Acta Myologica最新文献

{"title":"Causes of clinical variability in Duchenne and Becker muscular dystrophies and implications for exon skipping therapies.","authors":"Eric P Hoffman","doi":"10.36185/2532-1900-020","DOIUrl":"https://doi.org/10.36185/2532-1900-020","url":null,"abstract":"<p><p>Becker muscular dystrophy is caused by mutations in the DMD gene that permit significant residual dystrophin protein expression in patient muscle. This is in contrast to DMD gene mutations in Duchenne muscular dystrophy where little or no dystrophin is produced (typically < 3% normal levels). Clinically, Becker muscular dystrophy is extremely variable, from slightly milder than DMD, to asymptomatic hyperCKemia at old age. The factors driving clinical variability in Becker muscular dystrophy have now been studied in some depth, and the findings are likely highly relevant to anticipated clinical findings in exon skipping therapy in DMD. The specific mutations in Becker dystrophy play an important role, and clinical variability is less with high frequency mutations (deletions exons 45-47, 45-48). The percentage of dystrophin content in patient muscle is not well-correlated with clinical findings. Muscle MRI findings (degree of fibrofatty replacement) are very well-correlated with the degree of patient disability, regardless of mutation or muscle dystrophin content. Taken together, data to date suggest that the main determinant driving clinical disability in Becker dystrophy patients is the degree of fibrofatty replacement in muscle. Thus, as with DMD, DMD gene mutations and resulting dystrophin protein abnormalities initiate the disease process, but downstream tissue pathophysiology plays a dominant role in disease progression. Factors influencing the age-dependent rate of fibrofatty replacement of muscles are responsible for much of the clinical variability seen in Becker dystrophy, as well as Duchenne dystrophy. These fibrosis-related factors include genetic modifiers, degree of muscle inflammation, and induction of microRNAs in muscle that bind to dystrophin mRNA and down-regulate dystrophin protein content in patient muscle. Studies to date regarding clinical variability in Becker dystrophy suggest that exon skipping therapy in DMD may show variable efficacy from patient to patient.</p>","PeriodicalId":35953,"journal":{"name":"Acta Myologica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/52/am-2020-04-179.PMC7783439.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38833312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late-onset myopathies: clinical features and diagnosis.","authors":"Marianne de Visser","doi":"10.36185/2532-1900-027","DOIUrl":"10.36185/2532-1900-027","url":null,"abstract":"<p><p>Late-onset myopathies are not well-defined since there is no clear definition of 'late onset'. For practical reasons we decided to use the age of 40 years as a cut-off. There are diseases which only manifest as late onset myopathy (inclusion body myositis, oculopharyngeal muscular dystrophy and axial myopathy). In addition, there are diseases with a wide range of onset including 'late onset' muscle weakness. Well-known and rather frequently occurring examples are Becker muscular dystrophy, limb girdle muscular dystrophy, facioscapulohumeral dystrophy, Pompe disease, myotonic dystrophy type 2, and anoctamin-5-related distal myopathy. The above-mentioned diseases will be discussed in detail including clinical presentation - which can sometimes lead someone astray - and diagnostic tools based on real cases taken from the author's practice. Where appropriate a differential diagnosis is provided. Next generation sequencing (NGS) may speed up the diagnostic process in hereditary myopathies, but still there are diseases, e.g. with expansion repeats, deletions, etc, in which NGS is as yet not very helpful.</p>","PeriodicalId":35953,"journal":{"name":"Acta Myologica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/5f/am-2020-04-235.PMC7783434.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38830849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spinal cord injuries, human neuropathology and neurophysiology.","authors":"Milan R Dimitrijevic, Byron A Kakulas","doi":"10.36185/2532-1900-039","DOIUrl":"10.36185/2532-1900-039","url":null,"abstract":"<p><p>A correlative approach to human spinal cord injuries (SCI) through the combination of neuropathology and neurophysiology provides a much better understanding of the condition than with either alone. Among the benefits so derived is the wide range of interventions applicable to the restorative neurology (RN) of SCI so that the neurological status of the SCI patient is thereby much improved. The neurophysiological and neuropathological elements underlying these advances are described.