Background
The rearranged during transfection (RET) V804M proto-oncogene mutation is rare and
associated with medullary thyroid carcinoma (MTC). We present 40 members from a total
cohort of 107 family members with this mutation.
Methods
Family members were tested for RET mutations, calcitonin levels, and screened for
pheochromocytoma and primary hyperparathyroidism (PHPT). Thyroidectomies were performed
on 15 members. Surgery and pathology reports were obtained and reviewed. A pedigree
was constructed.
Results
A high penetrance was found for MTC and simultaneous papillary thyroid carcinoma (PTC; 40%).
The incidence of PHPT was low (13%). There were no findings of pheochromocytoma. The
course in the first family generation was indolent, with late onset of MTC. The second
generation experienced earlier disease development; onset occurred earliest in the
third generation. The second generation experienced a higher incidence of PTC than
the first.
Conclusion
This is the largest family with this mutation reported to date. However, it does not
fit the classic familial MTC or MEN 2A cancer syndrome. Considering that PTC is not
an incidental finding, but the result of an inherited RET V804 M mutation, we propose
to identify this phenotypic expression as a unique syndrome consistent with manifestations
of MTC, PHPT, and PTC.
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Article info
Publication history
Accepted:
September 24,
2009
Identification
Copyright
© 2009 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
