Spinal abnormalities in neurofibomatosis type 1

描述(申请人提供)：神经纤维瘤病1型(NF1)是一种常见的遗传性疾病，具有高度的临床表现变异性，包括超过三分之一的患者的骨骼异常。这种疾病与脊柱异常、长骨发育不良和蝶骨翅膀发育不良有关。这些骨性表现是不可预测的，其发病机制、自然病史和临床结果仍然相对不明。脊柱异常多种多样，包括脊柱侧弯(常见形式和营养不良形式)、神经纤维瘤、硬膜扩张症、脑膜膨出和脊椎缺陷。这项临床研究的主要目标是确定3年来120名患有NF1的青春期前儿童中与NF1相关的脊柱异常的发生率和临床病史。次要目标是确定各种放射学筛查工具作为营养不良性脊柱侧弯预测指标的有效性。这些目标将通过三个具体目标来实现。目的1是确定脊髓硬膜扩张症、脊髓神经纤维瘤和脑膜膨出与发育不良骨性异常和营养不良性脊柱侧弯的关系。脊柱X光片和核磁共振将被用来检验这一假设，即具有某些症状的NF1患者更有可能发展为营养不良性脊柱侧弯。目的2是根据不同的放射学指标，确定营养不良性脊柱侧弯和脊柱异常的临床病史和短期预后。它验证了这样的假设，即当存在与之相关的额外营养不良异常时，椎体横截面积、椎体横截面积和椎体横截面积存在数量上的差异，这些差异是营养不良脊柱侧弯的预后指标。目的3是确定NF1患者与非NF1患者、无营养不良脊柱侧凸的NF1患者与发生营养不良脊柱侧凸的NF1患者之间的骨健康变量的差异。将使用双能X线骨密度仪(DXA)和外周定量计算机断层扫描(PQCT)来验证NF1存在骨密度、骨面积、骨量、肌骨比和皮质厚度的细微骨异常的假设。将测量尿镝的交联度，以检测骨吸收的差异。NF1的脊柱异常还不是很清楚，营养不良性脊柱侧弯是一种高度病态的情况。这项建议将确定NF1患者的变量作为营养不良性脊柱侧凸的预后因素，以改善临床治疗。

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.