Fetal Genetic Testing

Rare Disease

The NE&Y GLH provides access to fetal genetic testing in line with the eligibility criteria in the National Test Directory.

For information on how to order a test and the testing available, please see the relevant sections below.

Clinical Indication Code Clinical Indication Comment
R401 Common aneuploidy testing – prenatal (e.g. QFPCR)
R318 Recurrent miscarriage with products of conception available for testing (QFPCR and microarray). These would usually be first trimester miscarriages. R28 microarray, WGS or R412 WES may be more appropriate for later pregnancy loss
R22 Fetus with a likely chromosomal abnormality (QFPCR and microarray)
R21 Fetal anomalies with a likely genetic cause – rapid fetal exome

(after QFPCR and microarray)

Clinical Genetics involvement and additional form required
R412 Non-Urgent Fetal Whole Exome Sequencing Clinical Genetics involvement and additional form required

Urgent testing of a current pregnancy should be tested via R21 where eligible

R240 Diagnostic testing for known familial mutation
R321 Maternal cell contamination testing – if sent separately to the fetal sample
R320 Invasive prenatal diagnosis requiring fetal sexing
R251 Non-invasive prenatal sexing
R249 R249 NIPD using paternal exclusion testing for very rare conditions where familial mutation is known This can only be requested by Clinical Genetics
R250 NIPD for congenital adrenal hyperplasia – CYP21A2 haplotype testing
R304 NIPD for cystic fibrosis – haplotype testing
R305 NIPD for cystic fibrosis – mutation testing
R306 NIPD for Apert syndrome – mutation testing
R307 NIPD for Crouzon syndrome with acanthosis nigricans – mutation testing
R308 NIPD for FGFR2-related craniosynostosis syndromes – mutation testing
R309 NIPD for FGFR3-related skeletal dysplasias – mutation testing
R310 NIPD for Duchenne and Becker muscular dystrophy – haplotype testing
R311 NIPD for spinal muscular atrophy – mutation testing
R389 NIPD – pre-pregnancy test work-up. This needs to be requested on the rare disease request form
R92 Thalassaemia and other haemoglobinopathies This needs to be requested on the specific rare disease request form
R94 Sickle Cell anaemia This needs to be requested on the specific rare disease request form
R184 Cystic Fibrosis diagnostic test

Sample Types

A separate maternal sample to exclude maternal cell contamination (MCC) is required for all invasive procedures including amnio, CVS, fetal blood, cord blood and products of conception unless maternal DNA is already stored in the lab. Please indicate on the prenatal form whether a maternal sample is accompanying the prenatal sample.

Referral Forms

Please select the appropriate request form for your sample type and test request:

1. Prenatal request form for fetal samples (including maternal samples for NIPD).
2. Rare disease request form for all postnatal samples including neonatal and maternal samples (non NIPT)
3. Haemoglobinopathy disorder request forms (prenatal or postnatal version according to sample)
4. WGS
5. R412 Additional non-urgent exome request form and record of discussion for non-continuing pregnancies
6. Whole Genome Sequencing request form and record of discussion for non-continuing pregnancies
7. R21 Additional rapid fetal exome request form and record of discussion for continuing pregnancies

Completing the Referral Form

The prenatal request form should be completed with the maternal identifiers whereas the rare disease form should include the neonates details.
All request forms require an R number and a test description in order to avoid delay and ensure the most appropriate test is activated.

Genetic testing after abnormal first trimester combined screening

  • R401 Common Aneuploidy Testing for trisomy 13, 18 and 21
  • NIPT

Genetic testing after fetal abnormalities detected on ultrasound scan

  • R401 Common Aneuploidy Testing – after characteristic findings of a common aneuploidy on ultrasound scan
  • R22 Fetus with likely Chromosomal Abnormality (common aneuploidy and/or microarray)
  • R306 NIPD for Apert syndrome – mutation testing.

Abnormal ultrasound findings suggestive of Apert syndrome with acrocephaly, proptosis AND symmetrical syndactyly.

  • R309 NIPD for FGFR3-related skeletaldysplasias – mutation testing.

Abnormal ultrasound findings compatible with sonographic diagnosis of achondroplasia, other rare FGFR3-related skeletal dysplasia (including Muenke syndrome, hypochondroplasia or hypochondroplasia with acanthosis nigricans), thanatophoric dysplasia or severe achondroplasia with developmental delay

  • R21 Urgent exome sequencing for Fetal anomalies with a likely genetic cause (add in link to link to forms and guidance)

Urgent exome testing is offered where the observed anomalies are likely to have a monogenic cause. Please refer to the local Clinical Genetics Service who will liaise with the testing centre in Birmingham to ensure eligibility. This test will only be carried out after normal rapid and microarray test results.

