Paula R Clemens, Heather Gordish-Dressman, Gabriela Niizawa, Ksenija Gorni, Michela Guglieri, Anne M Connolly, Matthew Wicklund, Tulio Bertorini, Jean Mah, Mathula Thangarajh, Edward C Smith, Nancy L Kuntz, Craig M McDonald, Erik Henricson, S Upadhyayula, Barry Byrne, Georgios Manousakis, Amy Harper, Susan Iannaccone, Utkarsh J Dang
{"title":"纵向CINRG贝克尔自然历史研究的发现。","authors":"Paula R Clemens, Heather Gordish-Dressman, Gabriela Niizawa, Ksenija Gorni, Michela Guglieri, Anne M Connolly, Matthew Wicklund, Tulio Bertorini, Jean Mah, Mathula Thangarajh, Edward C Smith, Nancy L Kuntz, Craig M McDonald, Erik Henricson, S Upadhyayula, Barry Byrne, Georgios Manousakis, Amy Harper, Susan Iannaccone, Utkarsh J Dang","doi":"10.3233/JND-230178","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype.</p><p><strong>Objective: </strong>A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials.</p><p><strong>Methods: </strong>A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes.</p><p><strong>Results: </strong>Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter.</p><p><strong>Conclusions: </strong>There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"201-212"},"PeriodicalIF":3.2000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789327/pdf/","citationCount":"0","resultStr":"{\"title\":\"Findings from the Longitudinal CINRG Becker Natural History Study.\",\"authors\":\"Paula R Clemens, Heather Gordish-Dressman, Gabriela Niizawa, Ksenija Gorni, Michela Guglieri, Anne M Connolly, Matthew Wicklund, Tulio Bertorini, Jean Mah, Mathula Thangarajh, Edward C Smith, Nancy L Kuntz, Craig M McDonald, Erik Henricson, S Upadhyayula, Barry Byrne, Georgios Manousakis, Amy Harper, Susan Iannaccone, Utkarsh J Dang\",\"doi\":\"10.3233/JND-230178\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype.</p><p><strong>Objective: </strong>A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials.</p><p><strong>Methods: </strong>A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes.</p><p><strong>Results: </strong>Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter.</p><p><strong>Conclusions: </strong>There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset.</p>\",\"PeriodicalId\":16536,\"journal\":{\"name\":\"Journal of neuromuscular diseases\",\"volume\":\" \",\"pages\":\"201-212\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789327/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of neuromuscular diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3233/JND-230178\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neuromuscular diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3233/JND-230178","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Findings from the Longitudinal CINRG Becker Natural History Study.
Background: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype.
Objective: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials.
Methods: A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes.
Results: Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter.
Conclusions: There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset.
期刊介绍:
The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, letters-to-the-editor, and will consider research that has negative findings. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.