Hyperparathyroidism-jaw tumor syndrome: a report of three large kindred.
BACKGROUND
Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal disease caused by inactivating germ-line mutations of HRPT2 gene, with subsequent loss of Parafibromin expression. It is characterized by familial HPT, ossifying jaw tumors, and other associated neoplasms.


METHODS
Clinical, histopathological, and genetic features of three large Italian unrelated HPT-JT kindred were assessed.


RESULTS
Three different germ-line HRPT2 inactivating mutations were identified. Seventeen affected members and six healthy mutation carriers were found. HPT was diagnosed in virtually all affected patients, at a median age of 36.3 years (range 11-71). In all cases, a single parathyroid involvement was found at surgery, although a metachronous multiglandular involvement causing recurrence after selective parathyroidectomy occurred in 17.6% of cases, after a mean disease-free interval of 13.7 years (range 5-27). Parathyroid carcinoma, atypical parathyroid adenoma, and jaw tumor occurred in one case; uterine involvement in 61.5% of women; other associated neoplasms were thyroid carcinoma (two cases) and renal and colon carcinoma (one case). Immunohistochemistry confirmed the loss of Parafibromin as the distinctive feature of the disease both in parathyroid and uterine tumors.


CONCLUSIONS
HPT-JT has a frequent single-gland parathyroid involvement and a relatively increased risk of parathyroid carcinoma. The penetrance of the disease is high but incomplete. Regardless of the denomination of the syndrome, jaw tumors occur rarely, while uterine involvement is frequently present. Selective parathyroidectomy may be an effective strategy, but a prolonged follow-up is required because of the risk of recurrences and malignancies. A systematic investigation is also required because of associated malignancies.
Iacobone
Maurizio
M
Endocrine Surgery Unit, Department of Surgical and Gastroenterological Sciences, University of Padua, Via Giustiniani, 2, 35128, Padua, Italy. maurizio.iacobone@unipd.it
Masi
Giulia
G
Barzon
Luisa
L
Porzionato
Andrea
A
Macchi
Veronica
V
Ciarleglio
Francesco Antonio
FA
Palù
Giorgio
G
De Caro
Raffaele
R
Viel
Giovanni
G
Favia
Gennaro
G
D000236:Adenoma / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000209:etiology / Q000235:genetics*; D007150:Immunohistochemistry; D007573:Jaw Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary; D010282:Parathyroid Neoplasms / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics; D055815:Young Adult
C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins