From the Guidelines
Prenatal testing for Smith-Lemli-Opitz syndrome (SLOS) is available and recommended for at-risk pregnancies, with testing typically involving measuring 7-dehydrocholesterol (7-DHC) levels in amniotic fluid or chorionic villus sampling, as elevated 7-DHC is the biochemical hallmark of this disorder. The testing is typically performed between 15-18 weeks gestation for amniocentesis or 10-13 weeks for chorionic villus sampling, as suggested by studies such as 1. SLOS is an autosomal recessive disorder affecting cholesterol synthesis, resulting in multiple congenital anomalies, intellectual disability, and growth problems. Early diagnosis allows for preparation for potential medical interventions after birth, including cholesterol supplementation. If both parents are carriers, each pregnancy has a 25% risk of producing an affected child. Ultrasound findings may show characteristic features but are not always reliable for diagnosis, making biochemical or genetic testing essential for confirmation, as noted in 1 and 1.
Key Points
- Prenatal testing for SLOS is recommended for at-risk pregnancies
- Testing involves measuring 7-DHC levels in amniotic fluid or chorionic villus sampling
- The testing is typically performed between 15-18 weeks gestation for amniocentesis or 10-13 weeks for chorionic villus sampling
- SLOS is an autosomal recessive disorder with significant morbidity and mortality implications
- Early diagnosis allows for preparation for potential medical interventions after birth, including cholesterol supplementation, as discussed in 1 and 1.
Testing Options
- Chorionic villus sampling (CVS) between 10-13 weeks gestation
- Amniocentesis between 15-18 weeks gestation
- Genetic testing for mutations in the DHCR7 gene, which encodes the enzyme 7-dehydrocholesterol reductase, can also be performed on fetal cells, as mentioned in 1 and 1.
Importance of Early Diagnosis
- Allows for preparation for potential medical interventions after birth, including cholesterol supplementation
- Enables parents to make informed decisions about the pregnancy
- Can help identify potential complications early on, as noted in 1 and 1.
Recommendations
- Parents with a previously affected child or known carriers should be offered genetic counseling and prenatal diagnosis in subsequent pregnancies, as recommended by 1 and 1
- The American College of Medical Genetics recommends that all women should have the option of invasive diagnostic testing for fetal aneuploidy by CVS, if available, or amniocentesis, as stated in 1 and 1.
From the Research
Prenatal Testing for Smith-Lemli-Opitz Syndrome
- Prenatal diagnosis of Smith-Lemli-Opitz syndrome (SLOS) is possible through various methods, including measurement of 7-dehydrocholesterol (7-DHC) levels in chorionic villus (CV) biopsies or amniotic fluid [ 2 ].
- Low maternal serum unconjugated estriol (uE3) levels and abnormal fetal ultrasound findings, such as limb deformities and ventriculomegaly, can also indicate SLOS [ 3 ].
- The predictive value of these criteria, combined with family history, can be evaluated by quantifying sterols in amniotic fluid [ 4 ].
Diagnostic Evaluation
- The diagnosis of SLOS is confirmed by demonstrating an abnormally elevated concentration of 7-DHC in serum or other tissues, or by the presence of two DHCR7 mutations [ 5 ].
- Sterol analysis in CV biopsies or amniotic fluid can be used to confirm the diagnosis [ 2, 4 ].
- Careful evaluation of family history, maternal serum uE3 levels, and clinical presentation is recommended before determining sterols in amniotic fluid [ 4 ].
Implications for Prenatal Testing
- Prenatal testing for SLOS can be considered in pregnancies with a family history of the condition, abnormal fetal ultrasound findings, or low maternal serum uE3 levels [ 3, 4 ].
- The wide phenotypic spectrum of SLOS and the need for a high index of suspicion for the disorder highlight the importance of careful evaluation and consideration of prenatal biochemical testing [ 3 ].