The McCune-Albright syndrome: a lethal gene surviving by mosaicism

In the McCune-Albright syndrome, fibrous dysplasia of bones and various forms of endocrine dysfunction are associated with multiple pigmented skin lesions. Examination of a 4-year-old female patient and comparison with photographs published in the literature revealed that the cutaneous pigmentation is arranged in a systematized pattern following the lines of Blaschko. Apparently, this pattern visualizes the dorso-ventral outgrowth of two different populations of cells during early embryogenesis. As all cases of the syndrome are sporadic, it is postulated that the disease is caused by an autosomal "dominant" lethal gene, leading to loss of the zygote in utero. Cells bearing the mutation can only survive when they are intermingled with normal cells. The mosaic may arise either from a gametic half chromatid mutation, or from an early somatic mutation. This concept offers an explanation for the scattered asymmetric distribution of bone lesions, and for the observation that the endocrinopathy may be either of central or peripheral origin, according to the random distribution of the mutant population of cells.