Smith-Lemli-Opitz syndrome and differential diagnosis [36 genes]

Smith-Lemli-Opitz syndrome is a polymalformative condition associated with cognitive impairment caused by an alteration in cholesterol metabolism resulting from a deficiency of the 7-dehydrocholesterol reductase. It is characterized by prenatal and postnatal growth retardation, microcephaly, moderate to severe intellectual disability, and multiple major and minor malformations. Malformations include characteristic facial features, cleft palate, heart defects, hypoplastic external genitalia in males, postaxial polydactyly, and syndactyly of the 2nd and 3rd toes. However, the clinical spectrum is broad, and certain patients present only minor malformations.

Smith-Lemli-Opitz syndrome: between 1 / 20,000-40,000 newborns (ORPHA:818).

The benefits derived from a genetic diagnosis in this context are especially aimed at closing the diagnosis and family genetic counseling, as well as carrying out symptomatic management well adapted to the patient’s diagnosis and prognosis.

Service is indicated when the clinical and analytical data suggest the disease. If a compatible phenotype and inconclusive analytical data are identified, requesting the service could also be considered, given that the differential diagnosis genes are included.

Among patients who meet clinical diagnostic criteria, the possibility of finding a genetic cause approaches 100% after analysis of SNVs and CNVs. The exome directed to the analysis of the DHCR7 gene has a theoretical diagnosis rate close to 100%, except for variants that may not be identified due to the technical limitations of the approach.