The lentiginoses: cutaneous markers of systemic disease and a window to new aspects of tumourigenesis

• Published in: Journal of Medical Genetics Vol. 42; no. 11; pp. 801 - 810
• Main Authors: Bauer, A J, Stratakis, C A
• Format: Journal Article Book Review
• Language: English
• Published: London BMJ Publishing Group Ltd 01.11.2005; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Biological and medical sciences; Cardiology. Vascular system; Carney complex; Cell cycle; Cowden disease; Cyclic AMP-Dependent Protein Kinases - metabolism; Disease; General aspects. Genetic counseling; Genetic Linkage; Growth hormones; Humans; Hyperplasia - metabolism; Intellectual disabilities; Kinases; Lentigo - genetics; LEOPARD syndrome; Medical genetics; Medical sciences; Metastasis; Models, Biological; Models, Molecular; mTOR pathway; Mutation; Neural Crest - metabolism; Noonan syndrome; Peutz-Jeghers syndrome; Peutz-Jeghers Syndrome - genetics; Prostate cancer; Protein Kinases - metabolism; Proteins; Review; Signal Transduction; Skin; Skin - metabolism; Skin Neoplasms - genetics; Sun; TOR Serine-Threonine Kinases; Tumors; Human; Biological marker; Genetics; Skin disease; Disseminated
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2003.017806

Familial lentiginosis syndromes cover a wide phenotypic spectrum ranging from a benign inherited predisposition to develop cutaneous lentigines unassociated with systemic disease, to associations with several syndromes carrying increased risk of formation of hamartomas, hyperplasias, and other neoplasms. 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 PTEN 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.