Sorted By Test Name - Mayo Medical Laboratories

MENKM
81082
MENMS
80573
Multiple Endocrine Neoplasia Type 2 (2A, 2B, FMTC) Known
Mutation
Clinical Information: Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant cancer
syndrome that has classically been divided into 3 subtypes: MEN 2A, MEN 2B, and familial medullary
thyroid carcinoma (FMTC). The characteristic features of MEN 2A include multifocal medullary thyroid
carcinoma (MTC), bilateral pheochromocytoma, and primary hyperparathyroidism. MEN 2B is
characterized by MTC, pheochromocytoma, and multiple mucosal neuromas. Other features of MEN 2B
include enlarged nerves of the gastrointestinal tract (ganglioneuromatosis), marfanoid habitus, hypotonia,
and corneal nerve thickening. FMTC is diagnosed in families with 4 or more cases of MTC in the absence
of pheochromocytoma or parathyroid involvement. Age of onset is variable but may range from childhood
to the seventh decade. For MEN 2A, there is incomplete penetrance with only about two thirds of gene
carriers being symptomatic by age 70. Early diagnosis and appropriate surgical intervention can prevent
metastatic MTC and can reduce the morbidity and mortality associated with MTC. Biochemical screening
can increase the detection rate in asymptomatic individuals with a family history of MEN 2. This testing
involves the measurement of calcitonin with and without stimulation by calcium or pentagastrin to detect
early signs of thyroid disease (hyperplasia of calcitonin-producing cells [C-cells] of the thyroid). Missense
mutations in the RET proto-oncogene (located on chromosome 10) are responsible for the variable
phenotypes of MEN 2A, MEN 2B, and familial MTC (FMTC). The majority of mutations occur at
conserved cysteine residues within exons 10 and 11. Additional mutations in exons 13, 14, 15, and 16
account for the preponderance of other RET mutations. Taken together, mutations in these codons account
for approximately 98% of MEN 2A, >99% of MEN 2B, and 96% of FMTC. Although gain of function
mutations in the RET proto-oncogene may result in MEN2, loss of function mutations have been reported
in patients with Hirschsprung disease (HSCR). It has been reported that up to 50% of familial cases of
HSCR and 3% to 35% of sporadic HSCR are due to RET germline mutations. However, most of the
mutations that cause HSCR occur outside of the codons that are typically mutated in MEN2. Therefore,
the absence of a mutation utilizing this test does not rule out the diagnosis of HSCR.
Useful For: Screening of at-risk individuals when a mutation in the RET proto-oncogene has been
identified in an affected family member
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Hansford J, Mulligan L: Multiple endocrine neoplasia type 2 and RET: from
neoplasia to neurogenesis. J Med Genet 2000;37(11):817-827 2. Marini F, Falchetti A, Del Monte F,
Carbonell Sala S, et al: Multiple endocrine neoplasia type 2. Orphanet J Rare Dis. 2006 Nov 14;1:45 3.
Ruiz-Ferrer M, Fernandez RM, Antinolo G, et al: A complex additive model of inheritance for
Hirschsprung disease is supported by both RET mutations and predisposing RET haplotypes. Genet Med
2006;8(11):704-710
Multiple Endocrine Neoplasia Type 2 (2A, 2B, FMTC) Mutation
Screen
Clinical Information: Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant cancer
syndrome that has classically been divided into 3 subtypes: MEN 2A, MEN 2B, and familial medullary
thyroid carcinoma (FMTC). The characteristic features of MEN 2A include multifocal medullary thyroid
carcinoma (MTC), bilateral pheochromocytoma, and primary hyperparathyroidism. MEN 2B is
characterized by MTC, pheochromocytoma, and multiple mucosal neuromas. Other features of MEN 2B
include enlarged nerves of the gastrointestinal tract (ganglioneuromatosis), marfanoid habitus, hypotonia,
and corneal nerve thickening. FMTC is diagnosed in families with four or more cases of MTC in the
absence of pheochromocytoma or parathyroid involvement. Age of onset is variable but may range from
childhood to the seventh decade. For MEN 2A, there is incomplete penetrance with only about two thirds
of gene carriers being symptomatic by age 70. Early diagnosis and appropriate surgical intervention can
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