Multiple endocrine neoplasia type 2B

Title

Other Names:

MEN 2B; Mucosal neuroma syndrome; Multiple endocrine neoplasia, type 3 (formerly); MEN 2B; Mucosal neuroma syndrome; Multiple endocrine neoplasia, type 3 (formerly); Wagenmann-froboese syndrome See More

Categories:

Congenital and Genetic Diseases; Digestive Diseases; Endocrine Diseases; Congenital and Genetic Diseases; Digestive Diseases; Endocrine Diseases; Hereditary Cancer Syndromes; Metabolic disorders; Rare Cancers See More

Summary Summary

Multiple endocrine neoplasia type 2B (MEN2B) is a genetic disease in which one or more of the endocrine glands are overactive and form a tumor (neoplasia). Common tumors that may be associated with MEN2B include medullary thyroid carcinoma (MTC) and tumors of the adrenal glands called pheochromocytomas. Other features of MEN2B can include having bumps on the lips, eyelids, and tongue. People with MEN2B typically have a body type with long arms, legs, and fingers. They may also have joints that are very loose (hyperextensible).^[1]

MEN2B is caused by a specific genetic change (mutation or pathogenic variant) in the RET gene. The disease is inherited in an autosomal dominant manner. A diagnosis of MEN2B is suspected when a person has a personal or family history of medullary thyroid cancer, pheochromocytoma, or physical findings suggestive of MEN2B. The diagnosis can be confirmed with genetic testing. Treatment for MEN2B typically includes removal of the thyroid and screening for the development of additional tumors.^[2]

There is another type of multiple endocrine neoplasia type 2 that causes an increased risk for medullary thyroid carcinoma and pheochromocytomas. This disease is known as multiple endocrine neoplasia type 2A (MEN2A).

Last updated: 3/8/2018

Symptoms Symptoms

The signs and symptoms of multiple endocrine neoplasia type 2B (MEN2B) include the development of tumors (neoplasias) of the endocrine glands. Endocrine glands are located throughout the body and are responsible for secreting hormones. The most common tumors that are found in people with MEN2B are medullary thyroid carcinoma (MTC) and tumors of the adrenal glands called pheochromocytomas. MTC is a type of thyroid cancer. In addition, tumor cells from medullary thyroid carcinomas can spread (metastasize) to other parts of the body. The risk for a person with MEN2B to develop a medullary thyroid carcinoma or changes in the production of the cells of the thyroid gland (hyperplasia) is nearly 100%. People with MEN2B are most likely to develop medullary thyroid carcinomas in childhood or early adulthood.^[2]

Pheochromocytomas are typically not cancerous (they are usually benign), but they can cause other health problems such as high blood pressure (hypertension). The risk for a person with MEN2B to develop a pheochromocytoma is about 50%.^[2]

MEN2B can also cause changes in the skin. People with MEN2B may have lumps and bumps on the lips, eyelids, and tongue. They also may have eyelids and lips that appear thicker than in most people. Children with MEN2B may not have tears when they cry.^[3] Some people with MEN2B have growths that can form in the gastrointestinal tract called ganglioneuromas. These growths can cause signs and symptoms including diarrhea or constipation and may present as early as infancy.^[4] People with MEN2B are often tall and may have long fingers, toes, arms, and legs (marfanoid habitus). They may have hyperflexible joints, especially during childhood.^[1]^[2]

