Recent results of basic and clinical research in MEN1: opportunities to improve early detection and treatment

Abstract

Due to the variable expression of multiple endocrine neoplasia type 1 (MEN1), it is difficult to predict the course of the disease. However, knowledge about the normal function of the MEN1 gene product, together with the effects of cellular derangement by subsequent genetic events, has increased considerably. At first, the possible existence of a genotype–phenotype correlation is discussed. Thus, mild- and late-onset phenotypes may be distinguished from more malignant phenotypes depending on the character of the primary MEN1 disease gene mutation. Subsequently, tumor-promoting factors such as gender, additional genetic mutations and ecogenetic factors may contribute to the course of the disease. New developments in management are based on the knowledge and experience of the multidisciplinary teams involved. Finally, the metabolic effects of MEN1 mutations in aged patients are discussed. Early identification of predisposition to the disease, together with knowledge about the natural history of specific mutations, risks of additional mutations and periodic clinical monitoring, allow early treatment and may improve life expectancy and quality of life.

Keywords::

• DNA diagnosis
• genetic testing
• genotype–phenotype correlation
• MEN1
• menin
• multiple endocrine neoplasia type 1
• mutation analysis
• periodic clinical monitoring
• preimplantation genetic diagnosis
• presymptomatic treatment
• target-directed treatment
• variable expression

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

^†In families with early manifestation of the disease or if suspicion arises because of clinical symptoms, early screening is recommended; if clinical suspicion regarding insulinomas is present, a fasting test should not be postponed; use of proton-pump inhibitors or H2-receptor blockers may increase gastrin and chromogranin A levels; oral contraceptives may increase prolactin levels.

MEN1: Multiple endocrine neoplasia type 1.

MEN1: Multiple endocrine neoplasia type 1; NET: Neuroendocrine tumor.