Smith-Lemli-Opitz syndrome: A multiple malformation/mental retardation syndrome caused by defective cholesterol synthesis

Smith-Lemli-Opitz syndrome (SLOS) is a genetic condition characterized by d ysmorphic facies, mental retardation and multiple malformations. A specific defect in cholesterol metabolism, 7-de hydrocholesterol-Delta (7) reductas e (DKCR7) defficiency due to mutation of the DHCR7 gene is the underlying c ause of this syndrome. DHCR7 is a microsomal enzyme that catalyzes the conv ersion of 7-dehydrocholesterol (7DHC) to cholesterol. Hence, affected indiv iduals exhibit low plasma cholesterol and high 7DHC levels. The phenotype m ost likely results from the combination of cholesterol deficiency and 7DHC accumulation. Diagnosis is based on clinical findings with confirmation by plasma sterol analysis. Prenatal diagnosis may be performed by sterol analy sis of amniotic auid/amniocytes or chorionic villi, or enzyme assay of chor ionic villi. Maternal serum estriol and urine sterol analyses provide the o pportunity for noninvasive prenatal diagnostic testing. Preliminary evidenc e from animal and human studies shows that dietary cholesterol supplementat ion may be beneficial for SLOS patients, but issues including prenatal onse t of damage plus poor transport of cholesterol across the blood-brain barri er may limit treatment efficacy. The incidence of SLOS has been estimated t o be one in 20,000 to one in 60,000 making it one of the most common autoso mal recessive disorders. Recent studies suggest that the carrier frequency is much higher than the disease incidence would suggest.