SPORADIC
MEDULLARY THYROID CANCER-IS GENETIC TESTING INDICATED?
Most
medullary thyroid carcinomas (MTC) are sporadic. However, approximately 25 %
are familial as part of the multiple endocrine neoplasia type 2 (MEN2)
syndrome. Familial MTC (FMTC), an inherited syndrome characterized by the
presence of only MTC, without the other manifestations of MEN2 syndrome (such
as hyperparathyroidism or pheochromocytoma) was considered as a separate
clinical entity, but is now considered a variant of MEN2A.
Germline
RET testing should be considered in all patients with newly diagnosed C-cell
hyperplasia (CCH) or apparently sporadic medullary thyroid cancer (MTC). This
genetic testing should include sequencing of exons 10, 11 and 13 through 16 of
the RET gene. Sequencing of the remaining exons in the RET gene should be
considered in patients with clinical features or family history highly
suggestive of hereditary MTC who demonstrate no mutations in exons 10, 11 or 13
through 16. Despite that genetic testing can be ordered by the clinician,
consultation with genetic counselors should be preferred since they are
familial with the ethical issues and legal informed consent requirements
involved in germline testing. When the index patient is positive for a germline
mutation, family members should be offered genetic counseling and genetic screening.
It is
estimated that, on average, approximately 6 – 7 % (range, 1.5 to 24 %) of
unselected patients with MTC have germline RET mutations and in about half of
these cases gene carriers were identified in relatives. Interestingly, 75 % of
patients with familial MTC had no prior family history.
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