Health Professionals

Prenatal Diagnostic Genomic testing can be ordered by Maternal Fetal Medicine teams in consultation with Clinical Genetics teams.
Please see here [link] for further information on what is required to order prenatal diagnostic genomic testing

Sample Requirements

• If CVS/Amnio had already been completed, send information on what prior testing was undertaken (chromosome microarray, karyotype), whether amniotic/chorionic sample was used, date of the sample and the laboratory, and where sample was analysed. 
• If CVS/Amnio had not been completed, send 2 x 20ml of amniotic samples to NSWHP Randwick, VCGS or SA Pathology. 
• 5-10ml EDTA blood for DNA from both parents (trios) for extraction and storage 
• Maternal EDTA blood is required for maternal cell contamination studies (all studies). 
• If insufficient DNA is available, DNA cell culture or a new amniocentesis will be required. 

Prenatal Diagnostic Genomic Testing Documentation Requirements

For requests to NSW Health Pathology Genomic Laboratory Randwick:
• Send test request form to: NSWPATH-RandwickGenomics@health.nsw.gov.au
• Please note where consent is stored

For requests to VCGS:
• Test request form (https://vcgs.link/genomics-request) with a clinical summary
• Signed informed consent form (https://vcgs.link/genomics-consent)
• For more information you may contact the laboratory on P: 1300118247 or E: vcgs@vcgs.org.au

For requests to SA Pathology:
• Enquiries on 8222 3000 or free call 1800 188 077 outside the metropolitan area.
• Prenatal genomic testing enquiries should be discussed with a genetic pathologist (Dr Tristan Hardy or Dr Sui Yu) prior to acceptance by the laboratory.
• Once accepted, please contact the Prenatal Co-ordinator, Wendy Waters (wendy.waters@sa.gov.au)
• SA Pathology request forms and genomic test consents are available on request.

General Inclusion Criteria

PreGen is limited to those families who will undergo genomic diagnostic testing as a family trio or where both the mother/egg donor and father/sperm donor are available for testing. Single parent families or those requiring a gene panel or singleton test may access prenatal genomic testing but cannot be included in the translational PreGen project.

PreGen will also accept:

• Families considering the option of termination if they fulfill other inclusion criteria
• Referrals from private practitioners if the patient/ family meets the inclusion criteria and a clinical geneticist or clinical genetic counsellor is involved in their care.
• Public referrals when alternatives for funded genomic testing (e.g. a clinically appropriate genomic panel) is available as a local alternative test.

Eligible participants must also be able to:

• Provide informed consent
• Be Medicare eligible 

Testing in PreGen is limited to:

Families where the fetus is believed to be alive at the time of enrolment (preterminal imaging findings are exclusion criteria). Families must have clinical testing consent facilitated by a genetic service to be included in the PreGen study.

Clinical Inclusion Criteria

A fetus with a structural anomaly likely to have a single gene germline aetiology.  Some examples include (but are not limited to):

• A significant/ severe brain abnormality
• Bilateral ventriculomegaly over 12 mm
• A significant cardiac abnormality
• Renal anomalies with a likely Mendelian basis
• A phenotype consistent with skeletal dysplasia
• Evidence of multi-joint arthrogryposis
• Non-immune fetal hydrops
• Isolated NT of over 5mm
• Isolated agenesis of the corpus callosum or a significant abnormality of the corpus callosum

Significant isolated malformations (i.e., bilateral talipes, cleft lip/palate, or others) that usually occur in isolation may also be included if they have an early onset, are severe and/or combined with other ultrasound abnormalities.

Significantly abnormal biometry:

• Growth restriction (<3^rd centile) without placental insufficiency

Exclusion Criteria

• The family do not wish to take part in PreGen
• The process of termination of pregnancy has begun or the family have decided to have a termination of pregnancy no matter what is reported on genomic testing
• Likely non-genetic or undiscoverable aetiologies including teratogenesis, viral infections, and poorly controlled maternal diabetes.
• Recognised syndromes/ malformation complexes with no known gene associations (Pentalogy of Cantrell/ limb body wall complex/ cloacal anomalies/ field defects)
• Prior gene sequencing, gene panels, WES or WGS testing

Anomalies with a low diagnostic yield including

• Apparently isolated anatomical cardiovascular defect with minimal implications for postnatal clinical care (such as ASD, VSD, PDA)
• Isolated mild unilateral or bilateral ventriculomegaly without other cerebral malformations

Inclusion criteria when unclear will be discussed in a PreGen subcommittee meeting.

Additional non-PreGen funded clinical diagnostic testing may be requested by the treating clinician outside of these criteria after discussion with the testing laboratory.

Turn-around Time (TAT)

• TAT is usually within 4 weeks of sample receipt. TAT may be longer if cells need to be cultured to obtain sufficient DNA.

What May or May Not be Reported
• Variants are reported if pathogenic/likely pathogenic with a clear link to a disorder
• Variants of unknown significance (VOUS) will not be reported unless (1) in an autosomal recessive condition where there is a likely pathogenic or pathogenic variant in trans with a VOUS or (2) additional clinical information changes the prior assessment of a variant as a VOUS to pathogenic or likely pathogenic
• Variants associated with an untreatable adult-onset condition in the fetus and/or a parent will not be reported
• Variants associated with a treatable adult-onset condition in a parent will be discussed with the referring clinician prior to reporting
• Carrier status for autosomal recessive conditions outside the clinical phenotype are generally not reported

PreGen will provide funded genomic testing via WES and WGS trios in 3 national diagnostic genomic laboratories (NSW Health Pathology Randwick, VCGS, SA Pathology) for families who meet imaging inclusion criteria in pregnancy.

Families may be considered for enrolment in PreGen by the clinical genetic and maternal fetal medicine teams from the 14 PreGen-associated major national hospitals after they have been consented for prenatal genomic diagnostic genomic testing. Clinical teams will discuss and consent the family for prenatal genomic testing using their usual counselling and consent processes

To qualify for a PreGen funded prenatal WES or WGS trio, families will need to agree to complete two psychosocial questionnaires with the PreGen Genetic Counsellor and to permit the study to access their MBS and PBS data.

For more information on who you can refer for a PreGen exome or genome and how to refer them, please click here

For the PreGen Genetic Counsellor referral form please click here

PreGen is part of the Fetal Sequencing Consortium – read more here