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Dean JCS, Gray ES, Stewart KN, Brown T, Lloyd DJ, Smith NC, Pope FM. Restrictive dermopathy: a disorder of skin differentiation with abnormal integrin expression. Clin Genet 1993: 44: 287–291. © Munksgaard, 1993 Clinical features and histological findings in two sibs who died from restrictive dermopathy in the neonatal period are described. Fibroblasts cultured from a skin biopsy from the second sib and fibroblasts from normal neonatal skin were studied using monoclonal antibodies to visualise integrin subunits by immunocytochemistry. Restrictive dermopathy fibroblasts displayed increased expression of the alpha-1 and alpha-2 subunits of integrin, those responsible for collagen binding. The increase was not matrix dependent. Integrins may play an important role in tissue differentiation, and our findings support the hypothesis that restrictive dermopathy is a disorder of skin differentiation.

Background Familial adenomatous polyposis (FAP) is a dominantly inherited disorder characterized by the presence of more than 100 adenomatous polyps in the colon and rectum starting in the second decade of life. FAP is associated with extra colonic manifestations, including desmoid tumors. Methods A 2-year-old girl presented with a rapidly enlarging tumor of the forehead and a family history of FAP. The tumor was cultured for cytogenetic studies. A DNA linkage study using flanking and intragenic polymorphisms of the adenomatous polyposis coli (APC) gene was performed to identify the allele loss in the tumor. Germline mutation identification was by single strand conformation polymorphism analysis of exon 15 of the APC gene, with subsequent double stranded sequencing of fragments with conformational changes. A mutation-induced loss of a restriction site was used to confirm allele loss in the tumor. Results Microscopically, the tumor had desmoid features. Cytogenetic analysis of the tumor demonstrated loss of chromosome region 5(q21q22). A truncating adenomatous polyposis coli (APC) gene mutation was identified in the leukocyte DNA from the child and her affected father. Linked DNA markers suggested that the tumor had lost the maternal, wild-type allele. A mutation-induced restriction endonuclease site alteration demonstrated hemizygosity of the mutant sequence in the tumor DNA. Conclusions These findings are compatible with the presence of a "second hit" inactivation of the APC gene and implicate this gene in the pathogenesis of desmoid tumors.

To understand the pathological lesions found in disorders of the endocrine system of the fetus and neonate it is necessary to have a knowledge of the interrelationships which exist within the developing endocrine system and its target tissues. Although the feedback and regulatory mechanisms are similar to those of the adult, the fetal endocrine system has also to incorporate an additional endocrine organ in the placenta, the steroidogenic zone in the adrenal cortex (fetal zone), and a contribution from the central nervous system, which in the fetus is probably capable both of the production of certain tropic hormones and of being a target organ for certain steroid hormones produced by the gonads, adrenal and placenta.

A premature male infant is described in whom the presence of coarse facies, diaphragmatic hernia, genital anomalies and Dandy-Walker malformation suggested a diagnosis of Fryns' syndrome. Lymphocyte karyotype revealed a partial trisomy 22, and his mother carried an apparently balanced 11/22 translocation. Three infants have been described recently with features of Fryns' syndrome and various aneuploidies. It is suggested that amplified developmental instability of the midline developmental field may account for some of the phenotypic resemblances between these cases.

SUMMARY In seventy-eight patients with alopecia areata, the incidence of auto-antibodies to smooth muscle was greater than that in an age and sex matched control population.

The adrenal glands of 12 anencephalic fetuses and 17 norma lfetuses of 11 to 21 weeks' gestation were examined histometrically. The volume of the adrenal gland occupied by the fetal zone in the anecncephalic fetuses was 57.5% compared with 76.5% in normal fetuses. The fetal zone in anecncephaly showed involution in all speciemsn,. which suggests that this invoulution begins well before 20 weeks' gestation.

The fetotoxicity of cyclosporin A (CsA) was examined in multiparous Sprague-Dawley rats given the drug (25 mg/kg/day) during different phases of gestation, the effects on the outcome of pregnancy being ascertained on day 19. CsA given from days 1 to 7 caused a small but significant reduction in litter size, with no significant increase in the number of resorptions. When the drug was administered from day 8 to 14 there was no significant change in litter size, but a very striking increase in the incidence of resorptions. This fetotoxic effect was also evident but less marked when the drug was witheld until day 15. Reduction in fetal weight was only present in the group given CsA from days 8 to 14. In surviving fetuses the presence of focal decidual necrosis was more frequent in mothers receiving CsA, suggesting a possible mechanism whereby CsA may mediate its fetotoxic effects.

An indirect immunoperoxidase technique was used to investigate the site of prealbumin synthesis in the human fetus from between 8 and 43 weeks. Prealbumin staining was noted in the A cells of the fetal pancreas, both in the primary and secondary generations of the islets of Langerhans, from as early as 12 weeks gestation. Electron microscopy localized the staining to the cytoplasmic secretory granules. Prealbumin was also present in the gastrointestinal mucosa in cells which had a distribution similar to that of argentaffin cells. Positive staining was noted in the lining epithelium of the renal proximal convoluted tubules, but ultrastructural studies indicated that this was probably related to reabsorption, and not to synthesis.

This study is based on the processing of 115 samples of pure chorion. The different types of colony morphology, together with cytogenetic analysis, indicate the predisposition of chorion cells to artefacts of culture. Chorion survives longer than other foetal tissues and can be cultured when those are dead or contaminated (e.g. in macerated foetuses and missed abortions) making it a suitable and popular tissue for cytogenetic purposes. However, our results indicate that it is slow in culture and prone to chromosome variation so that pseudomosaicism frequently arises and may lead to misdiagnosis. We therefore suggest that cytogenetic analysis of spontaneous abortion material is interpreted with caution in cases where chorion is the only tissue cultured, especially when mosaicism is found.

Twelve triploid abortuses were investigated to determine the origin of the additional haploid set and were retrospectively examined for the development of partial hydatidiform mole. Eight out of ten suitable triploids were diagnosed as partial mole. Dispermy was indicated as the cause of triploidy in 6 informative cases of which 3 were also partial moles. However, one diandric triploid had no features of partial mole. The problem of maternal cell contamination in triploids and the difficulty of diagnosing partial moles on pathological grounds alone are discussed.

Human parvovirus is the causative agent of erythema infectiosum, a mild epidemic illness. In a recent outbreak in northeast Scotland, six women had serologic evidence of having contracted human parvovirus infection during pregnancy. Two of the women had midtrimester abortions, and both abortuses were grossly hydropic with anemia. They had similar microscopical histopathological features--a pronounced leukoerythroblastic reaction, hepatitis, excessive iron pigment in the liver, and eosinophilic changes in the hematopoietic cell nuclei. Dot hybridization with radiolabeled human parvovirus DNA probes revealed viral DNA in several tissues from both fetuses, indicating that they had been infected by the virus in utero. The remaining four women had uncomplicated pregnancies and delivered apparently healthy babies, none of whom had human parvovirus-specific IgM antibody at delivery. We conclude that this common virus may pose a serious risk to the fetus after maternal infection.

2, ~~~~l~~ s, ~~~~i~~~j~~ of products or cl,nception terminated after prenatal investigatacts. It is, however, important to examine by histology all such lesions. Recently we had a case” in which a macerated male fetus of 15 weeks’ gestation presented a paravertebral mass rnacroscopically identical to several artifactual ones we had previously seen. To our surprise, histological examination showed numerous rosette forming neuroblasts (i.e., as in neuroblastoma), and not the disorganized neural and ependymal tissue which is present in the artifactually extruded neural tissue.