The Principles of Clinical Cytogenetics - Extra Materials - Springer

554 Sarah Hutchings Clark
The relatively new integrated screen takes advantage of both of the aforementioned screening
tests through the collection of both a first- and second-trimester maternal blood sample. The results
of these analyses are combined to yield a second-trimester result. A nuchal translucency measurement,
obtained via first-trimester ultrasound, can also be factored into the risk calculation. The integrated
screen is expected to yield a higher detection rate and lower false-positive rate for Down
syndrome than either first- or second-trimester screening alone (36).
An ultrasound examination to evaluate a pregnancy for the presence of certain birth defects and
sonographic findings associated with aneuploidy can also be used to screen for Down syndrome and
certain other chromosome abnormalities. Such an ultrasound is generally performed during the second
trimester of pregnancy, although some aneuploidy markers are identifiable during the first trimester,
as is the case with increased nuchal translucency (see the subsection First-Trimester
Screening). The percentage of aneuploid pregnancies with a demonstrable abnormality on ultrasound
depends on the particular chromosome abnormality and the experience of the sonographer. Some of
the aneuploidy markers that are potentially detectable on prenatal ultrasound include cardiac malformations,
altered fetal growth, duodenal atresia, and cystic hygroma, among others. In addition to
conferring an increased risk for aneuploidy, certain congenital anomalies identifiable on ultrasound
could be associated with certain genetic syndromes. At times, when prenatal chromosome analysis
produces an ambiguous or unclear result, ultrasound is utilized in an attempt to evaluate the fetal
anatomy and to search for any fetal abnormalities that could be associated with the karyotype. As
with all other screening, the limitations of ultrasound should be made clear to the patient or couple
(10,37,38). See Chapter 12.
Prenatal Identification of a Chromosome Abnormality
When a chromosome abnormality is identified prenatally, the genetic counselor provides information
to the patient or couple regarding the phenotype associated with the abnormality in question.
Options for continuation or termination of the pregnancy and adoption are also discussed, as is the
fact that many chromosomally abnormal pregnancies are at an increased risk to miscarry, and not
only in the first trimester of pregnancy (39). For example, this risk is particularly high in pregnancies
affected with Turner syndrome, with at least 99% of affected pregnancies aborting spontaneously
early in pregnancy (10). The prenatal identification of a chromosome abnormality (or any anomaly or
genetic condition for that matter) can be traumatic and heartbreaking for a couple, as they face difficult
decisions about an often much wanted pregnancy. It is especially important for the genetic counselor
to support the individual, couple, and family during and after such a diagnosis. No matter what
the final decision regarding the future of the pregnancy might be, the emotional support of the counselor,
as well as referrals to appropriate resources and support groups, can be vital in helping the
pregnant woman and/or couple cope with the diagnosis.
Although the majority of the common chromosome abnormalities are associated with a rather
well-defined phenotype, results associated with unclear or ill-defined phenotypes can understandably
be anxiety provoking. This is particularly true if the couple/patient is struggling to make a decision
regarding termination versus continuation of the pregnancy.
The general phenotypes associated with the more common autosomal chromosome aneuploidies,
trisomies 13, 18, and 21, are described in a previous section and in Chapter 8. Although these phenotypes
are well defined, there is a range of severity, particularly associated with Down syndrome or
with mosaicism where a normal cell line is also present. As noted previously, the degree of severity
of the condition cannot be predicted from the karyotype. Some individuals find this to be a difficult
situation, as they might feel capable of caring for a child with mild disabilities, but unable to care for
a child with more severe disabilities.
The common sex chromosome abnormalities are generally associated with less severe phenotypes than
the aforementioned autosomal trisomies. Although for some this is encouraging, for others the milder
phenotypic features complicate the decision of whether to continue the pregnancy or terminate (40).