</p>","PeriodicalId":35953,"journal":{"name":"Acta Myologica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9c/0f/am-2020-04-353.PMC7783432.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38829369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-sarcoglycanopathy presenting as myalgia and hyperCKemia in two adults with a long-term follow-up. Case reports.","authors":"Claudia Dosi,&nbsp;Anna Rubegni,&nbsp;Denise Cassandrini,&nbsp;Alessandro Malandrini,&nbsp;Lorenzo Maggi,&nbsp;M Alice Donati,&nbsp;Filippo M Santorelli","doi":"10.36185/2532-1900-025","DOIUrl":"https://doi.org/10.36185/2532-1900-025","url":null,"abstract":"<p><p>Two patients with a paucisymptomatic hyperckemia underwent a skeletal muscle biopsy and massive gene panel to investigate mutations associated with inherited muscle disorders. In the SGCA gene, sequence analyses revealed a homozygous c.850C > T/p.Arg284Cys in patient 1 and two heterozygous variants (c.739G > A/p.Val247Met and c.850C > T/p.Arg284Cys) in patient 2. Combination of histology and immunofluorence studies showed minimal changes for muscular proteins including the α-sarcoglycan. These two cases highlight the advantages of next-generation sequencing in the differential diagnosis of mild myopathic conditions before considering the more invasive muscle biopsy in sarcoglycanopathies.</p>","PeriodicalId":35953,"journal":{"name":"Acta Myologica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/64/8b/am-2020-04-218.PMC7783442.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38833317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myotonic dystrophy type 2: the 2020 update.","authors":"Giovanni Meola","doi":"10.36185/2532-1900-026","DOIUrl":"https://doi.org/10.36185/2532-1900-026","url":null,"abstract":"<p><p>The myotonic dystrophies are the commonest cause of adult-onset muscular dystrophy. Phenotypes of DM1 and DM2 are similar, but there are some important differences, including the presence or absence of congenital form, muscles primarily affected (distal vs proximal), involved muscle fiber types (type 1 vs type 2 fibers), and some associated multisystemic phenotypes. There is currently no cure for the myotonic dystrophies but effective management significantly reduces the morbidity and mortality of patients. For the enormous understanding of the molecular pathogenesis of myotonic dystrophy type 1 and myotonic dystrophy type 2, these diseases are now called \"spliceopathies\" and are mediated by a primary disorder of RNA rather than proteins. Despite clinical and genetic similarities, myotonic dystrophy type 1 and type 2 are distinct disorders requiring different diagnostic and management strategies. Gene therapy for myotonic dystrophy type 1 and myotonic dystrophy type 2 appears to be very close and the near future is an exciting time for clinicians and patients.</p>","PeriodicalId":35953,"journal":{"name":"Acta Myologica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2f/0f/am-2020-04-222.PMC7783423.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38830848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Core myopathies - a short review.","authors":"Haluk Topaloglu","doi":"10.36185/2532-1900-029","DOIUrl":"https://doi.org/10.36185/2532-1900-029","url":null,"abstract":"<p><p>Congenital myopathies represent a clinically and genetically heterogeneous group of early-onset neuromuscular diseases with characteristic, but not always specific, histopathological features, often presenting with stable and/or slowly progressive truncal and proximal weakness. It is often not possible to have a diagnosis on clinical ground alone. Additional extraocular, respiratory, distal involvement, scoliosis, and distal laxity may provide clues. The \"core myopathies\" collectively represent the most common form of congenital myopathies, and the name pathologically corresponds to histochemical appearance of focally reduced oxidative enzyme activity and myofibrillar changes on ultrastructural studies. Because of the clinical, pathological, and molecular overlaps, central core disease and multiminicore disease will be discussed together.</p>","PeriodicalId":35953,"journal":{"name":"Acta Myologica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e9/93/am-2020-04-266.PMC7783431.