E. Fleerakkers , J. Broos , R. Hoek , Y. Krom , M. Michaels , H. Kan , H. van Duyvenvoorde , M. van der Holst , E. Niks
{"title":"180p不同基因型杜氏肌营养不良患者下肢和上肢运动功能下降的研究","authors":"E. Fleerakkers , J. Broos , R. Hoek , Y. Krom , M. Michaels , H. Kan , H. van Duyvenvoorde , M. van der Holst , E. Niks","doi":"10.1016/j.nmd.2025.105533","DOIUrl":null,"url":null,"abstract":"<div><div>In patients with Duchenne muscular dystrophy (DMD) loss of lower limb function precedes prior to arm function. Additionally, the risk of losing ambulation (LoA) as a clinical milestone is associated with specific genotypes. However, it is less clear if the timing of losing lower and upper limb milestones is related and if the same genotypes are related to loss of hand-to-mouth movement (LoHM) as major upper limb milestone. Outpatient clinical data from DMD patients at Leiden Univ Med Center was obtained from the Dutch Dystrophinopathy Database. Patients were categorized by location of the pathogenic variant (proximal ≤exon 44 vs. distal ≥exon 45) and by exon skipping eligibility (amenable to skipping of exon 44, 45, 51, or 53). The association between age at LoA and LoHM (defined as PUL 2.0 entry score <3) was tested using Spearman correlation. Kaplan-Meier curves were used to visualize the time to LoA and LoHM. Timing of LoA and LoHM were compared across different subgroups using log-rank tests. A total of 120 patients were included (mean baseline age: 9.9 y, SD 7.35; mean follow-up: 6.64 y, SD 4.37; average 7.4 visits/patient). Eighty patients reached LoA (mean age at LoA 10.7 y (SD 2.05)) and 41 LoHM (mean age at LoHM 18.1 y (SD 5.88)). LoA and LoHM were moderately correlated (r=0.421, p=0.003). The mean time to LoA was 2.9 years earlier in exon 51 skippable patients than in exon 44, without reaching statistical significance (p=0.186). However, a significant difference was observed in time to LoHM, the mean time to LoHM was 6.6 years earlier in exon 51 skippable patients than in exon 44 (p=0.017). In the other subgroups no significant differences were observed. Our data show that earlier LoA is associated with earlier LoHM and that the group amenable to exon 51 skipping experiences earlier LoHM than those eligible for exon 44 skipping. These results may serve as a predictive marker for upper limb function and support clinical monitoring and decision-making.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105533"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"180PExploring motor function decline in lower and upper extremity function across different genotypes in Duchenne muscular dystrophy\",\"authors\":\"E. Fleerakkers , J. Broos , R. Hoek , Y. Krom , M. Michaels , H. Kan , H. van Duyvenvoorde , M. van der Holst , E. Niks\",\"doi\":\"10.1016/j.nmd.2025.105533\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>In patients with Duchenne muscular dystrophy (DMD) loss of lower limb function precedes prior to arm function. Additionally, the risk of losing ambulation (LoA) as a clinical milestone is associated with specific genotypes. However, it is less clear if the timing of losing lower and upper limb milestones is related and if the same genotypes are related to loss of hand-to-mouth movement (LoHM) as major upper limb milestone. Outpatient clinical data from DMD patients at Leiden Univ Med Center was obtained from the Dutch Dystrophinopathy Database. Patients were categorized by location of the pathogenic variant (proximal ≤exon 44 vs. distal ≥exon 45) and by exon skipping eligibility (amenable to skipping of exon 44, 45, 51, or 53). The association between age at LoA and LoHM (defined as PUL 2.0 entry score <3) was tested using Spearman correlation. Kaplan-Meier curves were used to visualize the time to LoA and LoHM. Timing of LoA and LoHM were compared across different subgroups using log-rank tests. A total of 120 patients were included (mean baseline age: 9.9 y, SD 7.35; mean follow-up: 6.64 y, SD 4.37; average 7.4 visits/patient). Eighty patients reached LoA (mean age at LoA 10.7 y (SD 2.05)) and 41 LoHM (mean age at LoHM 18.1 y (SD 5.88)). LoA and LoHM were moderately correlated (r=0.421, p=0.003). The mean time to LoA was 2.9 years earlier in exon 51 skippable patients than in exon 44, without reaching statistical significance (p=0.186). However, a significant difference was observed in time to LoHM, the mean time to LoHM was 6.6 years earlier in exon 51 skippable patients than in exon 44 (p=0.017). In the other subgroups no significant differences were observed. Our data show that earlier LoA is associated with earlier LoHM and that the group amenable to exon 51 skipping experiences earlier LoHM than those eligible for exon 44 skipping. These results may serve as a predictive marker for upper limb function and support clinical monitoring and decision-making.</div></div>\",\"PeriodicalId\":19135,\"journal\":{\"name\":\"Neuromuscular Disorders\",\"volume\":\"53 \",\"pages\":\"Article 105533\"},\"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/S0960896625002603\",\"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":"Neuromuscular Disorders","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960896625002603","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
180PExploring motor function decline in lower and upper extremity function across different genotypes in Duchenne muscular dystrophy
In patients with Duchenne muscular dystrophy (DMD) loss of lower limb function precedes prior to arm function. Additionally, the risk of losing ambulation (LoA) as a clinical milestone is associated with specific genotypes. However, it is less clear if the timing of losing lower and upper limb milestones is related and if the same genotypes are related to loss of hand-to-mouth movement (LoHM) as major upper limb milestone. Outpatient clinical data from DMD patients at Leiden Univ Med Center was obtained from the Dutch Dystrophinopathy Database. Patients were categorized by location of the pathogenic variant (proximal ≤exon 44 vs. distal ≥exon 45) and by exon skipping eligibility (amenable to skipping of exon 44, 45, 51, or 53). The association between age at LoA and LoHM (defined as PUL 2.0 entry score <3) was tested using Spearman correlation. Kaplan-Meier curves were used to visualize the time to LoA and LoHM. Timing of LoA and LoHM were compared across different subgroups using log-rank tests. A total of 120 patients were included (mean baseline age: 9.9 y, SD 7.35; mean follow-up: 6.64 y, SD 4.37; average 7.4 visits/patient). Eighty patients reached LoA (mean age at LoA 10.7 y (SD 2.05)) and 41 LoHM (mean age at LoHM 18.1 y (SD 5.88)). LoA and LoHM were moderately correlated (r=0.421, p=0.003). The mean time to LoA was 2.9 years earlier in exon 51 skippable patients than in exon 44, without reaching statistical significance (p=0.186). However, a significant difference was observed in time to LoHM, the mean time to LoHM was 6.6 years earlier in exon 51 skippable patients than in exon 44 (p=0.017). In the other subgroups no significant differences were observed. Our data show that earlier LoA is associated with earlier LoHM and that the group amenable to exon 51 skipping experiences earlier LoHM than those eligible for exon 44 skipping. These results may serve as a predictive marker for upper limb function and support clinical monitoring and decision-making.
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.