Clinical features as specific indicators in the diagnosis of Smith-Lemli-Opitz syndrome (SLOS) and the reliability of ultraviolet spectrophotometry (UVS) as a biochemical screening test were examined by an Italian SLOS Collaborative Group of investigators. Of 20 patients with clinical suspicion of SLOS, referred to 11 Italian pediatric and clinical genetic centers in 1994, the diagnosis was confirmed biochemically by gas chromotography/mass spectrometry analysis (GC/MS) of serum sterols in 10, and serum sterols were normal in 10. Comparison of clinical signs in confirmed cases and biochemically negative patients did not reveal a specific group of manifestations of SLOS. UVS measurement of 7-dehydrocholesterol, which accumulates in the plasma in SLOS, correlated with GC/MS profiles. Serum bile acid concentrations were lower than normal in 4 of 5 patients with the syndrome. 
COMMENT. The “gestalt” impression formed by an experienced clinician examining the facial appearance of a child is perhaps the most practical and reliable method of diagnosis of Smith-Lemli-Opitz syndrome. Signs and symptoms of the syndrome are variable and non-specific and include mental retardation, failure to thrive, feeding difficulties, hypotonia, microcephaly, ptosis and epicanthal folds, anteverted nostrils, micrognathia, low set ears, syndactyly, simian creases, and hypospadias. Ultraviolet spectrophotometry determination of serum 7-DHC levels is 100% sensitive, relatively inexpensive, and specific for the biochemical diagnosis of SLOS.