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.
Familial primary hyperparathyroidism with multiple ossifying jaw fibromas and familial cystic parathyroid adenomatosis
Subunit of the PAF1 protein complex, which functions as a transcription factor
Genotype-phenotype correlation Missense mutations tend to be associated with isolated familial hyperparathyroidism.
No additional mutations have been identified.
80-90%, around 70% in women
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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
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.
Sporadic, non-genetic PHPT
Multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 2A
Sporadic renal cysts
Autosomal-dominant polycystic kidney disease
Tuberous sclerosis complex
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
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.
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
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.
Bei zystischen Erkrankungen muss je nach Ausmaß und Erscheinungsbild eine individuelle Therapie festgelegt werden. Spezifische Richtlinien für HPT-JT-Patienten liegen nicht vor.
With uterine tumors, an appropriate therapy should be selected based on extent and appearance. There are no specific guidelines for HPT-JT patients.
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.
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.
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.