Lanzaro Francesca, De Biasio Delia, Cesaro Francesco Giustino, Stampone Emanuela, Tartaglione Immacolata, Casale Maddalena, Bencivenga Debora, Marzuillo Pierluigi, Roberti Domenico
Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via Luigi De Crecchio 2, 80138 Naples, Italy.
Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via Luigi De Crecchio, 7, 80138 Naples, Italy.
J Clin Med. 2024 Sep 18;13(18):5510. doi: 10.3390/jcm13185510.
Multiple endocrine neoplasia (MEN) syndromes are part of a spectrum of clinically well-defined tumor syndromes ultimately characterized by histologically similar tumors arising in patients and families with mutations in one of the following four genes: , , , and . The high level of genetic and phenotypic heterogeneity has been linked to phenocopies and modifying genes, as well as unknown mechanisms that might be investigated in the future based on preclinical and translational considerations. MEN1, also known as Wermer's syndrome (OMIM *131100), is an autosomal dominant syndrome codifying for the most frequent MEN syndrome showing high penetrance due to mutations in the MEN1 gene; nevertheless, clinical manifestations vary among patients in terms of tumor localization, age of onset, and clinical aggressiveness/severity, even within the same families. This has been linked to the effect of modifying genes, as described in the review. MEN 2-2b-4 and 5 also show remarkable clinical heterogeneity. The traditional view of genetically predisposing monogenic or multifactorial disorders is no longer valid, and mandates a change in scientific focus. Phenotypes are indeed rarely consistent across genetic backgrounds and environments. In the future, understanding factors and genetic variants that control cellular functions and the expression of disease genes should provide insights into fundamental disease processes, providing implications for counseling and therapeutic and prophylactic possibilities.
多发性内分泌肿瘤（MEN）综合征是一系列临床明确的肿瘤综合征的一部分，最终表现为在具有以下四个基因之一发生突变的患者及其家族中出现组织学相似的肿瘤： 、 、 和 。高度的遗传和表型异质性与表型模拟和修饰基因有关，也与基于临床前和转化研究考虑未来可能研究的未知机制有关。MEN1，也称为韦默综合征（OMIM *131100），是一种常染色体显性综合征，由于MEN1基因突变导致最常见的MEN综合征具有高外显率；然而，即使在同一家族中，患者在肿瘤定位、发病年龄以及临床侵袭性/严重程度方面的临床表现也各不相同。如本综述所述，这与修饰基因的作用有关。MEN 2-2b-4和5也表现出显著的临床异质性。传统上认为基因易感性单基因或多因素疾病的观点已不再成立，这就要求改变科学重点。事实上，表型在不同的遗传背景和环境中很少是一致的。未来，了解控制细胞功能和疾病基因表达的因素和基因变异，应能深入了解基本疾病过程，为咨询以及治疗和预防可能性提供启示。
