It is estimated that approximately 5% to 12% of melanoma is hereditary, and approximately 40% of that is caused by CDKN2A mutations. Based on these estimates, approximately 3,200 to 6,700 cases of melanoma per year are caused by mutations in CDKN2A.
Since this syndrome is a mutation in a gene, does genetic testing increase the chances of finding melanoma at an early stage?
There is controversy regarding whether or not to use genetic testing for CDKN2A mutations for screening of patients. Benefits may include the ability to identify some high-risk kindreds and refer them to a clinical research screening program (1). However, given the lack of understanding of the genotype-phenotype relationship in CDKN2A kindreds, others argue that knowledge of the genotype would not alter the management of these individuals and that high-risk kindreds should be enrolled in research screening programs regardless of CDKN2A mutation status. In addition, it is important to note that patients with the clinical phenotype of FAMMM may have molecular defects other than CDKN2A. Therefore, negative genetic testing for this mutation does not exclude hereditary melanoma syndromes, increases cost, and may give false reassurance.
It is also worth noting that families have an earlier age of onset of melanoma in FAMMM relatives compared to the general population, which may be due to increased susceptibility to ultraviolet radiation.
FAMMM is a clinical diagnosis based on numerous nevi, including atypical nevi with ABCDE (see below) characteristics resembling early melanoma, and a family history of melanoma. It is associated with mutations in the CDKN2A gene. Some FAMMM kindreds show an increased risk for the development of pancreatic cancer and possibly other malignancies. An integral aspect of the diagnosis is a comprehensive cancer family history.
The diagnostic criteria for FAMMM syndrome:
1. Malignant melanoma in one or more first- or second-degree relatives;
2. High total body nevi count (often >50) including some of which are clinically atypical (asymmetric, raised, color variegation present, of variable sizes);
3. Nevi with certain histologic features on microscopy.