Prenatal Diagnosis


Prenatal diagnosis is the process of ruling in or out fetal anomalies or genetic disorders, to provide expecting parents with information and the opportunity to modify pregnancy management and/or postnatal care.

Keywords: chromosome; diagnosis; genetic; genetic counselling; human; prenatal

Figure 1.

Risk of chromosomal abnormalities by maternal age. Adapted from Ferguson‐Smith and Yates , Hook and Chamber , Hook ( and ).

Figure 2.

Normal meiosis (left) and nondisjunction (right). Only one of the 23 chromosome pairs is demonstrated; assume all other chromosome pairs undergo normal meiosis. Numbers reflect the total number of chromosomes in the gamete at that stage in meiosis.

Figure 3.

(a) Normal karyotype. (b) Karyotype of an individual with Down syndrome, characterized by an extra chromosome 21, provided by either egg or sperm. This karyotype is written: 47,XY,+21, demonstrating that there are 47 total chromosomes, the sex chromosomes are X and Y (male), and the extra chromosome is a number 21. For a female with Down syndrome, the karyotype would be: 47,XX,+21. Courtesy of Dynagene Cytogenetics Laboratory, Swedish Medical Centre, Seattle, WA, USA.

Figure 4.

Development of various cell lines in the human embryo. The fertilized egg (1) gives rise to a trophoblast precursor (1b) and a totipotent stem cell (2), which produces another trophoblast precursor (2b) and a stem cell (3), which give rise to the inner cell mass. This divides into stem cells and becomes the hypoblast (hy, 3b) and epiblast (ep, 4). Only a few of the epiblast cells go on to form the embryo in the inner cell mass. (5) CVS, chorionic villus sampling. ys, yolk sac; ps, primitive streak. Reproduced with permission of Wiley Liss Inc., New York, from Bianchi DW et al. (1993) Origin of extraembryonic mesoderm in experimental animals: relevance to chorionic mosaicism in humans. American Journal of Medical Genetics46: 542–550.

Figure 5.

(a) Transabdominal and (b) transcervical chorionic villus sampling. Courtesy of Dr Robert Saul, Greenwood Genetic Center, Greenwood, SC; from Counseling Aids for Geneticists, 3rd edn, 1995.

Figure 6.

Prenatal diagnosis by amniocentesis. Courtesy of Dr Robert Saul of Greenwood Genetic Center, Greenwood, SC; from Counselling Aids for Geneticists, 3rd edn, 1995.

Figure 7.

Percutaneous umbilical blood sampling. Courtesy of Dr Robert Saul of Greenwood Genetic Center, Greenwood, SC; from Counseling Aids for Geneticists, 3rd edn, 1995.

Figure 8.

Ultrasound image demonstrating the measurement of nuchal translucency (the ‘nuchal fold’) at the back of the fetal neck. Increased nuchal thickness (>2 mm in the first trimester; >5 mm in the second trimester) has been associated with increased risk of Down syndrome (and other aneuploidies) and is therefore considered a marker for these conditions. Courtesy of Dr Vivienne Souter, Swedish Medical Center, Seattle, WA, USA.

Figure 9.

An example of fluorescence in situ hybridization (FISH) analysis, wherein interphase nuclei from an amniocentesis sample are hybridized with probes for chromosomes 13, 18, 21, X and Y. (a) A nucleus has been hybridized with probes for chromosomes 18 (aqua), X (green) and one Y (red). (If this had been a female fetus, there would have been two green lights and no red.) (b) A nucleus has been hybridized with probes for chromosomes 13 (green) and 21 (red). There are two number 13 chromosomes (normal) and three copies of chromosome number 21 (indicating Down syndrome). Overall result: male fetus with Down syndrome. Courtesy of Dynagene Cytogenetics Laboratory, Swedish Medical Center, Seattle, WA, USA.

Figure 10.

