PDF(Pubmed)
Abstract：
Neurofibromatosis type 2 (NF2) is a genetic condition marked by the development of multiple benign tumors in the nervous system. The most common tumors associated with NF2 are bilateral vestibular schwannoma, meningioma, and ependymoma. The clinical manifestations of NF2 depend on the site of involvement. Vestibular schwannoma can present with hearing loss, dizziness, and tinnitus, while spinal tumor leads to debilitating pain, muscle weakness, or paresthesias. Clinical diagnosis of NF2 is based on the Manchester criteria, which have been updated in the last decade. NF2 is caused by loss-of-function mutations in the NF2 gene on chromosome 22, leading the merlin protein to malfunction. Over half of NF2 patients have de novo mutations, and half of this group are mosaic. NF2 can be managed by surgery, stereotactic radiosurgery, monoclonal antibody bevacizumab, and close observation. However, the nature of multiple tumors and the necessity of multiple surgeries over the lifetime, inoperable tumors like meningiomatosis with infiltration of the sinus or in the area of the lower cranial nerves, the complications caused by the operation, the malignancies induced by radiotherapy, and inefficiency of cytotoxic chemotherapy due to the benign nature of NF-related tumors have led a march toward exploring targeted therapies. Recent advances in genetics and molecular biology have allowed identifying and targeting of underlying pathways in the pathogenesis of NF2. In this review, we explain the clinicopathological characteristics of NF2, its genetic and molecular background, and the current knowledge and challenges of implementing genetics to develop efficient therapies.
摘要：
2型神经纤维瘤病（NF2）是一种遗传性疾病，其特征是神经系统中多种良性肿瘤的发展。与NF2相关的最常见肿瘤是双侧前庭神经鞘瘤，脑膜瘤,还有室管膜瘤.NF2的临床表现取决于受累部位。前庭神经鞘瘤可表现为听力损失，头晕,和耳鸣,而脊柱肿瘤会导致使人衰弱的疼痛，肌肉无力,或感觉异常。NF2的临床诊断基于曼彻斯特标准，在过去的十年里已经更新了。NF2是由22号染色体上NF2基因的功能丧失突变引起的，导致merlin蛋白发生故障。超过一半的NF2患者有从头突变，这一组中有一半是马赛克。NF2可以通过手术管理，立体定向放射外科,单克隆抗体贝伐单抗，密切观察。然而,多种肿瘤的性质和一生中多次手术的必要性，无法手术的肿瘤，如脑膜瘤病，窦或下颅神经区域浸润，手术引起的并发症，放疗引起的恶性肿瘤，由于NF相关肿瘤的良性性质，细胞毒性化疗的低效率导致了对靶向治疗的探索。遗传学和分子生物学的最新进展允许鉴定和靶向NF2发病机理中的潜在途径。在这次审查中,我们解释了NF2的临床病理特征，其遗传和分子背景，以及实施遗传学以开发有效疗法的当前知识和挑战。
