Isotretinoin, a potent human teratogen, has been available by prescription since 1982 for the treatment of severe cystic acne and related skin conditions. We have bee following a sample of 47 children who were identified prospectively during the first 60 days of gestation, as part of a larger study on pregnancy and outcome following embryonic exposure (Lammer et al 1985). Of these pregnancies, 17% ended in spontaneous abortion and a 23% risk for malformation was documented for fetuses that reached 20 weeks gestation (Lammer et al, 1987). The pattern of malformations includes central nervous system, craniofacial, thymic, and cardiac structures. The liveborn infants and controls from this original study are now being examined at the age of 5 years. At a current sample size of 44 cases and 40 controls, 43% of the exposed children have been found to be functioning in the subnormal range of general intelligence. This includes children with and without major malformations. A pattern of deficits in executive and spatial processing is suggested. The long-range consequences of these functional deficits at 5 years of age is specifically unknown, but may be expected to include characteristics such as attentional difficulties, math, and handwriting disorders. The purpose of this grant is to evaluate the developmental characteristics of this sample of embryonically exposed children at the age of 10 years using tests which will examine a range of physical and cognitive abilities as well as elaborate and extend our understanding of the specific functional deficits of these children. In addition, we also wish to examine the teratogenic outcome of additional children exposed during fetal development. This work will allow us to better understand relationships between structural and functional teratogenesis, and between stage at exposure, disruptions in brain development, and corresponding physical and mental development. Studies of Isotretinoin exposed children who have received both prenatal and postnatal medical care, and have been identified prospectively during gestation provide a unique opportunity to address these important issues in teratology in a reasonably unconfounded human sample.