79577

CDC73

C1orf28|HPTJT|HRPT2|HYX;cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae);CDC73;cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae)

cell division cycle protein 73 homolog|hyperparathyroidism 2 protein|parafibromin

1q25

protein-coding

OBJECTIVE: To report the case of a man who presented with profoundly elevated parathyroid hormone levels in the setting of hypercalcemia, a palpable neck mass, renal disease, and metabolic bone disease. METHODS: We describe the clinical, imaging, and laboratory findings of the patient, including results from genetic testing of the CDC73 gene (HRPT2), and review the relevant literature. RESULTS: A 28-year-old man with a history of childhood abdominal neuroblastoma treated withchemotherapy and field radiation therapy presented with a 2-week history of persistent left scapular pain and swelling. He had a freely mobile, 1-cm, homogeneous, nontender, firm nodule in the right anterior neck. Parathyroid hormone concentration at hospital admission was 1127 pg/mL. Single-photon emission computed tomography after intravenous administration of technetium Tc 99m-labeled sestamibi revealed an intense focus of abnormal radiotracer uptake on early and delayed images in the right anterior inferior neck. Computed tomography imaging of the chest and neck revealed a 1.9-cm, smooth, calcified nodule posterior to the right lobe of the thyroid gland and diffusely osteopenic bones with trabecular resorption and numerous scattered lucent regions consistent withbrown tumors. On bilateral neck exploration, a right inferior parathyroid mass and the left superior parathyroid gland were excised. The remaining 2 parathyroid glands were identified intraoperatively and appeared normal. Genetic testing of the CDC73 gene did not detect germline mutations. CONCLUSIONS: This case highlights the overlap between the clinical findings seen in primary hyperparathyroidism and parathyroid carcinoma. Enhanced understanding of the genetic and molecular bases of primary hyperparathyroidism and parathyroid carcinoma should aid in the diagnosis of these diseases and the care of affectedpatients.

BTI - GeneReviews#. The spectrum of CDC73-related disorders includes the following phenotypes: Hyperparathyroidism-jaw tumor syndrome (HPT-JT). Parathyroid carcinoma. Familialisolated hyperparathyroidism (FIHP) . Primary hyperparathyroidism, the main finding of HPT-JT syndrome, occurs in more than 70% of affected individuals; onset is typically in late adolescence or early adulthood. HPT-JT-associated primary hyperparathyroidism is usually caused by a single parathyroid adenoma. In approximately 10%-15% of cases, primary hyperparathyroidism is caused by parathyroid carcinoma. Ossifying fibromas of the mandible or maxilla, also knownas cementifying fibromas and cemento-ossifying fibromas, occur in 30%-40% of individuals with HPT-JT syndrome. Although benign, these tumors are aggressive and continue to enlarge if not treated. Approximately 20% of individuals with HPT-JT syndrome have kidney lesions, most commonly cysts; renal hamartomas and (more rarely) Wilms tumor have also been reported. Benign and malignant uterine tumors appear to be common in women with HPT-JT syndrome. Diagnosis is based on clinical findings, biochemical findings of primary hyperparathyroidism, ossifying fibroma(s) of the maxilla and/or mandible, family history, and molecular genetictesting. CDC73 (formerly known as HRPT2), which encodes the parafibromin protein, is the only gene in which mutations cause CDC73-related disorders. Treatment of manifestations: The optimal surgical approach to primary hyperparathyroidism in HPT-JT syndrome has not yet been established; however, because many individuals with HPT-JT syndrome present with a single benign parathyroid tumor, a minimallyinvasive approach to remove the abnormal parathyroid gland followed by close monitoring for recurrent primary hyperparathyroidism has been suggested. Cinacalcet hydrochloride has been approved for the treatment of severe hypercalcemia secondary to primary hyperparathyroidism in individuals who are unable to undergo parathyroidectomy and for the treatment of parathyroid carcinoma-related hypercalcemia. If parathyroid carcinoma (characterized by extremely elevated serum calcium and iPTH levels, more profound symptoms, and clear radiographic evidence of parathyroid neoplasia) is suspected, an en bloc resection should be considered. Jaw tumors should be treated surgically as indicated by size, location, and symptoms; treatment of choice is complete resection, which may not be possible in ALL cases. Renal and uterine manifestations are managed on a case-by-case basis. Prevention of secondary complications: Precautions to reduce the risk for hypoparathyroidism following parathyroid tumor resection. Surveillance: Starting at age five to ten years: lifelong serum testing for biochemical evidence of hyperparathyroidism every 12 months and panorex dental imaging at least every five years. Those who have undergone surgery for a jaw tumor require close follow-up for possible tumor recurrence. Renal ultrasound examination at least every five years starting at the age of diagnosis; for women, annual pelvic ultrasound examination and regular gynecologic care. Agents/circumstances to avoid: Dehydration; radiation exposureto the neck; biopsy of extrathyroidal tissue in the neck, which may increase therisk of seeding of a possible parathyroid carcinoma. Evaluation of relatives at risk: If the family-specific CDC73 germline mutation is known, molecular genetictesting of at-risk relatives around age five to ten years. CDC73-related disorders are inherited in an autosomal dominant manner. Most individuals diagnosed with HPT-JT syndrome have an affected parent. De novo mutations, including one person with somatic/germline mosaicism, have been reported. Each child of an individual with a CDC73-related disorder has a 50% chance of inheriting the mutation. Prenatal diagnosis for pregnancies at increased risk ispossible if the disease-causing mutation in the family is known.#CI- Copyright (c) 1993-2013, University of Washington, Seattle. ALL rights reserved.#FED - Pagon, Roberta A#ED- Pagon RA#FED - Adam, Margaret P#ED- Adam MP#FED - Bird, Thomas D#ED- Bird TD#FED - Dolan, Cynthia R#ED- Dolan CR#FED - Fong, Chin-To#ED- Fong CT#FED - Stephens, Karen#ED- Stephens K#FAU - Rich, Thereasa A