Spinal abnormalities in neurofibomatosis type 1

1 型神经纤维瘤病的脊柱异常

• 批准号: 7038788
• 负责人: DAVID H. VISKOCHIL
• 金额: $ 37.92万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7038788
• 关键词: bone; clinical research

DESCRIPTION (provided by applicant): Neurofibromatosis type 1 (NF1) is a common genetic disorder with a high degree of variability of clinical expression, including skeletal abnormalities in over 1/3 of patients. This disorder is associated with spinal abnormalities, long bone dysplasia, and sphenoid wing dysplasia. These osseous manifestations are unpredictable, and the pathogenesis, natural history, and clinical outcome remain relatively obscure. The spinal abnormalities are varied and include scoliosis (common and dystrophic forms), neurofibromas, dural ectasias, meningoceles, and vertebral defects. The primary objectives of this clinical study are to determine the incidence and clinical history of NF1-related spinal abnormalities in a prepubertal cohort of 120 children with NF1 over 3 years. Secondary objectives are to determine the efficacy of various radiographic screening tools as predictors for dystrophic scoliosis. These goals will be accomplished in 3 specific aims. Aim 1 is to identify associations of spinal cord dural ectasias, spinal neurofibromas, and meningoceles with dysplastic osseous abnormalities and dystrophic scoliosis. Spine radiographs and MRI will be used to test the hypothesis that NF1 patients with certain manifestations are more likely to develop dystrophic scoliosis. Aim 2 is to define the clinical history and short-term outcome of dystrophic scoliosis and spine abnormalities with respect to various radiographic indices. It tests the hypothesis that there are quantitative differences in vertebral scalloping and spinal canal and vertebral body cross-sectional areas when there is an associated additional dystrophic abnormality and these differences are prognostic indicators for dystrophic scoliosis. Aim 3 is to determine the differences in bone health variables between NF1 patients and individuals without NF1, and between NF1 individuals without dystrophic scoliosis versus NF1 individuals who develop dystrophic scoliosis. Dual energy x-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT) will be used to test the hypothesis that there-are subtle bone abnormalities of bone mineral density, bone area, bone mass, muscle-to-bone ratios, and cortical thickness in NF1. Urinary Dyridinium cross-links will be measured to detect differences in bone resorption. Spinal abnormalities in NF1 are not well understood, and dystrophic scoliosis is a highly morbid condition. This proposal will identify variables in patients with NF1 as prognostic factors for dystrophic scoliosis to improve clinical management.

描述（申请人提供）：1型神经纤维瘤病（NF 1）是一种常见的遗传性疾病，临床表现具有高度变异性，包括超过1/3的患者骨骼异常。这种疾病与脊柱异常、长骨发育不良和蝶骨翼发育不良有关。这些骨表现是不可预测的，发病机制，自然史和临床结果仍然相对模糊。脊柱异常是多种多样的，包括脊柱侧凸（常见和营养不良形式），神经纤维瘤，硬脊膜扩张，脑膜膨出和脊椎缺损。本临床研究的主要目的是确定120名3年以上NF 1儿童青春期前队列中NF 1相关脊柱异常的发生率和临床病史。次要目的是确定各种影像学筛查工具作为营养不良性脊柱侧凸预测指标的有效性。这些目标将在三个具体目标中实现。目的1是确定脊髓硬脊膜扩张、脊髓神经纤维瘤和脑膜膨出与发育不良性骨质异常和营养不良性脊柱侧凸的关系。脊柱X线片和MRI将被用于检验具有某些表现的NF 1患者更可能发展为营养不良性脊柱侧凸的假设。目的2是确定营养不良性脊柱侧凸和脊柱异常的临床病史和短期预后，并与各种影像学指标相关。它检验了这样一个假设，即当存在相关的额外营养不良异常时，椎体扇形化、椎管和椎体横截面积存在定量差异，这些差异是营养不良性脊柱侧凸的预后指标。目的3是确定NF 1患者和无NF 1个体之间，以及无营养不良性脊柱侧凸的NF 1个体与发生营养不良性脊柱侧凸的NF 1个体之间骨健康变量的差异。将使用双能X线吸收测定法（DXA）和外周定量计算机断层扫描（pQCT）来检验以下假设：NF 1中存在骨矿物质密度、骨面积、骨量、肌骨比和皮质厚度的细微骨异常。将测量尿二吡啶鎓交联，以检测骨吸收的差异。NF 1的脊柱异常尚不清楚，营养不良性脊柱侧凸是一种高度病态的疾病。该建议将确定NF 1患者的变量作为营养不良性脊柱侧凸的预后因素，以改善临床治疗。