Yourgene Health has recently launched IONA®Care, an advanced prenatal screening test that performs whole-genome analysis to measure the likelihood that a pregnant woman is carrying a fetus with one the most common trisomies (trisomy 21, 18 and 13), any other Autosomal Aneuploidy (AA) or a Sex Chromosome Aneuploidy (SCA). IONA® Care is available from the Yourgene Genomic Services laboratory in Manchester, UK. The test is available as a menu, enabling pregnant women, their families and clinicians to only find out information on the conditions specifically requested. Yourgene felt this was the responsible thing to do as screening for AAs and SCAs and the follow-up counselling can be more complicated than the more common trisomies and therefore felt this additional information should be optional. We spoke with Dr Greg Fitzgibbon, our Director of Clinical Affairs, to find out more about screening for AAs and SCAs and the clinical implications and benefits.
Dr Greg Fitzgibbon, PhD, DipRCPath, HCPC – Director of Clinical Affairs
Greg is a Clinical Laboratory Director with New York State Department of Health Certificate of Qualification and provides the clinical expertise required for Yourgene Health’s expanding business and product portfolio. Greg previously lead the operations team in performing product development, as well as ensuring the compliance to regulatory requirements and performing business management activities.
Greg holds a Doctorate in Molecular Biology, he is a Diplomate of the Royal College of Pathologists and has over 8 years management experience in Clinical Science for the NHS. He also has over 8 years involvement with the inception, growth and development of Biotechnology businesses including Syngenta, Gen-Probe, Hologic and Epistem on top of validating technologies for corporate giants including GSK and Government Institutions.
When thinking about testing for SCAs and AAs, are there particular groups of women who are at a higher risk of having a baby that is affected by one of the conditions? For example, we know that the risk of having a baby affected by Down’s syndrome increases with maternal age; is the same true for these other conditions and are there other factors that affect the incidence?
Yes, like Down’s syndrome SCAs and AAs are aneuploidy syndromes and therefore the incidences of certain SCAs and AAs increase as maternal age increases. This is caused due to an erroneous event called nondisjunction, essentially a failure of homologous chromosome to separate within the egg, which occurs more frequently with advanced maternal age. I say ‘certain’ SCAs however because in the case of Turner Syndrome (monosomy X) there is much higher incidence of sperm production errors therefore the majority of cases of Turners are paternal in origin.
What are the clinical benefits of testing for SCAs and AAs?
For SCAs, the main clinical benefit is earlier detection of the conditions. Unlike Down’s syndrome and the more common autosomal trisomies, SCAs can sometimes have quite subtle features on ultrasound scans which can make them more difficult to detect prenatally. Consequently, a large proportion of cases, particularly Klinefelter’s syndrome (47,XXY) are identified and diagnosed either postnatally, at puberty, or even later on in life (if at all). Routine SCA screening using NIPT allows for the detection of these conditions prenatally from 10 weeks gestational and at no risk to the fetus. This approach not only provides parents with insight, but facilitates improved care by allowing clinical teams to arrange patient care and obstetric management as appropriate.
For AAs there is the opportunity for improved patient management by providing information around recurrence risks. The vast majority of AA cases are not viable and unfortunately will often end in miscarriage. In these cases, the identification of AAs offers clinical benefit as it has determined that the cause is not hereditary, but is in fact a random (nondisjunction) event and therefore recurrence is less likely in subsequent pregnancies.
Should a result come back as high risk, what would the recommended next step be? What would the clinical pathway be?
Testing approaches can vary depending on the testing laboratory and local regulations but the next steps in the testing pathway should always be to discuss the results carefully with the clinician/genetic counsellor in consideration with the patient’s medical background, preferences, test limitations, positive predictive values for the conditions and the need for further confirmatory testing. NIPT is a screening test, not diagnostic; it is recommended that high-risk results be confirmed using diagnostic methods. This may well require invasive sampling either by chorionic villus sampling (CVS) or amniocentesis in order to karyotype the fetus using either cytogenetic or molecular methods (or both).
If the invasive testing confirms the screening result a general clinical pathway would be a consultation where a clinician would speak to the parent(s) and would explain the findings, provide them with sufficient information so that they can make an informed choice regarding their next steps.
How does this test compare to the current pathway for identifying babies affected by these conditions?
The current testing pathway requires invasive sampling of placental or fetal cells by CVS or amniocentesis respectively. CVS is taken at around 10-13 weeks and amniocentesis at around 14-18 weeks gestation, whereas NIPT can be taken as early as 10 weeks gestation. The invasive sampling methods do have the added benefit of being used in diagnostic testing as opposed to screening testing but there is a risk of miscarriage of up to 2% for CVS and 1% for amniocentesis sampling which is negated by the NIPT approach. NIPT only requires a small blood sample from the mother which present no risk to the fetus. If the invasive samples are used for cytogenetic investigations, they will require cell culture with expected reporting times of up to 14 days. Molecular applications including QF-PCR can however provide preliminary results in less than 24 hours.
What support is available for families should they get a high risk result and subsequently confirmed via a diagnostic procedure?
There are several support organisations for families and families would be signposted by their healthcare providers. Antenatal Results and Choices (ARC) offer non-directive individualised information and support to parents. We have included some support organisations below, please note this list is not exhaustive and is provided for information only. Inclusion on this list does not indicate an endorsement by Yourgene Health and Yourgene accept no responsibility for the content of external websites.
- Unique – Support for Rare Chromosome Disorders
- The Klinefelter’s Syndrome Association (KSA) (UK)
- XYY Syndrome (for Parents) – Nemours KidsHealth
- Turner Syndrome Support Society