Age of MTC Diagnosis for RET634F Mutation
Individuals with the RET634F mutation typically develop medullary thyroid carcinoma (MTC) by adolescence or early adulthood, with C-cell hyperplasia beginning in early childhood and most patients developing it by age 5 if left untreated. 1
Risk Classification and Timing of Disease Development
The RET634F mutation is classified as a high-risk (Level B) mutation according to the American Thyroid Association guidelines 1. This classification has important implications:
- C-cell hyperplasia, the precursor to MTC, begins in early childhood in patients with RET634F mutation
- The probability of developing invasive MTC increases significantly with age
- 100% of patients with codon 634 mutations will develop MTC if left untreated 1
Age-Related Findings from Clinical Studies
Research shows a clear progression of disease development with age in patients with codon 634 mutations:
In high-risk mutations like codon 634, MTC was found in:
- 30% of children aged 3 years or less
- 44% of children aged 4-6 years
- 69% of children aged 7-12 years 2
The yield of cancer in removed thyroid specimens was 100% for codon 634 mutations (9/9 patients across 5 families) in one study 3
MTC has been diagnosed in children as young as 5 years old with RET mutations 3
Implications for Management
Due to the high risk of early MTC development with RET634F mutation:
- Prophylactic total thyroidectomy is strongly recommended by age 5 years for children with codon 634 mutations 1, 4
- For carriers with C634F mutation specifically, surgery can be postponed until age 5 unless calcitonin levels increase 4
- Annual calcitonin measurement and thyroid ultrasound are recommended starting at age 3 while awaiting surgery 1
Important Considerations
- Serum calcitonin levels may be physiologically elevated in infancy, limiting their utility before age 3 1
- Waiting for an increase in calcitonin levels may not guarantee that surgery is performed before MTC develops in high-risk mutations 3
- Early prophylactic thyroidectomy has been shown to have a high cure rate and lower complication rates compared to delayed surgery 2
Monitoring After Diagnosis
For patients with RET634F mutation:
- Postoperative monitoring should include calcitonin and CEA measurements
- Lifelong surveillance is necessary for MEN2A-associated conditions:
- Screening for pheochromocytoma starting at age 10 (every 2 years)
- Annual hyperparathyroidism screening with serum calcium and PTH monitoring 1
The age of MTC diagnosis in RET634F mutation carriers varies based on when screening or prophylactic surgery is performed, but without intervention, most patients will develop MTC by adolescence or early adulthood, with C-cell hyperplasia beginning much earlier in childhood.