Multiple endocrine neoplasia type 1: Definition and genetics

1.Multiple endocrine neoplasia type 1 (MEN1) is a rare heritable disorder

classically characterized by a predisposition to tumors of the parathyroid glands,
anterior pituitary, and pancreatic islet cells 

2. The presence of MEN1 is defined clinically as the occurrence of two or more

primary MEN1 tumor types, or in family members of a patient with a clinical
diagnosis of MEN1, the occurrence of one of the MEN1-associated tumors

3. The incidence ranges from 1 to 18, 16 to 38, and less than 3 percent in patients
with parathyroid adenomas, gastrinomas, and pituitary adenomas, respectively

4. Patients with MEN1 may have tumors other than those in the parathyroid and
pituitary, and pancreatic islet cells

5. The duodenum is a common site of tumors (gastrinomas) in these patients, and

thymic or bronchial carcinoid tumors, enterochromaffin cell-like gastric tumors,
adrenocortical adenomas, and lipomas are more frequent than in the general
population

6. Patients with classical multiple endocrine neoplasia type 1 (MEN1) have often
inherited one inactivated copy of the MEN1 gene from an affected parent

7. The actual outgrowth of a tumor is thought to require the subsequent somatic

inactivation, often by gross deletion, of the remaining normal copy of the gene in
one cell (so-called "two-hit" effect described by Knudson)

8. The MEN1 tumor suppressor gene is located on the long arm of chromosome 11

(11q13). Its protein product is termed "menin."

9. Over 1000 MEN1 gene mutations have been detected that inactivate or disrupt

menin function. Inactivation of menin results in loss of tumor suppression

10. Families with the same types of mutations do not necessarily have the same
clinical phenotype
11. Syndromes clinically related to but genetically distinct from MEN1 do exist, and
mutations in the MEN1 gene are not responsible for all individuals, or even
kindreds, with an MEN1 phenotype

12. Direct DNA testing for MEN1 mutation is available for clinical use, has a useful
role in certain settings, and should be considered on an individual basis

13. In contrast to testing for RET gene mutations in MEN2, presymptomatic DNA
diagnosis has not been shown to yield equally clear benefit in preventing morbidity
and mortality in individuals at risk for MEN1