FAQs - Section 4: The Conditions Detected by Harmony

No.

Harmony detects the most common chromosome abnormalities that are identified in infants, i.e. aneuploidy of chromosome 21, 18, 13, X or Y; it can also detect the most common chromosome deletion, 22q11.2 deletion. These chromosome disorders account for approximately 80% of all chromosome disorders identified at birth. This means that approximately 20% of all chromosome disorders are not detected by Harmony and other forms of NIPT. These other disorders could potentially be identified by invasive genetic testing (amniocentesis or CVS), and this carries a small but definite risk of a miscarriage.

The chromosome disorders that would not be detected by NIPT are often associated with abnormal ultrasound features in the fetus. For this reason, NIPT is not recommended as the primary test if there are structural abnormalities noted on ultrasound; invasive genetic testing is the more appropriate investigation.

Trisomy 13

  • This is due to the fetus having three, rather than the normal two, copies of chromosome 13.
  • This condition is also called Patau syndrome. It is an uncommon form of aneuploidy at birth.
  • The chance of trisomy 13 at 12 weeks’ gestation and at birth rises with maternal age.
  • Trisomy 13 causes severe intellectual disability and major malformations.

Further information for doctors

Further information for patients

Trisomy 18

  • This is due to the fetus having three, rather than the normal two, copies of chromosome 18.
  • This condition is also called Edwards syndrome. It is an uncommon form of aneuploidy at birth.
  • The chance of trisomy 18 at 12 weeks’ gestation and at birth rises with maternal age.
  • Trisomy 18 causes severe intellectual disability and major malformations.

Further information for doctors

Further information for patients

Trisomy 21

  • This is due to the fetus having three, rather than two, copies of chromosome 21.
  • This condition is also called Down syndrome. It is the most common aneuploidy identified at birth.
  • The chance of trisomy 21 at 12 weeks’ gestation and at birth rises with maternal age.
  • Trisomy 21 causes intellectual disability and places the fetus at relatively high risk of major malformations.

Further information for doctors

Further information for patients

Harmony provides the option to test for the most common chromosome deletion syndrome, 22q11.2 deletion. Harmony is the only NIPT performed in Australia that has this option.

22q11.2 Deletion Syndrome

  • This is due to the fetus having some genes missing on chromosome 22. The precise location of the deleted genes is called 22q11.2.
  • A deletion of 22q11.2 can cause a wide variety of medical problems and, for many years, doctors did not realise that many different conditions were due to the same underlying deletion. The different conditions had been called DiGeorge syndrome, velocardiofacial syndrome (VCFS), Shprintzen syndrome, conotruncal anomaly face syndrome, Takao syndrome, Sedlackova syndrome, Cayler cardiofacial syndrome. These conditions are now appropriately grouped together as the ‘22q11.2 deletion syndrome’.
  • The chance of 22q11.2 deletion syndrome at 12 weeks’ gestation and at birth does not change with maternal age.
  • 22q11.2 deletion syndrome symptoms can be variable but often include congenital heart problems, specific facial features, developmental delay, learning problems, frequent infections and cleft palate.

Other resources

There are many other chromosome deletion syndromes. These are less common than 22q11.2 deletion, and the accuracy of screening for such deletions by NIPT is largely unknown. For these reasons, Harmony does not currently test for other chromosome deletions.

Harmony always tests for aneuploidies of chromosomes 21, 18 or 13. This is the default analysis.

Harmony can also test for 22q11.2 deletion on request (and for an additional fee).

In addition, there are three options regarding the sex chromosomes; these options are available at no additional charge. Please note that sex chromosome analysis is not provided by default, and such a request must be clearly indicated on the request form.

  • A test for fetal sex may be requested. This is a test for the presence of Y chromosome material. In the case of a singleton pregnancy, the presence of Y chromosome material indicates that the fetus is likely to be male. In the case of twins, the presence of Y material indicates that one or both twins are likely to be male. The absence of Y chromosome material indicates that the fetus (or both, in the case of twins) are likely to be female.
  • A test for Turner syndrome (monosomy X) may be requested. If this test is normal, i.e. low chance of Turner syndrome, the sex will not be reported (unless requested separately). If the test is abnormal, i.e. high chance of Turner syndrome, the sex of the fetus will be revealed as female by default, because Turner syndrome only occurs in females.
  • A test for sex chromosome aneuploidy may be requested. If this test is normal, i.e. low chance of sex chromosome aneuploidy, the sex will not be reported (unless requested separately). If the test is abnormal, i.e. high chance of sex chromosome aneuploidy, the sex of the fetus will be revealed by default as the details of the sex chromosome aneuploidy will indicate the sex of the fetus.