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38830850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dominant or recessive mutations in the <i>RYR1</i> gene causing central core myopathy in Brazilian patients.","authors":"Leonardo Galleni Leão,&nbsp;Lucas Santos Souza,&nbsp;Letícia Nogueira,&nbsp;Rita de Cássia Mingroni Pavanello,&nbsp;Juliana Gurgel-Giannetti,&nbsp;Umbertina C Reed,&nbsp;Acary S B Oliveira,&nbsp;Thais Cuperman,&nbsp;Ana Cotta,&nbsp;Julia FPaim,&nbsp;Mayana Zatz,&nbsp;Mariz Vainzof","doi":"10.36185/2532-1900-030","DOIUrl":"https://doi.org/10.36185/2532-1900-030","url":null,"abstract":"<p><p>Central Core Disease (CCD) is an inherited neuromuscular disorder characterized by the presence of cores in muscle biopsy. CCD is caused by mutations in the RYR1 gene. This gene encodes the ryanodine receptor 1, which is an intracellular calcium release channel from the sarcoplasmic reticulum to the cytosol in response to depolarization of the plasma membrane. Mutations in this gene are also associated with susceptibility to Malignant Hyperthermia (MHS). In this study, we evaluated 20 families with clinical and histological characteristics of CCD to identify primary mutations in patients, for diagnosis and genetic counseling of the families. We identified variants in the RYR1 gene in 19/20 families. The molecular pathogenicity was confirmed in 16 of them. Most of these variants (22/23) are missense and unique in the families. Two variants were recurrent in two different families. We identified six families with biallelic mutations, five compound heterozygotes with no consanguinity, and one homozygous, with consanguineous parents, resulting in 30% of cases with possible autosomal recessive inheritance. We identified seven novel variants, four of them classified as pathogenic. In one family, we identified two mutations in exon 102, segregating in cis, suggesting an additive effect of two mutations in the same allele. This work highlights the importance of using Next-Generation Sequencing technology for the molecular diagnosis of genetic diseases when a very large gene is involved, associated to a broad distribution of the mutations along it. These data also influence the prevention through adequate genetic counseling for the families and cautions against malignant hyperthermia susceptibility.</p>","PeriodicalId":35953,"journal":{"name":"Acta Myologica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/cf/am-2020-04-274.PMC7783440.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38830851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beneficial effects of one-month sacubitril/valsartan treatment in a patient affected by end-stage dystrophinopathic cardiomyopathy.","authors":"Andrea Antonio Papa,&nbsp;Emanuele Gallinoro,&nbsp;Alberto Palladino,&nbsp;Paolo Golino","doi":"10.36185/2532-1900-018","DOIUrl":"https://doi.org/10.36185/2532-1900-018","url":null,"abstract":"<p><p>Dystrophinopathic cardiomyopathy (DCM) is an almost constant manifestation in Becker muscular dystrophy (BMD) patients significantly contributing to morbidity and mortality. The nearly complete replacement of the myocardium by fibrous and fatty connective tissue results in an irreversible cardiac failure, characterized by progressive reduction of the ejection fraction. According to PARADIGM-HF trial results, the European Society of Cardiology (ESC) guidelines recommend the use of sacubitril/valsartan in ambulatory patients with heart failure and reduced ejection fraction, who remain symptomatic despite an optimal medical therapy. To date, little is still known about the use of sacubitril/valsartan in DCM. We report the case of a patient with dystrophinopathic end stage dilated cardiomyopathy with reduced ejection fraction who successfully responded to sacubitril/valsartan treatment.</p>","PeriodicalId":35953,"journal":{"name":"Acta Myologica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/64/20/am-2020-03-136.PMC7711328.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38361267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of prognosis in type 1 myotonic dystrophy (DM1): longitudinal 18-years experience from a single center.","authors":"Marco Mazzoli, Alessandra Ariatti, Gian Carlo Garuti, Virginia Agnoletto, Maurilio Genovese, Manuela Gozzi, Shaniko Kaleci, Alessandro Marchioni, Marcella Malagoli, Giuliana Galassi","doi":"10.36185/2532-1900-015","DOIUrl":"10.36185/2532-1900-015","url":null,"abstract":"<p><p>The aim of the study was to identify possible predictors of neurological worsening and need of non-invasive ventilation (NIV) in individuals affected by myotonic dystrophy type 1 (DM1), the most common form of adult-onset muscular dystrophy.