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The lentiginoses: cutaneous markers of systemic disease and a window to new aspects of tumourigenesis
  1. A J Bauer1,2,
  2. C A Stratakis1
  1. 1Section on Endocrinology and Genetics (SEGEN), Developmental Endocrinology Branch (DEB), National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD 20892-1103, USA
  2. 2Walter Reed Army Medical Center, Department of Pediatrics, Washington, DC 20307, USA
  1. Correspondence to:
 Dr Constantine A Stratakis
 Section on Endocrinology and Genetics, DEB, NICHD, NIH, Building 10, CRC, Room I-3330, 10 Center Dr., MSC 1103, Bethesda, MD 20892, USA;


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.

  • Carney complex
  • Cowden disease
  • LEOPARD syndrome
  • mTOR pathway
  • Noonan syndrome
  • Peutz-Jeghers syndrome

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  • Published Online First 15 June 2005

  • Competing interests: none declared

  • Consent was received for the publication of personal details and photographs

    The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or to reflect the opinions of Walter Reed Army Medical Center, the United States Army, or the Department of Defense.