bromochloroacetic-acid and Contracture

Restrictive dermopathy (RD) is a lethal autosomal recessive genodermatosis (MIM No. 275210) in which tautness of the skin causes fetal akinesia or hypokinesia deformation sequence (FADS). Polyhydramnios with reduced fetal movements is followed by premature delivery at around 31 weeks gestation. Manifestations include a tightly adherent, thin, translucent skin with prominent vessels, typical facial changes, generalized joint contractures, enlarged fontanelles, dysplasia of clavicles, respiratory insufficiency, and an enlarged placenta with short umbilical cord. Histologic abnormalities of the skin include thin dermis with paucity and hypoplasia of the appendages and abnormally arranged collagen bundles. Elastic fibers are nearly missing. The subcutaneous fat is slightly increased. These skin findings usually appear after 22 or 24 weeks of gestation, which is why prenatal diagnosis with skin biopsy may fail. This disease is easily differentiated from other congenital FADS, such as Pena-Shokeir syndrome, COFS syndrome, Parana hard-skin syndrome, etc. We report on an affected boy of consanguineous parents and 30 previous cases are reviewed.

Topics: Calcification, Physiologic; Chromosome Inversion; Chromosomes, Human, Pair 9; Collagen; Contracture; Fatal Outcome; Female; Fetal Growth Retardation; Genes, Recessive; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Karyotyping; Keratins; Kyphosis; Male; Natal Teeth; Pregnancy; Skin Diseases; Syndrome

Skin graft contraction leading to loss of joint mobility and cosmetic deformity remains a major clinical problem. In this study we used a tissue-engineered model of human skin, based on sterilized human adult dermis seeded with keratinocytes and fibroblasts, which contracts by up to 60% over 28 days in vitro, as a model to investigate the mechanism of skin contraction. Pharmacologic agents modifying collagen synthesis, degradation, and cross-linking were examined for their effect on contraction. Collagen synthesis and degradation were determined using immunoassay techniques. The results show that skin contraction was not dependent on inhibition of collagen synthesis or stimulation of collagen degradation, but was related to collagen remodelling. Thus, reducing dermal pliability with glutaraldehyde inhibited the ability of cells to contract the dermis. So did inhibition of matrix metalloproteinases and inhibition of lysyl oxidase-mediated collagen cross-linking, but not transglutaminase-mediated cross-linking. In summary, this in vitro model of human skin has allowed us to identify specific cross-linking pathways as possible pharmacologic targets for prevention of graft contracture in vivo.

Topics: Adult; alpha-Macroglobulins; Aminopropionitrile; Catechin; Cell Culture Techniques; Cells, Cultured; Collagen Type IV; Contracture; Cross-Linking Reagents; Culture Media; Dermis; Dose-Response Relationship, Drug; Estrone; Female; Fibroblasts; Fluorescent Antibody Technique, Indirect; Glutaral; Humans; Image Processing, Computer-Assisted; Immunoassay; Immunohistochemistry; Keratinocytes; Keratins; Photography; Skin Transplantation; Skin, Artificial; Time Factors; Tissue Engineering

Topics: Adult; Base Sequence; Contracture; Fingers; Humans; Hyperkeratosis, Epidermolytic; Keratins; Male; Mutation; Proline; Threonine