Multiple endocrine neoplasia type 1 (MEN1) is a genetic condition that causes benign and malignant tumors in endocrine (hormone producing) and non-endocrine tissues. It occurs in approximately 1 in 30,000 individuals.
Endocrine tumors may arise in the:
Non-endocrine tumors may include:
Because MEN1 is hereditary, the risk of developing the features associated with MEN1 may be passed from generation to generation in a family. However, the type and severity of disease can vary widely between family members.
MEN1 is caused by alterations, also known as mutations, at specific areas within an individual’s genetic information. Each of us has a large amount of genetic information that is organized into smaller segments known as “genes.” Genes provide the necessary instructions that our cells require to perform their different functions within our bodies.
In most patients with MEN1, the disorder develops as the result of alterations in a specific gene known as MEN1, which is located on chromosome 11 at position q13. MEN1 is the only gene known to be associated with MEN1. Normally, the protein produced by the MEN1 gene acts as a “tumor suppressor," which means that it helps to keep cells from growing and dividing too quickly and it promotes cell death. It also plays a fundamental role in regulating DNA replication and repair. A person with MEN1 has one copy of the MEN1 gene that has lost its ability to carry out these duties.
With the exception of egg and sperm cells, each cell of the body normally has two working copies of the MEN1 gene. Patients with MEN1 generally carry an alteration in one copy of the MEN1 gene in all the cells of their body. Individuals who have MEN1 are born and develop normally, but are at an increased risk to develop specific types of tumors. These tumors are believed to develop because, over time, the second working copy of the MEN1 gene may become altered within one or more cells. The loss of function of the second MEN1 gene copy leads to abnormal growth of the affected cells, increasing their chance to form a tumor.
Approximately 90 percent of patients with MEN1 inherit an altered copy of the MEN1 gene from a parent who also has MEN1. In the remaining 10 percent of patients, MEN1 results from the development of a “new” mutation in the MEN1 gene in one of the father’s sperm, mother’s eggs, or in a cell of the developing fetus. In the latter scenario, the affected individuals will be the first ones in their family to carry this genetic change. Individuals who carry an alteration in one copy of the MEN1 gene in all the cells of their body have a 50 percent (or 1 in 2) chance of passing this same alteration on to his or her children. Children who inherit the altered gene copy will have MEN1 and will therefore be at risk to develop the features associated with this disorder.
An individual may be diagnosed as having MEN1 if he or she develops two of the three main MEN1-related endocrine tumors, including:
Alternatively, an individual who develops only one of these tumors may be diagnosed as having MEN1 when there is a family history consistent with the condition.
A careful and detailed review of an individual’s medical and family history may be performed to aid in the diagnosis of multiple endocrine neoplasia type 1. A doctor or genetic counselor may construct a pedigree, or a multi-generation family tree, that indicates which members of the family have developed cancer, the types of cancer and the ages of onset, as well as the presence of any clinical manifestations. If the pattern of clinical features and/or cancers is suggestive of MEN1 the physician or counselor may recommend that genetic testing be performed.
In order to confirm on a molecular level that an individual has MEN1, he or she can undergo genetic testing:
A person with MEN1 who is concerned about passing this disorder on to future children has several options, including:
Before one can proceed with prenatal testing or PGD, a MEN1 mutation must be identified in a parent with multiple endocrine neoplasia type 1.
Individuals with MEN1 are at increased risk to develop endocrine and non-endocrine tumors. These tumors are often benign (non-cancerous); however, they may require removal or treatment as they can cause symptoms due to pressure on nearby organs or excess hormone secretion.
Other non-endocrine tumors that have been reported in patients with MEN1 include leiomyomas and tumors of the central nervous system (specifically meningiomas and ependymomas). The true incidence of these tumors in individuals with MEN1 is not currently known.
In some cases, MEN1-associated tumors undergo malignant changes and behave more like cancers.
The two MEN1-related endocrine tumor types most likely to become malignant are:
Almost all individuals with a germline MEN1 mutation will develop features of the condition. Approximately 50 percent of individuals with MEN1 will develop features associated with MEN1 by age 20 years, and over 95 percent of individuals with MEN1 will develop features by age 50 years.
There are currently no standard screening recommendations for patients with MEN1. Screening guidelines may vary between experts and may be dependent on factors such as the patient’s age and clinical history. Management of patients with MEN1 should be provided by specialists with expertise in this condition. There are some annual screening recommendations that apply to all adults who have or are at risk for MEN1, including assessment of calcium, parathyroid hormone, gastrin, and prolactin levels. Occasionally, additional imaging tests such as ultrasound, CT or MRI may be necessary to screen for carcinoid, pancreatic, pituitary and other tumors. Screening recommendations may begin as early as age five for children at risk for MEN1.
If possible, individuals with MEN1 should avoid smoking cigarettes or cigars and should not be exposed to secondhand smoke, which is associated with an increased risk of developing thymic carcinoid tumors.
Adults and children who have MEN1 or who would like more information about MEN1 may contact the Medical Genetics Team at the Hospital of the University of Pennsylvania at 215-662-4740. Appointments can also be requested online at http://www.uphs.upenn.edu/penngen or by calling 1-800-789-PENN (7366).
National Endocrine and Metabolic Diseases Information Service
6 Information Way
Bethesda, MD 20892–3569
American Cancer Society
1599 Clifton Road NE.
Atlanta, GA 30329
National Library of Medicine Genetics Home Reference: MEN1
Gene Reviews: MEN1
MD Anderson: Cancer Information (MEN1)
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Reviewed by: Kim Nichols, MD, Kristin Zelley, MS
Date: September 2012