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Multiple Endocrine Neoplasia Type 2B, Genetic Testing

Multiple endocrine neoplasia type 2B (MEN 2B) is a rare genetic disorder that affects multiple endocrine glands, leading to the development of tumors. MEN 2B is one of the subtypes of multiple endocrine neoplasia type 2 (MEN 2), and the presence of specific tumors and distinctive physical features primarily characterize it. MEN 2 is divided into two subtypes: MEN 2A and MEN 2B. The prevalence is 13-24 and 1-2 per million individuals in MEN 2A and MEN 2B, respectively. MEN 2B is the more aggressive form of the disease. Therefore, patients with this subtype have a poorer prognosis than those with MEN 2A.

Multiple endocrine neoplasia type 2B genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).

Critical features of Multiple Endocrine Neoplasia 2B include:

  • Medullary Thyroid Carcinoma (MTC): MTC is a type of thyroid cancer originating from parafollicular C cells. Individuals with MEN 2B almost invariably develop MTC.
  • Pheochromocytomas: Some individuals with MEN 2B may develop pheochromocytomas arising from the adrenal glands. These tumors can cause the overproduction of adrenaline and noradrenaline, leading to symptoms such as hypertension, palpitations, and sweating.
  • Neuromas: MEN 2B is associated with developing neuromas, particularly mucosal neuromas. These benign tumors affect the mucous membranes, especially those of the lips, tongue, and gastrointestinal tract.
  • Marfanoid Habitus: Individuals with MEN 2B often exhibit a Marfanoid habitus, characterized by tall stature, long limbs, joint hypermobility, and a narrow face.
  • Ganglioneuromatosis: Ganglioneuromatosis involves the overgrowth of nerve tissue in the gastrointestinal tract, leading to symptoms such as constipation and diarrhea.
  • Autosomal Dominant Inheritance: MEN 2B is inherited in an autosomal dominant pattern, meaning that a person with a mutated gene has a 50% chance of passing the mutation to each of their offspring.
  • Genetic Basis: MEN 2B is primarily associated with mutations in the RET proto-oncogene. Genetic testing can identify these mutations and confirm the diagnosis.

Due to the aggressive nature of medullary thyroid carcinoma, early detection through genetic testing is crucial in individuals with a family history of MEN 2B or symptoms suggestive of the syndrome. Prophylactic thyroidectomy (removal of the thyroid gland) is often recommended for individuals with MEN 2B to prevent the development of MTC.

Genetic counseling is essential for individuals with MEN 2B and their families to understand the genetic basis of the condition, assess the risk of passing it to future generations, and discuss available preventive measures and treatment options. Regular monitoring and early intervention can improve outcomes for individuals with MEN 2B.

More Information

The disease is caused by mutations in the RET gene, a proto-oncogene encoding a receptor tyrosine kinase of the glia-derived neurotrophic factor family.
The most common mutation causing MEN2B is c.2753T>C (p.Met918Thr), which can occur de novo or be inherited. It accounts for approximately 95% of all reported MEN2B cases. Experimental studies have shown that this nonsense change activates the protein and its oncogenic transformation, increasing cell transformation and differentiation capacity.
The c.1900T>G (C634R) variant is one of the most common variants in MEN2A. According to the American Thyroid Association (ATA) classification, this mutation is classified as a high-risk or aggressive variant. Any pathogenic mutation at codon 634 (c.1900T>G, c.1901G>A) implies increased pheochromocytomas and hyperparathyroidism.

Multiple endocrine neoplasia type 2B genetic testing analyzes the 16 most frequent pathogenic mutations of the RET gene.

The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).

Additional information
Results Time4 - 5 Weeks
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