From genes to glands: The genetic framework of parathyroid syndromes

<h2>Abstract</h2> Primary and secondary disorders of parathyroid hormone (PTH) secretion including primary hyperparathyroidism (PHPT) and hypoparathyroidism can result from both sporadic and hereditary causes. Advances in molecular genetics have expanded our understanding of the genetic syndromes underlying these disorders. This review aims to summarize the genetic landscape of hereditary parathyroid disorders, highlighting their molecular mechanisms, clinical presentations, diagnostic challenges, and management implications. We synthesized evidence from published literature and genetic testing guidelines issued by major endocrine societies. Specific focus was given to syndromes such as Multiple Endocrine Neoplasia, Hyperparathyroidism-Jaw Tumor (HPT-JT), Familial Isolated Hyperparathyroidism (FIHP), and Autosomal Dominant Hypocalcemia (ADH), among others. While 95 % of PHPT cases are sporadic, a small but clinically significant proportion is linked to germline mutations in genes such as MEN1, RET, CDC73, and CASR. Hypoparathyroid syndromes, though less common, are genetically diverse, involving genes related to parathyroid development, hormone secretion, and calcium-sensing. Current guidelines recommend genetic testing based on early age of onset, multiglandular disease, family history, and associated tumors. As genetic testing becomes more accessible, a precision medicine approach incorporating molecular diagnostics and counseling will play a central role in optimizing patient outcomes.