Genetic testing after haemoglobinopathy trait detected on routine screening

  • R361 Haemoglobinopathy trait or carrier testing.

Individuals who are likely to have or carry a clinically significant haemoglobinopathy trait other than sickle cell disease based on initial protein testing or red cell indices . This needs to be requested on the specific rare disease request form

  • R362 Carrier testing for sickle cell disease Testing Criteria.

Individuals who are likely to carry sickle cell disease based on initial protein testing. This needs to be requested on the specific rare disease request form

Genetic testing after Pregnancy Loss

Referrals for testing will be triaged by the Genomic Laboratory; testing should be targeted at those where a genetic or genomic diagnosis will guide management for the proband or family

  • R318 Recurrent miscarriage with products of conception available for testing can be used where there has been recurrent miscarriage in the absence of additional features suggestive of chromosomal abnormality (common aneuploidy or microarray testing). Recurrent miscarriage is defined as three or more consecutive miscarriages.
  • R297 Possible structural chromosomal rearrangement

Karyotype test should be used in parents of recurrent miscarriage where products of conception are not available for testing

  • R22 Fetus with likely Chromosomal Abnormality (common aneuploidy and/or microarray) (QFPCR and microarray)
  • R321 Maternal Cell Contamination Testing.

Pregnancy requiring maternal cell contamination to inform interpretation of other testing, for example tests on fetal tissues or tests performed on cord blood.  Testing will often be initiated by the testing laboratory but relevant samples will be required in advance of testing

  • R412 Non-urgent exome sequencing for non-continuing pregnancies.

Turnaround time 84 days depending on capacity with the rapid R21 service taking priority

    • This service should only be used if it is not possible to offer testing via the WGS service (i.e. due to insufficient DNA)
    • Exome sequencing will be performed for a nationally agreed panel of genes known to cause disorders which may present prenatally.
    • Referral for testing will follow discussion with Clinical Genetics and the mother’s local management team.
    • Testing may need to be prioritised based on clinical need i.e. for a future pregnancy
    • Routine aneuploidy and microarray testing should be performed by the mother’s home GLH prior to referral.
    • Maternal cell contamination check of the fetal sample will be performed prior to testing, as well as identity checking of all samples in the Trio.
    • Trio testing (both parents and the fetus) is the preferred option to aid interpretation.
    • All relevant familial samples, fetal growth charts, imaging details, pathology reports, pedigree and any other relevant clinical details should be supplied with a test request form and record of discussion form by the mother’s home GLH.

R251 Non-invasive prenatal sexing.

Pregnancy requiring non-invasive prenatal sex determination to inform management in pregnancies at risk of severe sex-linked disorders, those affecting one sex in particular or where genitalia are ambiguous. Testing performed after 7 weeks in pregnancy as confirmed by dating scan.

R240 Diagnostic testing for known mutation(s).

Targeted testing for specific pathogenic variant(s) previously identified in family.

R321 Maternal Cell Contamination Testing.

Pregnancy requiring maternal cell contamination to inform interpretation of other testing, for example invasive prenatal testing, tests on fetal tissues or tests performed on cord blood. Testing will often be initiated by the testing laboratory but relevant samples will be required in advance of testing

NIPD testing is only available via referral from the local Clinical Genetics Department who will be able to advise on the appropriateness of testing.. Testing should be targeted at those where a genetic or genomic diagnosis will guide management for the proband or family.

Pre-pregnancy work up is required to enable confirmation that NIPD is possible and to allow timely delivery in pregnancy. Testing should be discussed in advance with the testing laboratory to ensure that necessary samples and validation work has been performed.

Testing may not be possible in multiple pregnancies. In such cases contact the laboratory for discussion

  • R389 NIPD-pre-pregnancy test work-up

Testing on parental and other family samples to prepare for NIPD in a planned future pregnancy. Note: this should only be requested in families who qualify for NIPD under the relevant indication and may require further multi-disciplinary or laboratory discussion before approval

  • R249 NIPD using paternal exclusion testing

For very rare conditions where familial mutation is known Testing can be offered when paternal exclusion testing can be offered in families at risk of a recessive disorder when parents carry different mutations or where the father has an autosomal dominant mutation or is known mosaic for a mutation.

