1/7. prenatal diagnosis of harlequin ichthyosis by the examination of keratinized hair canals and amniotic fluid cells at 19 weeks' estimated gestational age.Harlequin ichthyosis (HI) is an extremely severe and usually fatal congenital keratinization disorder whose responsible genes have not yet been identified. For prenatal diagnosis, the fetal skin biopsy is the only available method and has been usually performed at 21 to 22 weeks' estimated gestational age (wEGA). hair canal keratinization is thought to occur around 15 wEGA prior to the interfollicular keratinization, and characteristic abnormalities of HI are known to be expressed more strongly in the hair canal. Thus, we expected the fetal skin specimen at 19 wEGA to have sufficient information for prenatal diagnosis. Fetal skin biopsy was undertaken from a fetus at risk at 19 wEGA. Electron microscopy demonstrated abnormal vacuoles in keratinized cells and malformation of lamellar granules in the hair canal. Clumps of aberrantly keratinized cells containing lipid droplets were seen in the amniotic fluid. The fetus was diagnosed as affected. The abortus at 21 wEGA demonstrated HI phenotype clinically. The present results indicate that the prenatal diagnosis of HI is possible at 19 wEGA, an earlier stage of gestation than previously reported, by the ultrastructural observation of the hair canal and the amniotic fluid cells, but not the interfollicular epidermis, of fetuses at risk.- - - - - - - - - - ranking = 1keywords = epidermis (Clic here for more details about this article) |
2/7. Congenital ichthyosiform erythroderma: particulate staining pattern of TGK.A case of late onset non-bullous congenital ichthyosiform erythroderma (CIE) was studied. This patient was not born as a collodion baby and did not have skin abnormalities until 9-10 years of age. She gradually developed erythroderma and fine scales, callosities of her feet, and a mild ectropion. Since recent work has revealed that in the majority of CIE patients, transglutaminase (TGK) is distributed in the cytoplasm of granular cells and horny cells (11), TGK was studied in our case. It was found that TGK was distributed along the cell periphery of horny cells and also in the cytoplasm of granular cells. In the control skins, TGK was stained along the cell periphery of horny cells and granular cells. The marginal band formation was normal. Involucrine and loricrin, the building materials of the marginal band whose-cross-linking is mediated by TGK, were normally stained in the upper epidermis. Cytoplasmic TGK of granular cells and normal development of the marginal band may serve as a helpful diagnostic marker of CIE, particularly because the often confusing collodion baby of lamellar ichthyosis may lack TGK staining and the marginal band altogether.- - - - - - - - - - ranking = 1keywords = epidermis (Clic here for more details about this article) |
3/7. A novel homozygous mutation 371delA in TGM1 leads to a classic lamellar ichthyosis phenotype.Malformation of the cornified cell envelope (CCE) arising from mutations of the transglutaminase (TGase) 1 gene (TGM1) is the cause of some cases of lamellar ichthyosis (LI). However, genotype/phenotype correlation in TGM1 mutations has not yet been fully clarified. We report a typical case of LI caused by a novel mutation in TGM1. The patient, a 33-year-old woman, showed thick, lamellar scales on the entire body surface. Immunofluorescence labelling with anti-TGase 1 antibodies was negative in the patient's epidermis. In situ TGase activity assay detected markedly reduced TGase activity in granular layers of the patient's epidermis. Electron microscopy revealed incomplete thickening of the CCE during keratinization in the epidermis. Sequencing of the entire exons and exon-intron borders of TGM1 revealed that the patient was a homozygote for a novel deletion mutation 371delA in exon 3. This mutation leads to a frameshift resulting in a premature termination codon 43 bp downstream from the mutation site. According to the protein modelling of TGase 1, the truncated protein from this mutated allele loses the entire catalytic core domain of TGase 1. Thus, the present homozygous mutation is expected to cause total loss of TGase 1 activity, resulting in large, dark, lamellar scales on the entire body, the classic phenotype of LI, in this patient.- - - - - - - - - - ranking = 3keywords = epidermis (Clic here for more details about this article) |
4/7. Congenital ichthyosis with hypogonadism and growth retardation--a new syndrome with peculiar ultrastructural features.A male patient presented with a congenital ichthyosis clinically characterized by generalized erythroderma, fine scaling on the trunk and palmoplantar hyperkeratoses with severely affected nails. The acanthotic epidermis was characterized by hyperproliferation with a large quantity of mitoses and extremely suppressed keratinization without a normal granular layer. The horny layer was parakeratotic and contained remnants of cell debris and lipid droplets. Ultrastructurally the prickle cell layer was characterized by binuclear cells, oedematization of the keratinocytes and isolated dyskeratotic cells. Some suprabasal cells showed unusual morphological features, containing nuclei with cytoplasmic pseudoinclusions, sometimes leading to a complete disintegration of the nuclear structure, and bowl- and lens-shaped accumulations of a filamentous material. Instead of normal tonofibrils, the aggregated material consisted of fine interlacing filaments. The latter are compared with the filamentous shells in ichthyosis hystrix Curth-Macklin and congenital reticular ichthyosiform erythroderma. The clinical symptomatology--congenital ichthyosis, growth retardation, secondary hypogonadism, hepatomegaly--and the ultrastructural characteristics of the keratinization disorder indicate that the present case cannot be considered as a subtype of the recessively inherited ichthyosis congenita group, but suggest a new syndrome as a separate nosologic entity.- - - - - - - - - - ranking = 1keywords = epidermis (Clic here for more details about this article) |
