{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:09:59Z","timestamp":1790424599728,"version":"4.1.0"},"reference-count":44,"publisher":"Bioscientifica","issue":"12","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,10,15]]},"abstract":"<jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                    <jats:p>\n                      <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"images\/ERC-24-0139inf1.jpeg\"\/>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Multiple endocrine neoplasia type 2 (MEN 2) is a rare hereditary endocrine tumor syndrome caused by mutations in the rearranged during transfection (RET) gene. MEN 2 is divided into two main entities, MEN 2A and MEN 2B, both of which present with medullary thyroid cancer (MTC) in approximately 100% of cases and pheochromocytoma in 50% of cases. Specific RET mutations are associated with a risk of early onset of MTC, from 1 year of age (highest risk) to 5 years of age (high risk). This risk defines the optimal timing for thyroidectomy, ideally at an age when the disease has not spread. This is the most important genotype-phenotype correlation observed in MEN 2. Specific RET mutations also define the penetrance of pheochromocytoma. However, despite the presence of these highest\/high-risk variants, some patients unexpectedly present with non-aggressive MTC or never present with pheochromocytoma, suggesting that factors other than the major RET variant may modify the natural history and genotype-phenotype correlations. Improving our understanding of the genotype-phenotype correlations would allow individualizing the management and follow-up of patients with MEN 2. The aim of this brief review is to discuss the main genotype-phenotype correlations in MEN 2 and the potential factors that might influence these correlations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/erc-24-0139","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T10:57:24Z","timestamp":1728989844000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":9,"title":["Genotype\/phenotype correlations in multiple endocrine neoplasia type 2"],"prefix":"10.1530","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1808-8800","authenticated-orcid":true,"given":"Frederic","family":"Castinetti","sequence":"first","affiliation":[{"name":"Aix Marseille University, INSERM, MMG, Department of Endocrinology, La Conception Hospital, Assistance Publique Hopitaux de Marseille, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3693-5145","authenticated-orcid":true,"given":"Charis","family":"Eng","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Genomics, Medical Specialties Institute, Cleveland Clinic, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Recent Results in Cancer Research","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/978-3-319-22542-5_8","article-title":"Primary hyperparathyroidism in MEN2 syndromes","volume":"204","author":"Alevizaki","year":"2015","unstructured":"Alevizaki M & Saltiki K 2015 Primary hyperparathyroidism in MEN2 syndromes. 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