Hyperparathyroidism-Jaw Tumor Syndrome Associated With Novel Mutation in CDC73 (HRPT2) Gene

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 199-237-Disorders of Parathyroid Hormone & Calcium Homeostasis
Translational
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-201
Christopher E Hudak*1, Bridget Patricia Sinnott2 and Khashayar Sakhaee3
1Univ of TX Southwestern Med Ctr, Dallas, TX, 2UTSW, Dallas, TX, 3Univ TX SW Med Ctr - Dallas, Dallas, TX
Hyperparathyroidism-Jaw Tumor Syndrome Associated With Novel Mutation in CDC 73 (HRPT2) Gene.

C. Hudak, K. Sakhaee, B. Sinnott.
Int Med, Div of Endocrinology, UT Southwestern Med Cntr, Dallas, TX.

Background:  Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant disorder characterized by primary hyperparathyroidism (HPT), parathyroid cancer, ossifying jaw fibromas and other tumors.

Clinical Case:  38 year-old Hispanic male presented to our clinic for evaluation of asymptomatic hypercalcemia of 12.1 (n 8.4-10.2 mg/dL). He had not sustained any fractures or kidney stones.  Thirteen years earlier, he had undergone resection of two jaw tumors, pathology of which was remarkable for fibrous dysplasia.  His family history was notable for a brother who expired from a parathyroid disorder. His physical exam was negative for neck or jaw masses.

Laboratory work-up revealed PTH 191 (n 15.0-65.0 pg/mL),  25-OH vitamin D 14 (n 25-80 ng/mL) and 24 hour urine calcium 581 (n 50-300 mg/24hr) consistent with HPT.  Abdominal radiograph showed a left lower pole renal stone.  His bone density was below the expected range for age.  Neck ultrasound revealed a solid, hypoechoic mass abutting the posterior aspect of the left upper lobe of the thyroid measuring 1.9 cm x 1.2 cm x 2.3 cm.  Technetium-99m SPECT/CT scan revealed increased tracer uptake localized to the left thyroid lobe lesion consistent with an enlarged parathyroid gland.

Given his history of jaw fibromas and HPT, a diagnosis of HPT-JT was considered. Genetic analysis revealed a novel heterozygous inactivating germ-line mutation of the CDC73 gene, which caused a frameshift and resulted in a loss of the normal parafibromin protein function.

Conclusion:  We present a novel mutation of the CDC73 gene associated with HPT-JT. HPT-JT syndrome should be considered in patients presenting with primary hyperparathyroidism pre-operatively, as up to 10-15% of affected individuals may have parathyroid carcinoma and this would modify the surgical approach.

Nothing to Disclose: CEH, BPS, KS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm