A Genotypic and Histopathological Study of a Large Dutch Kindred with Hyperparathyroidism-Jaw Tumor Syndrome1

Abstract

Familial primary hyperparathyroidism is the main feature of 2 familial endocrine neoplasia syndromes: multiple endocrine neoplasia type 1 (MEN 1) and hyperparathyroidism-jaw tumor syndrome (HPT-JT). The latter is a recently described syndrome that has been associated with ossifying fibroma of the jaw and various types of renal lesions, including benign cysts, Wilms' tumor, and hamartomas. To further illustrate the natural history of this syndrome, we describe a large, previously unreported Dutch kindred in which 13 affected members presented with either parathyroid adenoma or carcinoma; in 5 affected individuals, cystic kidney disease was found. Additionally, pancreatic adenocarcinoma, renal cortical adenoma, papillary renal cell carcinoma, testicular mixed germ cell tumor with major seminoma component, and Hürthle cell thyroid adenoma were also identified. Linkage analysis of the family using MEN1-linked microsatellite markers and mutation analysis excluded the involvement of the MEN1 gene. Using markers from the HPT-JT region in 1q2531, cosegregation with the disease was found, with a maximum logarithm of odds score of 2.41 obtained for 6 markers using the most conservative calculation. Meiotic telomeric recombination between D1S413 and D1S477 was identified in 3 affected individuals, and when combined with previous reports, delineated the HPT-JT region to 14 centimorgan. Combined comparative genomic hybridization and loss of heterozygosity data revealed complex genetic abnormalities in the tumors, suggesting different possible genetic mechanisms for the disease. In conclusion, we report a family with hyperparathyroidism linked to chromosome 1q, and exhibiting several types of renal and endocrine tumors that have not been previously described.

Early-onset, severe, and recurrent primary hyperparathyroidism associated with a novel <i>CDC73</i> mutation

“…PTC was also seen in the present case. In a Dutch kindred with HPT-JT, Hürtle cell thyroid adenoma was identified [22]. In a large Italian unrelated HPT-JT kindred, thyroid adenoma and PTC were also found [23].…”

Clinical Features, Treatment, and Surveillance of Hyperparathyroidism-Jaw Tumor Syndrome: An Up-to-Date and Review of the Literature

“…yroid carcinoma, thyrotoxicosis, colon carcinoma, cholangiocarcinoma, chronic lymphatic leukemia, pancreatic adenocarcinoma, and pituitary cyst have also been described, but the association between these less common tumors and HPT-JT syndrome remains unclear [4,42,90].…”