Indications For Chromosomal Evaluation

3.1. AMNIOTIC FLUID The reasons for karyotypic evaluation vary by sample type. Amniotic fluids are the primary sample for prenatal evaluation. Genetic amniocenteses are ideally performed at about 16 wk of gestation and are generally offered to women when their risk of having a chromosomally abnormal fetus is greater than the inherent risk of the amnio-centesis procedure itself. Early amniocentesis can be performed at 10-12 wk. The most common reason for performing a genetic amniocentesis is advanced maternal age (AMA), defined as a maternal age of 35 yr or greater at the time of

Human Metaphases
Fig. 1. G-banded metaphase showing the unique banding pattern created along the length of each chromosome.

delivery. Women with AMA are at increased risk of carrying a fetus with a chromosomal abnormality, especially trisomy 21, and are routinely offered an amniocentesis.

A number of maternal serum screening tests such as maternal serum a-fetoprotein, unconjugated estriol, human chorionic gonadotrophin, and dimeric inhibin A have been developed. Women with abnormal values are also at higher risk for certain chromosomal anomalies and, therefore, are candidates for amniocentesis. This is especially important for women under the age of 35 because most cases of Down syndrome occur in this group, but these women are not generally offered amnio-centesis on the basis of age alone. Amniocentesis is also indicated when one of the parents is known to be a carrier of a balanced chromosomal rearrangement that could be passed to offspring in an unbalanced form. In addition, this procedure is performed as a follow-up to the finding of fetal anomalies on ultrasound and to clarify possible mosaicism seen in chorionic villus sampling (CVS).

3.2. BLOOD Peripheral blood studies are performed for a large number of reasons. Some of the more common ones are outlined here. Blood studies are often performed on newborns with multiple congenital anomalies. Certain constellations of findings might suggest specific chromosomal syndromes, and ambiguous genitalia might be associated with sex chromosome abnormalities. Chromosomal studies might be indicated for individuals with mental retardation or developmental delay of unknown origin, as they are common findings among individuals with unbalanced chromosomal rearrangements.

Family studies are often indicated once a chromosomal abnormality has been identified in order to rule out carrier status of at risk individuals. The clinical diagnosis of Down syndrome should be confirmed by chromosomal studies because a small portion of cases are the result of familially transmitted translocations and isochromosomes. Therefore, carriers will be at risk for passing on the abnormality.

Primary amenorrhea and premature ovarian failure are indications for chromosomal evaluation. Primary amenorrhea might be caused by Turner syndrome (45,X), a Turner variant or other abnormalities involving the X chromosome. Premature ovarian failure might also be associated with abnormalities involving the X chromosome.

Couples with a history of unexplained multiple pregnancy loss or infertility might harbor a balanced chromosomal aberration that they are passing on to offspring in an unbalanced form and are, therefore, candidates for chromosomal study.

Occasionally, percutaneous umbilical blood sampling (PUBS) is performed for prenatal fetal diagnosis. This could be done as a follow-up to an equivocal amniocentesis result or if fetal anomalies are seen on ultrasound at a later gestational age.

3.3. SOLID TISSUES There are a variety of solid tissues that can be studied cytogenetically. Chorionic villus samples obtained from the chorion frondosum of the developing placenta can be studied for prenatal diagnosis at 8-12 wk gestation, weeks earlier than routine amniocentesis. The earlier results are advantageous for many women in terms of privacy and easier therapeutic termination of pregnancy if one is chosen, but confined placental mosaicism can be problematic in CVS, resulting in equivocal results and the possible need for a follow-up amniocentesis.

Skin biopsies are sometimes performed when a non-hematologic sample is needed or to detect mosaicism that is

Table 1

Common Sex Chromosome Aneuploidies

Turner syndrome Short stature Primary amenorrhea Failure to develop 2° sex characteristics Short, webbed neck Low posterior hairline

Broad chest with hypoplastic, wide-spaced nipples Normal verbal IQ, but performance IQs slightly lower than controls Deficits in visual-spatial organization


Normal phenotype

Mental deficiency, psychosis or learning disabilities Normal fertility

Klinefelter syndrome Tall stature as children

Tendency toward obesity as adults without testosterone replacement

Testicular atrophy with azoospermia



Somewhat decreased IQ

47,XYY Tall Stature Large tooth size

No dysmorphology in most; minor skeletal and facial anomalies in some Severe acne Normal fertility tissue-specific, such as seen in Pallister-Killian syndrome. Solid tissue samples can be used to detect chromosomal abnormalities in stillbirths when blood is not available, and products of conception are useful in determining the cause of many spontaneous abortions (SABs). Approximately half of SABs and 5% of stillbirths are chromosomally abnormal (21). Cytogenetic studies can provide valuable information for couples who have experienced pregnancy loss.

Solid tumor tissues can be studied to detect one of the many acquired chromosomal changes associated with malignancy.

3.4. BONE MARROW The vast majority of bone marrow samples are from patients with suspected hematologic disorders for the detection of acquired chromosomal changes. Cytogenetic studies can help establish an initial diagnosis, can be used to detect evidence of relapse after treatment, and can be used to monitor disease progression or recurrence.

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