In summary, fetal sex can be explicitly requested as an option. If sex chromosome aneuploidy or Turner syndrome (monosomy X) alone are requested, i.e. without fetal sex, the sex of the fetus will be revealed if there is a high risk of either sex chromosome aneuploidy or Turner syndrome.

It is important that a woman makes a considered decision regarding the scope of the Harmony test that she is seeking. Please ensure that requests for fetal sex or analysis of sex chromosomes are clearly indicated on the request form.

Please note that sex chromosome aneuploidy, Turner syndrome (monosomy X) and 22q11.2 deletion cannot be accurately determined in twins. These assessments are not offered in the presence of twins.

The intended use of the Harmony Prenatal Test (as noted by the Australian Therapeutic Goods Administration) is to screen for common aneuploidies and the 22q11.2 deletion. Harmony is not principally intended as a screen for the sex of the fetus. We are pleased to provide testing of the sex chromosomes on request and at no additional charge. We apply the same standard of care to maintain the quality of reporting of the sex chromosomes as we do for other chromosomes, and will not report sex chromosome status if these quality standards are not met. In less than 1% of samples, sex chromosome analysis cannot be reported, despite analysis for other chromosomes being successful. This is due to the complex biology of pregnancy rather than a technical failure of the test. In such circumstances, no report of fetal sex chromosomes will be issued and we do not offer a re-collection or refund.

Triple X

  • This is due to the fetus having three, rather than two, sex chromosomes, i.e. XXX. The fetus is female.
  • The chance of triple X at 12 weeks’ gestation and at birth rises with maternal age.
  • The impact of sex chromosome aneuploidy is much milder than aneuploidy of chromosomes 13, 18 and 21.
  • Intellectual disability and malformations are uncommon, and many women with XXX are never diagnosed.

Further information for patients

Klinefelter syndrome (XXY)

  • This is due to the fetus having three, rather than two, sex chromosomes, i.e. XXY. The fetus is male.
  • The chance of Klinefelter syndrome at 12 weeks’ gestation and at birth rises with maternal age.
  • The impact of sex chromosome aneuploidy is much milder than aneuploidy of chromosomes 13, 18 and 21. Intellectual disability and major malformations are uncommon, but many men with Klinefelter syndrome have delayed puberty and are infertile.

Further information for patients

XYY

  • This is due to the fetus having three, rather than two, sex chromosomes, i.e. XYY. The fetus is male.
  • This condition is also called Jacobs syndrome.
  • The chance of XYY at 12 weeks’ gestation and at birth does not change with maternal age.
  • The impact of sex chromosome aneuploidy is much milder than aneuploidy of chromosomes 13, 18 and 21. Intellectual disability and malformations are uncommon, and many men with XYY are never diagnosed.

Further information for patients

Turner syndrome (monosomy X)

  • This is due to the fetus having one, rather than two, sex chromosomes, i.e. one X. The fetus is female.
  • The chance of Turner syndrome at birth does not change with maternal age. Turner syndrome is less common at birth than in early pregnancy, probably due to spontaneous miscarriages.
  • In the developing child, the impact of sex chromosome aneuploidy is much milder than aneuploidy of chromosomes 13, 18 and 21. Intellectual disability is uncommon, but there is an increased risk of malformations. In addition, the ovaries do not develop in women with Turner syndrome, resulting in short stature, delayed puberty and infertility.

Further information for patients

XXYY

  • This is due to the fetus having four, rather than two, sex chromosomes. The fetus is male.
  • This is a relatively rare condition for which there is little information regarding the chance in relation to maternal age.
  • Although this disorder is less severe than abnormalities of chromosome 21, 18 or 13, learning difficulties and delayed speech and language development are common.

Further information for patients

No.

The chromosome disorders detected by NIPT are usually new genetic errors that do not run in families, and have occurred as new events in the developing fetus.

NIPT does not provide information about the inheritance of single-gene disorders, such as cystic fibrosis, Fragile X syndrome and other familial disorders.

There have been reports of a few women having strikingly abnormal NIPT results that seem to be incorrect, i.e. the fetal chromosomes are normal when checked. Some of these women have subsequently been found to have cancer. The abnormal NIPT result reflected abnormal amounts of DNA from the cancer in the mother’s circulation rather than abnormal amounts of DNA from the fetus.

These are rare events (a handful of instances among millions of women tested). The reliability of NIPT in detecting cancer during pregnancy is not known.

We are not aware of any instances of cancer diagnosis among women having the Harmony Prenatal Test. This is probably because the Harmony test is specifically designed to test for specific chromosome abnormalities rather than being a general screen of DNA in the mother’s circulation. These trisomies are uncommon abnormalities in cancer and so the Harmony test is unlikely to detect cancer.