Format

Send to:

Choose Destination

Multiple endocrine neoplasia, type 2b(MEN2B)

MedGen UID:
9959
Concept ID:
C0025269
Neoplastic Process
Synonyms: MEN 2B; MEN IIB; MEN2B; Mucosal neuroma syndrome; Multiple endocrine neoplasia, type 3; Multiple endocrine neoplasia, type 3 (formerly); MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB; MULTIPLE ENDOCRINE NEOPLASIA, TYPE III; NEUROMATA, MUCOSAL, WITH ENDOCRINE TUMORS; Wagenmann-froboese syndrome
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Multiple endocrine neoplasia, type 3 (61530001); MEN, type 3 (61530001); Mucosal neuroma syndrome (61530001); Multiple endocrine neoplasia, type 2b (61530001); MEN 2B syndrome (61530001); MEN 3 - Multiple endocrine neoplasia type 3 (61530001); MEN 2B - Multiple endocrine neoplasia type 2B (61530001); Multiple endocrine neoplasia type 2B (61530001); MEN 3 syndrome (61530001); Multiple endocrine neoplasia type 3 (61530001)
 
Gene (location): RET (10q11.21)
OMIM®: 162300
Orphanet: ORPHA247709

Disease characteristics

Excerpted from the GeneReview: Multiple Endocrine Neoplasia Type 2
Multiple endocrine neoplasia type 2 (MEN 2) is classified into three subtypes: MEN 2A, FMTC (familial medullary thyroid carcinoma), and MEN 2B. All three subtypes involve high risk for development of medullary carcinoma of the thyroid (MTC); MEN 2A and MEN 2B have an increased risk for pheochromocytoma; MEN 2A has an increased risk for parathyroid adenoma or hyperplasia. Additional features in MEN 2B include mucosal neuromas of the lips and tongue, distinctive facies with enlarged lips, ganglioneuromatosis of the gastrointestinal tract, and a "marfanoid" habitus. MTC typically occurs in early childhood in MEN 2B, early adulthood in MEN 2A, and middle age in FMTC. [from GeneReviews]
Authors:
Jessica Marquard  |  Charis Eng   view full author information

Additional descriptions

From OMIM
Multiple endocrine neoplasia type IIB (MEN2B) is an autosomal dominant hamartoneoplastic syndrome characterized by aggressive medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuromas, and thickened corneal nerves. Most affected individuals have characteristic physical features, including full lips, thickened eyelids, high-arched palate, and marfanoid habitus. Other more variable features include skeletal anomalies and gastrointestinal problems (review by Morrison and Nevin, 1996). For a discussion of genetic heterogeneity of multiple endocrine neoplasia (MEN), see MEN1 (131100).  http://www.omim.org/entry/162300
From GHR
Multiple endocrine neoplasia is a group of disorders that affect the body's network of hormone-producing glands called the endocrine system. Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia typically involves tumors (neoplasia) in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, the condition can be life-threatening.The major forms of multiple endocrine neoplasia are called type 1, type 2, and type 4. These types are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms.Many different types of tumors are associated with multiple endocrine neoplasia. Type 1 frequently involves tumors of the parathyroid glands, the pituitary gland, and the pancreas. Tumors in these glands can lead to the overproduction of hormones. The most common sign of multiple endocrine neoplasia type 1 is overactivity of the parathyroid glands (hyperparathyroidism). Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, nausea and vomiting, high blood pressure (hypertension), weakness, and fatigue.The most common sign of multiple endocrine neoplasia type 2 is a form of thyroid cancer called medullary thyroid carcinoma. Some people with this disorder also develop a pheochromocytoma, which is an adrenal gland tumor that can cause dangerously high blood pressure. Multiple endocrine neoplasia type 2 is divided into three subtypes: type 2A, type 2B (formerly called type 3), and familial medullary thyroid carcinoma (FMTC). These subtypes differ in their characteristic signs and symptoms and risk of specific tumors; for example, hyperparathyroidism occurs only in type 2A, and medullary thyroid carcinoma is the only feature of FMTC. The signs and symptoms of multiple endocrine neoplasia type 2 are relatively consistent within any one family.Multiple endocrine neoplasia type 4 appears to have signs and symptoms similar to those of type 1, although it is caused by mutations in a different gene. Hyperparathyroidism is the most common feature, followed by tumors of the pituitary gland, additional endocrine glands, and other organs.  https://ghr.nlm.nih.gov/condition/multiple-endocrine-neoplasia

