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The molecular pathways involved in the aetiology of these syndromes have recently been more clearly defined and several major cellular signalling pathways are probably involved: the protein kinase A (PKA) pathway in Carney complex (CNC), the Ras\/Erk MAP kinase pathway in LEOPARD\/Noonan syndromes, and the mammalian target of rapamycin pathway (mTOR) in Peutz-Jeghers syndrome and the diseases caused by <jats:italic>PTEN<\/jats:italic> mutations. Here we discuss the clinical presentation of these disorders and discuss the molecular mechanisms involved. The presence of lentigines in these diseases caused by diverse molecular defects is probably more than an associated clinical feature and likely reflects cross talk and convergence of signalling pathways of central importance to embryogenesis, neural crest differentiation, and end-organ growth and function of a broad range of tissues including those of the endocrine, reproductive, gastrointestinal, cardiac, and integument systems.<\/jats:p>","DOI":"10.1136\/jmg.2003.017806","type":"journal-article","created":{"date-parts":[[2005,6,15]],"date-time":"2005-06-15T20:14:57Z","timestamp":1118866497000},"page":"801-810","source":"Crossref","is-referenced-by-count":53,"title":["The lentiginoses: cutaneous markers of systemic disease and a window to new aspects of tumourigenesis"],"prefix":"10.1136","volume":"42","author":[{"given":"A J","family":"Bauer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C A","family":"Stratakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2005,6,15]]},"reference":[{"key":"2025101713285789000_42.11.801.1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-55-3-421"},{"key":"2025101713285789000_42.11.801.2","doi-asserted-by":"publisher","DOI":"10.1159\/000053283"},{"key":"2025101713285789000_42.11.801.3","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1159\/000061045","volume":"28","year":"2001","journal-title":"Front Horm Res"},{"key":"2025101713285789000_42.11.801.4","doi-asserted-by":"publisher","DOI":"10.1038\/ng821"},{"key":"2025101713285789000_42.11.801.5","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970303)69:1<56::AID-AJMG11>3.0.CO;2-N"},{"key":"2025101713285789000_42.11.801.6","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.28.11.752"},{"key":"2025101713285789000_42.11.801.7","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0865"},{"key":"2025101713285789000_42.11.801.8","doi-asserted-by":"publisher","DOI":"10.1159\/000080856"},{"key":"2025101713285789000_42.11.801.9","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.134.3.333"},{"key":"2025101713285789000_42.11.801.10","doi-asserted-by":"publisher","DOI":"10.1159\/000079993"},{"key":"2025101713285789000_42.11.801.11","unstructured":"Maize JC, Ackerman AB. 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