Smith-Lemli-Opitz syndrome (RSH/SLO syndrome, SLOS, MIM# 270400) is an autosomal recessive, multiple malformation/mental retardation syndrome [Smith et al., 1964] with an estimated variable incidence among individuals of European ancestry of 1 in 15,000 to 1 in 60,000 births [Lowry and Yong, 1980; Ryan et al., 1998; Opitz, 1999a; Bzdúch et al., 2000; Kelley and Hennekam, 2000] and a probable average carrier frequency of 1%[Kelley and Hennekam, 2000]. Principal abnormalities include a characteristic facial appearance, microcephaly, hypotonia, postnatal growth retardation, 2-3 toe syndactyly, and hypogenitalism. Less common are malformations of the brain, lung, heart, and gastrointestinal tract. In 1993, SLOS was shown to be caused by a defect of cholesterol biosynthesis at the level of the 7-dehydrocholesterol reductase [Irons et al., 1993; Tint et al., 1994]. This defect results in the impaired conversion of 7-dehydrocholesterol to cholesterol, causing an increased level of 7-dehydrocholesterol in blood and tissues, and, in most patients, associated decreased blood and tissue choles-Disclaimer: The opinions and assertions contained herein are the private opinions of the authors and are not to be construed as official or as representing the views of the National Institute of Child Health and Human Development or the National Institutes of Health.