Experimental Study of Radial Ray Deficiency

Abstract

The teratogenic mechanisms of radial ray deficiency were investigated. Radial ray deficiencies were induced in WKAH/Hkm rat foetuses by maternal administration of myleran on day 10, 10.5, or 11 of pregnancy. The skeletal anomalies in rats were similar to those in human beings, suggesting that exposure to some environmental factors at a sensitive period of embryogenesis may cause radial ray deficiency in humans. Ulnar ray deficiency has also been induced in rat foetuses by maternal administration of myleran, so it is suggested that radial deficiency and ulnar deficiency are caused by a common teratogenic mechanism in humans. However, the critical period for radial deficiency is one day later than that for ulnar deficiency in rats, which may contribute to the greater frequency of radial deficiency than ulnar deficiency in clinical cases.

Classification and Developmental Biology of Congenital Anomalies of the Hand and Upper Extremity

“…The proposed category of abnormal induction of rays attempts to incorporate the concept of causation as suggested by experimental studies 37,38 ; the proposed category includes syndactyly (both simple and complex), the central polydactylycleft hand-osseous syndactyly complex, and triphalangeal thumb. These conditions would move from their current categories of failure of formation (transverse), failure of differentiation, and duplication on the premise that they represent induction abnormalities rather than formation abnormalities.…”

Radial Deficiency

“…Ogino and Kato have shown that WKAH/Hkm rats exposed to busulfan at weeks 10 through 11 of development develop limb deformities that are similar to longitudinal deficiencies seen in humans (Kato et al 1990;Ogino 2004). In Ogino's studies, limb changes were global suggesting that injuries to mesenchymal cells within the AER may have widespread implications for limb development.…”

“…Knowledge of the anatomical variations within the forearm is critical prior to embarking on any surgical procedure for RLD. Studies by Kato, Skerik, Flatt, Pardini, and Kelikian describe the anatomical variations in detail and should be reviewed by the inexperienced surgeon (Kelikian and Doumanian 1957;Pardini 1968;Skerik and Flatt 1969;Kato et al 1990;Flatt 1994). …”

Combined Congenital Radial and Ulnar Longitudinal Deficiencies: Report of 2 Cases

“…9,25,26,28 In early-stage embryos, before the induction of Shh expression or limb bud outgrowth, ulnar disruption predominates. After the limb bud and ZPA have already been established, cell death preferentially affects radial structures.…”

“…14,16,24 In rodents, maternal ingestion of antiproliferative chemotherapy agents from embryonic day 10 to 12 (comparable to weeks 5-6 in humans) led to radial deficiencies and digital abnormalities. 25,26 Furthermore, treatment with busulfan, an antiproliferative chemotherapy agent, causes increased apoptosis, disruption in AER morphology, loss of AER-related Fgf8 expression, and reduced bone morphogenetic protein 4 expression. 27,28 Together, these findings suggest that RLD results from fetal insults that disrupt cell proliferation and reduce limb bud volume.…”