Multiple Endocrine Neoplasia Type 2 is a hereditary cancer syndrome.
Multiple Endocrine Neoplasia Type 2 (MEN2) is a hereditary condition associated with an increased risk for developing tumours and cancers of the endocrine (hormone producing) glands.
Hereditary tumours and cancers develop because of the presence of a faulty gene. Some genes function to protect us from tumour/cancer growth. When they are not working well, it causes an increased risk for tumours/cancers to grow. We refer to genes that are not working well as faulty genes.
Individuals who carry a faulty tumour/cancer gene(s) have a higher chance of developing certain tumours/cancers over their lifetime compared to the general population. The types of tumours/cancers that they may be at increased risk of will depend on the gene(s) involved.
If you have a faulty tumour/cancer gene, you may be at increased risk of developing certain tumours/cancers. As genes are shared among family, other family members may have inherited the faulty gene and may be at increased risk of tumours/ cancer too.
Genetic testing is offered to individuals where a hereditary cause of their personal and/or family history of tumours/cancer is suspected.
Genes contain the instructions that our body reads to carry out different functions. Genetic testing involves analysing your genes to understand if there are faults (i.e., mutations) that may increase the risk of tumours/cancers developing.
There are 3 types of results you may receive:
Medullary thyroid cancer is a cancer of the thyroid gland. It is the most common tumour caused by MEN2. The thyroid is a small gland in the front of the neck, just below the voice box.
The symptoms of medullary thyroid cancer include:
The parathyroid glands are located just behind the thyroid gland, infront of the neck. If you have MEN2A, the parathyroid glands may become large and overactive (hyperparathyroidism). This mostly happens from ages 20 to 40.Parathyroid glands produce a hormone called parathyroid hormone (PTH) which helps to control the body’s calcium levels. People with overactive parathyroid glands may make too much PTH, which can result in high levels of calcium in the blood.This can make you:
The high levels of PTH can also cause bones to become weaker and more prone to fracture. High calcium levels can also affect the kidney, possibly leading to the development of kidney stones and kidney damage, which can be avoided if you are diagnosed and seek treatment early.
Phaeochromocytoma (PCC) is a tumour of the adrenal glands, the small glands above the kidneys. It is usually noncancerous.People with MEN2A or MEN2B can develop PCC, and one or both of the adrenal glands may be affected. PCC can cause the adrenal gland to make large amounts of hormones such as adrenaline (epinephrine) and adrenaline-like hormones.Adrenaline regulates the heart rate and blood pressure, and too much of it can cause symptoms such as:
All patients with medullary thyroid cancer, phaeochromocytoma or paraganglioma diagnosis are recommended to have genetic testing.
People with MEN2 are born with a faulty (i.e., disease-causing)
When working properly, the
RET gene provides instructions to produce a protein involved in signalling within cells. This signalling is needed to ensure normal development and controlled growth of cells.
If there is a fault (i.e., mutation) within the
RET gene, it can become dysfunctional, resulting in the production of an overactive protein which can signal cells to grow and divide uncontrollably, resulting in tumour formation and cancer.
The location of the fault within the RET gene can determine the age, likelihood and aggressiveness of the medullary thyroid cancer that may develop. Its management will be based on where the location of the fault is in the
Note: The conditions associated with a faulty RET gene and their risk estimates may change as more information is available.
Depending on your genetic result and personal/family history of cancer, your personal risk levels may differ from the values shown above.
There is a classification system that determines the medullary thyroid cancer risk level based on where the fault in the RET gene is located. It is best to ask your genetics service to understand your risk level in more detail.
Your managing doctors will also advise you on the medical care that might or might not be beneficial for you, according to your risk level.
MEN2 follows a dominant inheritance pattern. This means that having one faulty copy of the RET gene can result in an increased risk of tumours/cancer. It affects both males and females.
Everyone has 2 copies of each gene in their body’s cells:
You should consider genetic testing if you or your family members meet one or more of the following criteria:
Personalised managementIn individuals who are diagnosed with medullary thyroid cancer, genetic testing is important to determine if the cause of it is sporadic (spontaneous) or hereditary.If the cause is hereditary:
It is important to identify the type of faulty RET gene you may have, as the various types carry different tumour/cancer risks which would affect how doctors plan for your medical management.
Familial implicationsYour genetic test result can also help you understand if other family members are at risk of MEN2. They can subsequently consider their own testing (predictive testing) to clarify their carrier status to determine tumour and cancer risks.Family members who have inherited the same faulty RET gene may be at increased risk of tumours and cancer and can benefit from management options such as screening (to detect tumours and cancer at an early and manageable stage) or surgery (to reduce their risk of cancer).Family members who did not inherit the faulty RET gene can avoid unnecessary screening and worry. Their children will also not be at risk.
Screening helps to detect, and in some cases treat, tumours and/or cancer at an early and manageable stage.
Your managing doctor(s) will discuss screening recommendations with you in greater detail. The age and onset for screening is dependent on your risk level, and may change according to personal and/or family history of tumours/cancer. Screening guidelines may change as more information is known.
Risk-reducing surgery may be offered to help reduce the risk of cancer/tumours.
Your managing doctor(s) will discuss these options with you in greater detail. The time and age of surgery is usually advised according to your risk level and your personal and/or family history of tumours/cancers.
Q: Who is the best person in the family to undergo genetic testing?A: In order to determine if a hereditary cause exists in the family, genetic testing is usually initially offered to the family member whose personal history is most suggestive of MEN2 (e.g., someone with a personal history of medullary thyroid cancer at a young age or clinical presentations suggestive of MEN2).
It is usually not advisable to test someone without a history of cancer / tumours / clinical features unless a hereditary cause has already been identified in the family.
The genetic test results of an asymptomatic individual may have some limitations:
Once the faulty gene in the family is identified, genetic testing can be offered to other family members including those who do not have a tumour/cancer. This will help them understand if they have inherited the faulty gene change and if so, tailor their management to manage or reduce their risks.
If my genetic test result is positive, it means that I have or will have tumours/cancer, or my tumour/cancer will recur.
FALSE. The genetic test result cannot determine the likelihood of tumour/cancer recurrence or the presence of a tumour/cancer. A positive result only indicates that you have been diagnosed with MEN2 and are at an increased risk of developing tumours/cancer.
If I or my child tests positive, it means that my children/grandchildren will develop tumours/cancer.
FALSE. If you or your child has a positive genetic test result where a faulty
RET gene is identified, it means that each of your children/grandchildren has a 50% (1 in 2) chance of inheriting the faulty
My child looks a lot like me, so he/she must have inherited the faulty gene(s) since I have it.
FALSE. Genes that govern your appearance are different from the
RET gene that causes MEN2. All firstdegree relatives (siblings, children and parents) have a 50% (1 in 2) chance of inheriting the faulty
RET gene, regardless of whether they look like you or not.
I have two brothers, so one will inherit the faulty gene(s) and one will not, because there is a 50% chance.
FALSE. Each first-degree relative (parents, siblings and children) has a 50% (1 in 2) chance of inheriting the faulty gene(s). The genetic test result of one sibling does not impact the chances of the other sibling.
Download the Multiple Endocrine Neoplasia Type 2 brochure.
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