CDC73-related disorders / hyperparathyroidism-jaw tumour syndrome (HPT-JT)

Unknown.

The diagnosis is established primarily by identification of a heterozygous germline pathogenic variant in CDC73 on molecular genetic testing. Clinically, biochemical evaluation demonstrates elevated total calcium (corrected for albumin) or ionised calcium with elevated or inappropriately normal intact parathyroid hormone. The diagnosis for ossifying fibromas of the jaw is dependent on the radiologic characteristics of the lesions, specifically whether they are radiolucent, have mixed radiographic features, or are completely radiopaque; renal and pelvic ultrasound detect cystic kidney
lesions and uterine tumours, respectively. Absence of nuclear parafibromin staining on tumour immunohistochemistry provides supportive evidence.

Main differential diagnoses include:

• : most common hereditary cause of primary hyperparathyroidism with multiglandular parathyroid hyperplasia, pituitary adenomas and foregut neuroendocrine tumours; MEN1
• Familial hypocalciuric hypercalcaemia (FHH): benign hypercalcaemia with low urinary calcium excretion, normal to minimally elevated PTH and frequent hypermagnesaemia; CASR, AP2S1, GNA11
• : primary hyperparathyroidism in a minority, with medullary thyroid carcinoma and phaeochromocytoma as cardinal features; RET

• Establishing the molecular diagnosis confirms the clinical suspicion, distinguishes overlapping differential diagnoses, and resolves diagnostic uncertainty in atypical presentations.
• Identification of the causative germline pathogenic variant enables specific and individualised surveillance of parathyroid, jaw, renal and uterine manifestations and is a prerequisite for targeted medical care, as determined by the treating physicians in consultation with the affected individual.
• Once the familial pathogenic variant is known, predictive testing of at-risk relatives is technically possible and clarifies who would benefit from surveillance from age ten years onwards.

Skefos CM, Waguespack SG, Perrier ND, Hu MI. CDC73-related disorders. 2008 Dec 31 [Updated 2023 Sep 21]. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: PMID:20301744.