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 parat hyroid 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 parathyroi d glands and the adrenal medulla, and familial medullary thyroid carcinoma (FMTC), are caused by mutations in the RET oncogene. Finally, Carney comple x, which affects the adrenal cortex, the pituitary and thyroid glands, and the gonads, is caused by mutations in the gene that codes for regulatory su bunit type 1A of protein kinase A (PKA) (PRKAR1A) in at least half of the k nown patients. Molecular defects have also been identified in syndromes rel ated 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 im proves prognosis, the need for molecular testing in the diagnostic evaluati on of the MENs is less clear. This review presents the newest information o n the clinical and molecular genetics of the MENs (MEN 1, MEN 2, and Carney complex), including recommendations for genetic screening, and discusses b riefly the related syndromes PJS, CD and VHLD.