Familial and Hereditary Forms of Primary Hyperparathyroidism

© 2015 John P. Bilezikian, Robert Marcus, and Michael A. Levine Published by Elsevier Inc. All rights reserved.. Primary hyperparathyroidism (PHPT) may occur as part of a complex syndrome or as an isolated (non-syndromic) disorder, and both of these forms can occur as hereditary (i.e., familial) or non-familial (i.e., sporadic) diseases. Syndromic forms of PHPT include multiple endocrine neoplasia (MEN) types 1 to 4 (MEN1 to MEN4), and the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. MEN1 is caused by abnormalities of the MEN1 gene which encodes a tumor suppressor; MEN2 and MEN3 are due to mutations of the rearranged during transfection (. RET) proto-oncogene; MEN4 is due to mutations of a cyclin-dependent-kinase inhibitor (. CDNK1B); and HPT-JT is due to mutations of cell division cycle 73 (. CDC73) which encodes parafibromin. Non-syndromic PHPT, which may be familial and referred to as familial isolated hyperparathyroidism (FIHP), may also be due to mutations of the MEN1, CDC73, or calcium-sensing receptor (. CASR) genes. In addition, ≈10% of patients presenting below the age of 45 years with non-syndromic (sporadic) PHPT may have MEN1, CDC73, or CASR mutations, and overall more than 10% of patients with PHPT will have a mutation in one of 11 genes.