The influence of genotype on the natural history of types 1 - 3 spinal muscular atrophy

IF 2.7 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders Pub Date : 2025-02-01 DOI:10.1016/j.nmd.2024.105270

C. Simone Sutherland , Sophie Schneider , Valerie Aponte Ribero , Alex Simpson , Christos Kokaliaris , Renata S. Scalco , Carol Jean Guittari , Ksenija Gorni , Darryl C. De Vivo , William B. Martens , Teresa M. Karrer

{"title":"The influence of genotype on the natural history of types 1 - 3 spinal muscular atrophy","authors":"C. Simone Sutherland , Sophie Schneider , Valerie Aponte Ribero , Alex Simpson , Christos Kokaliaris , Renata S. Scalco , Carol Jean Guittari , Ksenija Gorni , Darryl C. De Vivo , William B. Martens , Teresa M. Karrer","doi":"10.1016/j.nmd.2024.105270","DOIUrl":null,"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":2.7000,"publicationDate":"2025-02-01","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/S0960896624017668","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

The severity of spinal muscular atrophy (SMA) is inversely correlated with the number of survival of motor neuron 2 (SMN2) 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 SMN2 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 SMN2 copies and 101 had 3 or more copies. Survival was linked to increasing SMN2 copy number: mean age at death for individuals with two SMN2 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 SMN2 copies. Increasing SMN2 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 SMN2 copy numbers. Prediction and assessment of disease progression may be stratified by SMN2 copy number, which will be important for evaluating the impact of treatment.

查看原文本刊更多论文

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.