Melanotic macules following Blaschko's lines in McCune-Albright syndrome

Hyperpigmented macules are a characteristic feature of neurofibromatosis and the McCune-Albright syndrome. Whereas neurofibromatosis 1 has an autosomal dominant mode of inheritance, it has been suggested that McCune-Albright syndrome is the result of a lethal gene surviving by mosaicism. Recent molecular studies have supported this concept by providing evidence of a somatic mutation of the gene encoding the G protein. We report two patients with McCune-Albright syndrome whose melanotic macules show a clear relation to the lines of Blaschko. The lines of Blaschko are thought to represent the dorso-ventral outgrowth of two different cell populations during embryogenesis, thus reflecting genetic mosaicism. A survey of published photographs of patients with McCune-Albright syndrome in the literature revealed additional cases with macules following Blaschko's lines. In other cases, the configuration of the macules was reminiscent of the flag-like rectangular pattern of pigmentation found in human chimaeras. A very early somatic mutation may have similar effects on the pigmentation pattern as a chimaeric state, which is the result of the double fertilization of an ovum. Cafe-au-lait spots in 10 of our own patients with neurofibromatosis 1 could not be associated with either Blaschko's lines or the rectangular pattern of pigmentation in chimaeras. We conclude that, in contrast with the cafe-au-lait spots in autosomal dominant neurofibromatosis 1, the configuration pattern of melanotic macules in McCune-Albright syndrome in many cases characteristically reflects the mosaic state of the organism.