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Multiple endocrine neoplasia, type 2(MEN2)

MedGen UID:
887211
•Concept ID:
C4048306
•
Neoplastic Process
Synonym: MEN2
SNOMED CT: Multiple endocrine neoplasia, type 2 (61808009); MEN, type 2 (61808009); Sipple syndrome (61808009); PTC syndrome (61808009); Familial chromaffinomatosis (61808009); MEA, type 2 (61808009); Multiple endocrine adenomatosis, type 2 (61808009); Sipple's syndrome (61808009)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (Orphanet)
 
Gene (location): RET (10q11.21)
 
Monarch Initiative: MONDO:0019003
Orphanet: ORPHA653

Disease characteristics

Excerpted from the GeneReview: Multiple Endocrine Neoplasia Type 2
Multiple endocrine neoplasia type 2 (MEN2) includes the following phenotypes: MEN2A, familial medullary thyroid carcinoma (FMTC, which may be a variant of MEN2A), and MEN2B. All three phenotypes involve high risk for development of medullary carcinoma of the thyroid (MTC); MEN2A and MEN2B involve an increased risk for pheochromocytoma; MEN2A involves an increased risk for parathyroid adenoma or hyperplasia. Additional features of MEN2B 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 MEN2B, early adulthood in MEN2A, and middle age in FMTC. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  GeneReview Scope  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Charis Eng  |  Gilman Plitt   view full author information

Professional guidelines

PubMed

Management of medullary carcinoma of the thyroid: a review.
Jayasinghe R, Basnayake O, Jayarajah U, Seneviratne S
J Int Med Res 2022 Jul;50(7):3000605221110698. doi: 10.1177/03000605221110698. PMID: 35822284Free PMC Article
PRECISION MEDICINE: AN UPDATE ON GENOTYPE/BIOCHEMICAL PHENOTYPE RELATIONSHIPS IN PHEOCHROMOCYTOMA/PARAGANGLIOMA PATIENTS.
Gupta G, Pacak K; AACE Adrenal Scientific Committee
Endocr Pract 2017 Jun;23(6):690-704. Epub 2017 Mar 23 doi: 10.4158/EP161718.RA. PMID: 28332883Free PMC Article
Biochemical diagnosis, localization and management of pheochromocytoma: focus on multiple endocrine neoplasia type 2 in relation to other hereditary syndromes and sporadic forms of the tumour.
Pacak K, Ilias I, Adams KT, Eisenhofer G
J Intern Med 2005 Jan;257(1):60-8. doi: 10.1111/j.1365-2796.2004.01425.x. PMID: 15606377

Curated

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Neuroendocrine and Adrenal Tumors, 2023

Recent clinical studies

Etiology

Multiple endocrine neoplasia type 2: towards a risk-based approach integrating molecular and biomarker results.
Machens A, Dralle H
Curr Opin Oncol 2024 Jan 1;36(1):1-12. Epub 2023 Nov 3 doi: 10.1097/CCO.0000000000001009. PMID: 37975407
Multiple endocrine neoplasia type 2: A review.
Mathiesen JS, Effraimidis G, Rossing M, Rasmussen ÅK, Hoejberg L, Bastholt L, Godballe C, Oturai P, Feldt-Rasmussen U
Semin Cancer Biol 2022 Feb;79:163-179. Epub 2021 Apr 1 doi: 10.1016/j.semcancer.2021.03.035. PMID: 33812987
Hereditary paragangliomas.
Raygada M, Pasini B, Stratakis CA
Adv Otorhinolaryngol 2011;70:99-106. Epub 2011 Feb 24 doi: 10.1159/000322484. PMID: 21358191Free PMC Article
Medullary thyroid carcinoma.
Pacini F, Castagna MG, Cipri C, Schlumberger M
Clin Oncol (R Coll Radiol) 2010 Aug;22(6):475-85. doi: 10.1016/j.clon.2010.05.002. PMID: 20627492
Temporal paragangliomas.
Suárez C, Sevilla MA, Llorente JL
Eur Arch Otorhinolaryngol 2007 Jul;264(7):719-31. Epub 2007 Mar 2 doi: 10.1007/s00405-007-0267-3. PMID: 17333230

Diagnosis

Multiple endocrine neoplasia type 2: towards a risk-based approach integrating molecular and biomarker results.
Machens A, Dralle H
Curr Opin Oncol 2024 Jan 1;36(1):1-12. Epub 2023 Nov 3 doi: 10.1097/CCO.0000000000001009. PMID: 37975407
Management of medullary carcinoma of the thyroid: a review.
Jayasinghe R, Basnayake O, Jayarajah U, Seneviratne S
J Int Med Res 2022 Jul;50(7):3000605221110698. doi: 10.1177/03000605221110698. PMID: 35822284Free PMC Article
Phaeochromocytomas and sympathetic paragangliomas.
Petri BJ, van Eijck CH, de Herder WW, Wagner A, de Krijger RR
Br J Surg 2009 Dec;96(12):1381-92. doi: 10.1002/bjs.6821. PMID: 19918850
Temporal paragangliomas.
Suárez C, Sevilla MA, Llorente JL
Eur Arch Otorhinolaryngol 2007 Jul;264(7):719-31. Epub 2007 Mar 2 doi: 10.1007/s00405-007-0267-3. PMID: 17333230
Phaeochromocytoma.
Lenders JW, Eisenhofer G, Mannelli M, Pacak K
Lancet 2005 Aug 20-26;366(9486):665-75. doi: 10.1016/S0140-6736(05)67139-5. PMID: 16112304

