Familial Hyperparathyroidism: Multiple Endocrine Neoplasia Types II and I; Familial Hypocalciuric Hypercalcemia; Hyperparathyroidism-Jaw Tumor Syndrome

Familial hyperparathyroidism occurs in a handful of genetic syndromes including Multiple Endocrine Neoplasia (MEN) type 1 and 2A, Familial Hypocalciuric Hypercalcemia (FHH), and Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT). MEN 1 is characterized by a loss of function in the tumor suppressor gene, Menin, whereas MEN 2 is characterized by a gain of function mutation in the RET proto-oncogene. FHH is characterized by mutations that alter the calcium-sensing receptor in the kidney and parathyroid glands, resulting in mild hypercalcemia and elevated PTH levels. HPT-JT is characterized by hereditary predisposition to jaw tumors and benign and malignant tumors of the parathyroids. All four syndromes are autosomal dominant, with variable penetrance of degree of clinical hyperparathyroidism. Each of these disorders requires careful evaluation, diagnostic testing, genetic analysis, and potentially, surgical management.