Smith-Lemli-Opitz syndrome: a treatable inherited error of metabolism causing mental retardation

Smith-Lemli-Opitz syndrome, a syndrome of multiple malformations and mental retardation that for years was relegated to the atlases of genetic esoterica, was recently found to be a relatively common inborn error of metabolism. The underlying defect is absent or deficient activity of 7-dehydrocholesterol- delta 7-reductase, the enzyme catalysing the final step of cholesterol synthesis. The discovery of the biochemical defect causing Smith-Lemli-Opitz syndrome has resulted in the development of a diagnostic test and a potentially beneficial treatment (dietary cholesterol supplementation). Infants and young children with the syndrome have shown marked improvement in growth, behaviour and general health after receiving cholesterol therapy; older children and adults have shown some improvement in development and intellectual functioning. Despite the excitement these developments have elicited among geneticists and biochemists, this syndrome remains relatively unknown to many primary care physicians. Increased awareness of Smith-Lemli-Opitz syndrome is needed to identify affected patients so that they and their families can benefit from appropriate treatment and genetic counselling.