Hereditary medullary thyroid carcinoma (MTC) presents within the context of 3 genetic syndromes. Multiple endocrine neoplasia type 2A (MEN2A, Sipple’s syndrome) is an autosomal-dominant genetic syndrome that includes MTC, pheochromocytoma, and primary hyperparathyroidism (PHPT). MEN2B is an autosomal-dominant genetic syndrome that includes MTC, pheochromocytoma, multiple mucosal neuromas, and a...

Dominantly inherited multiple endocrine neoplasia type 2B (MEN2B) is characterized by tumors of the thyroid C-cells and adrenal chromaffin cells, together with ganglioneuromas of the gastrointestinal tract and other developmental abnormalities. Most cases are caused by substitution of threonine for Met918 in the RET receptor tyrosine kinase, which is believed to convert the RET gene to an oncog...

Multiple endocrine neoplasia type 2B (MEN2B) is a highly aggressive thyroid cancer syndrome. Since almost all sporadic cases are caused by the same nucleotide substitution in the RET proto-oncogene, the calculated disease incidence is 100-200 times greater than would be expected based on the genome average mutation frequency. In order to determine whether this increased incidence is due to an e...

We present a 15-year-old female patient with medullary thyroid carcinoma, marfanoid habitus, and mucosal ganglioneuromatosis. Our case had a RET protooncogene mutation ser836 polymorphism in exon 14 and ser904 polymorphism in exon 15. Our patient is thought to be atypical MEN2B due to the absence of M918T or A883F mutations. Chilaiditi sign is an incidental radiographic finding of a usually asy...

We demonstrate that a Hirschsprung (HSCR) mutation in the tyrosine kinase domain of the RET proto-oncogene abolishes in cis the tyrosine-phosphorylation associated with the activating mutation in multiple endocrine neoplasia type 2A (MEN2A) in transiently transfected Cos cells. Yet the double mutant RET2AHS retains the ability to form stable dimers, thus dissociating the dimerization from the p...

Multiple endocrine neoplasias (MENs) are genetic syndromes distinguished by specific patterns of benign and malignant tumors of endocrine glands. MEN2 is caused by autosomal dominant inheritance of a gain-of-function mutation in the RET proto-oncogene on chromosome 10 (Mulligan & Ponder 1995, Santoro et al. 1995) and is further subclassified into three syndromes based on clinical phenotype: MEN...

The familial risk of medullary thyroid carcinoma (MTC alone or as part of multiple endocrine neoplasms, MEN2A/MEN2B) is high, so we aimed to answer open questions about the lifetime cumulative risk of thyroid cancer (LCRTC at 0-79 years) among relatives of MTC patients by age and sex. For this nationwide study, a cohort of 3217 first-/second-degree relatives (FDRs/SDRs) of 389 MTC patients diag...

127 Multiple endocrine neoplasia type 2 (MEN2) syndromes are autosomally dominant clinical associations characterised by a number of tumours, including medullary thyroid carcinoma (MTC), phaeochromocytoma, thyroid C-cell hyperplasia (CCH), parathyroid tumours (MEN2A) and ganglioneuroma of the gastrointestinal tract (MEN2B). The common factor in the MEN2 syndromes is MTC, a poorly differentiated...