Direct mutation analysis with restriction enzymes. (a) Sickle cell anaemia and β‐haemoglobin gene. Sickle cell anaemia is caused by a base‐pair substitution in which adenine is changed to a thymine. MstII is restriction enzyme that cuts the specific DNA sequence shown in the figure. MstII will splice exon I of the HbA; however, MstII will not splice HbS because it does not recognize the restriction site due to the A→T mutation. (b) Southern blot analysis depicts the results of gel electrophoresis of an individual homozygous for the sickle cell mutation (lane 1; sickle cell anaemia), heterozygous for normal and sickle cell (lane 2; sickle cell trait/carrier status) and homozygous for the normal alleles (lane 3; unaffected, not a carrier).

Figure 11.

Sequencing restriction enzymes and polymerase chain reaction (PCR) (Sanger dideoxy method).

Figure 12.

Representative dot blot analysis of one of the most common cystic fibrosis mutations (ΔF508). Individual membranes are hybridized with an end‐labelled oligonucleotide probe that detects either the normal sequence (left) or the sequence with the ΔF508 mutation (right). Individuals’ amplified DNA samples are each blotted twice, once on each membrane. (Each patient's DNA is blotted in the same column and row on each membrane.) Results from the first row of this blot are as follows: 1‐1 and 1‐5 are both normal, homozygous for the normal sequence. 1‐2 is a heterozygous carrier, amplifying on both membranes. Both 1‐3 and 1‐4 show affected individuals, hybridizing only with the ΔF508 probe. Courtesy of Kristen Skogerbe, Molecular Laboratory, Swedish Medical Center, Seattle, WA, USA.

Figure 13.

Linkage analysis. Polymorphisms A and B closely flank the disease gene locus, establishing the linkage phases: AB = mutation present; ab = mutation absent.

Figure 14.

Spectral karyotype demonstrating duplication of chromosome 9 affixed (arrow) to the bottom of chromosome 4. Further analysis with reverse chromosome banding (see images to the left of each chromosome) allowed for further analysis of the breakpoints. This individual is missing a small segment at the bottom of chromosome 4 (the ‘q arm’ of the chromosome), and has a duplication for the top of chromosome 9 (the ‘p arm’ of the chromosome). Results: 46,XY,der(4)t(4;9)(q35.1;p12). A subsequent review of the literature found that this patient's developmental delay and clinical features indeed matched those described for duplication 9p syndrome (Jones, ). Courtesy of Dr Kent Opheim, Children's Hospital and Medical Center of Seattle.



Abruzzo MA and Hassold TJ (1995) The etiology of nondisjunction in humans. Environmental and Molecular Mutagenesis 25 (supplement 2): 38–47.

Burton BK, Schulz CJ and Burd LI (1992) Limb anomalies associated with chorionic villus sampling. Obstetrics and Gynecology 79: 726–730.

Ferguson‐Smith and Yates RW (1984) Maternal age specific rates for chromosome aberrations and factors influencing them: report of a collaborative European study on 52 965 amniocenteses. Prenatal Diagnosis 4 (Spec. No.): 5–44.

Firth HV, Boyd PA, Chamberlain P et al. (1991) Severe limb abnormalities after chorionic villus sampling at 56–66 days’ gestation. Lancet 337: 762–763.

Gardner RJM and Sutherland GR (1996) Chromosome Abnormalities and Genetic Counseling, 2nd edn. Oxford: Oxford University Press.

Hook EB (1981) Rates of chromosomal abnormalities of different maternal ages. Obstetrics and Gynecology 58: 282.

Hook EB (1990) Chromosome abnormalities in older women by maternal age: evaluation of regression‐derived rates in chorionic villus biopsy specimens. American Journal of Medical Genetics 35: 184–187.

Hook EB and Chamber GM (1977) Estimated rates of Down syndrome in live births by one year maternal age intervals for mothers aged 20–49 in a New York State study: implications of the risk figures for genetic counselling and cost–benefit analysis of prenatal diagnosis programs. Birth Defects Original Article Series 13(3A): 123–141.

Jones KL (1997) Smith's Recognizable Patterns of Human Malformation, 5th edn. London: WB Saunders.

