The CDC73-associated (hyperparathyroid-jaw tumor) syndrome (HPT-JT; OMIM #145001) is a rare genetic disease caused by mutations in the CDC73 gene (and also HRPT-2). It results in a predisposition to primary hyperparathyroidism (PHPT) and parathyroid carcinomas, ossifying fibromas of the maxilla and/or mandible, and renal and uterine tumors.

Key Data

< swipe to see entire table >
Synonym Familial primary hyperparathyroidism with multiple ossifying jaw fibromas and familial cystic parathyroid adenomatosis
Gene CDC73
Gene product Parafibromin
Function Subunit of the PAF1 protein complex, which functions as a transcription factor
Heredity Autosomal dominant
Prevalence Unknown
Genotype-phenotype correlation Genotype-phenotype correlation Missense mutations tend to be associated with isolated familial hyperparathyroidism.
No additional mutations have been identified.
Penetrance 80-90%, around 70% in women
< swipe to see entire table >


Clinical Diagnostic Criteria

  • PHPT and ossifying fibroma(s) of the maxilla and/or mandible

  • PHPT and closely related to HPT-JT syndrome

  • Ossifying fibroma(s) of the maxilla and/or mandible AND closely related to HPT-JT syndrome

Confirming the Diagnosis


  • Serum calcium corrected for serum albumin or ionized calcium:
    elevated with PHPT; extremely elevated with parathyroid carcinoma

  • Intact parathormone (iPTH):
    usually elevated with PHPT but may be at a normal level; extremely elevated with parathyroid carcinoma


  • Orthopantomography and possibly CT to detect ossifying fibromas in the jaw

  • Renal ultrasound (possibly MRI, CT) to detect renal tumors

  • Pelvic ultrasound (possibly MRI, CT) to detect uterine tumors

Genetic Diagnostics

The diagnosis of “HPT-JT” is confirmed with the detection of a heterozygous germline mutation of the CDC73 gene through sequence analysis or deletion/duplication analysis.

Differential Diagnoses

  • Sporadic, non-genetic PHPT

  • Multiple endocrine neoplasia type 1

  • CASR-associated diseases

  • Multiple endocrine neoplasia type 2A

  • Sporadic renal cysts

  • Autosomal-dominant polycystic kidney disease

  • Tuberous sclerosis complex

  • Von-Hippel-Lindau syndrome

Clinical Presentation

Primary Hyperparathyroidism

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

  • Usually caused by a single benign parathyroid adenoma, with a second possibly occurring synchronously or metachronously

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

  • Usually occurs in late adolescence to early adulthood

Tumors in the Jaw

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

  • In part a space-occupying lesion of increasing size, sometimes only detectable by X-rays

  • May interrupt dentition and/or impair breathing

Renal Manifestations

  • In 20% of HPT-JT patients, the kidneys are affected as well: usually cysts, hamartomas, or – more rarely – Wilms tumors.

  • Cystic diseases may involve a few small cysts or even bilateral cystic kidneys.

Uterine Tumors

  • 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: endometriosis, adenofibroma, endometrial hyperplasia, leiomyoma, and adenosarcoma

Therapeutic Considerations

Primary Hyperparathyroidism

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

  • Preoperative imaging (ultrasound, scintigraphy with 99mTc, CT/MRI) to locate the abnormal gland

  • Intraoperative measurement of iPTH to check that the hyperfunctioning gland is removed

If a parathyroid carcinoma has been detected, en bloc resection and resection of the ipsilateral thyroid lobe should be performed.

Tumors in the Jaw

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

Renale Manifestationen

Bei zystischen Erkrankungen muss je nach Ausmaß und Erscheinungsbild eine individuelle Therapie festgelegt werden. Spezifische Richtlinien für HPT-JT-Patienten liegen nicht vor.

Uterine Tumors

With uterine tumors, an appropriate therapy should be selected based on extent and appearance. There are no specific guidelines for HPT-JT patients.

Surveillance Recommendations

Surveillance Recommendations

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

  • Laboratory tests once a year from 5-10 years of age: serum calcium, iPTH and 25(OH) vitamin D3

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

  • Orthopantomography at least every 5 years; regular professional dental cleaning from 10 years of age

  • Renal ultrasound at least every 5 years from the time of diagnosis; serum creatinine should be determined regularly in patients with known cysts.

  • Women of childbearing age should undergo regular gynecological examinations. An abdominal or vaginal ultrasound should be performed if there are anomalies associated with menstruation, followed by other imaging examinations (CT or MRI) if necessary.

Additional Information

Open Clinical Trials / Registries

There are currently no open clinical trials or registries for patients with CDC73-associated (hyperparathyroid-jaw tumor) syndrome that we can recommend to you for more information.

Support Groups

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.