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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Teratological studies on craniofacial malformations.

Craniofacial malformations cause great human suffering. The purpose of the experimental studies was to investigate teratogenically induced craniofacial malformations in the rat, and to study if vitamin B6 could prevent the teratogenically induced malformations in the rat. The aim of the clinical investigation was to compare mandibulofacial dysostosis (MFD) with hemifacial microsomia ( HFM) and thalidomide-induced malformations restricted to the first and second branchial arches. In the experimental studies we used two different teratogenic agents, etretinate and BAPN (beta-aminoproprionitrile). Vitamin B6 was administered one day prior to and simultaneously with the teratogenic agent. The induced malformations were observed by direct microscopy, histology, differential staining, microdissection and enzyme histochemistry. Knowledge of isoenzymic differentiation was obtained by isoelectric focusing and polyacrylamide gel electrophoresis. The clinical features of 29 patients with MFD, 26 with HFM and seven with thalidomide-induced malformations were investigated. The patients underwent clinical investigations, radiography, tomography, computed tomography, surgical exploration and audiograms. The etretinate-induced syndrome in the rat shows similarities to first and second branchial arch syndromes in man. Defective formation of Meckel's cartilage and the cartilaginous skull base, the zygoma and the middle ear ossicles were prominent features of the observed malformations. The induced malformations were accompanied by increased staining for alkaline phosphatase (APase) in the skull and skull base cartilages and Meckel's cartilage. BAPN induced cleft palate in 95% of the cases and the teratogenically induced cleft palate was accompanied by a pathological differentiation pattern that could be traced by determination of isoenzymes in the palatal shelves as well as in amniotic fluid. Vitamin B6 could prevent the teratogenic malformations induced by etretinate and BAPN in the rat. Comparing MFD, HFM and thalidomide-induced malformations, all syndromes included patients with external, middle and inner ear malformations. Cranial nerve palsy/paresis was only seen in HFM and thalidomide-induced malformations. A relationship between disturbed neural crest cell migration and defects of the first and second branchial arches seems possible.[1]


  1. Teratological studies on craniofacial malformations. Jacobsson, C. Swedish dental journal. Supplement. (1997) [Pubmed]
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