Hyperparathyroidism-Jaw Tumor Syndrome

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant syndrome with incomplete penetrance and variable expression. It is associated with germline mutations in the tumor suppressor gene CDC73 that encodes for a protein named parafibromin with antiproliferative properties. Primary hyperparathyroidism (pHPT) in HPT-JT develops at young age in almost 100% of mutation carriers. It is usually caused initially by a single gland involvement, with high prevalence of atypical parathyroid adenoma or carcinoma (20%) and histological cystic changes (25%) unlike other forms of hereditary pHPT like MEN 1 or MEN 2. It can be associated with ossifying fibromas of the mandible and maxilla (30% of cases), arising typically prior to the third decade of life, with cystic and neoplastic renal abnormalities (20%) and hyperplastic, neoplastic uterine involvement at early age (50%). Surgery is the treatment for all these tumors, and the optimal surgical approach to pHPT remains controversial (both selective and extensive parathyroidectomy have been suggested). The diagnosis must be confirmed by genetic testing. In HPT-JT families, the screening should be performed in children before the age of 10, and long-term follow-up is indicated for all patients due to the 25% risk of recurrent pHPT and/or new tumors.