Hyperparathyroidism-jaw tumour syndrome (CDC73-related parathyroid carcinoma)

The syndrome is autosomal dominant and is caused by germline inactivating mutations of CDC73 (formerly HRPT2), which encodes parafibromin; the gene was identified in 2002 by finding 13 different heterozygous germline mutations in 14 affected families, and somatic mutations in the same gene were then found in most sporadic parathyroid carcinomas (Carpten 2002). Primary hyperparathyroidism is the main finding, usually from a single parathyroid gland (80 percent of cases), unlike the multigland disease of MEN1; fibro-osseous (ossifying fibroma) tumours of the mandible or maxilla, renal cysts, hamartomas or Wilms tumour, and uterine tumours complete the picture (Torresan 2019). Loss of nuclear parafibromin on immunohistochemistry distinguishes parathyroid carcinomas and HPT-JT adenomas from sporadic adenomas (Gill 2006). The WHO endocrine classification lists the syndrome among the genetic tumour syndromes.

How it differs from its parent: the parent page covers parathyroid carcinoma of any cause, most of it sporadic; this page is the inherited setting in which the cancer arises early and can recur in other glands, so surgery, surveillance and family testing are planned differently. About 15 to 20 percent of people with the syndrome develop parathyroid carcinoma against about 1 percent of all hyperparathyroidism (Kelly 2015; Torresan 2019).

Treatment: surgery is the treatment of choice for the hyperparathyroidism, and the extent, from focused removal of the affected gland to bilateral neck exploration, is debated because further glands can be affected later (Torresan 2019). Carcinoma is treated as on the parent page, with en bloc resection and cinacalcet for uncontrolled calcium; there is no drug trial in this syndrome. Carriers need lifelong calcium and parathyroid hormone monitoring, jaw and renal imaging, and their relatives should be offered CDC73 testing (Torresan 2019).