Dysplastic Nevus Syndrome in The Netherlands

Abstract

In Europe, the occurrence of familial melanoma in combination with the occurrence of dysplastic nevi in melanoma patients has been reported by groups from Scotland, France, Italy, and The Netherlands. The major publications of these groups are briefly mentioned and summarized. This report specifically describes nine extensive Dutch pedigrees. Clinical an genetic studies were performed in kindreds among whom three or more individuals with melanoma occurred in at least two consecutive generations. Three hundred sixty‐two living persons older than 10 years were screened. The mean number of family members was 60, which makes these pedigrees preeminently suited for genetic studies. Spouses were not included in the study. One hundred eighty individuals were recognized as gene carriers. After correction for bias of ascertainment, we calculated a segregation rate of 0.45, compatible with dominant inheritance. Of the 180 living or alive at the start of the study, 40 had a melanoma, 118 had dysplastic nevi, and 22 were regarded as obligate gene carriers on the basis of their position in the pedigree. The finding of nonpenetrance and reduced penetrance of the characteristic phenotype of the dysplastic nevus syndrome has important consequences for daily practice. When a family is requested to attend the pigmented lesion clinic, all members have an a priori risk of 50% of carrying the gene. Individuals without any abnormalities form the majority, and cases of nonpenetrance and low penetrance are mixed in with the seemingly normal cases. The consequence for our research group was to follow all family members until it is possible to distinguish definitely gene carriers from normal family members. Other malignancies occurred at an increased rate among these families. In two families, the occurrence of several kinds of cancer was obvious. Twenty‐four instances of nonmelanoma cancer were found, among which were seven cases of pancreatic carcinoma