Prenatal diagnosis of congenital non‐bullous ichthyosiform erythroderma (lamellar ichthyosis)

Abstract

We report the first positive prenatal diagnosis of congenital non-bullous ichthyosiform erythroderma or lamellar ichthyosis. Fetal skin samples were obtained by fetoscopy at 21 weeks' gestation and examined by light and electron microscopy. Light microscopy revealed a thickened interfollicular epidermis with multiple layers of flattened cells and excessive keratinization of the epidermal lining of the follicular infundibulum. Electron microscopy of the thickened epidermis revealed granular cells that contained larger-than-normal keratohyalin granules and multiple layers of parakeratotic cornified cells. Although there was regional variation in the degree of interfollicular keratinization, follicles from all regions showed greater and more complete keratinization, indicating that they express the abnormality early enough in development to permit prenatal diagnosis at about 20 weeks' gestation.

Formation of cornified cell envelope in human hair follicle development

“…In fact, malformation of CCE caused by TGase 1 gene mutation has been reported in lamellar ichthyosis, the onset of which is in the fetal period 39,40 and, in fetuses affected with lamellar ichthyosis, characteristic abnormalities in the hair canal are more severe than those in the interfollicular epidermis. 41,42 In harlequin ichthyosis, the most severe form of congenital ichthyosis of an unknown genetic defect, the phenotype is much more apparent in the hair canal in the fetal period. 33 In the early stage of skin development, characteristic abnormalities of harlequin ichthyosis can be seen only in the hair canal, and we have in fact succeeded in performing prenatal diagnosis of harlequin ichthyosis at 19 weeks' EGA by ultrastructural observation of the hair canal in the skin of the fetus at risk.…”

“…In addition, our results suggest that the observation of keratinization in the hair canal, which precedes interfollicular keratinization, may provide clues to our understanding of the pathogenetic process. In fact, malformation of CCE caused by TGase 1 gene mutation has been reported in lamellar ichthyosis, the onset of which is in the fetal period 39,40 and, in fetuses affected with lamellar ichthyosis, characteristic abnormalities in the hair canal are more severe than those in the interfollicular epidermis 41,42 . In harlequin ichthyosis, the most severe form of congenital ichthyosis of an unknown genetic defect, the phenotype is much more apparent in the hair canal in the fetal period 33 .…”

Gap junction development in the human fetal hair follicle and bulge region

“…Fetal skin was fixed in one‐half strength Karnovsky's fixative or 2% glutaraldehyde solution, postfixed in 1% OsO 4 , dehydrated, and embedded in Epon 812 21 . All the samples were ultrathin sectioned at a thickness of 70 nm, and stained with uranyl acetate and lead citrate 22 .…”

Regional difference in expression of characteristic abnormality of harlequin ichthyosis in affected fetuses

“…Skin autopsy and biopsy samples were fixed in one-half strength Karnovsky's fixative or 2 per cent glutaraldehyde solution, post-fixed in 1 per cent OsO 4 , dehydrated, and embedded in Epon 812 (Perry et al, 1987). All the samples were serially sectioned, sampled every 10-15 m for light microscopy (1 m thick), and thin-sectioned Fig.…”