Multiple Endocrine Neoplasia Type 2

Diagnostic test for MEN2

Familial Mutation, Targeted Sequencing 2001961
Method: Polymerase Chain Reaction/Sequencing

Useful when a pathogenic familial variant identifiable by sequencing is known

Related Test
Hereditary Cancer Panel, Sequencing and Deletion/Duplication 2012032
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Multiple endocrine neoplasia type 2 (MEN2) is a rare hereditary syndrome caused by pathogenic variants in the RET gene. MEN2 can be further classified into subtypes MEN2A, MEN2B, and familial medullary thyroid cancer (FMTC). All MEN2 types have an increased risk of medullary thyroid cancer (MTC). MEN2A (70-80% of MEN2 cases) is also associated with benign parathyroid adenomas, adrenal gland tumors (pheochromocytoma), and nerve cell tumors (ganglioneuromatosis). MEN2B is associated with more aggressive MTC that can occur during childhood and with benign neuromas often found in the mucous membranes. Pheochromocytomas develop in approximately 50% of individuals with MEN2B. FMTC is considered a variant of MEN2A and is characterized as multiple cases (often four or more) of MTC in a family, without the presence of pheochromocytomas or hyperparathryoidism.

Disease Overview




MEN2 has three defined subtypes 

  • MEN2A: 70-80% of cases
    • Early onset MTC: typically prior to 35 years
    • Pheochromocytoma
    • Parathyroid adenoma/hyperplasia
  • MEN2B: ~5% of cases
    • Early onset MTC: childhood
    • Pheochromocytoma
    • Mucosal abnormalities
    • Gastrointestinal ganglioneuromatosis
    • Eye abnormalities: eg, corneal nerve thickening
    • Skeletal abnormalities: eg, marfanoid body
  • FMTC: 10-20% of cases
    • Associated with MTC only
    • FMTC is considered a variant of MEN2A and is characterized as multiple cases (often four or more) of MTC in a family, without the presence pheochromocytomas or hyperparathryoidism





Autosomal dominant


  • Clinical course differs between subtypes
  • Penetrance of MTC 
    • 95% for MEN2A
    • Nearly 100% for FMTC and MEN2B

De novo Pathogenic Variants

  • 5% of MEN2A 
  • 50% of MEN2B pathogenic variants 

Test Interpretation


  • Clinical sensitivity
  • Analytical sensitivity/specificity: 99%


  • Positive: one RET pathogenic variant detected
    • Confirms diagnosis and etiology
  • Negative: no RET pathogenic variants detected
    • MEN2A, MEN2B, or FMTC is unlikely, but not excluded
  • Inconclusive: RET variant detected, but whether variant is benign or pathogenic is unknown


  • Not evaluated
    • Regulatory region variants
    • Deep intronic variants
    • Large deletions/duplications
    • RET exons other than 5, 8, 10, 11, 13-16
  • Diagnostic errors can occur due to rare sequence variations
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Last Update: August 2019