Spinal abnormalities in neurofibomatosis type 1

描述（由申请人提供）：1型神经纤维瘤病（NF1）是一种常见的遗传性疾病，具有高度的临床表现变异性，超过1/3的患者出现骨骼异常。这种疾病与脊柱异常、长骨发育不良和蝶翼发育不良有关。这些骨性表现是不可预测的，发病机制、自然史和临床结果仍然相对不清楚。脊柱异常多种多样，包括脊柱侧凸（常见和营养不良形式）、神经纤维瘤、硬脑膜扩张、脑膜膨出和椎体缺损。本临床研究的主要目的是确定120名3年以上NF1儿童的青春期前队列中NF1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。这些目标将通过3个具体目标来实现。目的1是确定脊髓硬膜扩张、脊髓神经纤维瘤和脑膜膨出与发育不良骨异常和营养不良性脊柱侧凸的关系。脊柱x线片和MRI将用于验证具有某些表现的NF1患者更容易发展为营养不良型脊柱侧凸的假设。目的2是根据各种影像学指标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。它验证了当存在额外的营养不良异常时，椎体扇形、椎管和椎体横截面积存在定量差异的假设，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NF1患者与非NF1患者之间，以及NF1无营养不良性脊柱侧凸患者与NF1有营养不良性脊柱侧凸患者之间骨骼健康变量的差异。双能x线吸收仪（DXA）和外周定量计算机断层扫描（pQCT）将用于检验NF1中存在骨矿物质密度、骨面积、骨量、肌骨比和皮质厚度等细微骨异常的假设。将测量尿吡啶交联以检测骨吸收的差异。NF1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NF1患者的变量作为营养不良性脊柱侧凸的预后因素，以改善临床管理。

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.