Incidence of Smith‐Lemli‐Opitz syndrome in Ontario, Canada

Smith-Lemli-Opitz syndrome (OMIM 270400) (SLOS) is caused by inherited enzymatic deficiency of 3beta-hydroxysterol-Delta7-reductase (7-dehydrocholesterol-Delta7-reductase, DHCR7). SLOS is diagnosed clinically by the demonstration of elevated levels of 7-dehydrocholesterol (7DHC) in body fluids or tissues. SLOS is associated with mental retardation of variable degree and severe behavior abnormalities. The physical abnormalities range from minor facial anomalies to lethal malformations of the central nervous system, heart, kidneys, and other organs. The exact incidence of SLOS is not known. Although there exist estimates of the incidence of SLOS ranging from 1 in 20,000 to 1 in 60,000, no prospective studies of the incidence of SLOS, based on the clinical data and biochemical diagnosis of SLOS, have been performed. Five unrelated cases of SLOS were diagnosed in Ontario during a 12-month period. The diagnoses were made based on the demonstration of elevated 7DHC in plasma or amniotic fluid. The birth rate for Ontario for that period was 132,000 births. The incidence of SLOS in Ontario was at least 1 in 26,500 pregnancies in 1999-2000. Given that 86% of the population of Ontario is of European origin, the incidence of SLOS in the Ontario population of European origin was at least 1 in 22,700. As infants with mild forms of SLOS born during this period may remain undiagnosed, these numbers likely are underestimates. This observation has implications for prenatal and newborn screening for this potentially treatable inherited disorder.