Evans D G, Freeman S, Gokhale C, Wallace A, Lloyd S K, Axon P, Ward C L, Rutherford S, King A, Huson S M, Ramsden R T
Genomic Medicine, University of Manchester, Manchester Academic Health Science Centre, Institute of Human Development, Central Manchester NHS Foundation Trust, Manchester Royal Infirmary, Manchester, UK.
Department of Otolaryngology, University of Manchester, Manchester Academic Health Science Centre, Institute of Human Development, Central Manchester NHS Foundation Trust, Manchester Royal Infirmary, Manchester, UK.
J Med Genet. 2015 Jun;52(6):422-4. doi: 10.1136/jmedgenet-2014-102973. Epub 2015 Feb 27.
Neurofibromatosis type 2 (NF2) is an autosomal dominant condition with high spontaneous mutation rate which predisposes to the development of multiple nerve sheath tumours (schwannomas), meningiomas and ependymoma. The cardinal feature and main diagnostic criterion for the diagnosis of NF2 remains the development of bilateral vestibular schwannoma (BVS). With increasing use of MRI screening the possibility of a 'chance' diagnosis of BVS has been mooted with a potential frequency of one in two million people in their lifetime. Until now, however, no evidence for such an event has been published. We aimed to demonstrate that chance occurrence can occur and to estimate its frequency among those with just BVS late in life.
Two vestibular schwannomas from the same patient were DNA sequenced and underwent loss of heterozygosity analysis.
We show that a man who developed BVS, at ages 52 and 67 years developed these tumours sporadically by demonstrating that there were no molecular events in common between the two tumours. Furthermore from a database of over 1200 patients with NF2, we have estimated that ~25% of cases of BVS over 50 years and 50% over 70 years of age where no other features of NF2 are present represent a chance occurrence rather than due to an underlying mosaic or constitutional NF2 mutation.
Patients presenting with BVS later in life should be appraised of the potential likelihood they may not have NF2 and the resultant further reduction in risks of transmission to offspring.
2型神经纤维瘤病（NF2）是一种常染色体显性疾病，自发突变率高，易引发多发性神经鞘瘤（施万细胞瘤）、脑膜瘤和室管膜瘤。NF2诊断的主要特征和主要诊断标准仍然是双侧前庭神经鞘瘤（BVS）的发生。随着MRI筛查的使用增加，有人提出了“偶然”诊断BVS的可能性，其潜在发生率为每200万人中有1人在其一生中会出现。然而，迄今为止，尚未发表关于此类事件的证据。我们旨在证明偶然发生的情况是可能的，并估计其在晚年仅患有BVS的人群中的发生率。
对同一患者的两个前庭神经鞘瘤进行DNA测序，并进行杂合性缺失分析。
我们发现，一名在52岁和67岁时患上BVS的男性，通过证明这两个肿瘤之间没有共同的分子事件，表明这些肿瘤是散发性发生的。此外，从一个超过1200例NF2患者的数据库中，我们估计，在50岁以上且无NF2其他特征的BVS病例中，约25%以及70岁以上的病例中50%是偶然发生的，而非由于潜在的嵌合体或遗传性NF2突变。
对于晚年出现BVS的患者，应告知他们可能没有NF2的潜在可能性以及由此导致的向后代传播风险的进一步降低。
