Smith-lemli-opitz syndrome

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by mutations in the gene encoding the 7-dehydrocholesterol reductase (7-DHC) resulting in decreased or absent function of this enzyme responsible for catalyzing the final step in cholesterol synthesis. Increased levels of 7-DHC and typically a reduction in cholesterol synthesis are seen in affected individuals. Diagnosis is made based on elevated 7-DHC. The estimated incidence of SLOS is 1:39, 000 conceptions, with a carrier rate of approximately 1%. Higher carrier prevalence is reported in individuals of European or North American heritage. SLOS is characterized by growth failure, cognitive delay, behavioral disturbances, dysmorphic faces, and congenital defects. There is marked variability in the presentation of this condition ranging from mild effects that an individual remains undiagnosed, to fetal or neonatal death. The following findings on ultrasound (syndactyly/polydactyly, growth restriction, microcephaly, micrognathia, cleft palate, cardiac defects, and ambiguous male genitalia) in association with low maternal serum estriol and normal karyotype are highly suggestive of SLOS. Prenatal testing is available in at-risk pregnancies. Common postnatal therapies for SLOS include dietary cholesterol supplementation and surgical intervention, for the given defect or defects as appropriate.