The Expression of Congenital Ichthyosiform Erythroderma in Second Trimester Fetuses of the Same Family: Morphologic and Biochemical Studies

Abstract

The first born offspring of first-cousin parents was affected with a keratinization disorder thought to be nonbullous congenital ichthyosiform erythroderma (CIE). In each of three subsequent pregnancies, the parents elected to have prenatal diagnosis based on evaluation of fetal skin biopsies. The epidermis of fetus 1 was identical to normal 21-wk estimated gestation age (EGA) fetal epidermis, but because keratinization begins normally around 24 wk EGA, the procedure was repeated 4 wk later. A thin epidermis with a few layers of stratum corneum indicated a normal fetus and a healthy infant was born at term. Skin biopsy samples from fetus 2 gave conflicting results; the epidermis of one sample appeared normal but the second had 5-15 layers of incompletely keratinized cells superficial to basal and intermediate layers. The hair canals of both samples were hyperkeratotic. Pelleted amniotic fluid cells contained aggregates of incompletely keratinized epidermal cells and concentric rings of keratinized cells. The fetus was thought to be affected and the pregnancy terminated. Regional variation in epidermal thickness and keratinization was noted upon gross examination of the fetus and by histology of the skin. Marked hyperkeratinization of follicles was evident in all regions. No abnormal keratins were expressed in the affected epidermis but epidermal lipids analyzed from two body regions had a lower triglyceride content and a higher content of free sterols compared with age-matched, normal fetal epidermis. Immunolabeling for markers of differentiation revealed variable stages of epidermal differentiation according to region. Four structurally identical biopsy samples were obtained from a third fetus. The epidermis appeared normal for age and hair canals were keratinized to various extents. The pregnancy was continued and at 33 wk a male infant was born with a severe ichthyosis of the face and scalp and fine, white scaling on the body. The epidermis of both the severely and mildly affected regions of the newborn had a thick, compact stratum corneum and other features of CIE. Scars from all four fetal biopsies were identified on the trunk, in areas which appeared less affected clinically. This study reports, for the first time, the criteria for prenatal diagnosis of CIE and the variable expression of this disorder in the midtrimester fetus. More importantly, it demonstrates the risks and pitfalls of this in utero diagnosis based on epidermal morphology.