The Principles of Clinical Cytogenetics - Extra Materials - Springer

Genetic Counseling 553
fetal amniocytes, which are placed in culture and the chromosomes analyzed. The level of α-fetoprotein
(AFP) in the amniotic fluid can also be analyzed to screen for open fetal defects, such as open
neural tube defects and abdominal wall defects. The risk of a miscarriage associated with an amniocentesis
is generally quoted as approximately 1/200 or 0.5% (10,15).
When rapid information about the fetal chromosomes is needed, generally the result of a particularly
high risk of aneuploidy or a late gestational age, FISH (see Chapter 17) for chromosomes 13, 18,
21, X, and Y can be performed on the direct amniotic fluid or chorionic villi. Chromosomes 13, 18,
21, X, and Y are the most common chromosomes involved in a prenatally diagnosed, potentially
viable chromosome abnormality and are, therefore, the focus of prenatal FISH analysis (25–27).
Although FISH can yield important information in a short period of time, it is not a substitute for
routine cytogenetic analysis. Furthermore, a recommendation from the American College of Medical
Genetics states that irreversible action should not be taken on the basis of a FISH result alone (28).
FISH can also be performed on prenatal specimens for the detection of several microdeletion syndromes,
when the ultrasound findings or family history indicates an increased risk for such a condition.
Additionally, FISH can be performed on prenatal specimens for the detection of translocations
involving the subtelomeres.
Abnormal Prenatal Screen
Although Down syndrome and trisomy 18 are commonly screened for prenatally, other chromosome
abnormalities can, at times, be detected using certain screening methods, although that is not
the goal of such screening. Serum screening is generally offered to women who are under age 35 but
can also be offered to women who are 35 or older and are undecided about pursuing invasive diagnostic
testing for chromosome abnormalities. The patient or couple should be fully counseled about
the limitations of screening, particularly if the mother is 35 or older. It is important for the patient to
appreciate the distinction between screening, which is designed to provide a risk estimate, and diagnostic
tests, which are designed to diagnose or rule out a chromosome abnormality. When screening
indicates that there is an increased risk for a chromosome abnormality in a pregnancy, the pregnant
woman or couple should be counseled about the implications of this result and the options for further
testing, such as CVS or amniocentesis. An individual or couple could be referred for genetic counseling
prior to pursuing a prenatal screen, so that an informed decision can be made about whether or not
to pursue such screening.
First-trimester screening is, as its name implies, performed during the first trimester of pregnancy.
This screening involves biochemical analysis of the levels of certain pregnancy-related proteins in the
maternal circulation. To increase the number of affected pregnancies detected by this screening, the
biochemical analyses can be used in conjunction with a nuchal translucency ultrasound measurement, a
measurement of the amount of fluid between the skin and soft tissue over the cervical spine of the
developing fetus. Combined with additional information about the pregnancy and family history, these
data are used to generate estimated risks for Down syndrome and trisomy 18 (29–31). In addition to
being associated with an increased risk for aneuploidy, an increased nuchal translucency measurement
is also associated with other fetal abnormalities, particularly cardiac malformations (32–35).
Second-trimester maternal serum screening is generally performed between 15 and 20 weeks of
gestation. This screening usually involves analyzing the maternal blood for the levels of three or four
pregnancy-related proteins and is often referred to as the triple screen or quad screen, depending on
the number of proteins analyzed. In the triple screen, AFP, human chorionic gonadotropin (hCG),
and unconjugated estriol (uE3) are analyzed. In the quad screen, dimeric inhibin A (DIA) is added.
As with first-trimester screening, the levels of these analytes, combined with certain other information,
yields a risk estimate for Down syndrome and trisomy 18. Unlike first-trimester screening,
second-trimester maternal serum screening also screens for the presence of an open fetal defect, such
as a neural tube or abdominal wall defect, through the analysis of the level of AFP present in the
maternal serum (10).