Multiple endocrine neoplasia (MEN) syndromes include several types of autosomal dominant inherited familial cancer syndromes, each characterized by a different pattern of endocrine gland tumors in affected individuals. The two major types are MEN1 (Wermer syndrome) and MEN2 (Sipple syndrome). MEN1 is an autosomal dominant disorder characterized by a high frequency of peptic ulcer disease and primary endocrine abnormalities involving the parathyroids (90-97% of patients), pancreatic islets (30-80% of patients; including adenoma, prolactinoma, insulinoma, glucagonoma, gastrinoma, etc.), and anterior pituitary (15-50% of patients).1 MEN2 includes subtypes MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC, non-MEN), with the primary clinical features of medullary thyroid carcinoma (MTC; 95% of patients), pheochromocytoma (pheo; 50% of MEN2A and MEN2B), parathyroid hyperplasia (15-30% of MEN2A and rarely in MEN2B), plus mucosal neuromas (lips and tongue), ganglioneuromas of the gastrointestinal tract, and marfanoid habitus in MEN2B only.1 The MEN2A diagnostic category characterizes approximately 60% to 90% of patients with MEN2, FMTC accounts for 5% to 35%, and MEN2B for about 5%.2 In addition, MTC and pheo may be bilateral or multifocal with an earlier age of onset than sporadic occurrence of the same tumor type.

Penetrance of both MEN1 and MEN2 is nearly complete by 60 years of age.1,3 While these syndromes are uncommon (1 in 10,000 to 100,000 for MEN1 and 1 in 25,000 to 30,000 for MEN2), diagnosis of these autosomal dominant disorders has important implications for other family members because first-degree relatives have a 50% risk of inheriting the causative mutation and developing the disease. Early detection is critical for the most effective intervention with the goal of treatment prior to tumor metastasis. However,these two syndromes and their underlying molecular pathology present very different challenges for the clinical molecular laboratory as a study in contrasts of allelic heterogeneity and detection sensitivity.


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