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Disease Profile

Multiple endocrine neoplasia type 2B

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Childhood

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ICD-10

D44.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

MEN 2B; Mucosal neuroma syndrome; Multiple endocrine neoplasia, type 3 (formerly);

Categories

Congenital and Genetic Diseases; Digestive Diseases; Endocrine Diseases;

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).

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]

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.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Aganglionic megacolon
Enlarged colon lacking nerve cells
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
Flushing
0031284
Ganglioneuroma
0003005
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Global developmental delay
0001263
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
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
Muscular hypotonia
Low or weak muscle tone
0001252
Myopathy
Muscle tissue disease
0003198
Nodular goiter
0005994
Parathyroid hyperplasia
Enlarged parathyroid glands
0008208
Pectus excavatum
Funnel chest
0000767
Pes cavus
High-arched foot
0001761
Pheochromocytoma
0002666
Proximal femoral epiphysiolysis
Slipped end part of innermost thighbone
0006461
Scoliosis
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

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]

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]

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]

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

    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

        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.

          References

          1. Brandi ML. Multiple endocrine neoplasia type 2B. Orphanet. April 2015; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=247709.
          2. 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/.
          3. 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.
          4. Multiple Endocrine Neoplasia, Type IIB; MEN2B. Online Mendelian Inheritance in Man. October 13, 2016; https://www.omim.org/entry/162300.
          5. 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.

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