AGE-RELATED DISEASE PENETRANCE IN A LARGE MEDULLARY-THYROID CANCER FAMILY WITH A CODON-609 RET GENE MUTATION

Background: Familial medullary thyroid cancer (MTC) is a form of type 2 multiple endocrine neoplasia in which individuals develop MTC as the sole phenotypic manifestation of their disease. A previous study has suggested that patients with familial MTC may have a later age of onse t (and more indolent course) of MTC than is observed in individuals wi th multiple endocrine neoplasia type 2A.Methods and Results: The age-r elated penetrance nf MTC, C-cell hyperplasia, and a positive pentagast rin test for carriers of a codon 609 mutation of the RET gene in a lar ge MTC family was determined. Pentagastrin testing and surgical pathol ogy findings for patients who had thyroidectomies were correlated with RET sequence analysis findings. The penetrance of this mutation for t he development of MTC was 0% at age 20, 10% at age 30, 50% at age 45, and approximately 100% at age 60. The ages of onset of C-cell hyperpla sia and a positive pentagastrin stimulation test were similar, and bot h preceded the age of onset of MTC. Carriers of the mutated gene in th is family had a later age of onset of disease than has been reported f or families with multiple endocrine neoplasia type 2A and 2B syndromes . Conclusions: These results may have implications for the clinical ma nagement of MTC families with a 609 mutation.