Last updated: 3/8/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
Percent of people who have these symptoms is not available through HPO
Abnormality of the skin		0000951
Aganglionic megacolon		0002251
Autosomal dominant inheritance		0000006
Colonic diverticula		0002253
Constipation		0002019
Diarrhea	Watery stool	0002014
Disproportionate tall stature		0001519
Elevated calcitonin		0003528
Elevated urinary epinephrine		0003639
Failure to thrive in infancy	Faltering weight in infancy Weight faltering in infancy [ more ]	0001531
Ganglioneuroma		0003005
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Global developmental delay		0001263
High, narrow palate	Narrow, high-arched roof of mouth Narrow, highly arched roof of mouth [ more ]	0002705
Hyperlordosis	Prominent swayback	0003307
Joint laxity	Joint instability Lax joints Loose-jointedness Loosejointedness [ more ]	0001388
Kyphosis	Hunched back Round back [ more ]	0002808
Medullary thyroid carcinoma		0002865
Myopathy	Muscle tissue disease	0003198
Nodular goiter		0005994
Parathyroid hyperplasia	Enlarged parathyroid glands	0008208
Pectus excavatum	Funnel chest	0000767
Pes cavus		0001761
Pheochromocytoma		0002666
Proximal femoral epiphysiolysis	Slipped end part of innermost thighbone	0006461
Scoliosis	Abnormal curving of the spine	0002650
Thick eyebrow	Bushy eyebrows Dense eyebrow Heavy eyebrows Prominent eyebrows Thick eyebrows [ more ]	0000574
Thick lower lip vermilion	Increased volume of lower lip Plump lower lip Prominent lower lip [ more ]	0000179

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 5/1/2018

Cause Cause

Multiple endocrine neoplasia type 2B (MEN2B) is caused by certain genetic changes (mutations or pathogenic variants) in the RET gene. This gene provides instructions to the body to make a protein that helps regulate the growth and division of cells of the endocrine system. This protein is supposed to tell the body when it is appropriate to allow the cells of the endocrine system to divide. When there is a pathogenic variant in the RET gene, the cells of the endocrine system are able to grow and divide out of control. This causes the signs and symptoms of MEN2B, as well as the increased risk for the development of tumors.^[2]

About 95% of people who have MEN2B have a pathogenic variant in one particular area of the RET gene known as codon 918. Genetic changes in this region of the RET gene are thought to cause the RET gene to be more highly activated than other genetic changes within the RET gene. This is why MEN2B causes a higher risk for tumor development at a younger age as compared to other pathogenic variants in the RET gene.^[2]

Last updated: 3/8/2018

Inheritance Inheritance

Multiple endocrine neoplasia type 2B (MEN2B) is inherited in an autosomal dominant manner.^[1] This means that a person only needs one copy of the RET gene to have a change (mutation or pathogenic variant) causing MEN2B. We inherit one copy of every gene from our mother and the other from our father. When a person who has MEN2B has children, for each child there is a:

50% chance that the child will inherit the copy of the RET gene with a pathogenic variant, meaning he or she will have MEN2B
50% chance that the child will inherit the working copy of the RET gene, meaning he or she will not have MEN2B

In some cases, people who have MEN2B are the first people to be diagnosed in the family. This may be because they inherited the genetic change from a parent, but the parent was never diagnosed with the disease. In other cases, the genetic change may be new in the person who was diagnosed with MEN2B. Genetic changes that are new in a person are called de novo. It is estimated that about 50% of people with MEN2B have a genetic change that is de novo.^[2]

Last updated: 3/8/2018

Diagnosis Diagnosis

Multiple endocrine neoplasia type 2B (MEN2B) is suspected when a doctor sees a person who has a personal or family history of medullary thyroid carcinoma or pheochromocytoma. The diagnosis may also be suspected based on physical features suggestive of MEN2B such as having bumps on the eyelids or lips and long arms, legs, fingers, and toes.^[2] The diagnosis of MEN2B can be confirmed with genetic testing of the RET gene.^[2]

Last updated: 3/8/2018

Treatment Treatment

People with multiple endocrine neoplasia type 2B (MEN2B) are recommended to have their thyroid removed (thyroidectomy) as soon as they are diagnosed. This is because the risk for medullary thyroid carcinoma is nearly 100% in people who have MEN2B, and a thyroidectomy can prevent a person from ever developing medullary thyroid carcinoma.^[2]

