Familial atypical multiple mole melanoma (FAMMM) syndrome: history, genetics, and heterogeneity

Fam Cancer. 2016 Jul;15(3):487-91. doi: 10.1007/s10689-016-9888-2.


Approximately 5-10 % of cutaneous melanoma occurs in kindreds with a hereditary predisposition. Mutations in the CDKN2A gene are found to occur in approximately 20-40 % of these kindreds. The first historical mention of what is now called the familial atypical multiple mole melanoma syndrome appears to be from 1820, with more reports throughout the 1950s, 1960s, and later years. In 1991, Lynch and Fusaro described an association between familial multiple mole melanoma and pancreatic cancer and work continues to elucidate the syndrome's genotypic and phenotypic heterogeneity. Individuals at risk for familial melanoma need periodic screenings. Unfortunately, adequate screening for pancreatic cancer does not currently exist, but pancreatic cancer's prominence in the hereditary setting will hopefully act as a stimulus for development of novel screening measures.

Keywords: CDKN2A; Familial atypical multiple mole melanoma syndrome; Hereditary melanoma; Pancreatic cancer; Skin cancer.

MeSH terms

  • Age Factors
  • Chromosomes, Human, Pair 9 / genetics
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18 / genetics*
  • Dermoscopy / methods
  • Dysplastic Nevus Syndrome / diagnosis
  • Dysplastic Nevus Syndrome / genetics*
  • Dysplastic Nevus Syndrome / mortality
  • Early Detection of Cancer / methods*
  • Genetic Predisposition to Disease*
  • Genetic Testing*
  • Germ-Line Mutation
  • Humans
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / surgery
  • Pedigree
  • Self-Examination


  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4