Genomic coordinate (human 10:43,077,069 RET) & (mouse 6:118,128,706 Ret).
Cytoband (human 10q11.21 RET) & (mouse 6qE3 Ret).
Here I present: “Multiple Endocrine Neoplasia”, Victor McKusick, Mendelian Inheritance in Man’, 1966.
Multiple Endocrine Neoplasia (MEN) is a genetic disorder causing tumors, often benign but sometimes cancerous, in multiple endocrine glands like the parathyroid, pituitary, pancreas, thyroid, and adrenals, leading to hormone overproduction and symptoms such as kidney stones, abdominal pain, or headaches, with main types being MEN1 (affecting parathyroid, pituitary, pancreas) and MEN2 (thyroid, adrenals, nervous system). It’s inherited, though new mutations can occur, and requires genetic counseling and regular monitoring for early detection and management.
Types of MEN
- MEN Type 1 (MEN1): Primarily affects the 3 Ps: Parathyroid (most common), Pituitary, and Pancreas (islets).
- MEN Type 2 (MEN2): Involves the thyroid (medullary thyroid cancer), adrenal glands (pheochromocytoma), and nervous system (MEN2A, MEN2B).
- MEN Type 4 (MEN4): Similar symptoms to MEN1 but with a different genetic cause (CDKN1B gene), rarer than MEN1 and MEN2.
Common Symptoms (Vary by Type)
- Hyperparathyroidism (MEN1, MEN2A): High calcium, kidney stones, bone loss, fatigue.
- Pituitary Tumors (MEN1):Headaches, vision changes, lactation (prolactinoma).
- Pancreatic Tumors (MEN1):Abdominal pain, ulcers, low blood sugar.
- Thyroid Tumors (MEN2):Thyroid lumps, potentially cancer.
- Adrenal Tumors (MEN2): High blood pressure, anxiety.
- Other: Muscle pain, weight loss, fatigue, mental changes.
Causes & Inheritance
- Caused by genetic mutations, usually inherited in an autosomal dominant pattern (one mutated copy from a parent).
- New mutations can occur without family history.
- MEN1: Due to mutations in the MEN1 gene.
- MEN2: Due to mutations in the RET gene. There is evidence that Multiple Endocrine Neoplasia-2A is caused by mutation in the RET proto-oncogene (RET) gene encoded on genomic coordinate 10:43,077,069 and cytoband 10q11.21 in humans.
The RET proto-oncogene (RET) encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor (GDNF) family of extracellular signaling molecules. RET loss of function mutations is associated with the development of Hirschsprung’s disease, while gain of function mutations are associated with the development of various types of human cancer, including papillary thyroid carcinoma, multiple endocrine neoplasias type 2A and 2B.
