FaCD Online Syndrome Fact Sheet

Last updated: 14 Jan 2010

Name: Familial Medullary Thyroid Carcinoma

Synonym: FMTC

Mode of Inheritance: AD

Genes

RET, mapped to 10q11.2

Tumor features

thyroid cancer, medullary

Non-tumor features

Hirschsprung disease

Comment

Medullary thyroid carcinoma in the absence of other features of multiple endocrine neoplasia type 2A or 2B (MEN2A and MEN2B) is the hallmark of familial medullary thyroid carcinoma (FMTC), which is associated with specific mutations in the RET proto-oncogene as well as with some of the mutations also reported in MEN2A[1,5,6]. The distinction between FMTC and MEN2 might be somewhat artificial: in a very large FMTC family reported by Moers et al.[2] pheochromocytoma was diagnosed after follow-up and a similar case was presented by Takami et al.[3].
As in MEN2A, the association of Hirschsprung disease with FMTC has been reported[4].

References

[1] Eng C, Mulligan LM. Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes, related sporadic tumours, and Hirschsprung disease. Hum Mutat 9[2], 97-109. 1997.
[2] Moers AMJ, Landsvater RM, Schaap C, Jansen-Schillhorn van Veen JM, de Valk IAJ, Blijham GH, Hoppener JWM, Vroom TM, Ploos van Amstel HK, Lips CJM. Familial medullary thyroid carcinoma: Not a distinct entity? Genotype-Phenotype correlation in a large family. Am J Med 1996; 101:635-641.
[3] Takami H, Thosen T, Shirahama S, Ogura K, Hikiji K. Does the syndrome of familial medullary thyroid carcinoma describe a distinct clinical entity? Eur J Cancer 34[10], 1639-1640. 1998.
[4] Sijmons RH, Hofstra RMW, Wijburg FA, Links TP, Zwierstra RP, Vermey A, Aronson DC, Tan-Sindhunata G, Brouwers-Smalbraak GJ, Maas SM, Buys CHCM. Oncological implications of RET gene mutations in Hirschsprung's disease. Gut 1998; 43:542-547.
[5] Kouvaraki MA, Shapiro SE, Perrier ND, Cote GJ, Gagel RF, Hoff AO, Sherman SI, Lee JE, Evans DB. RET proto-oncogene: a review and update of genotype-phenotype correlations in hereditary medullary thyroid cancer and associated endocrine tumors. Thyroid 2005; 15(6):531-44.
[6] Raue F, Frank-Raue K. Genotype-phenotype relationship in multiple endocrine neoplasia type 2. Implications for clinical management. Hormones (Athens). 2009 Jan-Mar;8(1):23-8.