186PPerformance of upper limb in steroid-treated Duchenne muscular dystrophy: genotype-phenotype correlations

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders Pub Date : 2025-09-01 DOI:10.1016/j.nmd.2025.105539

C. Wade , A. Zygmunt , P. Horn , K. Bonarrigo , L. Reebals , I. Rybalsky , C. Tian

{"title":"186PPerformance of upper limb in steroid-treated Duchenne muscular dystrophy: genotype-phenotype correlations","authors":"C. Wade , A. Zygmunt , P. Horn , K. Bonarrigo , L. Reebals , I. Rybalsky , C. Tian","doi":"10.1016/j.nmd.2025.105539","DOIUrl":null,"url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by absence or near absence of functional dystrophin protein that results in progressive weakness. Performance of Upper Limb (PUL) is a scale designed to measure upper limb motor performance changes of individuals with DMD. The latest iteration of PUL is 2.0, which has been used since 2015. Prior studies have demonstrated that the PUL scores of individuals with DMD begin to deviate from typically developing children at age 8 years. Differences have been reported between certain exon-skip amenable genotypes on the decline in PUL scores. The goal of this study was to assess the longitudinal changes in upper extremity motor function using PUL 2.0 scores of individuals with DMD treated with long-term glucocorticoid steroids and standard care at a single tertiary care center. Individuals were excluded if they were exposed to other disease modifying therapies. We retrospectively studied 188 patients with DMD with 972 PUL entry encounters that occurred from 4/12/2016 to 12/7/2023. The genotype distribution of our cohort was comparable to previously reported study cohorts. Mean steroid duration was 12.3 years. A mean total PUL score of 29.1 at ages <15 years, 23.5 between ages 15-20 years, and 18.2 at ages >20 years were demonstrated. The average PUL score decline of the entire group was 1.3 points per year. Secondary analysis was performed to evaluate the impact of genotype on PUL scores. Differences in PUL between certain exon skip-amenable genotypes were detected in the group above age 20 years with the exon 44 skip-amenable having higher scores and exon 51 skip-amenable having lower scores. Linear models demonstrated similar rates of decline by exon skip group but with a higher entry score for the exon 44 skip-amenable group, and lower for the exon 51 skip-amenable group. These data provide a reference dataset for PUL scores of steroid treated DMD patients.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105539"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuromuscular Disorders","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960896625002664","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by absence or near absence of functional dystrophin protein that results in progressive weakness. Performance of Upper Limb (PUL) is a scale designed to measure upper limb motor performance changes of individuals with DMD. The latest iteration of PUL is 2.0, which has been used since 2015. Prior studies have demonstrated that the PUL scores of individuals with DMD begin to deviate from typically developing children at age 8 years. Differences have been reported between certain exon-skip amenable genotypes on the decline in PUL scores. The goal of this study was to assess the longitudinal changes in upper extremity motor function using PUL 2.0 scores of individuals with DMD treated with long-term glucocorticoid steroids and standard care at a single tertiary care center. Individuals were excluded if they were exposed to other disease modifying therapies. We retrospectively studied 188 patients with DMD with 972 PUL entry encounters that occurred from 4/12/2016 to 12/7/2023. The genotype distribution of our cohort was comparable to previously reported study cohorts. Mean steroid duration was 12.3 years. A mean total PUL score of 29.1 at ages <15 years, 23.5 between ages 15-20 years, and 18.2 at ages >20 years were demonstrated. The average PUL score decline of the entire group was 1.3 points per year. Secondary analysis was performed to evaluate the impact of genotype on PUL scores. Differences in PUL between certain exon skip-amenable genotypes were detected in the group above age 20 years with the exon 44 skip-amenable having higher scores and exon 51 skip-amenable having lower scores. Linear models demonstrated similar rates of decline by exon skip group but with a higher entry score for the exon 44 skip-amenable group, and lower for the exon 51 skip-amenable group. These data provide a reference dataset for PUL scores of steroid treated DMD patients.

查看原文本刊更多论文

186p类固醇治疗的杜氏肌营养不良患者上肢功能：基因型-表型相关性

杜氏肌营养不良症（DMD）是一种由功能性肌营养不良蛋白缺失或接近缺失引起的x连锁隐性疾病，导致进行性虚弱。上肢运动能力（PUL）是一种测量DMD患者上肢运动能力变化的量表。PUL的最新版本是2.0，从2015年开始使用。先前的研究表明，DMD患者的PUL分数在8岁时开始偏离正常发育的儿童。在PUL评分下降的过程中，某些外显子跳变基因型之间存在差异。本研究的目的是利用PUL 2.0评分评估在单一三级护理中心接受长期糖皮质激素治疗和标准治疗的DMD患者上肢运动功能的纵向变化。如果个体暴露于其他疾病修饰疗法则被排除在外。我们回顾性研究了2016年12月4日至2023年7月12日期间发生的188例DMD患者972例PUL入路。本研究队列的基因型分布与先前报道的研究队列相当。平均服药时间为12.3年。15岁时PUL平均总分29.1分，15 ~ 20岁时平均总分23.5分，20岁时平均总分18.2分。整个组的PUL评分平均每年下降1.3分。进行二次分析以评估基因型对PUL评分的影响。在20岁以上的人群中检测到某些外显子可跳过基因型之间的PUL差异，其中外显子44可跳过得分较高，外显子51可跳过得分较低。线性模型显示外显子跳过组的下降率相似，但外显子44跳过组的进入分数较高，外显子51跳过组的进入分数较低。这些数据为类固醇治疗的DMD患者的PUL评分提供了参考数据集。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Neuromuscular Disorders 医学-临床神经学

CiteScore

4.60

自引率

3.60%

发文量

543

审稿时长

53 days

期刊介绍： This international, multidisciplinary journal covers all aspects of neuromuscular disorders in childhood and adult life (including the muscular dystrophies, spinal muscular atrophies, hereditary neuropathies, congenital myopathies, myasthenias, myotonic syndromes, metabolic myopathies and inflammatory myopathies). The Editors welcome original articles from all areas of the field: • Clinical aspects, such as new clinical entities, case studies of interest, treatment, management and rehabilitation (including biomechanics, orthotic design and surgery). • Basic scientific studies of relevance to the clinical syndromes, including advances in the fields of molecular biology and genetics. • Studies of animal models relevant to the human diseases. The journal is aimed at a wide range of clinicians, pathologists, associated paramedical professionals and clinical and basic scientists with an interest in the study of neuromuscular disorders.