Hyperparathyroidism-jaw tumor syndrome (HPT-JT): A case report with parathyroid carcinoma

Inactivating germline mutations in the HRPT2 tumor suppressor gene are the cause of the hyperparathyroidism-jaw tumor syndrome (HPT-JT). The most common feature of HPT-JT is primary hyperparathyroidism, followed by ossifying fibromas of the maxilla and mandible, renal cysts and solid tumors. As recently recognized, mutations of this gene also play a central role in the molecular pathogenesis of parathyroid carcinoma.

A 29-year old man presented with a giant cell granuloma of the maxilla, that was initially diagnosed as a brown tumor. Serum calcium and PTH were elevated. One year later, a parathyroid carcinoma and a brown tumor in the left femur were indentified and removed surgically. Renal sonography showed an increased echogenicity of both kidneys. Postoperatively serum calcium and PTH were within the normal range.

Mutation analysis revealed the heterozygous nonsense mutation R234X in exon 7 of the HRPT2 gene. Subsequent studies indicate that the patient inherited the HRPT2 mutation from his father. The father is 68 years old at present time and shows no signs of the hyperparathyroidism-jaw tumor syndrome, normal serum calcium and normal PTH. The R234X mutation was also found in the patient's sister. She was diagnosed for primary hyperparathyroidism at the age of 32. Serum calcium and PTH levels were in the normal range after subtotal parathyroidectomy, there are no signs of parathyroid cancer.

The identification of the R234X mutation is not only important for the patient himself, but it is also important for other family members who could benefit from the identification as mutation carriers. This information can be used for the early detection and removal of malignant parathyroid tumors.