A Novel Pathogenic CDC73 Gene Variant in Hyperparathyroidism-jaw Tumor Syndrome

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare hereditary disorder caused by pathogenic CDC73 gene variants. We report the case of a patient with HPT-JT who carried a novel germline pathogenic CDC73 variant. A 27-year-old woman presented with thirst, polyuria, fatigue, constipation, and a history of fibro-osseous mandible lesions and endometrial polyps. Examination revealed hypercalcemia and grossly elevated PTH levels with hypercalciuria accompanied by a right lower parathyroid tumor with concordant imaging, suggesting primary hyperparathyroidism (PHPT). Given that she had early-onset PHPT and a history of fibro-osseous mandible lesions, HPT-JT was suspected. Genetic testing identified a novel frameshift variant in exon 1 of CDC73. En bloc resection was planned based on the suspicion of parathyroid carcinoma. However, because no findings suggestive of carcinoma were observed intraoperatively, thyroidectomy was not performed. Despite the surgery, PHPT persisted postoperatively, and further evaluation revealed the presence of a residual ectopic left upper parathyroid adenoma, necessitating additional surgery. High-impact pathogenic CDC73 variants are linked to a high risk of parathyroid carcinoma and multiglandular disease. In patients with such variants and clinically suspected parathyroid carcinoma, bilateral neck exploration with subtotal parathyroidectomy may be recommended, with en bloc resection added if intraoperative findings suggest carcinoma.