title: Arrested epidermal morphogenesis in three newborn infants with a fatal genetic disorder (restrictive dermopathy).
abstract: Two sibs and one unrelated infant were born prematurely with taut, shiny, restrictive skin that was abnormal in structure, organization, biochemistry, and state of differentiation. Prominent abnormalities in all regions of the skin were recognized by light and electron microscopy, immunohistochemistry, and biochemistry. The epidermis was hyperplastic, hyperkeratotic, and parakeratotic. Keratohyaline granules were abnormal in structure, but the keratohyalin-derived protein filaggrin was apparently normal in quantity and biochemistry. The epidermal cells contained less than the expected quantity of high-molecular-weight, differentiation-specific keratins and the tissue stained with antikeratin antibodies in an aberrant pattern. Additional 48 and 56 kD keratin polypeptides, indicative of a hyperproliferative state, were expressed. The dermal-epidermal junction was remarkably flat and the dermis was thinner than normal. The connective tissue appeared stretched and was oriented like tendon rather than dermis. Collagen fiber bundles and fibrils were smaller in diameter than normal. The nails were normal but other epidermal appendages such as the pilosebaceous structures and the eccrine sweat glands were underdeveloped, suggesting that morphogenesis of these structures was arrested at an early stage in utero. The subcutaneous fat was at least twice the thickness of the dermis. The skin abnormalities appeared to be the cause of the flexion contractions, characteristic facies, and inability to survive because of restricted respiratory movements. The structural and biochemical abnormalities in the skin of affected infants may serve as markers for prenatal and postnatal diagnosis of the disorder, and may provide insight into the basic mechanism of the disease.
mesh_terms: D000091344:Filaggrin Proteins; D005804:Genes, Lethal; D006651:Histocytochemistry; D006801:Humans; D007120:Immunochemistry; D007231:Infant, Newborn; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D011506:Proteins / Q000378:metabolism; D012867:Skin / Q000196:embryology / Q000473:pathology / Q000648:ultrastructure; D012871:Skin Diseases / Q000196:embryology / Q000235:genetics* / Q000378:metabolism / Q000401:mortality
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D011506:Proteins; D007633:Keratins