From the Neuromuscular Unit (D.N.-d.B., C.O., L.C.-G., J.E.-E., M.A., J.C., C.J., C.J.-M., A.N.), Neuropaediatrics Department, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona; Center for the Biomedical Research on Rare Diseases (CIBERER), ISCIII, Spain; Neuromuscular and Neurogenetic Disorders of Childhood Section (A.R.F., S.D., Y.H., M.F., P.Y., T.O., M.E.L., J.D., C.G.B.), National Institute of Neurological Disorders and Stroke, Rehabilitation Medicine Department (M.J., A.M.), Clinical Research Center, and Neuromuscular Symptoms Unit (K.G.M.), Tissue Injury Branch, National Institute of Nursing Research, NIH, Bethesda, MD; Department of Neurology (C.D.-G., E.M.-M.), Hospital Universitario 12 de Octubre, Research Institute (imas12), Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Department of Rehabilitation and Physical Medicine (J.M., M.V.), Hospital Sant Joan de Deu, Barcelona, Spain; Neuromuscular Diseases Unit (J.D.-M.), Department of Neurology, Hospital de La Santa Creu i Sant Pau, Universitat Autònoma de Barcelona and Centre for Biomedical Network Research on Rare Diseases (CIBERER); Statistics Department (D.C.), Fundació Sant Joan de Déu; Department of Internal Medicine (J.C.M.), Hospital Clinic, Universitat de Barcelona and CIBERER, Villarroel 170; Neuropathology Unit (R.D.-R., M.O.), Department of Pathology and Neuromuscular Unit, IDIBELL-Hospital Universitari de Bellvitge, Barcelona, Spain; and Department of Pathology (C.J.), Hospital Sant Joan de Déu, Barcelona, Spain.
Neurology. 2021 Mar 9;96(10):e1413-e1424. doi: 10.1212/WNL.0000000000011499. Epub 2021 Jan 13.
To accurately categorize the phenotypes of individuals with collagen VI-related dystrophies (COL6-RDs) during the first years of life to predict long-term motor function and pulmonary function, to provide phenotype-specific anticipatory care, and to improve clinical trial readiness.
This retrospective, multicenter, international study analyzed the relationship of long-term motor and pulmonary function with the initial maximal motor ability achieved in individuals with COL6-RD.
We studied 119 patients with COL6-RD from Spain (n = 54) and the United States (n = 65). The early maximal motor milestones of ability to rise from the floor unassisted and ability to climb 4 steps without holding onto a railing demonstrated reliability in distinguishing between 3 COL6-RD phenotypic subgroups: (1) Ullrich congenital muscular dystrophy, (2) intermediate COL6-RD, and (3) Bethlem myopathy. Long-term motor function and pulmonary function are strongly correlated with the maximal motor ability achieved during the first years of life. Maximal motor capacity can predict other disease-relevant events such as the age at loss of ambulation and the need for the initiation of nocturnal noninvasive ventilation.
This work proposes a prospective phenotypic classification for COL6-RDs that will enable an accurate prediction of a patient's COL6-RD phenotype during the first years of life. The ability to establish a patient's COL6-RD phenotypic classification early will enable a more accurate prognosis of future motor and pulmonary function, thus improving anticipatory clinical care, and it will be instrumental in aiding the design of future clinical trials by allowing early stratification of trial cohorts.
在生命的最初几年准确分类胶原 VI 相关营养不良（COL6-RD）个体的表型，以预测长期运动功能和肺功能，提供表型特异性的预期护理，并提高临床试验准备。
这项回顾性、多中心、国际研究分析了个体 COL6-RD 长期运动和肺功能与 COL6-RD 个体最初获得的最大运动能力之间的关系。
我们研究了来自西班牙（n=54）和美国（n=65）的 119 名 COL6-RD 患者。从地板上独立起身和不扶扶手爬上 4 级台阶的早期最大运动能力里程碑在区分 3 个 COL6-RD 表型亚组方面具有可靠性：（1）Ullrich 先天性肌营养不良症，（2）中间型 COL6-RD，和（3）Bethlem 肌病。长期运动功能和肺功能与生命最初几年获得的最大运动能力密切相关。最大运动能力可以预测其他与疾病相关的事件，如丧失步行能力的年龄和开始夜间无创通气的需求。
这项工作提出了 COL6-RD 的前瞻性表型分类，能够在生命的最初几年准确预测患者的 COL6-RD 表型。早期确定患者 COL6-RD 表型分类的能力将能够更准确地预测未来的运动和肺功能，从而改善预期的临床护理，并通过允许早期分层临床试验队列，有助于未来临床试验的设计。
