KARYOTYPINGForewordThe obstetric care of a pregnancy, as it is practiced today, includes invasive procedures for the definitive prenatal diagnosis of fetal disorders correlations dependant on the results of the chromosomal analysis made upon fetal cells. Sex chromosome trisomies

(SCT), an extra X chromosome in females (triple X, XXX), males with an extra X chromosome (Klinefelter syndrome, XXY) or an extra Y chromosome (XYY) occur because of errors during meiosis and are relatively frequent in humans. Their identification has never been the goal of prenatal diagnosis (PD) but they almost escape detection. Testing for serious genetic abnormalities is more likely to uncover these trisomies. The indications to perform prenatal cytogenetic diagnosis for numerical chromosomal abnormalities

include: abnormal results of prenatal double or triple test, advanced maternal age, fetal abnormality detected through ultrasound examination, and positive family history for chromosomal anomalies. Only such an intervention will permit answers to the dilemma of whether to terminate the pregnancy or to carry it to term.Dr. Prakash TrivediMD [O&G], IVF specialist, Mumbai

IntroductionAt conception 23 chromosomes are passed from each parent to the embryo. The correct number of chromosomes that the cells/embryos should have is 46. However, there is a statistical chance that one chromosome will be missing or that one extra chromosome is present. When this happens it is termed fetal aneuploidy. Depending on the chromosomal abnormality fetal loss, developmental and speech delays, growth delays, and sexual characteristics may fail to develop. Down syndrome is an example where an extra copy of chromosome 21 is present.

BackgroundTrisomy 21 (Down syndrome) is associated with mental retardation, malformation of the heart, gastrointestinal tract, eyes and ears. The overall risk of having an affected fetus is one in 1,000 live births. Down syndrome is caused by an extra 21st chromosome and is characterized by mental retardation and specific physical characteristics. It has long

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been accepted that women who are 35 years or older at the time of delivery should be offered prenatal diagnosis with amniocentesis or chorionic villus sampling. Although the risk for trisomy 21 increases with maternal age, an estimated 75% of affected fetuses are born to mothers younger than 35 years. Because of this risk, it is important to provide pregnant women who are younger than 35 years with noninvasive screening for this trisomy.

Trisomy 18 (Edwards’ syndrome) occurs in one in every 6,000 births and is associated with low birth weight, mental retardation and cranial, cardiac and renal malformations. Trisomy 18 is also caused by extra genetic material (an extra 18th chromosome). Children with trisomy 18 have severe mental retardation and life-threatening birth defects. Most infants affected with this trisomy die within the first year of life. All three analytes (AFP, hCG, and UE3) help test for Down syndrome and trisomy 18.

Approach1. As a routine between 15-22 week of pregnancy;2. If the the screening test reveals abnormal analyte levels, then an ultrasound is

usually recommended because it can sometimes identify the reason for an abnormal result such as a misdated pregnancy, twins or a birth defect.

3. Amniocentesis will also be offered to test more accurately for spina bifida, Down syndrome and trisomy 18;

4. If a birth defect is detected, several options may be available including increased surveillance of the pregnancy, arrangements for special care needed at delivery, or discontinuation of the pregnancy.

Result interpretationHowever, it has to be borne in mind that a normal triple maternal screening test does not mean a baby has no neural tube defect, Down syndrome or trisomy 18. This is because the maternal serum triple

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screen does not detect every case of Down syndrome, trisomy 18 or spina bifida. We estimate that it detects 85% of neural tube defects, 80% of pregnancies with Down syndrome, and 80% of pregnancies with trisomy 18.

Summary

SummaryFindings from one study has categorically revealed that STDMS [second trimester double marker] is optimal for the detection of fetal DS [Down’s syndrome] in pregnant women aged under 35. For individual women, if economic condition permits, [second trimester triple marker] STTMS is the best choice, while for women aged above 35, STTMS is the best choice in this regard. Noninvasive alternatives to the triple test have been identified, but these have not been adopted despite 13 years of development. It is likely, therefore, that the triple test (or variants thereof) will continue to be used in routine antenatal care for the foreseeable future.

Reference:

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1. Am J Med Genet A. 2013 Nov;161A(11):2873-9, Counseling parents before prenatal diagnosis: do we need to say more about the sex chromosome aneuploidies? Lalatta F, Tint GS.

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