Exploring Recent Developments in the Manifestation, Diagnosis, and Treatment of Patients with Smith-Lemli-Opitz Syndrome: From Molecular Pathways to Clinical Innovations.

Smith-Lemli-Opitz syndrome (SLOS) is a rare, autosomal recessive genetic disorder caused by mutations in the gene, which encodes the enzyme responsible for the final step in cholesterol biosynthesis. Impaired enzyme function leads to cholesterol deficiency, affecting the development and function of the entire organism. The accumulation of cholesterol precursors enhances the formation of oxysterols, which are involved in the pathomechanism of neurological, ophthalmological, and vascular changes in patients. This review analyzes 53 studies published between 2020 and 2025 on the molecular mechanisms underlying the clinical features of SLOS, including cholesterol deficiency, oxysterol accumulation, and the latest diagnostic methods, including LC-MS/MS chromatography and biomarkers such as GFAP for monitoring disease progression. MRI is discussed as a supportive tool for neuroimaging, along with advances in prenatal diagnostics, such as the detection of cholesterol precursors in neonatal hair. Therapeutic options are also reviewed, with particular emphasis on cholesterol supplementation, cholic acid, and experimental treatments such as vitamin E supplementation, statin therapy, gene therapy, and liver transplantation. Current research indicates that expanding knowledge in this area not only improves patient prognosis but also provides hope for the development of effective therapies in the future.