5/7. Prenatal exclusion of harlequin ichthyosis; potential pitfalls in the timing of the fetal skin biopsy.BACKGROUND: Harlequin ichthyosis (HI) is a severe and usually fatal congenital skin disorder with autosomal recessive inheritance. Several cases of HI prenatal diagnosis have been performed using fetal skin biopsy, mainly at around 23 weeks estimated gestational age (EGA), and reported in the literature. However, prenatal testing must be done earlier than 21 weeks EGA in several countries including japan where the present HI families live, because termination is legally allowed only until 22 weeks EGA. OBJECTIVES: We report the successful prenatal exclusion of HI in two fetuses from two independent families and discuss the technical difficulties and potential pitfalls in the prenatal exclusion of HI at early gestation stages. methods: Fetal skin biopsy specimens and amniotic fluid samples at 19 and 20 weeks EGA from two fetuses at risk of HI were examined by light and electron microscopy. RESULTS: For the prenatal diagnosis in case 1, the fetal skin biopsy samples were obtained at 20 weeks EGA and showed normal keratinization in the hair canals; no abnormalities were observed in the keratinized cells. In case 2, the interfollicular epidermis and the hair follicles in the samples obtained at 19 weeks EGA had not differentiated enough to show proper keratinization. However, lamellar granules were normally formed in the inner root sheath cells of the late bulbous hair pegs. From these ultrastructural findings, the case 1 fetus was diagnosed as unaffected with HI, and the case 2 fetus was diagnosed as unlikely to be affected. Subsequently, both were born as healthy, unaffected babies. CONCLUSIONS: The timing of biopsies at 19 weeks EGA is not ideal for fetal skin biopsy because the samples are not always sufficiently differentiated for the prenatal diagnosis of HI. However, morphological observations of lamellar granules gives us important additional information useful for HI prenatal diagnosis.- - - - - - - - - - ranking = 1keywords = epidermis (Clic here for more details about this article) |
6/7. Harlequin ichthyosis--difficulties in prenatal diagnosis.Ichthyoses belong to the group of genodermatoses, characterized by hyperkeratosis and desquamation of the epidermis. Clinical manifestation is heterogeneous and depends on the type of the disease. Harlequin foetus is the most severe form of congenital ichtyosis, inherited as an autosomal recessive trait. The disfunction of the epidermis begins prenatally. Neonates are often born prematurely, in severe condition. At present better care and treatment prolong the length and quality of children's life. We report a case of harlequin ichthyosis. parents were healthy and there was no history of ichthyosis or other congenital anomalies in the family. Sonography at the 26th week of gestation revealed anomalies of the fetal face; however, the diagnosis of harlequin ichthyosis was not established prenatally. The male child was born alive at the 37th week of the third pregnancy, with birth weight of 2900 g. Typical features of harlequin ichthyosis were present at birth. Intensive neonatological care was necessary. The child survived and at the time of the report was 6 months old and in good condition.- - - - - - - - - - ranking = 2keywords = epidermis (Clic here for more details about this article) |
7/7. Unusual hyperpigmentation developing in congenital reticular ichthyosiform erythroderma (ichthyosis variegata).We present an unusual new clinical feature which developed in a patient with congenital reticular ichthyosiform erythroderma. This rare ichthyotic disorder is characterized by erythematous ichthyotic skin surrounding slowly enlarging areas of normal skin, and by a pathognomonic ultrastructural pattern, namely perinuclear deposits of a filamentous material in vacuolized keratinocytes. At the age of 18 years, a 23-year-old woman developed several irregular hyperpigmented macules on her limbs, which were almost black in colour. These lesions have not been observed in the other patients affected by the disease nor, to our knowledge, in other ichthyotic disorders. Electron microscopy and immunohistochemistry demonstrated that the lesions were strictly related to the ichthyotic skin and that their dark colour was especially due to melanosome accumulation in activated dendritic melanocytes. An unusual postinflammatory hyperpigmentation, in which the lack of pigment deposition in the keratinocytes is due to a transfer defect in pathological cells, is hypothesized. A characteristic hyperplastic stimulation of the epidermis is also taken into consideration to explain the lack of a similar picture in other erythrodermic ichthyotic disorders with a continuous inflammatory process.- - - - - - - - - - ranking = 1keywords = epidermis (Clic here for more details about this article) |