Clinical features

Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Colonic diverticula
MedGen UID:
3878
Concept ID:
C0012819
Disease or Syndrome
The presence of multiple diverticula of the colon.
Ganglioneuroma
MedGen UID:
6545
Concept ID:
C0017075
Neoplastic Process
Nodular goiter
MedGen UID:
42271
Concept ID:
C0018023
Disease or Syndrome
Hirschsprung disease
MedGen UID:
5559
Concept ID:
C0019569
Disease or Syndrome
Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a birth defect characterized by complete absence of neuronal ganglion cells from a portion of the intestinal tract. The aganglionic segment includes the distal rectum and a variable length of contiguous proximal intestine. In 80% of individuals, aganglionosis is restricted to the rectosigmoid colon (short-segment disease); in 15%-20%, aganglionosis extends proximal to the sigmoid colon (long-segment disease); in about 5%, aganglionosis affects the entire large intestine (total colonic aganglionosis). Rarely, the aganglionosis extends into the small bowel or even more proximally to encompass the entire bowel (total intestinal aganglionosis). HSCR is considered a neurocristopathy, a disorder of cells and tissues derived from the neural crest, and may occur as an isolated finding or as part of a multisystem disorder. Affected infants frequently present in the first two months of life with symptoms of impaired intestinal motility such as failure to pass meconium within the first 48 hours of life, constipation, emesis, abdominal pain or distention, and occasionally diarrhea. However, because the initial diagnosis of HSCR may be delayed until late childhood or adulthood, HSCR should be considered in anyone with lifelong severe constipation. Individuals with HSCR are at risk for enterocolitis and/or potentially lethal intestinal perforation.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
Pheochromocytoma
MedGen UID:
18419
Concept ID:
C0031511
Neoplastic Process
Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas (tumors that arise from neuroendocrine tissues symmetrically distributed along the paravertebral axis from the base of the skull to the pelvis) and by pheochromocytomas (paragangliomas that are confined to the adrenal medulla). Sympathetic paragangliomas hypersecrete catecholamines; parasympathetic paragangliomas are most often nonsecretory. Extra-adrenal parasympathetic paragangliomas are located predominantly in the skull base, neck, and upper medistinum; approximately 95% of such tumors are nonsecretory. In contrast, sympathetic extra-adrenal paragangliomas are generally confined to the lower mediastinum, abdomen, and pelvis, and are typically secretory. Pheochromocytomas, which arise from the adrenal medulla, typically hypersecrete catecholamines. Symptoms of PGL/PCC result either from mass effects or catecholamine hypersecretion (e.g., sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, forceful palpitations, pallor, and apprehension or anxiety). The risk for malignant transformation is greater for extra-adrenal sympathetic paragangliomas than for pheochromocytomas or skull base and neck paragangliomas.
Abnormality of the skin
MedGen UID:
11449
Concept ID:
C0037268
Congenital Abnormality
Joint laxity
MedGen UID:
39439
Concept ID:
C0086437
Pathologic Function
Slipped femoral capital epiphyses
MedGen UID:
57704
Concept ID:
C0149887
Disease or Syndrome
Medullary thyroid carcinoma
MedGen UID:
66772
Concept ID:
C0238462
Neoplastic Process
Parathyroid hyperplasia
MedGen UID:
75767
Concept ID:
C0271844
Disease or Syndrome
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
Scoliosis
MedGen UID:
195976
Concept ID:
C0700208
Finding
The presence of an abnormal lateral curvature of the spine.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
Disproportionate tall stature
MedGen UID:
323048
Concept ID:
C1836996
Finding
High, narrow palate
MedGen UID:
324787
Concept ID:
C1837404
Finding
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
Thick eyebrow
MedGen UID:
377914
Concept ID:
C1853487
Finding
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Failure to thrive in infancy
MedGen UID:
358083
Concept ID:
C1867873
Finding
Elevated urinary epinephrine
MedGen UID:
358197
Concept ID:
C1868393
Finding
Elevated calcitonin
MedGen UID:
401432
Concept ID:
C1868394
Finding
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Multiple endocrine neoplasia, type 2b in Orphanet.

