Chapter 063. Chromosome Disorders (Part 4)

Cytogenetic Testing in Prenatal DiagnosisThe vast majority of prenatal diagnostic studies are performed to rule out a chromosomal abnormality, but cells may also be propagated for biochemical studies or molecular analyses of DNA. Three procedures are used to obtain samples for prenatal diagnosis: amniocentesis, chorionic villus sampling (CVS), and fetal blood sampling. Amniocentesis is the most common procedure and is routinely performed at 15–17 weeks of gestation. On some occasions, early amniocentesis at 12–14 weeks is performed to expedite results, although less fluid is obtained at this time. Early amniocentesis carries a greater risk of spontaneous abortion or fetal...
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Chapter 063. Chromosome Disorders (Part 4) Chapter 063. Chromosome Disorders (Part 4) Cytogenetic Testing in Prenatal Diagnosis The vast majority of prenatal diagnostic studies are performed to rule out achromosomal abnormality, but cells may also be propagated for biochemicalstudies or molecular analyses of DNA. Three procedures are used to obtainsamples for prenatal diagnosis: amniocentesis, chorionic villus sampling (CVS),and fetal blood sampling. Amniocentesis is the most common procedure and isroutinely performed at 15–17 weeks of gestation. On some occasions, earlyamniocentesis at 12–14 weeks is performed to expedite results, although less fluidis obtained at this time. Early amniocentesis carries a greater risk of spontaneousabortion or fetal injury but provides results at an earlier stage of pregnancy. The vast majority of amniocenteses are performed in the context ofadvanced maternal age, the best-known correlate of trisomy (see below).Additional reasons for amniocentesis referral include an abnormal triple- or quad-marker assay and/or detection of ultrasound abnormalities. In this assay, levels ofhuman chorionic gonadotropin, α-fetoprotein, and unconjugated estriol (and, in thequad assay, inhibin) in the maternal serum are quantified and used to adjust thematernal age-predicted risk of a trisomy 21 or trisomy 18 fetus. Specificultrasound abnormalities, when detected at midtrimester, can also be associatedwith chromosomal defects. When a nonspecific ultrasound abnormality is present,the estimated risk of a chromosomal defect is ~16%. Associations of chromosomalabnormalities and specific types of abnormal ultrasound findings are listed inTable 63-1. Table 63-1 Frequency of Chromosome Abnormalities, Identified on theBasis of Abnormal Ultrasound Findings Ultrasound Finding Chromosomal Abnormalities (Frequency) Average, Range in Different % Studies, % Abnormal ultrasound 16 13–35(nonspecific) Omphalocele 39 26–54 Cystic hygroma 68 46–78 Congenital heart disease 30 8–40 Choroid plexus cyst 5 4–10 CVS is the second most common procedure for genetic prenatal diagnosis.Because this procedure is routinely performed at about 10–12 weeks of gestation,it allows for an earlier detection of abnormalities and a safer pregnancytermination, if desired. CVS is a relatively safe procedure (spontaneous abortions, Percutaneous umbilical blood sampling (PUBS) is a method for obtainingfetal blood during the second and third trimesters of pregnancy. PUBS is usuallyperformed when ultrasound abnormalities are detected late in the second trimester.PUBS is also used when cytogenetic results from amniocentesis need clarification,such as in the detection of mosaicism. Chromosome Abnormalities Chromosomes in Cell Division To understand the etiology of chromosome abnormalities, it is important toreview the movement of chromosomes during cell division. In somatic tissues,chromosomes are replicated during the S-phase of the cell cycle, so that eachreplicated chromosome consists of two identical sister chromatids. When the cellenters mitosis, each of the 46 chromosomes align on the metaphase plate, with thecentromeres co-oriented toward opposite spindle poles (Fig. 63-3). At anaphasethe sister chromatids separate, with each of the daughter cells receiving one sisterchromatid from each of the 46 chromosomes. Figure 63-3