Context: Mutations of the HRPT2 gene have recently been implicated in the development of parathyroid carcinoma.

Objective: Early diagnosis of parathyroid tumor in a family with germline HRPT2 mutation

Patients, methods and results: In a 40 yr-old male previously treated for parathyroid atypical adenoma, we screened the 17 translated HRPT2 exons and their exon-intron boundaries and found a germline frameshift mutation in exon 7 (685delAGAG) predicting a premature stop codon at nt 767-769. Nine family members (33.9 ± 19.8 yr, mean ± SD) also carry the mutation, but eight have had normal serum calcium. Biochemical and ultrasonographic evaluation uncovered a 27 yr-old hypercalcemic carrier niece with an atypical parathyroid adenoma, and a 43 yr-old normocalcemic carrier sister with an extrathyroidal nodule by ultrasonography which proved to be parathyroid carcinoma. The index case, twelve years after surgery, was normocalcemic but ultrasonography revealed an extrathyroidal nodule in the contralateral hemithyroid tissue which proved to be atypical adenoma.

Conclusions: Our report confirms that germline mutations of HRPT2 gene may be associated with multiple parathyroid neoplasms. Our experience suggests that longitudinal surveillance by serum biochemistry alone may not be 100% sensitive, and addition of routine neck ultrasonography is a readily accepted adjunct that may facilitate earlier disease detection in some families.