SNP Shot: Genomic Insights

Multiple endocrine neoplasia (MEN) encompasses a group of disorders impacting the endocrine system, the body's network of hormone-producing glands. Hormones act as chemical messengers, traveling through the bloodstream to regulate cell and tissue function throughout the body. MEN is characterized by the presence of tumors (neoplasia) in at least two endocrine glands, though tumors can also arise in other organs and tissues. These growths can be either noncancerous (benign) or cancerous (malignant). Cancerous tumors can make the condition life-threatening.

The primary forms of MEN are classified as type 1, type 2, and type 4. These classifications are based on the specific genes involved, the types of hormones produced, and the characteristic signs and symptoms associated with each type.

Various types of tumors are linked to MEN. Type 1 commonly involves tumors in the parathyroid glands, pituitary gland, and pancreas. Tumors in these glands can lead to hormone overproduction. The most frequent symptom of MEN type 1 is overactivity of the parathyroid glands, known as hyperparathyroidism. This condition disrupts the normal calcium balance in the blood, potentially causing kidney stones, bone thinning, nausea, vomiting, high blood pressure (hypertension), weakness, and fatigue.

The most common symptom of MEN type 2 is medullary thyroid carcinoma, a type of thyroid cancer. Some individuals with this disorder also develop pheochromocytoma, a tumor of the adrenal glands that can lead to dangerously elevated blood pressure. MEN type 2 is further categorized into three subtypes: type 2A, type 2B (formerly known as type 3), and familial medullary thyroid carcinoma (FMTC). These subtypes are distinguished by their unique signs and symptoms and the risk of developing specific tumors. For instance, hyperparathyroidism is seen only in type 2A, while FMTC is characterized solely by medullary thyroid carcinoma. The symptoms of MEN type 2 tend to be consistent within a given family.

MEN type 4 exhibits similar signs and symptoms to type 1, although it is caused by mutations in a different gene. The most prevalent feature is hyperparathyroidism, followed by tumors of the pituitary gland, other endocrine glands, and other organs.

Inheritance:

MEN type 1 typically follows an autosomal dominant inheritance pattern. Individuals with this condition are born with one mutated copy of the MEN1 gene in each cell. In most instances, the altered gene is inherited from an affected parent. However, in some cases, the condition arises from new mutations in the MEN1 gene, occurring in individuals with no family history of the disorder. Unlike most other autosomal dominant conditions, where one altered copy of a gene is sufficient to cause the disorder, two copies of the MEN1 gene must be altered to trigger tumor formation in MEN type 1. A mutation in the second copy of the MEN1 gene occurs in a small number of cells during a person's lifetime. Almost all individuals born with one MEN1 mutation will acquire a second mutation in certain cells, leading to unregulated cell division and tumor formation.

MEN type 2 and type 4 also follow an autosomal dominant inheritance pattern. In these cases, one copy of the mutated gene is enough to cause the disorder. Affected individuals often inherit an altered RET or CDKN1B gene from one parent with the condition. However, some cases result from new mutations in the gene and occur in people without other affected family members.