Multiple Endocrine Neoplasia Type 2A and B (MEN2) [D44.8]
Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh
Approximately 20 to 25% of all medullary carcinomas of the thyroid are hereditary. MEN2 is a rare, usually hereditary, autosomal dominant tumor disease and has a prevalence of approx. 1 in 50,000. There are three subgroups (MEN2A, MEN2B and FMTC). In the most common form MEN2A (Sipple syndrome), the medullary thyroid carcinoma is accompanied by a pheochromocytoma and/or a parathyroid adenoma. Usually, clinical signs and symptoms first manifests within the 2nd or 3rd decade of life and include hyperparathyroidism, hyperthyrosis, Cushing syndrome and cutaneous lichen amyloidosis. FMTC (familial medullary thyroid carcinoma), which represents approx. 30-40% of all cases, is only accompanied by a medullary carcinoma of the thyroid. The prognosis can be improved significantly by pre-symptomatic diagnostics as well as a following thyroidectomy and surgical removal of pheochromocytomas.
MEN2A and FMTC are caused by mutations in RET proto-oncogene, which encodes a tyrosine kinase receptor. The most common mutations affect the exons 5, 8, 10, 11, 13, 14 and 15. A clear association has been made between specific mutations (genotypes), the age of onset and the aggressiveness of thyroid carcinomas.
Just like MEN2A, the less common form MEN2B (multiple endocrine neoplasia, type IIB, Wagenmann-Froboese syndrome) is also caused by mutations in the RET proto-oncogene. Inheritance is autosomal dominant; approx. 50% of all cases are de novo. The combination of medullary thyroid carcinomas, peochromocytomas and multiple neurinomas are characteristic. Major signs are café au lait spots, lip hypertrophy, marfanoid habitus, pectus excavatum and megacolon. The most important criteria for a differential diagnosis are the absence of nasal and laryngeal mucosa neurinomas as well as the presence of parathyroid adenomas in patients with MEN2A.
In predictive genetic testing, at-risk, asymptomatic individuals are tested, usually first-degree relatives of affected patients. According to the Genetic Diagnosis Act (GenDG) genetic counseling should be offered along with any genetic diagnostic procedure. In the case of predictive genetic testing, genetic counseling must be carried out prior to testing as well as after having received the result, unless there exists a written waiver of the at-risk person after having received written information on the content of the counseling.