Background: Primary Hyperparathyroidism - Jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterised by hyperparathyroidism and ossifying jaw fibromas. Inactivating germline mutations in CDC73 gene (previously known as HRPT2) is the main cause of this syndrome. There is higher incidence of parathyroid carcinoma in these individuals and also an association with other renal lesions have been described. We report a case of HPT-JT syndrome with mutation in the exon 2 of CDC73 gene.
Case: A 23 year old lady was referred to our department for evaluation of hypercalcaemia. She had history of swelling of the right jaw for the past one year. The swelling was fluctuant and sometimes painful. X ray of her mandible revealed a large radiolucent lesion. Biopsy of her right jaw lesion showed giant cell granuloma and she underwent successful enucleation. Further evaluation revealed hypercalcaemia (3.05 mmol/L) and elevated PTH (60.1 pmol/L), consistent with diagnosis of primary hyperparathyroidism. Ultrasound and nuclear medicine scan confirmed parathyroid adenoma of size 27×15×13 mm. Ultrasound also showed bilateral renal calculi. Hypercalcemia was initially managed with intravenous fluids and bisphosphonates. Subsequently she underwent successful surgical removal of parathyroid adenoma. Histology showed some atypical cells but did not meet the criteria to diagnose parathyroid carcinoma. Molecular genetic analysis revealed heterozygocity for T to C nucleotide substitution in the exon 2 of CDC73 (c.191T>C) which is predicted to result in replacement of the amino acid leucine with proline at the residue 64 (p.Leu64Pro).This was reported to be highly pathogenic and consistent with HPT-JT syndrome.
Conclusion: When a young patient presents with primary hyperparathyroidism, it is important to consider familial disorders like HPT-JT syndrome, Multiple Endocrine Neoplasia and familial isolated hyperparathyroidism. Individuals with HPT-JT syndrome are at higher risk of developing parathyroid carcinoma and screening of the family members for similar mutation is recommended.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.