**Question:** If the fetus has Down syndrome, quadruple marker will not show:

A. alpha-fetoprotein (AFP)
B. human chorionic gonadotropin (hCG)
C. estriol (E3)
D. inhibin A

**Core Concept:** Down syndrome is a genetic disorder caused by the presence of an extra copy of chromosome 21, which leads to developmental abnormalities and increased risk of certain conditions. The quadruple marker test is a screening test used to detect an increased risk of Down syndrome and other chromosomal abnormalities in a fetus. The test measures the levels of four different proteins in a woman's blood: AFP, hCG, E3, and inhibin A.

**Why the Correct Answer is Right:** In cases of Down syndrome, the levels of AFP, hCG, and E3 might be elevated due to the increased cell turnover and fetal membrane rupture. However, the levels of inhibin A are generally reduced because of the reduced activity in the fetal gonads. As a result, the combination of elevated AFP, hCG, and E3 with reduced inhibin A would indicate an increased risk of Down syndrome.

**Why Each Wrong Option is Incorrect:**

A. alpha-fetoprotein (AFP): A possible elevated level of AFP in the blood can indicate an increased risk of Down syndrome. However, in the context of Down syndrome, the combination of elevated AFP, hCG, and E3 with reduced inhibin A is more indicative of the condition.

B. human chorionic gonadotropin (hCG): Elevated hCG levels can be indicative of Down syndrome or other chromosomal abnormalities, but the combination of elevated hCG, AFP, E3, and reduced inhibin A is more indicative of the condition.

C. estriol (E3): Elevated E3 levels can be indicative of Down syndrome or other chromosomal abnormalities, but the combination of elevated hCG, AFP, E3, and reduced inhibin A is more indicative of the condition.

D. inhibin A: Reduced inhibin A levels are associated with Down syndrome due to reduced activity in the fetal gonads. However, the combination of elevated AFP, hCG, E3, and reduced inhibin A is more indicative of the condition.

**Clinical Pearl:** A negative result from the quadruple test does not rule out Down syndrome, but a positive result, particularly when combined with other risk factors, increases the probability of Down syndrome and is used in the decision of further diagnostic tests like CVS or amniocentesis.