Molecular genetics in primary hyperparathyroidism: the role of genetic tests in differential diagnosis, disease prevention strategy, and therapeutic planning. A 2017 update

Abstract

SummaryPrimary hyperparathyroidism (PHPT) is one of the most frequent endocrine disease in developed countries. It mainly occurs as sporadic cases (about 90-95% of cases), while only the remaining 5-10% is represented by familial inherited parathyroid disorders due to causative mutations in specific target genes. Clinical variability among the different familial parathyroid syndromes is generally linked to the specific mutated gene and it can predispose subjects to different manifestations of parathyroid pathology, various degrees of PHPT severity, persistence and/or after-surgery recurrences. Genetic tests is helpful in differential diagnosis favouring the recognition of the specific familial PHPT syndrome and, subsequently, in planning the most suitable surgical procedures and/or pharmacological interventions. Moreover, genetic test is important to recognise mutation carriers, within PHPT familial forms, even before the appearance of biochemical and/or clinical symptoms. This review resumes general concepts about genetic diagnosis of PHPT in familial hereditary syndromes, specifically describing why, when, and which genetic screenings should be performed in every specific PHPTassociated parathyroid disease.

Gnathic Bones and Hyperparathyroidism: A Review on the Metabolic Bony Changes Affecting the Mandible and Maxilla in case of Hyperparathyroidism

“…(1) Primary HPT (PHPT) which is either of a nonfamilial (sporadic) form representing about 90-95% of all PHPT or familial inherited form representing 5-10% of PHPT [5]. (2) Secondary HPT which results from a primary condition producing hypocalcemia such as rickets, osteomalacia, vitamin D deficiency, prolonged hypocalcemia caused by chronic renal failure, and long-term dialysis [6,7].…”

Gender Predilection in Sporadic Parathyroid Adenomas

“…The pathophysiology of parathyroid tumorigenesis involves inactivating germline mutations of suppressive oncogenes in the majority of cases with familial predisposition, i.e., in about one-third of sporadic parathyroid adenomas [51] and in approximately 50-75% of parathyroid carcinomas [52]. Genes that have been linked to the pathogenesis of sporadic parathyroid adenomas include MEN1, cyclin D1/PRAD1 and cyclin-dependent kinase inhibitors (CDKI), such as CDKN1B/p27 [4]. However, the genetic role in parathyroid tumorigenesis does not differ between genders, this being in line with what we know about the inherited syndromes, although the number of reported patients is up to now small.…”

“…In symptomatic cases, renal and bone manifestations are most commonly seen [3]. The vast majority of cases of pHPT (90-95%) occur sporadically, but they can also occur as part of inherited genetic syndromes caused by mutations in specific target genes, such as in multiple endocrine neoplasia type 1 (MEN 1), type 2A (MEN 2A) and type 4 (MEN 4), familial hypocalciuric hypercalcemia (FHH), neonatal severe hyperparathyroidism (NSHPT), HPT-jaw tumor (HPT-JT) syndrome, and familial isolated pHPT (FIPH) [4]. Compared to sporadic adenomas, pHPT occurring in the context of genetic familial syndromes is mainly caused by multiglandular disease and is characterized by an earlier age of onset [4,5].…”

Circulating and Tissue Expression Profile of MicroRNAs in Primary Hyperparathyroidism Caused by Sporadic Parathyroid Adenomas

“…The majority of cases (85%) are attributed to the development of a benign adenoma of clonal (monoclonal or oligoclonal) origin (1) , which occurs sporadically at approximately 90-95% of cases. On the other hand, primary hyperparathyroidism occurring in the context of genetic familial syndromes, is mainly caused by multiglandular disease and is characterized by an earlier age of onset (2,3) .…”