Review Question - QID 106510

The results of the quad screen are indicative of Down syndrome. A confirmatory amniocentesis and chromosomal analysis of the fetal cells is required to verify the diagnosis of a positive screening test.

Down syndrome is the most common cause of mental retardation and is due to trisomy 21. It is the most common chromosomal disorder, and the risk increases with advanced maternal age. All pregnant women, regardless of age, should be offered screening for Down syndrome. There are several screening modalities for Down syndrome, such as the quad screen and cell-free fetal DNA analysis, each with varying levels of sensitivity, specificity, timeline, and cost. All positive screens for Down syndrome should be confirmed with either amniocentesis or chorionic villus sampling.

Newberger discusses the prenatal risk assessment and diagnosis of Down syndrome. He explains the impact of maternal age on risk assessment and screening modality utilized. He recommends that women younger than 35 years of age be offered maternal serum screening. Furthermore, an ultrasound examination to estimate gestational age can be added to the serum screening to improve sensitivity and specificity.

Gil et al. review the use of cell free DNA in the maternal blood as a screening tool for trisomy 21. Cell free DNA is fetal DNA found in the maternal blood stream that can be collected non-invasively and utilized to screen for trisomy 21, 18, 13, and sex chromosome aneuploidies. They state that screening with cell free fetal DNA has improved of detection rates and decreased false-positive rates relative to other traditional screens.

Illustration A depicts the common facial findings in a patient with Down syndrome. Note the slanted eyes, protruding tongue, flat nasal bridge, abnormal ears, short neck, and flat head. Illustration B demonstrates how the risk of Down syndrome increases as maternal age increases. Illustration C shows a karyotype of a patient with Down syndrome with three copies of chromosome 21.

Incorrect Answers:
Answer 1: An abnormal prenatal screen warrants further workup, and amniocentesis or chorionic villus sampling should be offered.
Answer 3: Biopsy and pathologic examination of fetus is not used in the diagnosis of Down syndrome.
Answer 4: While the fetal karyotype may be abnormal, maternal karyotype is not used in the diagnosis of Down syndrome.
Answer 5: Cell-free fetal DNA analysis is used for screening rather than for confirming the diagnosis.