Prenatal diagnosis as a test for genodermatoses: its past, present and future.

The prenatal diagnosis (PND) of severe hereditary skin diseases started in the early 1980s using fetal skin biopsy techniques based on ultrastructural and immunohistochemical abnormalities of the fetal skin. Recent success in identifying responsible genes and demonstrating mutations in such genes has set the stage for DNA-based PND in the 1990s. Common examples of skin conditions which can be prenatally diagnosed include epidermolysis bullosa, oculocutaneous albinism and Harlequin ichthyosis in which the severity of the clinical phenotype appears to justify PND in families at risk. More recently, preimplantation diagnoses of inherited diseases have become possible using in vitro fertilization techniques. The diagnosis consists of a blastomere biopsy of the six to ten-cell embryo and a DNA analysis of single blastomeres. Disease-free embryos are selected for transfer to the uterus, thereby avoiding the need for termination of a fetus found to be affected by conventional PND. Furthermore, carrying out a PND using a single fetal cell from the maternal blood, such as nucleated erythrocytes, has become technically feasible. Although there are many questions that remain unanswered, the outlook for further development of noninvasive PND in the future appears optimistic.