.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105271"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UPDATE IN NEUROMUSCULAR DISORDERS","authors":"","doi":"10.1016/j.nmd.2025.105316","DOIUrl":"10.1016/j.nmd.2025.105316","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105316"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of presymptomatic juvenile patients with late-onset Pompe disease (LOPD)","authors":"M. Porcino ,&nbsp;O. Musumeci ,&nbsp;C. Usbergo ,&nbsp;A. Pugliese ,&nbsp;I.G. Arena ,&nbsp;C. Rodolico ,&nbsp;B. Schoser ,&nbsp;A. Toscano","doi":"10.1016/j.nmd.2025.105277","DOIUrl":"10.1016/j.nmd.2025.105277","url":null,"abstract":"<div><div>Late-onset Pompe disease (LOPD) includes patients from 1 year of age to adulthood. The vast heterogeneity in clinical manifestations and disease progression is not fully explained; however, a short disease duration and a young age seem to be good predictors of a better response to treatment. For this purpose, we investigated and followed up a cohort of 13 juvenile patients with LOPD from the clinical and therapeutic point of view, mainly pointing out the transition from presymptomatic to symptomatic status.</div><div>We retrospectively collected clinical, morphological, biochemical and molecular data from 13 juvenile LOPD patients. Motor and respiratory functional data, obtained during annual follow-up visits, were analyzed. The data included serial evaluations of the Medical Research Council (MRC) scale, the 6-Minute Walking Test (6MWT), the Gait, Stairs, Gower, and Chair (GSGC) score, and seated and supine Forced Vital Capacity (FVC). Muscle Magnetic Resonance Imaging (MRI) was also included, although it was not performed in all cases.</div><div>Currently, patients mean age is 18 years. All patients but one were diagnosed because of an isolated hyperCKemia: the mean age at diagnosis was 6.8 years (range 1–18). The onset of symptoms occurred from 6 months to 12 years after the diagnosis. The mean clinical follow-up duration was 9 years (range 2–18). From the genetic point of view, the most shared mutation was c.32–13T&gt;<em>G</em>, found in twelve patients as compound heterozygosis. Seven patients underwent muscle biopsy, which showed vacuolar myopathy with glycogen accumulation in four of them with unspecific changes in the other three cases. Five patients developed proximal muscle weakness during the follow-up with a mild waddling gait and a positive Gowers manoeuver. Muscle MRI revealed mild hypotrophy of the thighs at the development of symptoms in four out of five cases. Four patients started alglucosidase alfa, and one avalglucosidase alfa. These five patients on Enzyme Replacement Therapy (ERT) showed motor and respiratory stability in the following years.</div><div>Timely identification of emerging clinical manifestations in presymptomatic LOPD patients, as a result of careful follow-up, is essential to start prompt treatment to modify the disease natural course.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105277"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WMS General Information","authors":"","doi":"10.1016/j.nmd.2025.105307","DOIUrl":"10.1016/j.nmd.2025.105307","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"47 ","pages":"Article 105307"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}