Genetics of Peutz-Jeghers syndrome, Carney complex and other familial lentiginoses

Peutz-Jeghers syndrome (PJS, #175200) and Carney complex (CNC, OMIM#160980) are the two most common multiple neoplasia syndromes associated with lenti ginosis. Both disorders are inherited in an autosomal dominant manner and t hey have recently been elucidated at the molecular level. PJS and CNC share manifestations with Cowden syndrome (or Cowden, disease) (CS, OMIM#158350) and Bannayan-Riley-Ruvalcaba syndrome (BRR, OMIM#153480). The endocrine tu mors of CS and PJS, which could classify these disorders as variant types o f multiple endocrine neoplasias (MENs), are not present in most CS and BRR patients, but lentigines are shared by PJS, CNC and BRR. The serine-threoni ne kinase STK11 (or LKB1), located on 19p13, is mutated in more than half o f all PJS kindreds. The R1 alpha subunit of c-AMP-dependent protein kinase A, located on 17q22-24, is mutated in 40% of CNC kindred's. The protein pho sphatase PTEN is mutated in most cases of CS and in almost 50% of BRR kindr eds, despite significant clinical heterogeneity in these syndromes. The mol ecular elucidation of the lentiginoses and their related syndromes identifi es new pathways of growth control and cellular regulation that are importan t for endocrine signaling, tumorigenesis, cutaneous function and embryonic development. Copyright (C) 2001 S. Karger AG, Basel.