Therapy

RET aberrant cancers and RET inhibitor therapies: Current state-of-the-art and future perspectives.
Addeo A, Miranda-Morales E, den Hollander P, Friedlaender A, O Sintim H, Wu J, Mani SA, Subbiah V
Pharmacol Ther 2023 Feb;242:108344. Epub 2023 Jan 9 doi: 10.1016/j.pharmthera.2023.108344. PMID: 36632846Free PMC Article
Novel targeted therapeutics for MEN2.
Redaelli S, Plaza-Menacho I, Mologni L
Endocr Relat Cancer 2018 Feb;25(2):T53-T68. doi: 10.1530/ERC-17-0297. PMID: 29348306
Pheochromocytomas in Multiple Endocrine Neoplasia Type 2.
Tsang VH, Tacon LJ, Learoyd DL, Robinson BG
Recent Results Cancer Res 2015;204:157-78. doi: 10.1007/978-3-319-22542-5_7. PMID: 26494388
Inherited cancer syndromes and the thyroid: an update.
Metzger R, Milas M
Curr Opin Oncol 2014 Jan;26(1):51-61. doi: 10.1097/CCO.0000000000000030. PMID: 24300902
Development of RET kinase inhibitors for targeted cancer therapy.
Mologni L
Curr Med Chem 2011;18(2):162-75. doi: 10.2174/092986711794088308. PMID: 21110809

Prognosis

Multiple endocrine neoplasia type 2: A review.
Mathiesen JS, Effraimidis G, Rossing M, Rasmussen ÅK, Hoejberg L, Bastholt L, Godballe C, Oturai P, Feldt-Rasmussen U
Semin Cancer Biol 2022 Feb;79:163-179. Epub 2021 Apr 1 doi: 10.1016/j.semcancer.2021.03.035. PMID: 33812987
Age and MEN2 outcome.
Castinetti F
Aging (Albany NY) 2019 Jun 12;11(11):3416-3417. doi: 10.18632/aging.102030. PMID: 31188782Free PMC Article
Temporal paragangliomas.
Suárez C, Sevilla MA, Llorente JL
Eur Arch Otorhinolaryngol 2007 Jul;264(7):719-31. Epub 2007 Mar 2 doi: 10.1007/s00405-007-0267-3. PMID: 17333230
Pheochromocytomas and secreting paragangliomas.
Plouin PF, Gimenez-Roqueplo AP
Orphanet J Rare Dis 2006 Dec 8;1:49. doi: 10.1186/1750-1172-1-49. PMID: 17156452Free PMC Article
Phaeochromocytoma.
Lenders JW, Eisenhofer G, Mannelli M, Pacak K
Lancet 2005 Aug 20-26;366(9486):665-75. doi: 10.1016/S0140-6736(05)67139-5. PMID: 16112304

Clinical prediction guides

Clinical presentation of MEN 2A in index vs. non-index patients.
Machens A, Lorenz K, Weber F, Brandenburg T, Führer-Sakel D, Dralle H
Endocrine 2023 Nov;82(2):450-455. Epub 2023 Jul 21 doi: 10.1007/s12020-023-03459-8. PMID: 37477781
Children are at a high risk of hypocalcaemia and hypoparathyroidism after total thyroidectomy.
de Jong M, Nounou H, Rozalén García V, Christakis I, Brain C, Abdel-Aziz TE, Hewitt RJ, Kurzawinski TR
J Pediatr Surg 2020 Jul;55(7):1260-1264. Epub 2019 Jul 19 doi: 10.1016/j.jpedsurg.2019.06.027. PMID: 31383578
New insights into the pathophysiology of achalasia and implications for future treatment.
Furuzawa-Carballeda J, Torres-Landa S, Valdovinos MÁ, Coss-Adame E, Martín Del Campo LA, Torres-Villalobos G
World J Gastroenterol 2016 Sep 21;22(35):7892-907. doi: 10.3748/wjg.v22.i35.7892. PMID: 27672286Free PMC Article
Pheochromocytomas in Multiple Endocrine Neoplasia Type 2.
Tsang VH, Tacon LJ, Learoyd DL, Robinson BG
Recent Results Cancer Res 2015;204:157-78. doi: 10.1007/978-3-319-22542-5_7. PMID: 26494388
Head and neck paragangliomas in von Hippel-Lindau disease and multiple endocrine neoplasia type 2.
Boedeker CC, Erlic Z, Richard S, Kontny U, Gimenez-Roqueplo AP, Cascon A, Robledo M, de Campos JM, van Nederveen FH, de Krijger RR, Burnichon N, Gaal J, Walter MA, Reschke K, Wiech T, Weber J, Rückauer K, Plouin PF, Darrouzet V, Giraud S, Eng C, Neumann HP
J Clin Endocrinol Metab 2009 Jun;94(6):1938-44. Epub 2009 Mar 31 doi: 10.1210/jc.2009-0354. PMID: 19336503Free PMC Article

Recent systematic reviews

Risk-reduction surgery in pediatric surgical oncology: A perspective.
Sandoval JA, Fernandez-Pineda I, Malkan AD
J Pediatr Surg 2016 Apr;51(4):675-87. Epub 2016 Feb 3 doi: 10.1016/j.jpedsurg.2016.01.004. PMID: 26898681
The association between Hirschsprung's disease and multiple endocrine neoplasia type 2a: a systematic review.
Coyle D, Friedmacher F, Puri P
Pediatr Surg Int 2014 Aug;30(8):751-6. Epub 2014 Jun 28 doi: 10.1007/s00383-014-3538-2. PMID: 24972642

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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NCCN, 2023
      NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Neuroendocrine and Adrenal Tumors, 2023

    Reviews

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