Clinical genetics of multiple endocrine neoplasias, Carney complex and related syndromes.
The list of multiple endocrine neoplasias (MENs) that have been molecularly elucidated is growing with the most recent addition of Carney complex. MEN type 1 (MEN 1), which affects primarily the pituitary, pancreas, and parathyroid glands, is caused by mutations in the menin gene. MEN type 2 (MEN 2) syndromes, MEN 2A and MEN 2B that affect mainly the thyroid and parathyroid glands and the adrenal medulla, and familial medullary thyroid carcinoma (FMTC), are caused by mutations in the REToncogene. Finally, Carney complex, which affects the adrenal cortex, the pituitary and thyroid glands, and the gonads, is caused by mutations in the gene that codes for regulatory subunit type 1A of protein kinase A (PKA) (PRKAR1A) in at least half of the known patients. Molecular defects have also been identified in syndromes related to the MENs, like Peutz-Jeghers syndrome (PJS) (the STK11/LKB1 gene), and Cowden (CD; the PTEN gene) and von Hippel-Lindau disease (VHLD; the VHL gene). Although recognition of these syndromes at a young age generally improves prognosis, the need for molecular testing in the diagnostic evaluation of the MENs is less clear. This review presents the newest information on the clinical and molecular genetics of the MENs (MEN 1, MEN 2, and Carney complex), including recommendations for genetic screening, and discusses briefly the related syndromes PJS, CD and VHLD.
Stratakis
C A
CA
Unit on Genetics and Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1862, USA. stratakc@cc1.nichd.nih.gov
D000310:Adrenal Gland Neoplasms / Q000235:genetics; D003480:Cushing Syndrome / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics; D006801:Humans; D008297:Male; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D010580:Peutz-Jeghers Syndrome / Q000235:genetics; D010911:Pituitary Neoplasms / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013577:Syndrome; D013736:Testicular Neoplasms / Q000235:genetics; D006623:von Hippel-Lindau Disease / Q000235:genetics
D029721:Drosophila Proteins; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D017868:Cyclic AMP-Dependent Protein Kinases