Characteristic morphologic abnormality of harlequin ichthyosis detected in amniotic fluid cells

We have examined cells from amniotic fluid obtained at 17 and 21 weeks' gestation and fetal skin biopsy samples from a fetus at risk of harlequin ichthyosis by light and electron microscopy. Clumps of abnormally keratinized cells that had a large number of lipid droplets in the cytoplasm were seen within both the 17- and 21-week amniotic fluid cell pellets. The cells in these clumps were similar to the thick layers of keratinized cells observed in the skin biopsy and autopsy samples. Morphologic examination of the fetal skin biopsy samples obtained at 21 weeks gestation revealed the characteristic changes of harlequin ichthyosis. The intraepidermal portions of hair canals had an excessive number of layers of keratinized cells. Normal lamellar granules were absent but abundant membrane-bound vesicles of a similar size and a number of dense bodies were observed in the cells of the upper intermediate layers of the epidermis. Autopsy skin samples of the terminated fetus at the twenty-third week of gestation showed structural changes that corresponded to those of the amniotic fluid cells and the fetal skin biopsy samples, although the periderm was gone in all the regions. Our findings of amniotic fluid indicate that the characteristic epidermal abnormality of harlequin ichthyosis has been expressed at 17 weeks gestation in some parts of the body or structures of fetal skin (e.g., hair canals) that keratinize before interfollicular epidermis. Moreover, the results suggest that harlequin ichthyosis can be detected in utero by morphologic analysis of amniotic fluid cells obtained by amniocentesis.