{"id":27129,"date":"2024-05-26T13:26:53","date_gmt":"2024-05-26T11:26:53","guid":{"rendered":"https:\/\/www.krebs-praedisposition.de\/?post_type=kompendium&p=27129"},"modified":"2025-08-26T11:45:00","modified_gmt":"2025-08-26T09:45:00","slug":"multiple-endocrine-neoplasia-type-2a-and-2b","status":"publish","type":"kompendium","link":"https:\/\/www.krebs-praedisposition.de\/en\/kompendium\/multiple-endocrine-neoplasia-type-2a-and-2b\/","title":{"rendered":"Multiple Endocrine Neoplasia Type 2A and 2B"},"content":{"rendered":"

Multiple Endocrine Neoplasia Type 2A and 2B \u2013\u00a0Definition<\/h2><\/div>
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Multiple endocrine neoplasia type 2 (MEN2) includes MEN2A (OMIM #171400), familial medullary thyroid carcinoma (FMTC, OMIM #155240) and MEN2B (OMIM #162300). All three entities are based on pathogenic variants in the RET <\/em>protooncogene and predispose to medullary thyroid carcinoma (MTC) and pheochromocytoma (PHEO). In addition, MEN2A can lead to parathyroid adenomas or hyperplasia with primary hyperparathyroidism (PHPT). Certain pathogenic variants show a combination of MEN2A and cutaneous lichen amyloidosis or Hirschsprung’s disease.<\/p>\n<\/div>

Synonyms:<\/p>\n<\/div><\/div><\/div>

MEN2A: Sipple syndrome<\/p>\n

MEN2B: Mucosal neuroma syndrome, Wagenmann-Frob\u00f6se syndrome<\/p>\n<\/div><\/div><\/div><\/div>

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Gene:<\/p>\n<\/div><\/div><\/div>

RET<\/i><\/p>\n<\/div><\/div><\/div><\/div>

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Gene \u00adproduct:<\/p>\n<\/div><\/div><\/div>

RET<\/p>\n<\/div><\/div><\/div><\/div>

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Function:<\/p>\n<\/div><\/div><\/div>

Tyrosine kinase receptor mediates growth and differentiation signals intracellularly and from the intracellular compartment to the extracellular space. Pathogenic MEN2\u00a0variants confer a gain of function, i.e., increased enzyme activity.<\/p>\n<\/div><\/div><\/div><\/div>

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Pattern of inheritance:<\/p>\n<\/div><\/div><\/div>

Autosomal-dominant
\nMEN2A 9% de novo<\/em> mutations, MEN2B 50% de novo<\/em> mutations<\/p>\n<\/div><\/div><\/div><\/div>

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Prevalence:<\/p>\n<\/div><\/div><\/div>

Total MEN2: 1:35.000 \u2013 1:40.000
\n91% MEN2A (35% isolated FMTC), 9% MEN2B<\/p>\n<\/div><\/div><\/div><\/div>

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Genotype-phenotype correlation:<\/p>\n<\/div><\/div><\/div>

Codon 918 pathogenic variants are considered to be at the highest risk of MTC; associated with the majority of cases with MEN2B; no PHPT.
\nCodon 883 pathogenic variants are considered to be at a high risk of MTC; associated with MEN2B, including mucosal neuromas and PHEO.
\nCodon 634 pathogenic variants are considered to be at a high risk of MTC, PHEO, and PHPT.
\nCodon 634 and 804 pathogenic variants are associated with cutaneous lichen amyloidosis.
\nCodon 609, 611, 618, and 620 pathogenic variants are associated with Hirschsprung\u2019s disease.<\/p>\n<\/div><\/div><\/div><\/div>

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Penetrance:<\/p>\n<\/div><\/div><\/div>

MEN2A: MTC 95%, PHEO 50%, parathyroid adenoma 20-30%
\nFMTC: MTC 100%, PHEO 0%, parathyroid adenoma 0%
\nMEN2B: MTC 100%, PHEO 50%, parathyroid adenoma rare<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/div>

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Overview of the Chapters on This Page:<\/h4><\/div><\/div><\/div>