</p><p><strong>Methods: </strong>A retrospective observational cohort study was undertaken. Thirty-three patients with genetic diagnosis of DM1 were followed at our Neuromuscular unit in Modena. Abnormal trinucleotide repeat (CTG) expansion of dystrophy protein kinase gene (MDPK) on chromosome 19q 13.3 was the prerequisite for inclusion. The number of CTG repeats was determined. All the participants were older than 14 at the time of enrolment, therefore they could be included into the juvenile or adult form of the disease. Participants were neurologically evaluated every 6-8 months up to 18 years. Neurological impairment was assessed by Muscular Impairment Rating (MIRS), Medical Research Council (MRC), and modified Rankin (mRS) scales. The independent variables considered for prognosis were age at first evaluation, duration of the disease, CTG repeat number, gender, and presence of cardiac and vascular morbidities.Male patients were 51.5% and female patients 48.5%. Sixteen patients were younger than the mean age of 30.1 years, while the remaining 17 were up to 65. Twelve subjects (36.4%) underwent NIV before the end of follow-up. Muscle force and disability scores showed statistically significant deterioration (p < 0.001) during follow-up. The worsening was significantly higher among patients carrying higher number of CTG repeats and of younger age. The presence of cardio-vascular involvement has significant impact on neurological and respiratory progression.Neurological worsening is predicted by CTG expansion size, young age and presence of cardio-vascular morbidities.</p>","PeriodicalId":35953,"journal":{"name":"Acta Myologica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/d4/am-2020-03-109.PMC7711325.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38710811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Respiratory function and therapeutic expectations in DMD: families experience and perspective.","authors":"Claudia Brogna,&nbsp;Simona Lucibello,&nbsp;Giorgia Coratti,&nbsp;Gianluca Vita,&nbsp;Valeria A Sansone,&nbsp;Sonia Messina,&nbsp;Emilio Albamonte,&nbsp;Francesca Salmin,&nbsp;Gloria Ferrantini,&nbsp;Elisa Pede,&nbsp;Chiara Consulo,&nbsp;Lavinia Fanelli,&nbsp;Nicola Forcina,&nbsp;Giulia Norcia,&nbsp;Marika Pane,&nbsp;Eugenio Mercuri","doi":"10.36185/2532-1900-016","DOIUrl":"https://doi.org/10.36185/2532-1900-016","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to use a structured questionnaire in a large cohort of Duchenne Muscular Dystrophy (DMD) patients to assess caregivers and patients views on respiratory function and to establish if their responses were related to the patients' age or level of functional impairment.</p><p><strong>Methods: </strong>Questionnaires were administered to caregivers in 205 DMD patients of age between 3 and 36 years (115 ambulant, 90 non-ambulant), and to 64 DMD patients (3 ambulant, 61 non-ambulant) older than 18 years, subdivided into groups according to age, FVC, ambulatory and ventilatory status.</p><p><strong>Results: </strong>Some differences were found in relation to FVC % values (<i>p</i> = 0.014), ambulatory (<i>p</i> = 0.043) and ventilatory status (<i>p</i> = 0.014). Nearly half of the caregivers expected deterioration over the next years, with the perspective of deterioration more often reported by caregivers of non-ambulant (<i>p =</i> 0.018) and ventilated patients (<i>p =</i> 0.004). Caregivers appeared to be aware of the relevance of respiratory function on quality of life (84%) showing willingness to enter possible clinical trials if these were aiming to stabilize the progression of respiratory function with a very high number of positive responses across the spectrum of age, FVC, ambulatory and ventilatory status. The boys older than 18 years showed similar results.</p><p><strong>Conclusions: </strong>Our study showed that the concern for respiratory function increases with age and with the reduction of FVC or the need for ventilation, but the need for intervention was acknowledged across the whole spectrum of age and functional status.</p>","PeriodicalId":35953,"journal":{"name":"Acta Myologica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/4a/am-2020-03-121.PMC7711327.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38710812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}