Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®): Genetics - Health Professional Information [NCI] - Introduction
Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms. When a linked term is clicked, the definition will appear in a separate window.
Many of the genes described in this summary are found in the Online Mendelian Inheritance in Man (OMIM) database. When OMIM appears after a gene name or the name of a condition, click on OMIM for a link to more information.
The initial approach to the patient is to evaluate the following parameters:
Detection of a monoclonal (or myeloma) protein (M protein) in the serum or urine.
Detection of more than 10% of plasma cells on a bone marrow examination.
Detection of lytic bone lesions or generalized osteoporosis in skeletal x-rays.
Presence of soft tissue plasmacytomas.
Serum albumin and beta-2-microglobulin levels.
Detection of free kappa and lambda serum immunoglobulin light...
There are several hereditary syndromes that involve endocrine or neuroendocrine glands, such as multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2 (MEN2), pheochromocytoma, paraganglioma, and von Hippel-Lindau syndrome. This summary currently focuses on MEN1 and MEN2. Additional sections are in progress.
The term multiple endocrine neoplasia is used to describe a group of heritable tumors of endocrine tissues that may be benign or malignant. They are typicially classified into two main categories: MEN1 and MEN2. The tumors usually manifest themselves by overproduction of hormones, tumor growth, or both.
Comprising varying combinations of more than 20 endocrine and nonendocrine tumors, MEN1 may be a difficult syndrome to define clinically. In general, however, MEN1 is characterized by tumors of the parathyroids, pancreas, and pituitary gland. This syndrome may also include carcinoid tumors, adrenocortical tumors, and nonendocrine tumors, such as facial angiofibromas, collagenomas, lipomas, meningiomas, ependymomas, and leiomyomas.
MEN1 syndrome, also known as Wermer syndrome, results from a mutation in the MEN1gene. It has a prevalence of about 1 in 30,000 individuals.
MEN2 is caused by a mutation in the RET proto-oncogene. Historically, MEN2 has been further stratified into the following three subtypes based on the presence or absence of certain endocrine tumors in the individual or family:
All three subtypes of MEN2 (MEN2A, FMTC, and MEN2B) impart a high risk of developing medullary thyroid cancer (MTC). MEN2A has an increased risk of pheochromocytoma and parathyroid adenoma and/or hyperplasia. MEN2B has an increased risk of pheochromocytoma and includes additional clinical features, such as mucosal neuromas of the lips and tongue, distinctive faces with enlarged lips, ganglioneuromatosis of the gastrointestinal tract, and an asthenic Marfanoid body habitus. FMTC has been defined as the presence of at least four individuals with MTC without any other signs or symptoms of pheochromocytoma or hyperparathyroidism in the proband or other family members.
Some families previously classified as having FMTC will go on to develop one or more of the MEN2A-related tumors, suggesting that FMTC is simply a milder variant of MEN2A. Offspring of affected individuals have a 50% chance of inheriting the RET gene mutation.
The age at onset of MTC is different for each subtype of MEN2. MTC typically occurs during early childhood in patients with MEN2B, predominantly during early adulthood in patients with MEN2A, and during middle-age in patients with FMTC.