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CDC73 Gene

The spectrum of CDC73-related disorders includes the following conditions:

  • Hyperparathyroidism-jaw tumor syndrome (HPT-JT)
  • Parathyroid carcinoma
  • Familial isolated hyperparathyroidism (FIHP)

(Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is also known as familial primary hyperparathyroidism with multiple ossifying jaw fibromas and familial cystic parathyroid adenomatosis)

Hyperparathyroidism-jaw tumor syndrome

More than 45 inherited mutations in the CDC73 gene have been found to cause hyperparathyroidism-jaw tumor syndrome, which is a condition characterized by a type of benign tumor called a fibroma in the jaw and parathyroid tumors that cause hyperparathyroidism. Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, osteoporosis, nausea, vomiting, hypertension, weakness, and fatigue in people with hyperparathyroidism-jaw tumor syndrome.

Most of the CDC73 gene mutations that cause this condition result in a parafibromin protein that is abnormally short and nonfunctional. Without functional parafibromin, cell proliferation is not properly regulated. Uncontrolled cell division resulting from the loss of parafibromin function can lead to the formation of tumors in the parathyroid glands, jaw, and other tissues in people with hyperparathyroidism-jaw tumor syndrome. Parathyroid tumors, which can be cancerous or noncancerous, interfere with the gland's normal function and lead to primary hyperparathyroidism in people with hyperparathyroidism-jaw tumor syndrome.

  • Primary hyperparathyroidism, the main finding of HPT-JT syndrome, occurs in >70% of affected individuals, typically in late adolescence or early adulthood, and 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 known as "cementifying fibromas" and "cemento-ossifying fibromas", occur in 30%-40% of individuals with HPT-JT syndrome. Although benign, these tumors can be locally aggressive and may continue to enlarge if not treated.
  • Kidney lesions are seen in approximately 20% of individuals with HPT-JT syndrome and most commonly include cysts; renal hamartomas and (more rarely) Wilms tumor
  • Benign and malignant uterine tumors appear to be common in women with HPT-JT syndrome.


  • 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 minimally invasive 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 of the parathyroid gland with surrounding, adherent tissue and the ipsilateral thyroid lobe 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.


  • Starting at age five to ten years:
    • serum testing for biochemical evidence of primary hyperparathyroidism annually
    • dental panoramic x-ray with neck shielding at least every five years
      • Those who have undergone surgery for a jaw tumor require closer follow-up for possible tumor recurrence.
  • To monitor for kidney lesions, renal ultrasound examination is recommended at least every five years, starting at the age of diagnosis
  • For women, starting at reproductive age, lifelong monitoring for uterine tumors with routine gynecologic care and ultrasound examination as clinically indicated.


  • Dehydration
  • radiation exposure
  • biopsy of extrathyroidal tissue in the neck or seemingly atypical thyroid nodular disease which may increase the risk of seeding of a possible parathyroid carcinoma

More information:

  • The youngest patient reported with hypercalcemia is 7 years.
  • The youngest patient reported with parathyroid carcinoma is 20 years
  • The youngest patient reported with metastatic parathyroid carcinoma is 26 years

However, onset may be delayed until the 50s.

Individuals with primary hyperparathyroidism may or may not show symptoms which include the following:

  • Kidney Stone
  • Reduced bone mass
  • Fatigue
  • Muscle weakness
  • Bone or joint pain
  • Constipation

Parathyroid Carcinoma:

Symptoms of parathyroid carcinoma can include the following:

  • Palpable neck mass
  • Kidney Stones
  • Hoarseness
  • Difficulty speaking or swallowing
  • Muscle weakness
  • Nausea/vomiting
  • Altered mental status
  • Bone pain and/or fractures

Familial Isolated Hyperparathyroidism (FIHP)

FIHP is characterized by primary hyperparathyroidism without other features. The vast majority of individuals with FIHP and a germline CDC73 mutation have at least one family member with a known diagnosis of parathyroid carcinoma and/or had a parathyroid adenoma with atypical or cystic features.