Genotype/phenotype correlations in multiple endocrine neoplasia type 2.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing clinical concepts without systematic review methodology
PubMed 39404342 · doi:10.1530/ERC-24-0139
What was done
This brief narrative review summarizes established and emerging genotype-phenotype correlations in multiple endocrine neoplasia type 2 (MEN 2) driven by rearranged during transfection (*RET*) gene mutations, as well as potential modifier factors influencing disease presentation.
What was found
Medullary thyroid cancer (MTC) occurs in approximately 100% of MEN 2A and MEN 2B cases, while pheochromocytoma occurs in roughly 50%. Specific *RET* mutations are linked to early-onset MTC risk starting from 1 year of age (highest risk) or 5 years of age (high risk), determining the optimal timing for prophylactic thyroidectomy. Specific variants also govern pheochromocytoma penetrance, though phenotypic variation exists where some carriers of high-risk mutations show non-aggressive MTC or never develop pheochromocytoma. No additional statistical data or quantitative measures were reported in the abstract.
Why it matters
Clarifying genotype-phenotype relationships and identifying disease modifiers can optimize the timing of preventive thyroidectomy and allow personalized surveillance for patients carrying pathogenic *RET* variants.
Limits
As a brief narrative review, it lacks a systematic literature search, pooled effect estimates, or standardized quality assessment of included studies. No patient sample sizes or specific modifier mechanisms are detailed in the abstract.
Cited by
- contradicts There is no cancer-associated gene mutation that is 100% penetrant.