Cutaneous Mosaicism: Special Considerations for Women

Abstract Genetic mosaicism results from postzygotic mutations during embryogenesis. Cells harboring pathogenic mutations distribute throughout the developing embryo and can cause clinical disease in the tissues they populate. Cutaneous mosaicism is readily visualized since affected tissue often follows predetermined patterns, such as lines of Blaschko. Due to its clinical accessibility, cutaneous mosaicism is well suited for genetic analysis. An individual's unaffected tissue can be used as an intra-patient genetic control, a technique that has yielded insight into the genetic etiologies of many disorders, several of which bear mutation in genes which would otherwise be embryonic-lethal. Particular mosaic diseases can also disproportionally impact women. Two such diseases, Incontinentia Pigmenti and CHILD Syndrome, arise from mutations on the X chromosome. Both diseases result in fetal demise in males in most cases, thus making the two diseases largely specific to women. Women with McCune-Albright Syndrome, caused by somatic mutations in GNAS, often experience precocious puberty and infertility as a result of uncontrolled cAMP regulation in affected tissues. Women with cutaneous mosaicism carry a risk of transmission to offspring when gonosomal mosaicism is present, and cutaneous disease burden does not correlate with germline transmission risk. Cutaneous mosaic disease represents a biologically unique set of disorders that can warrant special clinical attention in women.