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Genetics of parathyroid tumours
Author(s) -
Thakker R. V.
Publication year - 2016
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12523
Subject(s) - medicine , primary hyperparathyroidism , multiple endocrine neoplasia , hyperparathyroidism , mutation , parathyroid hormone , endocrinology , calcium sensing receptor , cancer research , genetics , gene , biology , calcium
Primary hyperparathyroidism ( PHPT ), due to parathyroid tumours, may occur as part of a complex syndrome or as an isolated (nonsyndromic) disorder, and both forms can occur as familial (i.e. hereditary) or nonfamilial (i.e. sporadic) disease. Syndromic PHPT includes multiple endocrine neoplasia ( MEN ) types 1 to 4 ( MEN 1 to MEN 4) and the hyperparathyroidism‐jaw tumour ( HPT ‐ JT ) syndrome. Syndromic and hereditary PHPT are often associated with multiple parathyroid tumours, in contrast to sporadic PHPT , in which single parathyroid adenomas are more common. In addition, parathyroid carcinomas may occur in ~15% of patients with the HPT ‐ JT syndrome. MEN 1 is caused by abnormalities of the MEN 1 gene which encodes a tumour suppressor; MEN 2 and MEN 3 are due to mutations of the rearranged during transfection ( RET ) proto‐oncogene, which encodes a tyrosine kinase receptor; MEN 4 is due to mutations of a cyclin‐dependent kinase inhibitor ( CDNK 1B ); and HPT ‐ JT is due to mutations of cell division cycle 73 ( CDC 73 ), which encodes parafibromin. Nonsyndromic PHPT , which may be hereditary and referred to as familial isolated hyperparathyroidism, may also be due to MEN 1, CDC 73 or calcium‐sensing receptor ( CASR ) mutations. In addition, ~10% of patients presenting below the age of 45 years with nonsyndromic, sporadic PHPT may have MEN 1 , CDC 73 or CASR mutations, and overall more than 10% of patients with PHPT will have a mutation in one of 11 genes. Genetic testing is available and of value in the clinical setting, as it helps in making the correct diagnosis and planning the management of these complex disorders associated with parathyroid tumours.