Rod photoreceptor responses in children with Smith-Lemli-Opitz syndrome

Objective: To test the hypothesis that the kinetics of activation and deactivation of rod phototransduction are altered in children with Smith-Lemli-Optiz syndrome (SLOS), a common genetic disorder caused by an inborn error in cholesterol biosynthesis. Methods: Thirteen patients with SLOS (median age, 4 years) were studied by means of scotopic full-field electroretmography. The kinetics of activation and deactivation of rod phototransduction were derived from the electroretinographic a-wave. Postreceptoral electroretinographic components were also evaluated. Results: The kinetics of activation were below normal limits in all but 3 of the 13 patients. Rod cell recovery (deactivation) in SLOS was slower than normal in all 8 patients in whom it was studied. Postreceptoral sensitivity was below normal limits in all but 1 of the 13 patients. Conclusions: The kinetics of phototransduction are slow in children with SLOS. This is likely a consequence of altered sterol composition in the cell membranes of the rod photoreceptors. To our knowledge, this is the first demonstration of altered kinetics of a membrane-bound signaling system in SLOS. Investigation of other membrane-bound signaling systems may be warranted in the quest to understand development and phenotype of individuals with SLOS.