After the thyroid is removed, a person with MEN2B may still have tests to make sure a medullary thyroid carcinoma did not develop and spread before the thyroid was removed.^[2] If the medullary thyroid carcinoma cannot be completely removed, there are therapies available such as tyrosine kinase inhibitors. These therapies can slow the growth of medullary thyroid carcinomas.^[5] People who have thyroidectomies need to take medications that contain the hormones that are normally produced by the thyroid.^[2]

People with MEN2B may also be recommended to have frequent tests such as analysis of the blood or urine for signs that there may be a tumor in the adrenal glands(pheochromocytoma). Imaging tests such as MRI or CT scan can also be used to monitor for the development of a pheochromocytoma.^[2] If a pheochromocytoma is identified, it may be removed with surgery.^[2]

Last updated: 3/8/2018

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Prognosis Prognosis

The long-term outlook for people with multiple endocrine neoplasia type 2B (MEN2B) may depend upon when a person with the disease was diagnosed. If the disease is identified early, prior to the development of a medullary thyroid carcinoma, the thyroid can be removed. Because medullary thyroid cancer often metastasizes, spreading cancer to other tissues in the body, removal of the thyroid (thyroidectomy) greatly reduces the chances that a person with MEN2B develops cancer. The other types of tumors which develop in people with MEN2B are usually not cancerous (benign) and therefore do not tend to be life-threatening.^[2]

If a person is diagnosed with MEN2B after he or she has already developed medullary thyroid carcinoma, the thyroid can be removed. If the cells of the tumor have already spread to other parts of the body (metastasized), surgery may not be able to remove all of the cancer. This can increase the risk for a person to pass away from the disease.^[2]

Other symptoms of MEN2B, such as gastrointestinal symptoms, are not life-threatening but can impact a person’s quality of life.^[5]

Last updated: 3/8/2018

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Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Multiple endocrine neoplasia type 2B. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

American Multiple Endocrine Neoplasia Support
1027 Hampshire Drive
Maryville, TN 37801
Telephone: 865-238-5842
E-mail: http://amensupport.org/contact%20us
Website: http://www.amensupport.org/
Association for Multiple Endocrine Neoplasia Disorders (AMEND) (UK, New Zealand, and USA)
The Warehouse
No 1 Draper Street
Southborough
Tunbridge Wells Kent TN4 0PG
United Kingdom
Telephone: + 44 (0)1892 516076
E-mail: info@amend.org.uk
Website: http://www.amend.org.uk

Social Networking Websites

RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

Organizations Providing General Support

Rare Cancers Australia
PO Box 440
Bowral New South Wales, 2576 Australia
Telephone: +61 2 4862 276
E-mail: contact@rarecancers.org.au
Website: http://rarecancers.org.au/

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Multiple endocrine neoplasia type 2B. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Brandi ML. Multiple endocrine neoplasia type 2B. Orphanet. April 2015; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=247709.
Hughes MS, Feliberti E, Perry RR, and Vinik A. Multiple Endocrine Neoplasia Type 2A (including Familial Medullary Carcinoma) and Type 2B. Endotext. October 8, 2017; https://www.ncbi.nlm.nih.gov/books/NBK481898/.
Lee R, Hyer J, Chowdhury H, and Teimory M. Ocular signs of multiple endocrine neoplasia type 2B (MEN2B). The Journal of Clinical Endocrinology and Metabolism. March 2012; 97(3):725-726. https://www.ncbi.nlm.nih.gov/pubmed/22238409.
Multiple Endocrine Neoplasia, Type IIB; MEN2B. Online Mendelian Inheritance in Man. October 13, 2016; https://www.omim.org/entry/162300.
Grey J and Winter K. Patient quality of life and prognosis in multiple endocrine neoplasia type 2. Endocrine-related Cancer. February 2018; 25(2):T69-T77. https://www.ncbi.nlm.nih.gov/pubmed/29066504.