Familial syndromes associated with thyroid cancer in the era of personalized medicine.

Background: Well-differentiated thyroid cancer accounts for 95% of thyroid malignancies, and 5% of these patients will have familial disease. This compares to 25% of patients with medullary thyroid cancer (MTC) having a familial form; however, this accounts for only 1% of all patients with thyroid cancer. Most cases of familial thyroid cancer are nonmedullary (NMFTC), and have been shown to be present in familial cancer syndromes such as familial adenomatous polyposis, Cowden syndrome, Carney complex, Pendred syndrome, and Werner syndrome. This review discusses the contemporary management of the patients with familial-syndrome-associated thyroid cancer based on their individual risks for developing thyroid cancer.
Summary: Most of the progress in the genetics of familial thyroid cancer has been in patients with MTC. The mutations in patients with isolated NMFTC have not been as well defined as in MTC. They are likely autosomal dominant with reduced penetrance. The patients with these familial syndromes most likely have a susceptibility gene that increases the risk of thyroid cancer. Most of the patients with a familial syndrome and NMFTC will have papillary thyroid carcinoma, suggesting that a specific gene for papillary thyroid carcinoma may also be present. In many cases, patients have a known familial syndrome that has defined risk for thyroid cancer.
Conclusions: Patients with familial syndromes that are associated with thyroid cancer can be individually categorized based on syndrome risks for developing thyroid cancer. The clinician must also be knowledgeable in recognizing the possibility of an underlying familial syndrome when a patient presents with thyroid cancer.