What is CDC73-associated (hyperparathyroid-jaw) syndrome?

CDC73-associated (hyperparathyroid-jaw) syndrome (HPT-JT) is a rare disease caused by mutations – or genetic changes – in the CDC73 gene (also HRPT-2). Those affected have a much higher risk of parathyroid tumors and also parathyroid hyperfunction (primary hyperparathyroidism, PHPT), bone tumors (ossifying fibromas) in the upper and lower jaw, and tumors of the kidneys and uterus.

How is CDC73-associated (hyperparathyroid-jaw) syndrome diagnosed?

Clinical Diagnostic Criteria

  • PHPT AND ossifying fibroma(s) of the upper and/or lower jaw

  • PHPT AND a close relative with HPT-JT syndrome

  • Ossifying fibroma(s) of the upper and/or lower jaw AND a close relative with HPT-JT syndrome

Confirming the Diagnosis

The clinical diagnosis is made through blood tests (measuring calcium and parathormone) and imaging diagnostics (X-ray of the jaw, ultrasound of the kidneys and pelvis).

Genetic Diagnostics

The diagnosis of “HPT-JT” is confirmed by detection of a mutation – or genetic change – in the CDC73 gene.

What is the risk of cancer?

Primary Hyperparathyroidism

  • Main finding with HPT-JT and in up to 95% of patients

  • Usually caused by a single benign parathyroid tumor, and a second may occur at the same time or later on.

  • In 10-15% of cases, PHPT is caused by a malignant parathyroid carcinoma.

  • Usually occurs in late adolescence to early adulthood

Tumors in the Jaw

  • In up to 30-40% of HPT-JT patients

  • Sometimes a space-occupying lesion of increasing size, sometimes only detectable on the X-ray image

  • May prevent the eruption of teeth in the jaw and/or impair breathing

Disease of the Kidneys

  • The kidneys are involved in 20% of HPT-JT patients: usually cysts, hamartomas (tumor-like benign tissue alteration), or more rarely Wilms tumor (malignant kidney tumor)

  • Cystic diseases may involve a few small cysts or even kidneys full of cysts on both sides.

Tumors in the Uterus

  • Found in approximately 75% of female HPT-JT patients, with an average age of 35 at the time of diagnosis

  • May be benign or malignant

  • The following may occur: endometriosis, adenofibroma, endometrial hyperplasia, leiomyoma, and adenosarcoma.

What causes CDC73-associated (hyperparathyroid-jaw) syndrome?

CDC73-associated (hyperparathyroid-jaw) syndrome is brought about by a mutation – or genetic change – in the CDC73 gene. This gene encodes for the protein parafibromin, which plays a role in the reproduction of genetic material. Now if the CDC73 gene is in an altered form, the protein parafibromin can no longer function properly, resulting in the development of a tumor.

It is not yet known how frequently HPT-JT syndrome occurs. What is known is that the disease can be passed on to children from their parents. In these cases, it is inherited as an autosomal dominant disease.

Is there a treatment?

Primary Hyperparathyroidism

Since it is usually the case that there is only one parathyroid tumor causing the PHPT, a minimally invasive approach for removing the parathyroid tumor is preferred, which involves the following:

  • Imaging prior to the surgery (ultrasound, scintigraphy with 99mTc CT/MRI) to locate the tumor

  • Measuring the parathormone (the hormone produced by the parathyroid) to ensure that the gland with the hyperfunction has been removed

If malignant parathyroid cancer is present, the parathyroids and the thyroid lobe on the same side should be removed.

Tumors in the Jaw

If possible, the tumor should be removed completely. There are no known medicinal approaches to date for tumors that have not been fully removed. Due to the risk of relapse, patients should undergo aftercare checkups.

Disease of the Kidneys

With cystic diseases, it is necessary to lay out individual treatment depending on their extent and manifestation. There are no specific guidelines for HPT-JT patients.

Tumors in the Uterus

With tumors of the uterus, it is necessary to lay out individual treatment depending on their extent and manifestation. There are no specific guidelines for HPT-JT patients.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

There are no standard surveillance recommendations for patients with a CDC73 mutation to date. Based on the literature currently available, the following is recommended:

  • Laboratory tests once a year from 5-10 years of age

  • Regular ultrasound examinations of the parathyroid glands to detect the rare occurrence of non-functional parathyroid cancer as part of a CDC73 mutation

  • X-ray of the jaw at least every 5 years; regular professional dental cleaning from 10 years of age

  • Ultrasound of the kidneys at least every 5 years starting from the time the diagnosis is made; creatinine in the blood should be determined regularly in patients with known cysts.

  • Women in childbearing age should undergo regular gynecological examinations. An ultrasound of the pelvis should be performed if anomalies become apparent during menstruation, followed by other imaging examinations (CT or MRI) if necessary.

Self-Care and Support

What should I pay special attention to?

Hyperparathyroidism may present as bone pain. In addition, kidney or gall stones may occur and cause pain in the flanks and/or upper abdomen regions. Kidney cysts can trigger pain in the area of the flanks, and urine anomalies or urinary tract infections may occur as well. Tumors in the uterus usually present themselves through bleeding or changes in menstruation. Tumors in the jaw may prevent the eruption of teeth in the jaw and cause swelling and pain.

Should you notice one of the symptoms or other complaints or anomalies listed above, be sure to see a doctor right away.

Support Groups and Additional Information

Unfortunately, we are as yet unaware of any existing support groups for patients with a CDC73-associated (hyperparathyroid-jaw tumor) syndrome. We will add new information as it becomes available.