Unidad de Genética Molecular, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria and Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Spain.
BMC Cancer. 2010 Aug 5;10:407. doi: 10.1186/1471-2407-10-407.
Neurofibromatosis type 1 is a common autosomal dominant disorder with full penetrance and variable expression. The condition predisposes individuals to the development of malignant nervous system tumours, most frequently Malignant Peripheral Nerve Sheath Tumours (MPNSTs). Previous studies indicate that genetic factors other than mutations in NF1 may be responsible for the condition's variable expression.
Here we present data from a pair of monozygotic twins affected by Neurofibromatosis type 1 resulting from a de novo mutation. Both twins developed a left sciatic plexiform neurofibroma that evolved into MPNST at a similar age and they also developed pulmonary metastasis at the same age. Other concordant traits between the twins were: macrocephaly, psychomotor delay, café-au-lait spots, cutaneous neurofibromas, retroperitoneal, pleural and paraspinal neurofibromas. The main discordant features observed were tibial pseudoarthrosis, pectus carinatum, osteoporosis and thymus hyperplasia.
This is the first report of monozygotic twins with Neurofibromatosis type 1 that develop MPNSTs, the localization and chronological evolution of which, and its metastasis, is concordant in both twins. These cases suggest that the events involved in the transformation of benign plexiform neurofibromas to MPNSTs in Neurofibromatosis type 1, follow a spatiotemporally programme that is influenced by heritable factors other than NF1 mutations.
神经纤维瘤病 1 型是一种常见的常染色体显性遗传病，具有完全外显率和可变表达。这种情况使个体易患恶性神经系统肿瘤，最常见的是恶性外周神经鞘瘤（MPNST）。先前的研究表明，除 NF1 突变外，其他遗传因素可能导致该病症的可变表达。
在这里，我们提供了一对同卵双胞胎的资料，他们患有神经纤维瘤病 1 型，这是由新生突变引起的。这对双胞胎都患上了左侧坐骨丛状神经纤维瘤，在相似的年龄发展成 MPNST，并且在相同的年龄也发生了肺转移。双胞胎之间还有其他一致的特征：大头畸形、精神运动发育迟缓、咖啡牛奶斑、皮肤神经纤维瘤、腹膜后、胸膜和脊柱旁神经纤维瘤。观察到的主要不一致特征是胫骨假关节、鸡胸、骨质疏松症和胸腺增生。
这是首例报道的同卵双胞胎患有神经纤维瘤病 1 型，发展为 MPNST，其定位和时间演变，以及在双胞胎中的转移，是一致的。这些病例表明，在神经纤维瘤病 1 型中，从良性丛状神经纤维瘤向 MPNST 转化所涉及的事件遵循一个时空程序，受 NF1 突变以外的遗传因素影响。
