Smith-Lemli-Opitz Syndrome (DHCR7)
Smith-Lemli-Optiz syndrome is an autosomal recessive disease caused by pathogenic variants in the gene DHCR7. While it is a pan-ethnic disease, it is identified more frequently in people of Caucasian or Ashkenazi Jewish ancestry. Smith-Lemli-Optiz syndrome is characterized by impaired cholesterol synthesis, which results in congenital abnormalities including a small head, dysmorphic features, cleft palate, extra and/or fused fingers and toes, gastrointestinal anomalies and genital abnormalities in males. Intellectual deficits and behavioral problems, including autistic features, self-harm behaviors and hyperactivity may be present. While most patients have a severe phenotype and are identified at birth, more mildly affected patients who have been diagnosed in childhood or adolescence have been reported. It is thought that many conceptions affected with Smith-Lemli-Optiz syndrome are lost in early embryonic development, as the disease frequency is much rarer than what would be expected based on the frequency of carriers. Life expectancy varies with the severity of disease; it has been reported that approximately 25% of patients die in infancy, while others live to adulthood. A clear genotype-phenotype correlation has not been reported.
For information about carrier frequency and residual risk, please see the residual risk table.