Among 173 patients with pheochromocytomas, those with MEN2 or NF1 had higher plasma MN concentrations than those with VHL or SDH mutations, whereas those with SDH mutations had higher plasma 3MT concentrations than those with VHL.
2] Nonstandard abbreviations: MEN2, multiple endocrine neoplasia type 2; VHL, von Hippel-Lindau disease; NF1, neurofibromatosis type 1; SDH, succinate dehydrogenase; MN, metanephrine; NMN, normetanephrine; 3MT, 3-methoxytyramine.
7,8) Children of families with MTC and the MEN2 syndromes have been reported to develop early metastatic tumours even before the age of 5 years.
The aim of this study was to evaluate the profile of RET in MEN2 families with special attention to the risk to children, and to assess risk and determine treatment protocols for their management.
A further cysteine radical mutation at the 620 position was related to MEN2 in 3 families, plus 1 other unique family referred from elsewhere, in which MEN and HSCR co-existed.
11) It has also been postulated to be one of the reasons why patients with VHL are less likely to present with hypertension (especially of the paroxysmal type) than patients with MEN2
The RET variants that alter RET function to cause MEN2
syndromes are mutations, whereas variants that do not cause MEN2
syndromes are polymorphisms (2,16-20).
Missense mutations in the RET protooncogene have been shown to cause MEN2, and these occur primarily in exons 10, 11, 13, 14, 15, and 16 (1 ).
An association between alterations at specific codons and the MEN2 subtypes has been shown (2,3).
At present, testing for a total of 17 diseases is offered, with the most recent additions being DNA sequencing-based challenges for familial cancers associated with MEN2
Thus, given that >92% of MEN2 families have been found to carry a RET mutation , identification of gene carriers by direct means offers a more reliable, age-independent alternative to biochemical screening.
Given the important decisions that must be made in light of a diagnosis of MEN2, this type of rapid mutation detection will undoubtedly continue to have great clinical utility.