Epidemiology, clinical features, and genetics of multiple endocrine neoplasia type 2B in a complete population.

Introduction Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary autosomal dominant endocrine syndrome comprising MEN 2A,MEN2B,and familialmedullary thyroid cancer (MTC) [1, 2]. MEN 2B is characterized by early development of aggressive MTC, and prophylactic total thyroidectomy is advocated by 6 months of age [3–5]. Multiple and bilateral pheochromocytoma occur in 50% of patients, and some with undiagnosed pheochromocytomamay die of cardiovascular crisis perioperatively [4, 6]. MEN 2Bmay be identified in infancy or early childhood [7] by the presence of mucosal neuromas of the anterior dorsal surface of the tongue, palate, or pharynx. Identification of RET gene mutations in MEN 2B in 1994 allowed the possibility of direct DNA-based mutation testing [3]. Before that, linkage testing was available [8, 9]. RET molecular genetic testing should be performed as soon as possible after birth in all children known to be at risk or, if no family history exists, as soon as the clinical diagnosis is suspected [2]. Most patients have mutations in codon 918 and, rarely, in codons 883 and 922. The epidemiology of MEN 2B is unknown. The prevalence of allMEN2cases is∼1 in35,000 [2].TheprevalenceofMEN2B is estimated as between 1 in 600,000 [10] to 1 in 4million [11], but no figures exist. The annual incidence has been estimated at 4 per 100 million per year [12].