MEN2 Phenotype Definitions
The ‘Comments’ for each database entry may contain more MEN2 phenotype information.
The MEN2A, MEN2B, FMTC, and Unclassified phenotype definitions were derived from the international RET consortium guidelines for classification of MEN2 disease phenotypes. Note: these definitions may lead to two different phenotype designations (e.g. FMTC and MEN2A) for the same mutation, depending on the clinical symptoms per family.
MEN2A: Family (or individual) with MTC, and at least one individual developing HPT, pheo, or both.
MEN2B: MTC (with or without pheo) and characteristic clinical features: mucosal ganglioneuromas, GI ganglioneuromas, eye abnormalities including CNT, and skeletal abnormalities including marfanoid body habitus.
FMTC: Four or more family members with MTC only. No clinical evidence of Pheo, HPT, or any MEN2B-specific clinical features in affected or at-risk family members.
Unclassified: A family (or individual) with suspected or known hereditary MEN2 disease who do not meet the clinical criteria to be classified by a specific MEN2 syndrome.
- An MEN2 family with less than four cases of MTC only.
- An MEN2 family with four or more cases of MTC, but the family’s clinical history was not well documented (e.g. no pheo or HPT screening was reported or a possible pheo was not confirmed).
- MEN2 disease is suspected, because at least three unrelated individuals with MTC only had the same germline RET sequence change.
- MEN2 disease is suspected, because literature reports generally describe family as having MEN2 disease or inherited MTC (limited or no available clinical information).
Unknown: Not enough clinical information to conclusively determine the MEN2 Phenotype. It is "unknown" if the individualís or familyís phenotype is due to MEN2 disease or due to other causes.
- Family (or individual) with one case of MTC. It is unknown if MTC was due to hereditary MEN2 disease or was an isolated, sporadic MTC.
- Germline RET sequence variation was always found in cis with another RET sequence change (no reports of the variation alone).
- A HSCR patient with a rare or novel RET sequence change (located within a codon usually associated with MEN2/MTC RET sequence changes) that was not screened for MEN2 symptoms.
- Family (or individual) is affected by MEN2 clinical features, but without MTC. Some MEN2 clinical features, such as pheos, HPT, and Marfanoid body habitus, can be associated with other sporadic or hereditary diseases.
No MEN2 disease: No known reports of the sequence change causing MEN2 disease.
- A family with a RET sequence change that had no clinical evidence of MEN2 in the at-risk family members.
- The family had one member with the sporadic form of MTC.
- The family (or individual) was affected by HSCR only, no evidence of MEN2 upon screening.