Professional guidelines

PubMed

ACMG Board of Directors.
Genet Med 2015 Jan;17(1):68-9. Epub 2014 Nov 13 doi: 10.1038/gim.2014.151. PMID: 25356965
Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, Naruse M, Pacak K, Young WF Jr; Endocrine Society.
J Clin Endocrinol Metab 2014 Jun;99(6):1915-42. doi: 10.1210/jc.2014-1498. PMID: 24893135
Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG; American College of Medical Genetics and Genomics.
Genet Med 2013 Jul;15(7):565-74. Epub 2013 Jun 20 doi: 10.1038/gim.2013.73. PMID: 23788249Free PMC Article
Raue F, Rondot S, Schulze E, Szpak-Ulczok S, Jarzab B, Frank-Raue K
Eur J Hum Genet 2012 Jan;20(1) Epub 2011 Aug 24 doi: 10.1038/ejhg.2011.142. PMID: 21863057Free PMC Article
Chen H, Sippel RS, O'Dorisio MS, Vinik AI, Lloyd RV, Pacak K; North American Neuroendocrine Tumor Society (NANETS).
Pancreas 2010 Aug;39(6):775-83. doi: 10.1097/MPA.0b013e3181ebb4f0. PMID: 20664475Free PMC Article
American Thyroid Association Guidelines Task Force., Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA Jr
Thyroid 2009 Jun;19(6):565-612. doi: 10.1089/thy.2008.0403. PMID: 19469690
Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, Lips CJ, Lombardi G, Mannelli M, Pacini F, Ponder BA, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson NW, Tomassetti P, Tonelli F, Wells SA Jr, Marx SJ
J Clin Endocrinol Metab 2001 Dec;86(12):5658-71. doi: 10.1210/jcem.86.12.8070. PMID: 11739416
Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, van Amstel HK, Lips CJ, Nishisho I, Takai SI, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xue F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjöld M, Komminoth P, Hendy GN, Mulligan LM
JAMA 1996 Nov 20;276(19):1575-9. PMID: 8918855

External

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

Recent clinical studies

Etiology

Jones BA, Sisson JC
J Pediatr 1983 Feb;102(2):219-23. PMID: 6130134
Carney JA, Sizemore GW, Hayles AB
Pathobiol Annu 1978;8:105-53. PMID: 364372
Carney JA, Sizemore GW, Lovestedt SA
Oral Surg Oral Med Oral Pathol 1976 Jun;41(6):739-52. PMID: 1063979
Carney JA, Go VL, Sizemore GW, Hayles AB
N Engl J Med 1976 Dec 2;295(23):1287-91. doi: 10.1056/NEJM197612022952304. PMID: 980061

Diagnosis

Damm DD
Gen Dent 2010 Sep-Oct;58(5):457, 459. PMID: 20829172
Jones BA, Sisson JC
J Pediatr 1983 Feb;102(2):219-23. PMID: 6130134
Carney JA, Sizemore GW, Hayles AV
Cancer 1979 Dec;44(6):2173-83. PMID: 389410
Cuthbert JA, Gallagher ND, Turtle JR
Aust N Z J Med 1978 Oct;8(5):518-20. PMID: 33647
Carney JA, Hayles AB
Mayo Clin Proc 1977 Sep;52(9):543-8. PMID: 895196

Prognosis

Carney JA, Go VL, Sizemore GW, Hayles AB
N Engl J Med 1976 Dec 2;295(23):1287-91. doi: 10.1056/NEJM197612022952304. PMID: 980061

Clinical prediction guides

Winkelmann RK, Carney JA
J Invest Dermatol 1982 Nov;79(5):307-12. PMID: 6127365

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center