The biology of hyperpigmentation syndromes

Pigment Cell Melanoma Res. 2014 Jul;27(4):512-24. doi: 10.1111/pcmr.12235. Epub 2014 Mar 20.


Hyperpigmentation is a key feature in a variety of inherited and acquired syndromes. Nonetheless, determining the exact diagnosis only on the clinical phenotype can be challenging, and a detailed search for associated symptoms is often of crucial importance. As pigmentation pathways are regulated by complex signaling transduction cascades (e.g. MSH/cAMP, KIT signaling pathways), the underlying defects leading to elevated melanin production are numerous. With regard to treatment, limited therapeutic options exist, each with specific side effects. In acquired hyperpigmentation, the melanin deposition may, however, be reversible after adequate therapy of the underlying disorder or even disappear spontaneously. In this review, we provide an overview of the biology of hyperpigmentation syndromes classified according to the main underlying defect that deregulates physiological melanogenesis. The identification of novel genes or key players involved in hyperpigmentary disorders is becoming increasingly important in view of the development of safer and more efficient treatments.

Keywords: hyperpigmentation; melanin; melanocyte; pigmentation pathway; syndrome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Genetic Diseases, Inborn / classification
  • Genetic Diseases, Inborn / diagnosis
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / metabolism*
  • Humans
  • Hyperpigmentation / classification
  • Hyperpigmentation / diagnosis
  • Hyperpigmentation / genetics
  • Hyperpigmentation / metabolism*
  • Melanins / genetics
  • Melanins / metabolism*
  • Signal Transduction*
  • Syndrome


  • Melanins