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Multiple Endocrine Neoplasia Type 2B, MEN2B - RET

MEN2B

Clinical Features

As in multiple endocrine neoplasia type 2A in the rare multiple endocrine neoplasia type 2B, medullary thyroid carcinoma and usually non-malignant tumors of the adrenal medulla (pheochromocytoma) occur. The risk for medullary thyroid cancer is almost 100%, with a frequent childhood manifestation. The risk for pheochromocytoma is app. 50%, with a later age of onset compared to the medullary thyroid cancer. Additionally, mucosal neuromas of the lips, tongue, buccal mucosa, or eyelid margins are common first symptoms. Along with the marfanoid habitus and the common developmental retardation, clinical diagnosis is evident. Intestinal ganglioneuromatosis may lead to symptoms resembling Hirschsprung disease with obstipation. The medullary thyroid carcinoma in individuals affected by MEN2B appears to follow a more aggressive course than in other forms with early metastases and onset in early childhood.

Genetic Information

MEN2B is an autosomal dominant disease, which is in app. 50% of the cases caused by a de novo mutation of the RET gene. The gene locus is mapped to chromosome 10q11.2. MEN2B is caused by a mutation either in codon 918 of exon 16 or to a lesser extend in codon 883 in exon 15 of the RET-proto-oncogene (re-arranged-during-transfection), which affects the signal transducting amino acid tyrosine in the receptor molecule. The mutation underlying MEN2B is located in the same gene but at another location as in MEN2A.

Prevalence

Rare

Diagnostic