Neuromuscular Disorders最新文献

{"title":"Obstetric and gynaecological features in females carrying variants in the skeletal muscle ryanodine receptor type 1 (RYR1) gene: a questionnaire study","authors":"Arti M Mistry ,&nbsp;Georgia Saldanha ,&nbsp;Luuk R van den Bersselaar ,&nbsp;Greg A Knock ,&nbsp;Michael F Goldberg ,&nbsp;Maria I Vanegas ,&nbsp;Miguel A Fernandez-Garcia ,&nbsp;Susan Treves ,&nbsp;Nicol C Voermans ,&nbsp;Rachel M Tribe ,&nbsp;Heinz Jungbluth","doi":"10.1016/j.nmd.2025.105335","DOIUrl":"10.1016/j.nmd.2025.105335","url":null,"abstract":"<div><div>Mutations in the ryanodine receptor type 1 (<em>RYR1)</em> gene are amongst the most common causes of early-onset, non-dystrophic neuromuscular disorders. <em>RYR1</em> mutations have also anecdotally been implicated in non-skeletal muscle symptoms such as an increased bleeding tendency particularly prominent in females, but the prevalence of these features is currently unknown. In this questionnaire-based study, we aimed to evaluate smooth muscle function, bleeding, obstetric, and gynaecological outcomes in <em>RYR1</em>-variant carrying females. Questions were developed using a modified version of the MCMDM-1VWD questionnaire, and the NHS-heavy periods self-assessment tool. Obstetric and gynaecological symptoms explored included pregnancy-related complications, gestation length, parturition duration, post-partum haemorrhage and offspring birthweight. Recruitment was online via the <em>RYR1</em>-Foundation patient support group and covered countries across the world. We identified 66 <em>RYR1</em>-variant carrying females and 88 non-mutated controls including unaffected relatives and the general healthy population. Women with <em>RYR1</em> variants exhibited a higher incidence of pathological bleeding scores (<em>p</em> &lt; 0.0001), severe menstrual bleeding, complications during pregnancy (preeclampsia and placenta praevia), frequent planned Caesarean sections, offspring with lower birthweight, and gastrointestinal symptoms, compared to controls. Considering their population frequency in otherwise pauci-symptomatic individuals, <em>RYR1</em> variants ought to be considered as a cause of unexplained menorrhagia and other gynaecological and obstetric manifestations.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"49 ","pages":"Article 105335"},"PeriodicalIF":2.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520469","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":"Exploring sleep quality, depressive symptoms, and quality of life in adults with spinal muscular atrophy","authors":"Valentina Baldini ,&nbsp;Giorgia Varallo ,&nbsp;Stefania Redolfi ,&nbsp;Rocco Liguori ,&nbsp;Giuseppe Plazzi","doi":"10.1016/j.nmd.2025.105317","DOIUrl":"10.1016/j.nmd.2025.105317","url":null,"abstract":"<div><div>Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disorder caused by the mutation of the survival motor neuron 1 (SMN1) gene. Sleep disturbances and their impact on mental health and quality of life in patients with SMA are being understudied, and most of the evidence comes from pediatric SMA patients. We conducted a cross-sectional survey of adult patients with SMA. The participants underwent questionnaires exploring sleep quality with the Pittsburgh Sleep Quality Index (PSQI), depressive symptoms with the Patient Health Questionnaire-9 (PHQ-9), and quality of life with the Short-Form Health Survey 36 (SF-36). Fifty patients with SMA were enrolled in the study: 66 % were females with a median age of 41 years. Of them, 60 % had poor sleep quality, and 72 % had depressive symptoms. SMA 2 patients showed higher PSQI and PHQ-9 scores than SMA 3 patients (8 ± 3 vs 6 ± 1, <em>p</em> &lt; 0.001 and 13±5 vs 7 ± 5, <em>p</em> &lt; 0.001). PSQI total score correlated with the PHQ-9 (<em>r</em> = 0.32, <em>p</em> = 0.02), which was higher in patients with respiratory symptoms. Poor sleep is associated with depressive symptoms and respiratory dysfunction in adult SMA patients. Clinicians should consider sleep quality in SMA patients for optimal care; future studies are needed to understand this aspect better.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"50 ","pages":"Article 105317"},"PeriodicalIF":2.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768840","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":"Mortality of symptomatic children with spinal muscular atrophy in the era of disease-modifying therapies","authors":"R Finnegan ,&nbsp;AM Rohwer ,&nbsp;M Scoto ,&nbsp;M Main ,&nbsp;G Baranello ,&nbsp;A Manzur ,&nbsp;F Muntoni ,&nbsp;P Munot ,&nbsp;the SMA REACH UK","doi":"10.1016/j.nmd.2025.105313","DOIUrl":"10.1016/j.nmd.2025.105313","url":null,"abstract":"<div><div>With the availability of novel disease-modifying therapies (DMT), survival in spinal muscular atrophy (SMA) has significantly increased, but mortality is not rare in severely affected cases. To improve care further, we aimed to characterise causes of mortality in children with SMA over the last five years since the introduction of DMT. This was a retrospective review of all patients with SMA registered on SMA REACH UK database, who died between 2019 and 2023. In the last 5 years, 533 patients were registered with SMA REACH (6 pre-symptomatic; 1-SMA0; 247-SMA1; 188-SMA2; 91-SMA3). Twenty-five paediatric patients with SMA died in this period: 1 SMA0(4 %;1 copy-<em>SMN2</em>), 20 SMA1(80%;17 patients-2 copies of <em>SMN2</em> and 1 with 3 copies of <em>SMN2</em>) and 4 SMA2(16%). In SMA 1 cohort, 7/20(35%) patients were treatment naïve (5 ineligible; 1 died prior to commencement; 1 declined). Twelve patients received nusinersen; median age at treatment initiation of 6 months (range:1 month-12.3 years old) and median treatment duration of 6 months (range:1 month-6.5 years). One patient switched from nusinersen to risdiplam at age 4 years (died 19 months later) and 1 received onasemnogene abeparvovec at 2 years old (died 10 months later). The median age of death was 10.5 months(range:8 weeks-13 years), and 80%(16/20) died from respiratory-related causes. In SMA 2 cohort, 2/4 patients were not eligible for DMT and one received risdiplam at age 13 years for duration of 2.7 years and died as result of traumatic brain injury. The median age of death was 18 years 4 months (range:16–21 years). Two deaths were respiratory-related and one of sudden cardiac arrest. In conclusion, over the last 5 years, 5% of SMA patients registered with SMA REACH died. The majority had symptomatic SMA1 with 2 <em>SMN2</em> copies at the severe end of the spectrum and were either treatment naïve or had initiation of DMT after significant disease progression. Respiratory-related deaths occurred in 72% of known causes of death. Standard of care for respiratory management and ceiling of care discussions should continue to be a key part of the overall management particularly in those with severe disease at onset. These outcomes will be considerably improved once newborn screening will be available also in the UK.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"49 ","pages":"Article 105313"},"PeriodicalIF":2.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520468","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":"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}