Moore KL and Persaud TVN (1998) The Developing Human: Clinically Oriented Embryology, 6th edn. London: WB Saunders.

Reed S (1955) Counselling in Medical Genetics. London: WB Saunders.

Sherman SL, Petersen MB, Freeman SB et al. (1994) Nondisjunction of chromosome 21 in maternal meiosis I: evidence for a maternal‐age dependent mechanism involving reduced recombination. Human Molecular Genetics 3: 1529–1535.

Tongsong T, Wanapirak C, Kunavikatikul C et al. (2000) Cordocentesis at 16–24 weeks of gestation: experience of 1320 cases. Prenatal Diagnosis 20: 224–228.

Further Reading

Baker DL, Schuette JL and Uhlmann WR (1998) A Guide to Genetic Counselling. Brisbane: Wiley‐Liss. [A basic overview of topics relevant to the genetic counselling profession.]

GeneClinics. [] [For clinical synopsis of selected genetic conditions, including manifestations, causative genetic mutation (if known), inheritance patterns and means of treatment and testing.]

GeneTests. [] [Lists a selection of facilities offering clinical and research testing for selected genetic disorders. Includes the means of diagnosis and contacts at each facility. Included facilities provide their own information, and thus are not expressly endorsed by the website. Only available to registered researchers and health professionals.]

Genetic Alliance. [] [Provides support group information for selected genetic disorders and advocates for consumers with genetic disorders.]

Harper JC, Delhanty JDA and Handyside AH (2000) Preimplantation Genetic Diagnosis. Chichester: Wiley.[A guide to preimplantation diagnosis.]

Harper PS (1998) Practical Genetic Counselling, 5th edn. Oxford: Butterworth‐Heinemann. [Provides basic information regarding genetic counseling for specific inheritance patterns, disorders and indications. Includes risk assessment. A useful introductory resource.]

Hook EB, Cross PK, Schreinemachers DM et al. (1983) Chromosomal abnormality rates at amniocentesis and liveborn infants. JAMA 249: 2043.

Jones KL (1997) Smith's Recognizable Patterns of Human Malformation, 5th edn. London: WB Saunders. [A comprehensive guide to human genetic diseases and associated dysmorphology. Many photographs throughout. Resource intended for clinical use.]

March of Dimes. [] [Provides basic, patient‐friendly information regarding selected genetic disorders.]

Milunsky A (1998) Genetic Disorders of the Fetus: Diagnosis, Prevention and Treatment, 4th edn. Baltimore: Johns Hopkins University Press.

Online Mendelian Inheritance in Man (OMIM). [] [Public database of Mendelian traits and disorders in humans. Each entry has an overview of clinical manifestation and genetic basis of disease, if known. Regularly updated. Technical language used. Intended for clinical use.]

Rimoin DL, O'Connor JL and Ryeritz RE (1997) Emery and Rimoin's Principles and Practice of Medical Genetics, 3rd edn. New York: Churchill Livingstone. [A clinical synopsis of many genetic disorders, including clinical features, genetics and management. Technical language used. Intended for clinicians’ use.]

Saraiya M, Berg CJ, Shulman H, Green CA and Atrash HK (1999) Estimates of the annual number of clinically recognized pregnancies in the United States (1981–1991). American Journal of Epidemiology 149: 1025–1029.

Thompson MW, McInnes RR and Thompson HF (1991) Genetics in Medicine, 5th edn. London: WB Saunders. [A useful introductory resource to inheritance patterns, risk assessment, prenatal diagnosis, and various classifications of genetic disease.]

Watson JD, Gilman M, Witkowski J, Zoller M and Witkowski G (1992) Recombinant DNA. New York: Freeman. [A comprehensive textbook that covers the basics of molecular biology. Slightly outdated: many of the basic techniques are still used, but have been modified.]

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How to Cite close
Binns, Victoria, and Hsu, Nancy(Jun 2001) Prenatal Diagnosis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0002291]