FAQs - Section 4: What Conditions May be 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. These abnormalities account for approximately 80% of all the chromosome abnormalities that are observed at birth. This means that 20% or so of chromosome abnormalities will be missed by Harmony but could potentially be identified by invasive genetic testing (amniocentesis or CVS). However, invasive genetic testing carries a small but definite risk of causing a miscarriage.

The chromosome abnormalities that would be missed by Harmony are often associated with abnormal physical development of the fetus, and hence have an abnormal ultrasound examination. For this reason, Harmony 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 risk 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 risk 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 risk of trisomy 21 at 12 weeks gestation and at birth rises with maternal age.
  • Trisomy 21 causes intellectual disability and places the fetus at high risk of major malformations.

Further information for doctors.

Further information for patients.

Harmony always tests for aneuploidies of chromosomes 21, 18, or 13.

In addition, there are three options regarding the sex chromosomes.

  • A test for fetal gender may be requested. This is a test for the presence of Y chromosome material. In the case of a singleton, 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 monosomy X may be requested. If this test is normal i.e. low risk of monosomy X, the gender will not be revealed by this test. If the test is abnormal i.e. high risk of monosomy X, the gender of the fetus will revealed as female because monosomy X only occurs in female fetuses.
  • A test for sex chromosome aneuploidy may be requested. If this test is normal i.e. low risk of sex chromosome aneuploidy, the gender will not be revealed by this test. If the test is abnormal i.e. high risk of sex chromosome aneuploidy, the gender of the fetus will be revealed by the details of the sex chromosome aneuploidy identified.

It is important that a woman make a considered decision regarding the scope of the Harmony test that she is seeking. We ask that the doctor make the woman’s choice clear on the request form.

Please note that sex chromosome aneuploidy cannot be accurately determined in twins by the Harmony test. This assessment is not offered in the presence of twins.

Triple X

  • This is due to the fetus having three, rather than two, sex chromosomes i.e. XXX. The fetus is female.
  • The risk 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 doctors.

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 risk 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 doctors.

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 risk 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 doctors.

Further information for patients.

Turner syndrome

  • This is due to the fetus having one, rather than two, sex chromosomes i.e. one X. The fetus is female.
  • The risk of Turner syndrome at birth does not change with maternal age. Turner syndrome is more common in early pregnancy than at birth, 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 doctors.

Further information for patients.

XXYY

  • This is due to the fetus having four, rather than to, sex chromosomes. The fetus is male.
  • This is a relatively rare condition for which there is little information regarding the risk 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 doctors.

Further information for patients.

A number of types of NIPT include analysis of rare microscopic deletions of chromosomes, or “microdeletions”. Microdeletions result in the loss of one or more important genes, and can cause significant disabilities in children. Microdeletions are too small to be seen by conventional chromosome studies, but can be reliably detected in an affected child or adult using recent genetic techniques.

We recognise that the offer of this testing has appeal, but the sensitivity of the prenatal assay for these microdeletions is largely unknown. Furthermore, this assay yields many false-positives, necessitating invasive genetic testing of fetuses that turn out to be healthy. The inclusion of microdeletion assays results in so many unnecessary amniocenteses that one of the principle benefits of NIPT (avoiding unnecessary invasive tests) is lost. For this reason, the Harmony™ Prenatal Test does not currently offer testing for rare microdeletions.

As data on test performance improves, we may incorporate selected rare microdeletions in the Harmony™ Prenatal Test which we provide.

No.

NIPT is not designed to detect changes in a single gene that account for a familial condition. The major chromosome aneuploidies 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 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 hundreds of thousands 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 certain conditions (Trisomy 21, 18, and 13) 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.