多发性内分泌肿瘤(MEN)是一组具有内分泌肿瘤遗传易感性的综合征,并显示常染色体显性传播。分子遗传学的出现导致了MEN在诊断方面的管理改进,预后和治疗。男性遗传学是定期更新的主题,这将在本文全文中介绍。MEN1,第一个要描述的,与MEN1基因相关。MEN1在观察到的表型方面是众所周知的,基因分析对90%具有典型表型的患者是决定性的,但在大约10%的MEN1家庭中呈阴性。分析技术的改进和对表型响应的其他基因的鉴定可以解决一些问题,但不是全部,cases,特别是非家族性形式,怀疑与肿瘤偶然相关。MEN4是与CDKN1B基因中的结构性突变相关的MEN1的罕见表型。尽管它与MEN1的表型非常相似,但已发表的数据表明,MEN4中肿瘤的出现较晚且频率较低。MEN2是由RET癌基因的突变引起的,显示出强的基因型-表型相关性。这种相关性在MEN2的主要表现,甲状腺髓样癌(MTC),其中疾病侵袭性取决于RET的致病变异。然而,最近的研究对MTC和致病变异之间的这种相关性产生了怀疑。最后,最近对携带MAX突变的家族的描述,众所周知,嗜铬细胞瘤和副神经节瘤的发展易感,并呈现一个能唤起男性的表型谱,表明另一种综合症的存在,MEN5.
Multiple endocrine neoplasia (MEN) is a group of syndromes with a genetic predisposition to the appearance of endocrine tumors, and shows autosomal dominant transmission. The advent of molecular genetics has led to improvements in the management of MEN in terms of diagnosis, prognosis and therapy. The genetics of MEN is the subject of regular updates, which will be presented throughout this paper. MEN1, the first to be described, is associated with the MEN1 gene. MEN1 is well known in terms of the observed phenotype, with genetic analysis being conclusive in 90% of patients with a typical phenotype, but is negative in around 10% of families with MEN1. Improvement in analysis techniques and the identification of other genes responsable for phenocopies allows the resolution of some, but not all, cases, notably non-familial forms suspected to be fortuitous assocations with tumors. MEN4 is a rare phenocopy of MEN1 linked to constitutional mutations in the CDKN1B gene. Though it closely resembles the phenotype of MEN1, published data suggests the appearance of tumors is later and less frequent in MEN4. MEN2, which results from mutations in the RET oncogene, shows a strong genotype-phenotype correlation. This correlation is particularly evident in the major manifestation of MEN2, medullary thyroid carcinoma (MTC), in which disease aggressiveness is dependent on the pathogenic variant of RET. However, recent studies cast doubt on this correlation between MTC and pathogenic variant. Lastly, the recent description of families carrying a mutation in MAX, which is known to predispose to the development of pheochromocytoma and paraganglioma, and presents a phenotypic spectrum that evokes MEN, suggests the existence of another syndrome, MEN5.