  • R250 NIPD for congenital adrenal hyperplasia-CYP21A2 haplotype testing

Testing can be offered where parents have both been confirmed as carriers, have had a previous child affected with CAH and current pregnancy has been confirmed as female. Samples are required from both parents and affected child.

  • R304 NIPD for cystic fibrosis – haplotype testing

Testing can be offered where parents are not consanguineous and each partner carries a confirmed mutation.  DNA is available from both parents, AND

DNA is available from either an affected child/pregnancy OR a confirmed unaffected non-carrier child/pregnancy

  • R305 NIPD for cystic fibrosis – mutation testing

Testing is available for pregnancy at risk of cystic fibrosis due to known CFTR mutation(s) Both parents should be confirmed to be carriers of a different mutation, and father is a carrier of one of the following CFTR mutations p.(Phe508del), c.489+1G>T, p.(Gly542*), p.(Gly551Asp), p.(Trp1282*) p.(Arg553*), p.(Ile507del), p.(Arg560Thr), p.(Ser549Asn), p.(Ser549Arg)

  • R306 NIPD for Apert syndrome – mutation testing

Testing is available where there are abnormal ultrasound findings suggestive of Apert syndrome with acrocephaly, proptosis AND symmetrical syndactyly, the pregnancy is at risk due to paternal Apert syndrome or there is a previous pregnancy with confirmed Apert syndrome

  • R307 NIPD for Crouzon syndrome with acanthosisnigricans-mutation testing

Pregnancy in which NIPD for Crouzon syndrome with acanthosis nigricans is required due to paternal Crouzon syndrome with acanthosis nigricans and the mutation is confirmed OR a previous pregnancy with confirmed Crouzon syndrome with acanthosis nigricans with mutation confirmed

  • R308 NIPD for FGFR2-related craniosynostosis syndromes-mutation testing

Pregnancy in which NIPD for FGFR2-related craniosynostosis is required due to paternal FGFR2-related craniosynostosis with mutation confirmed OR a previous pregnancy with confirmed FGFR2-related craniosynostosis with mutation confirmed

  • R309 NIPD for FGFR3-related skeletaldysplasias – mutation testing

Pregnancy in which NIPD for FGFR3-related skeletal dysplasia is required

    1. Abnormal ultrasound findings compatible with sonographic diagnosis of achondroplasia or other rare FGFR3-related skeletal dysplasia including Muenke syndrome, hypochondroplasia or hypochondroplasia with acanthosis nigricans:
      • Femoral length within the normal range at the routine 18-20-week scan, AND
      • Femur length and all long bones below the 3rd percentile after 25 weeks gestation, AND
      • Head circumference on or above 95th percentile or above the normal range for gestation at diagnosis and/or frontal bossing present, AND
      • Fetal and maternal dopplers should be normal
      • Other features may include polyhydramnios or short fingers

OR

    1. Abnormal ultrasound findings compatible with sonographic diagnosis of thanatophoric dysplasia or severe achondroplasia with developmental delay:
      • All long bones below the 3rd percentile from early pregnancy, AND
      • Small chest with short ribs,AND
      • At least one of: bowed femora, frontal bossing, cloverleaf skull, short fingers

OR

    1. At risk pregnancy due to paternal FGFR3-related skeletal disorder OR a previous pregnancy with confirmed FGFR3-related skeletal disorder

 

  • R310 NIPD for Duchenne and Becker muscular dystrophy-haplotype testing

Pregnancy at risk of Duchenne or Becker muscular dystrophy due to known mutation for which NIPD by mutation testing is required following discussion with testing laboratory and a NIPD fetal sexing result that together indicate a single male fetus.

  • R311 NIPD for spinal muscular atrophy – mutation testing

Pregnancy at risk of spinal muscular atrophy due to known SMN1 mutation(s) for which NIPD by mutation testing is required following discussion with testing laboratory, AND Both parents confirmed to be carriers

Genomic Multi-Disciplinary Team Meetings

In order to support the interpretation of genomic data and its integration within the clinical Multi-Disciplinary Team process a series of genomic advisory boards have been established.

These are multi-disciplinary teams who analyse the more complex genomic results which arise from testing for larger numbers of gene abnormalities.

GMT Meetings

National Genomic Test Directory

The 2020/2021 National Genomic Test Directory for rare and inherited disorders and cancer.

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