Multiple Endocrine Neoplasia

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Retrieved

2021-01-23

Source

Orphanet

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Genes

RET, CDKN1B, MEN1, GHRL, GHSR, CALCA, VHL, TICAM2, TMED7-TICAM2, TMED7, IFI27, ZNRD2, CIB1, PTH, PSMD9, PRKAR1A, DCTN6, H3P23, CASR, HPT, GDNF, CDC73, AIP, FGF2, SDHB, GAST, SST, PPY, POMC, FUT4

RET, CDKN1B, MEN1, GHRL, GHSR, CALCA, VHL, TICAM2, TMED7-TICAM2, TMED7, IFI27, ZNRD2, CIB1, PTH, PSMD9, PRKAR1A, DCTN6, H3P23, CASR, HPT, GDNF, CDC73, AIP, FGF2, SDHB, GAST, SST, PPY, POMC, FUT4, CDKN2C, SARDH, CXADR, CDKN3, FRS2, SDS, SMUG1, PDE11A, CDKN2A, NR1I3, GFRA4, MEA1, CD109, SMAD3, CXADRP1, CALB1, TRIM13, GNAS, PTEN, SDHD, PTPN11, RENBP, BCL2, RPA2, RYK, SDHC, SLC8A1, PDE8B, SORD, SPG7, GRN, TP53, NF1, ZNF22, ARR3

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Multiple endocrine neoplasia (MEN) is a group of rare inherited cancer syndromes characterized by the development of two or more endocrine gland tumors, sometimes with tumor development in other tissues or organs.

Epidemiology

The overall prevalence and incidence of MEN are not known. The prevalence of MEN1 is estimated to be approximately 1/10,000 to 1/30,000, while the total prevalence of MEN2 variants is approximately 1/35,000. MEN4 is extremely rare. The incidence of MEN1 has been estimated from random postmortem studies to be 0.25%, and to be 1-18% in patients with primary hyperparathyroidism, 16 to 38% in patients with gastrinomas, and less than 3% in patients with pituitary tumors.

Clinical description

Multiple endocrine neoplasia syndromes can develop in patients of all ages: from infants to elderly patients over 70 years of age. Manifestations vary depending on the affected endocrine glands. There are three types of MEN (multiple endocrine neoplasia types 1, 2, and 4; see these terms) based on the underlying genetic abnormalities, the endocrine glands involved and the clinical manifestations. Each type includes a different combination of pituitary, pancreatic, parathyroid, medullary, thyroid, and adrenal tumors. MEN1 is characterized by parathyroid, pituitary gland, and pancreatic tumors. MEN2 is divided into two subtypes: MEN2A characterized by medullary thyroid carcinoma (see this term) in combination with pheochromocytoma (see this term) and primary mild hyperparathyroidism; and MEN2B (formerly MEN3), a rare form, involving medullary thyroid carcinoma, pheochromocytoma, mucosal ganglioneuromas and marfanoid habitus. MEN4 involves the development of parathyroid and anterior pituitary tumors.

Etiology

MEN1 is caused by inactivating mutations in the MEN1 gene (11q13), and in some patients by mutations in the cyclin-dependent kinase inhibitor genes (CDKN1A, CDKN2B, CDKN2C). MEN2A and MEN2B are due to activating mutations in the RET gene (10q11.2), and MEN4 to inactivating mutations in the CDKN1B gene (12p13.1-p12). Patients with MEN1-like phenotypes (primary hyperparathyroidism associated with various tumors and lesions of the pituitary gland, pancreas, and duodenum) have also been found to have inactivating germline heterozygote mutation in CDKN1B.

Genetic counseling

MEN follows an autosomal dominant pattern of inheritance and some sporadic cases are reported. First-degree relatives have a 50% risk of developing the disorder, making appropriate genetic counseling very important in affected families. Biochemical and genetic screening may be suggested to family members.