Teratogenic effects of retinoic acid in pigtail monkeys (Macaca nemestrina). II. Craniofacial features

The teratogenic effects of retinoic acid, the alcohol-soluble acid form of vitamin A, on the craniofacial complex of 11 macaque (Macaca nemestrina) whose mothers had received the compound from days 20 to 44 are described. The fetuses ranged in gestational age from 81 to 185 days and exhibited features of the so-called retinoic acid syndrome (RAS). The syndrome includes both craniofacial defects and postcranial anomalies of the musculoskeletal and urogenital systems. The craniofacial anomalies were described with reference to gross external appearance and radiographic observations. The most frequent findings were cleft palate, malformed ears, hypertelorism, exophthalmos, hypoplasia of the bone of the mid-face and mandible, a curvature of the inferior border of the mandible, retrognathia, and distortion of the cranium. Lateral cephalograms on nine animals of the RAS sample were measured using six linear dimensions which define the cranial base, face height, palatal length, and mandibular length. The measurements were plotted relative to normal curves which describe growth of the dimensions through the macaque fetal period. For their age, the abnormal animals were small in the craniofacial region. The same measurements were then plotted relative to the size of the fetus, to investigate the possibility of a differential response of the various craniofacial areas to the teratogen. Mandibular length and anterior cranial base were the most reduced dimensions, followed by anterior and posterior face height, with palatal length the least affected. Comparison of the features of the RAS syndrome in the macaque fetus with those reported for various human mandibulofacial dysostosis syndromes yields similarities, but there are enough differences to indicate that the syndromes are not identical in the two species. The utility of the approach used, wherein several craniofacial dimensions of the abnormal are assessed relative to normal growth curves and relative to body size, is emphasized.