title: Teratogenic mechanisms of longitudinal deficiency and cleft hand.
abstract: In order to better understand the teratogenic mechanisms of congenital defects of the digits, we analyzed clinical cases and induced similar types of congenital hand anomalies in rat fetuses by oral administration of busulfan. In clinical cases, radial and ulnar deficiencies had common characteristic features. We induced radial and ulnar deficiencies in rat fetuses with the same drug. Radial and ulnar deficiencies induced in rats have similar clinical manifestations and these anomalies might be caused by the same teratogenic mechanism. Then, the formation of the digital rays was examined histologically. The results of histological examination suggested that these deficiencies were not caused by localized damage of the limb bud. They also suggested that the cause of missing digits in longitudinal deficiency is closely related to a deficit of mesenchymal cells in the limb bud. Cleft hand is considered to be one of the types of longitudinal deficiency. However, several investigators have suggested that the abnormal induction of finger rays in the process of formation of fingers induced central polydactyly, osseous syndactyly and also cleft hand. X-rays of the clinical cases and skeletal changes of the anomalies induced in rats appear to demonstrate that cleft hand formation proceeds from osseous syndactyly and central polydactyly. The results of our experimental study show that the critical periods of central polydactyly, osseous syndactyly and cleft hand are the same. They also suggest that central polydactyly, syndactyly and cleft hand might be induced when the same teratogenic factor acts on embryos at the same developmental stage in the human being. Because they have a similar causation, cleft hand, syndactyly and central polydactyly should be classified into the same entity, that is, abnormal induction of digital rays. Based on these clinical and experimental studies, we modified the Swanson classification. In our modified classification, typical cleft hand, syndactyly and polydactyly are included in the same category of abnormal induction of digital rays as the fourth new category.
authors.affiliation: Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, Japan. togino@med.id.yamagata-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Ogino
mesh_terms: D000818:Animals; D002066:Busulfan; D004480:Ectromelia / Q000139:chemically induced* / Q000196:embryology / Q000473:pathology; D005260:Female; D005385:Fingers / Q000002:abnormalities / Q000473:pathology; D005865:Gestational Age; D006228:Hand Deformities, Congenital / Q000139:chemically induced* / Q000196:embryology / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018878:Limb Buds / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D017689:Polydactyly / Q000139:chemically induced / Q000196:embryology / Q000473:pathology; D011247:Pregnancy; D011884:Radius / Q000002:abnormalities / Q000196:embryology / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013576:Syndactyly / Q000139:chemically induced / Q000196:embryology / Q000473:pathology; D013723:Teratogens; D014457:Ulna / Q000002:abnormalities / Q000196:embryology / Q000473:pathology
chemical_list: D013723:Teratogens; D002066:Busulfan