WHAT IS
TRISOMY TEST +?

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, foetal sex chromosome aberrations, and selected chromosome microdeletions, as well as to determine the chromosome sex of the foetus.

Laboratórium

WHAT DOES TRISOMY TEST + EXAMINE?

Differences TRISOMY tests

Trisomies

Down syndrome (trizómia 21)

Edwards syndrome (trizómia 18)

Patau syndrome (trizómia 13)

Sex

Foetal sex determination

Sex chromosome abnormalities

Turner syndrome 

(monozómia X)

Klinefelter syndrome (XXY)

XYY syndrome (XYY)

XXX syndrome (XXX)

Microdeletion syndromes

DiGeorge syndrome (22q11)

Prader-Willi syndrome and Angelman syndrome (15q11)

Cri-du-chat syndrome (5p15)

1p36 deletion syndrome

Wolf-Hirschhorn syndrome (4p16.3)



probable


X

X

X

X


X

X

X

X

X



chromosome-based







X

X

X

X

X



chromosome-based












 


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).

WHO IS TRISOMY TEST + DESIGNED FOR?

TRISOMY test + is designed for pregnant women upon request and following a genetic consultation. It is particularly suitable: 

  • for those mothers-to-be who have previously been diagnosed with one of the foetal chromosome disorders targeted by TRISOMY test +;
  • for pregnant women with an increased risk of potential foetal disability caused by one of the syndromes targeted by TRISOMY test +, e.g. based on ultrasound screening results;
  • for enhancing the accuracy of standard TRISOMY test screening (e.g. in multiple pregnancies);
  • for pregnant women who want to avoid amniocentesis or are suffering from complications that increase the risk of amniocentesis, such as: an increased risk of spontaneous miscarriage, impaired blood clotting, immunization risk due to Rh incompatibility (Rh-negative), the period between the 14th and the 16th weeks of pregnancy, uterine myoma, or placenta praevia.

TRISOMY TEST PROCEDURE

The procedure for TRISOMY test + is identical to standard TRISOMY screening. Mothers-to-be are referred for the test by a specialist in medical genetics.

Blood taking is possible on condition that the patient has completed her 10th week of pregnancy. With teh exception of cases when blood samples are taken for medical reasons, the laboratory does not provide information on the sex of the foetus before the mother has completed her 12th week of pregnancy.

TRISOMY test + is not covered by public health insurance. TRISOMY test + costs 500 €.

Further information on how to pay for the test will be available soon.

INFORMATION FOR PROFESSIONALS

Clinical significance

TRISOMY test + can be used in early stages of pregnancy to detect other 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 and TRISOMY test +, similarly to all other non-invasive prenatal tests, are considered 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, sex chromosome number abnormalities, or other chromosome disorders monitored by TRISOMY test +.

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 + 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. 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).

XYY 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 + 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).

MICRODELETION SYNDROMES

 

Due to biological and technological limitations, the accuracy of our microdeletion syndrome examination is relatively lower compared to trisomy 21, 18, and 13. Given the generally low occurrence of microdeletions in the population, there have been no studies that would reliably validate the accuracy of our test targeting these syndromes.

Syndrome nameLocalisationIncidenceDeletion extent
DiGeorge syndrome22q111 : 40003 – 5 Mb
1p36 deletion syndrome1p361 : 5000 – 10 0001 – 10 Mb
Prader-Willi syndrome and Angelman syndrome15q111 : 10 000 – 30 0002 – 9 Mb
Cri-du-chat syndrome5p151 : 20 000 – 50 0005 – 35 Mb
Wolf-Hirschhorn syndrome4p161 : 50 0002,5 – 30 Mb

 

22q11 DIGEORGE SYNDROME

The most frequent microdeletion syndrome, DiGeorge syndrome causes a severe disorder that can manifest in any system or any part of the human body. The symptoms can be treated only in some cases. The disorder is characterised by congenital heart defects (CHDs), immune system disorders, kidney defects, and cleft palate issues, frequently combined with severe mental retardation. The symptoms vary considerably. In some cases (especially those involving less pronounced symptoms), familial transmission and intrafamilial variability can be assumed.

Since CHDs may actually be the only symptom of 22q11 deletion, the syndrome is frequently indicated by prenatal genetic examinations when a congenital hear disorder is detected or when such a disorder is indicated by ultrasound screening.

 

1p36 DELETION SYNDROME

Similarly to DiGoerge syndrome, 1p36 deletion syndrome is one of the most frequent microdeletion syndromes. It leads to an extremely severe and untreatable disorder characterised by very heterogeneous symptoms. Its main characteristics include mental retardation combined with behavioural disturbances, growth delays, and hypotonia.

 

15q11 PRADER-WILLI SYNDROME & ANGELMAN SYNDROME

Although they are different from one another in terms of their clinical symptoms, both syndromes are caused by an absence or dysfunction of gene functions in one and the same critical region of chromosome 15. Although most cases are caused by a deletion affecting a critical region of chromosome 15, other cases can be caused by sporadic mutation, methylation disorders, or uniparental disomy rather than deletion. Under the circumstances, it cannot be expected that microdeletion screening will detect all actual Prader-Willi and Angelman syndrome cases.

Prader-Willi syndrome is characterised by hypotonia, poor sucking reflexes, feeding difficulties in early infancy, followed by hyperphagia and obesity from age 2 onwards. Mental retardation is relatively mild, but various other behavioural disorders are present in addition to excessive eating.

Angelman syndrome characteristics are less expressed. Usually not obvious at birth, the clinical symptoms start developing around the age of 12 months. They include psychomotor activity and speech development delays. The patient’s medium mental retardation is accompanied by progressively pronounced behavioural disturbances.

5p15 CRI-DU-CHAT SYNDROME

Cri-du-chat syndrome is an older, cytogenetically defined syndrome (also known as Lejeune syndrome or 5p- syndrome) because more extensive deletions could already be detected using optical microscopes in the era of traditional cytogenetics.

The name “cri-du-chat” (cat’s cry) comes from the leading clinical symptom this syndrome is characterised by in the period of early infancy. Combined with characteristic facial dysmorphia, the symptom is a distinguishing feature of this syndrome in comparison to other disorders involving growth delays, psychomotor retardation, microcephaly, and hypotonia. The scope of actual deletion correlates with the severity of the patient’s disability.

 

4p16 WOLF-HIRSCHHORN SYNDROME

Wolf-Hirschhorn syndrome (also known as 4p- syndrome) belongs to the same group of syndromes identified by traditional cytogenetics. The severity of its clinical symptoms correlates with the actual scope of deletion. Similarly to cri-du-chat syndrome, this syndrome comes with characteristic facial dysmorphia combined with microcephaly, hypertelorism, protruding eyes, and a short philtrum. Severe growth and psychomotor retardation is accompanied by other serious symptoms, such as hypotonia, epileptic fits, and congenital development defects affecting internal organs (esp. heart and kidney defects).