Smith-Lemli-Opitz syndrome is caused by recessive mutations of the DHCR7 gene at chromosome 11q12, encoding the enzyme 7-dehydro-cholesterol reductase, leading to metabolic abnormalities of the cholesterol pathway and deficient synthesis of steroid hormone derivatives.
Phenotypic abnormalities of the disease include microcephaly, hypospadias, ambiguous genitalia, mental retardation and dysmorphic features. Some of these features may be revealed during a prenatal ultrasound examination (e.g. hypospadias and/or cryptorchidism) and because low levels of unconjugated estriol in the serum of a pregnant mother may be associated with the disease, the need for prenatal screening for DHCR7 gene mutations in the fetus is relatively frequent. However, genotype-phenotype correlations should be considered carefully as there is a significant heterogeneity in disease severity between patients (usually double heterozygotes) with the same mutations.
We perform full DNA sequencing (automated bi-directional fluorescent DNA sequencing) of all the exons and splice sites (intron/exon boundaries) of the DHCR7gene, allowing the detection of greater than 95% of disease mutations.