Genetic Testing in a Patient With Suspected Hyperparathyroidism- Jaw Tumor Syndrome (HPT-JT)

Abstract

Abstract Introduction: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant disorder characterized by parathyroid tumors in association with fibro-osseous jaw tumors, uterine tumors and renal lesions. We present a case of suspected HPT-JT. Clinical Case: A 50-year-old female with suspected HPT-JT was referred for treatment of osteoporosis. Patient was initially diagnosed with osteosarcoma in 1980 at age 10, and underwent resection with leg amputation and chemotherapy. Around 1995, she was found to have primary hyperparathyroidism secondary to a parathyroid adenoma and underwent one gland parathyroidectomy. At age 30, she was then found to have multiple uterine tumors requiring hysterectomy. In 2017, she underwent CT abdomen for suspected appendicitis, which revealed multiple renal cysts and hepatic hemangiomas. In 2019, patient was found to have recurrent parathyroid adenoma and underwent revision parathyroidectomy. Pathology revealed hypercellular parathyroid gland consistent with adenoma. Based on constellation of symptoms, HPT-JS was suspected. Patient was referred to genetic counselor. Detailed family history revealed multiple family members affected by malignancies including melanoma, breast cancer, prostate cancer, liver cancer and two cousins with suspected MEN1. She underwent testing for hereditary hyperparathyroidism and melanoma including CDC73 gene. All genetic testing was surprisingly unrevealing. Discussion: CDC73 gene (also known as HRPT2 gene) is responsible for the pathogenesis of HPT-JT. While HPT-JT itself is a rare condition, 60% of patients affected by it, harbor the HRPT2 gene mutation. About 10–15% of these individuals are affected by parathyroid carcinoma. HRPT2 mutated parathyroid adenomas also seem to have some malignant potential. The autosomal dominant inheritance of HPT-JT makes gene testing important since it has implications for other family members and carries weight in clinical management of genetic carriers. Therefore patients with extensive personal or family history of malignancy should be followed closely. Endocrinologists should have a low threshold to refer such patients for genetic counseling and testing. However genetic testing also has its limitations and can only explain 50–75% of cases of HPT-JT syndrome. Hence, even though our patient has a negative genetic screen, the possibility of HPT-JT is not complete ruled out.