A large extended family with hyperparathyroidism-jaw tumor syndrome due to deletion of the third exon of CDC73: clinical and molecular features

Collen, Lauriane Le; Barraud, Sara; Braconnier, Antoine; Coppin, Lucie; Zachar, D.; Boulagnon, Camille; Deguelte, Sophie; Souchon, Pierre François; Spodenkiewicz, Marta; Poirsier, Céline; Aubert, Sébastien; Odou, M.F.; Delemer, Brigitte

doi:10.1007/s12020-021-02756-4

Cited by 3 publications

(28 citation statements)

References 28 publications

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“…The youngest age at presentation for HPT-JT syndrome reported in the literature is 10 years [ 8 ]. In a study conducted by Le Collen et al, a family carrier of CDC73 gene exon 3 deletion was reported characterized by hypercalcemia, renal deterioration, and atypical parathyroid adenomas [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Hyperparathyroidism Jaw-Tumor Syndrome: A Case Report From a Radiological View

Khan¹,

Fazli²,

Khan³

et al. 2022

Cureus

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Limited formal guidelines, scarcity of cases, and variable manifestation forms all contribute to the challenges of diagnosing hyperparathyroidism-jaw tumor (HPT-JT) syndrome. This condition characterized by parathyroid tumors, fibro-osseous jaw tumors, and renal and gynecological pathologies results in significant morbidity, restricted functionality, and malignancy risk. Genetic testing is the gold standard investigation to evaluate for CDC73 mutations, that cause HPT-JT syndrome. Genetic testing for CDC73 mutations should be encouraged among family members of affected individuals. Surgery is the mainstay of treatment for many of the encountered pathologic entities.We report a 42-year-old female with a history of infertility and right subtrochanteric femoral fracture secondary to osteoporosis. The patient was suspected to have primary hyperparathyroidism secondary to parathyroid adenomas that were later biochemically and scintigraphically proved with subsequent partial parathyroidectomy.One and a half years following the initial presentation, the patient developed gradual swelling of the lower face with regional osseous involvement in addition to the clinical and radiological picture of recurrent parathyroid adenoma. We present this rare diagnosis of HPT-JT syndrome to promote awareness among physicians regarding this essential differential diagnosis. A low threshold for genetic testing and a high index of suspicion for HPT-JT syndrome must be kept in cases of patients presenting with high parathyroid hormone levels and masses. The screening must extend to all the family members as well. With this approach, the high morbidity, facial disfigurement, and significant malignancy risk can be lowered in the affected individuals improving their life expectancy.

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Section: Discussionmentioning

confidence: 99%

Hyperparathyroidism Jaw-Tumor Syndrome: A Case Report From a Radiological View

Khan¹,

Fazli²,

Khan³

et al. 2022

Cureus

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“…Germline and somatic mutations occurring in CDC73 gene seem to be associated with pathogenic phenotypes of HPT-JT syndrome, familiar isolated hyperparathyroidism (FIH) and sporadic PC 4,7,[23][24][25] . Indeed, from the patients harboring a CDC73 mutation, 55% have manifestations related to HPT-JT syndrome, 21% to FIH, whilst a percentage of 15-20% appears to develop PC 9,20,23,24 .…”

Section: Mutationsmentioning

confidence: 99%

“…However, as Li et al assert in a very recent cohort study, not all mutations draw the same impact on the functionality of parafibromin but instead, they can be distinguished into "high and low impact" mutations 12 . Indeed, it has been underscored by several studies and reviews that mutations causing gross disruption of parafibromin's structure (frameshift, nonsense, deletions) are more likely to be associated with classical features of HPT-JT syndrome and development of PC, whereas more rare mutations (missense) are linked to other pHPT syndromes without typical features (FIH) 5,7,8,12,15,23,25 .…”

Section: Mutationsmentioning

confidence: 99%

“…All research advocates that the penetrance of the syndrome is incomplete and it usually ranges from 70% to 95% 7,8,25,29,30,34 . That means approximately 10-30% of the probands bearing a CDC73 germline mutation will lack any clinical feature related to the syndrome 5,9,18,33 .…”

Section: Penetrance-expressivitymentioning

confidence: 99%

“…That means approximately 10-30% of the probands bearing a CDC73 germline mutation will lack any clinical feature related to the syndrome 5,9,18,33 . Recent cohort studies in affected families demonstrated that penetrance seems to increase with age and, more specifically, it is formulated as follows: 25-30 years old: 15%, 40-50 years old: 60%, 70 years old: 85% 4,25 . Intriguingly, for reasons unknown, it appears to be slightly more increased in females 17 .…”

