WHAT IS

TRISOMY TEST XY ?

A non-invasive, prenatal screening test based on a sample of maternal blood, designed to determine the risk of the most frequent foetal trisomy types and foetal sex chromosome aberrations. In addition, it can also determine the chromosome sex of the foetus from the 11th week of pregnancy.

WHAT DOES TRISOMY TEST XY EXAMINE?

*If a blood sample cannot be processed by the laboratory in accordance with the principles of good laboratory practice (e.g. in the event of a low foetal DNA concentration in the sample), or if the analytical results do not provide an answer to the diagnostic question, the laboratory offers a repeat examination based on the same blood sample free of charge. Under the circumstances, the period for the delivery of test results will change from 5 to 8 days (this generally applies to about 10% of all samples).

INFORMATION FOR PROFESSIONALS

Clinical significance

TRISOMY test XY can be used in early stages of pregnancy to detect additional foetal chromosome aberrations provided that there are relevant reasons to use differential diagnostics to do so.

Despite their high detection sensitivity to the trisomy types monitored, TRISOMY test, TRISOMY test XY and TRISOMY test + are considered – similarly to all other non-invasive prenatal tests – to be forms of screening rather than diagnostic methods.

This procedure is commonly called “Non-Invasive Prenatal Testing” (NIPT), which reflects the method of obtaining blood samples used in the process. The test is based on a sample of maternal blood obtained as early as in the 10th week of pregnancy – since it is non-invasive, it poses no risk to the foetus whatsoever.

Every screen-positive test result must be confirmed by a genetic test based on a sample obtained using invasive sampling (amniocentesis or chorionic villus sampling).

A screen-negative test result means that, in connection with the chromosomes or chromosome parts studied, the examination detected no foetal DNA molecule over-/underrepresentation indicating the presence of chromosome 21, 18 or 13 trisomy or sex chromosome number abnormalities.

A non-informative test result means that the blood sample provided could not be processed in accordance with the standard laboratory practice (e.g. the sample contained a low proportion of foetal DNA) or the result of the screening test does not answer the diagnostic question. In the event of a non-informative test result:

  • the same blood sample is analysed promptly again, free of charge, which means that the period for the delivery of test results will be prolonged from 5 to 8 days;
  • we analyse a new blood sample, which has to be taken 14 days after the previous blood sample was taken.

In the event that the repeated analysis is non-informative, the laboratory will refund the patient’s payment for the test.

 

 

SEX CHROMOSOME ABERRATIONS

TURNER SYNDROME 45,X

In laboratory terms, Turner syndrome corresponds to karyotype 45,X, which means that one sex chromosome is missing from the standard set and there is only one X chromosome remaining in the complement. The cell line with the missing X chromosome may have a mosaic form and the resulting clinical symptoms may be less severe. Turner syndrome has an incidence ratio of 1 out of 2,500 girls born. When untreated, developed clinical cases are characterised by short stature (at the time of birth or at a very young age) and underdeveloped secondary sexual characteristics, including amenorrhoea and infertility. Partially treatable using hormonal substitution, the impaired stature and sex characteristics in patients with Turner syndrome have been treated increasingly successfully in the recent years. Although infertility associated with Turner syndrome can be treated using advanced assisted reproduction methods, successes on this front have been rare so far.

KLINEFELTER SYNDROME XXY

In laboratory terms, Klinefelter syndrome corresponds to karyotype 47,XXY, which means that the standard chromosome set with a male complement of XY contains at least one extra X chromosome. The cell line with an extra X chromosome may have a mosaic form and the resulting clinical symptoms may be less severe; however, if there several extra X chromosomes are present, the clinical symptoms can be more developed. Klinefelter syndrome has an incidence ratio of 1 out of 500 boys born. When untreated, developed clinical cases are characterised by greater height accompanied by underexpressed female secondary sexual characteristics (gynaecomastia, gynoid obesity), incomplete puberty, and infertility. Generally more subdued and sensitive, patients frequently develop speech and learning defects. Their genitals are small or characterised by undescended testicles and a smaller penis; patients are more likely to suffer from hypospadias. As opposed to other men, patients with Klinefelter syndrome run a high risk of developing diseases determined by the XX sex chromosome complement, such as breast cancer. Their low testosterone, incomplete puberty, and underdeveloped sexual characteristics are partially treatable using hormonal substitution. Although infertility associated with this syndrome can be treated using advanced assisted reproduction methods, successes on this front have been rare so far.

Current guidelines mostly recommend that the mother-to-be should not be told about running a risk of Turner or Klinefelter syndromes; they also recommend that the patient should not be referred for an invasive verification method (e.g. amniocentesis). Respecting these recommendations, our TRISOMY test results contain information about the most likely sex of the foetus but no details of any sex chromosome number abnormalities even if they are found in the course of our analysis. Before she undergoes a TRISOMY test XY or TRISOMY test + screening, the mother-to-be needs to decide, in the light of all general indication criteria, whether she wishes to know the chromosome-based sex of her foetus. If she does, she also has to decide whether she wants to know about potential findings related to syndromes 45,X and 47,XXY, which are responsible for Turner and Klinefelter syndromes, respectively. Compared to autosome aberrations (chromosome 21, 18, and 13 trisomy in particular), there has been a drop in the number of requests for an abortion when sex chromosome aberrations (45,X and 47,XXY) are detected as part of prenatal genetic diagnostics. For this reason, we respect the current guidelines that recommend informing the patient about potential risks or results of differential diagnostics in the postnatal period only. This information is provided on condition that the mother-to-be wishes to be told and her treating doctor grants her request.

XYY syndrome and XXX syndrome

XYY syndrome affects men with karyotype 47,XYY. The cell line with an extra Y chromosome may have a mosaic form. The syndrome occurs with an incidence ratio of 1 out of 1 000 boys born. The clinical symptoms are inconspicuous: XYY men are usually characterised by an above-average height and physiological sexual development. In early childhood, XYY syndrome is associated with light disorders (speech development, learning, motor activity, and emotional difficulties, as well as some of the symptoms in what is called the autistic spectrum).

XXX syndrome affects women with karyotype 47,XXX. The cell line with an extra X chromosome may have a mosaic form, frequently with a monosomy X share. The syndrome occurs with an incidence ratio of 1 out of 1 000 girls born. The clinical symptoms are inconspicuous: XXX women are usually characterised by an above-average height and physiological sexual development. In early childhood, XXX syndrome is associated with light disorders (speech development, learning, motor activity, and emotional difficulties) and congenital kidney disorders are more frequent, too.

Current guidelines mostly recommend that the mother-to-be should not be told about XYY or XXX syndrome risks; they also recommend that the patient should not be referred for an invasive verification method (e.g. amniocentesis). Respecting these recommendations, our TRISOMY test results contain information about the most likely sex of the foetus but no details of any sex chromosome number abnormalities even if they are found in the course of our analysis. Before she undergoes a TRISOMY test XY or TRISOMY test + screening, the mother-to-be needs to decide, in the light of all general indication criteria, whether she wishes to know the chromosome-based sex of her foetus. If she does, she also has to decide whether she wants to know about potential findings related to syndromes XYY and XXX, or only those related to syndromes 45,X and 47,XXY, which are responsible for Turner and Klinefelter syndromes, respectively (along with the limitations specified above).