Hereditary Medullary Thyroid Carcinoma: Genetic Analysis of Three Related Syndromes

Hereditary medullary thyroid carcinoma (MTC) appears in three forms: 1) in association with pheochromocytomas and parathyroid hyperplasia (multiple endocrine neoplasia type 2 A [MEN 2A]); 2) with pheochromocytomas, neuromas of the mucous membranes, and a marfanoid appearance (MEN 2B): and 3) without pheochromocytoma. Despite these differences in presentation, age of onset, and clinical severity, limited genetic studies suggest that the three MTC variants may be due to inherited mutations at the same gene locus. We present further data in support of the hypothesis that allelic variation may underlie the diversity of these endocrine neoplasia syndromes