Hyperparathyroidism-jaw tumor syndrome

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disorder characterized by the development of parathyroid tumors, ossifying fibromas of the mandible and maxilla, cystic and neoplastic renal abnormalities, and uterine tumors. One of its unique characteristics is its association with a high prevalence of atypical parathyroid adenomas and carcinomas. HPT-JT is caused by mutations in the HRPT2 gene that reduce expression or function of parafibromin, a nuclear protein that regulates gene expression and inhibits cellular proliferation (Carpten et al., Nat Genet 32(4):676-680, 2002; Yart et al., Mol Cell Biol 25(12):5052-5060, 2005; Zhang et al., Biochem Biophys Res Commun 350(1):17-24, 2006; Woodard et al., Oncogene 24(7):1272-1276, 2005). Prior to recognition of HRPT2, HPT-JT was diagnosed using clinical criteria and was based on the presence of ossifying jaw tumors in a patient with primary hyperparathyroidism (PHPT) who lacked features of other complex syndromes associated with hyperfunctioning parathyroid glands. Patients with HPT-JT also manifest a more aggressive form of PHPT than is typical of sporadic or other genetic forms of PHPT, due in part to the presence of atypical parathyroid tumors and the increased risk of parathyroid carcinoma (Marx, N Engl J Med 343(25):1863-1875, 2000). Moreover, patients with HPT-JT have asynchronous development of parathyroid tumors, so recurrence of PHPT is common after removal of one or more parathyroid tumors.