Multiple endocrine neoplasia type 2B: A genotype-phenotype diagnostic and therapeutic approach

Abstract

Multiple endocrine neoplasia type 2B (MEN 2B) is a rare genetic syndrome with an estimated prevalence of 0.9 to 1.6 per million individuals and an annual incidence of 1.4 to 2.6 per million live births. It is caused by a mutation in the RET proto-oncogene and is characterized by the presence of medullary thyroid carcinoma (MTC) in 100% of cases, pheochromocytoma in up to 50%, and extraendocrine features such as a marfanoid phenotype, musculoskeletal and dental abnormalities, mucosal neuromas, alacrimia, and diffuse intestinal ganglioneuromatosis with symptoms of esophageal and gastrointestinal dysmotility. This syndrome is associated with a diminished quality of life and poor survival, primarily due to the aggressiveness of MTC, which often presents at an early or metastatic stage. Diagnosis is often delayed, resulting in a delayed comprehensive approach that includes genetic profiling, early surgical management of MTC, and specific therapies such as tyrosine kinase inhibitors (TKIs) for advanced MTC. Surgery remains the mainstay and the only potential cure, although the advent of targeted therapies appears to improve progression-free survival in advanced cases.

Keywords

• carcinoma
• medullary
• nanoparticles;
• pheochromocytoma
• multiple endocrine neoplasia type 2b
• neuroma