Analysis of skin-derived amniotic fluid cells in the second trimester; detection of severe genodermatoses expressed in the fetal period.

Amniotic fluid contains skin-derived cells. To determine whether populations of amniotic fluid cells reflect genetic conditions, we surveyed the population of amniotic fluid cells from 36 fetuses at 16-21 weeks estimated gestational age at risk for junctional epidermolysis bullosa, recessive dystrophic epidermolysis bullosa, epidermolysis bullosa Dowling-Meara, harlequin ichthyosis, lamellar ichthyosis (nonbullous congenital ichthyosiform erythroderma), or Sjögren-Larson syndrome. Periderm cells, keratinocytes, cells of unknown epithelial origin, fibroblasts, fibrin clots, and urinary cast-like materials were seen in the amniotic fluid from normal fetuses. A large number of small macrophages phagocytizing collagen fibers was found in the amniotic fluid from all recessive dystrophic epidermolysis bullosa, some junctional epidermolysis bullosa fetuses, and a single epidermolysis bullosa Dowling-Meara fetus. Immuno-gold electron microscopy with anti-lysozyme and anti-CD68 antibodies confirmed that the cells morphologically identified as macrophages were active macrophages containing many lysosomes. The percentage of macrophages/total amniotic fluid cells in amniotic fluid samples from the fetuses affected with recessive dystrophic epidermolysis bullosa was significantly increased (12.30 +/- 0.20%) compared with that in the amniotic fluid from normal fetuses (1.30 +/- 0.65%) (p < 0.001). In amniotic fluid samples from fetuses affected with harlequin ichthyosis and lamellar ichthyosis, clumps of keratinized cells that contained disease-specific abnormal granules and lipid droplets were observed. These results indicate that the morphologic analysis of amniotic fluid cells can provide important supportive information for the prenatal diagnosis of several severe genodermatoses.