Section: Penetrance-expressivitymentioning

confidence: 99%

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Hyperparathyroidism-jaw tumor syndrome: A rare disorder with significant clinical features

Kourkouliotis¹

2023

JRPMS

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Hyperparathyroidism-jaw tumor syndrome is a rare disorder that is inherited in an autosomal dominant manner and predisposes to the development of parathyroid adenomas and carcinoma, ossifying jaw tumors, uterine neoplasms and renal cysts. It is caused by inactivating mutations in the gene CDC73 that it was first identified in 2002. The purpose of this narrative review is to highlight the genetic background of the syndrome and its clinical manifestations as well as to emphasize the significance of genetic testing in diagnosis from an early age. The clinical and familial features of the syndrome were collected by searching on electronic database PubMed/Medline using the MeSH terms "Hyperparathyroidism-jaw tumor syndrome" or "HPT-JT syndrome". 246 articles were returned of which, 44 were reviews and 59 case reports. Two nationwide retrospective studies were found. This article is focused mainly on data from the last decade, as there seems to be a better understanding of the genetic basis due to the evolution of DNA sequencing techniques. To date, there have been over 200 patients reported in approximately 50 families carrying a germline mutation of CDC73 gene, suggesting that there should be an augmented awareness of identifying both patients and their relatives.

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Insights into Hyperparathyroidism–Jaw Tumour Syndrome: From Endocrine Acumen to the Spectrum of CDC73 Gene and Parafibromin-Deficient Tumours

Gheorghe,

Sima,

Florescu

et al. 2024

IJMS

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A total of 1 out of 10 patients with primary hyperparathyroidism (PHP) presents an underlying genetic form, such as multiple endocrine neoplasia types 1, 2A, etc., as well as hyperparathyroidism–jaw tumour syndrome (HJT). We aimed to summarise the recent data, thus raising more awareness regarding HJT, from the clinical perspective of PHP in association with the challenges and pitfalls of CDC73 genetic testing and parafibromin staining. This narrative review included a sample-focused analysis from the past decade according to a PubMed search. We identified 17 original human studies (≥4 patients per article). The mean age at disease onset was between 20.8 and 39.5 years, while the largest study found that 71% of patients had HJT recognised before the age of 30. Males and females seemed to be equally affected, in contrast with sporadic PHP. PHP represented the central manifestation of HJT, occurring as the first manifestation in up to 85% of HJT cases. A biochemistry panel found a mean serum calcium level above the level of 12 mg/dL in PHP. PTH was elevated in HJT as well, with average values of at least 236.6 pg/mL. The most frequent pathological type in PHP was a parathyroid adenoma, but the incidence of a parathyroid carcinoma was much higher than in non-HJT cases (15% of all parathyroid tumours), with the diagnosis being established between the age of 15 and 37.5. In some families up to 85% of carriers suffered from a parathyroid carcinoma thus indicating that certain CDC73 pathogenic variants may harbour a higher risk. An important issue in HJT was represented by the parafibromin profile in the parathyroid tumours since in HJT both parathyroid adenomas and carcinomas might display a deficient immunoreactivity. Another frequent manifestation in HJT was ossifying fibromas of the jaw (affecting 5.4% to 50% of patients; the largest study found a prevalence of 15.4%). HJT was associated with a wide variety of kidney lesion (mostly: kidney cysts, with a prevalence of up to 75%, and renal tumours involved in 19% of patients). The risk of uterine lesions seemed increased in HJT, especially with concern to leiomyomas, adenofibromas, and adenomyosis. The underlying pathogenic mechanisms and the involvement of CDC73 pathogenic variants and parafibromin expression are yet to be explored. Currently, the heterogeneous expression of parafibromin status and, the wide spectrum of CDC73 mutations including the variety of clinical presentations in HJT, make it difficult to predict the phenotype based on the genotype. The central role of HJT-PHP is, however, the main clinical element, while the elevated risk of parathyroid carcinoma requires a special awareness.

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A large extended family with hyperparathyroidism-jaw tumor syndrome due to deletion of the third exon of CDC73: clinical and molecular features

Cited by 3 publications

References 28 publications

Hyperparathyroidism Jaw-Tumor Syndrome: A Case Report From a Radiological View

Hyperparathyroidism Jaw-Tumor Syndrome: A Case Report From a Radiological View

Hyperparathyroidism-jaw tumor syndrome: A rare disorder with significant clinical features

Insights into Hyperparathyroidism–Jaw Tumour Syndrome: From Endocrine Acumen to the Spectrum of CDC73 Gene and Parafibromin-Deficient Tumours

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