Endocrine Abstracts

Heterozygote mutations of the gene CDC73 are responsible for 3 types of parathyroid diseases: familial hyperparathyroidism, parathyroid carcinoma, hyperparathyroidism-jaw tumor syndrome (and uterine or kidney lesions). The goal of our study was to describe the phenotype associated with the deletion of the 3rd exon of CDC73 found in a large family.

Patients: We have medical records for 25 patients of a large family composed of 44 individuals through 4 generations. 17 patients had a genetic analysis: the deletion was found in 11 individuals; was absent in 6 people. Additionally, 3 patients were assumed carriers of the deletion and 5 patients were children of non mutated patients. 4 patients were asymptomatic with among them, mostly children but also, one patient of 43 years. 8 mutated patients had primary hyperparathyroidism (HPT) with two acute hypercalcemic crisis (maximum calcium level 4.48 mmol/L, parathormone plasmatic level of 1100 pg/mL (N < 60 pg/mL). The median age of onset of hypercalcemia was 37 years (range from 14 to 59 years). We reported 2 patients with brown tumors (median age at onset was 37 years). Six patients had kidney diseases related to hypercalcemia: 5 urinary lithiasis (median age at onset was 41.5 years) 2 nephrocalcinosis, 3 chronic kidney failures with 1 chronic endstage kidney failure. Hypercalcemia was surgically resolved in the 8 patients and we found only a single parathyroid adenoma in each patient; no carcinoma or atypic lesion. Recurrence of moderate hypercalcemia occured in one patient after 7 years. In this family, the phenotype variability was emphasized by 2 cases: in 2 monozygotic twins, one patient is still asymptomatic at 43 years of age and the other presented with acute hypercalcemia and kidney failure. The youngest symptomatic patient was 13 years old (calcium level 3,4 mmol/L). The other lesions associated to this mutation in the family were: 1 ossifiying fibroma (surgically treated at 31 years of age, with a relapse at 36 years); and one kidney cyst. No gynecological lesions were described.

Conclusion: We report a new large family of HPT jaw tumor syndrome with deletion of the 3rd exon of CDC73 which led mostly to HPT with a particularly severe impact on kidney. The presentation is highly variable highlighting the importance of a precocious genetic screening and a regular follow-up of the patients.