Presentation: Pregnancy at risk of an autosomal recessive condition

A woman is eight weeks pregnant with her first child. She and her male partner are both carriers of an autosomal recessive genetic condition. The couple present at their booking appointment with questions about the risk to the pregnancy and whether any genomic testing is available.

• When a history of an autosomal recessive condition is suspected in both the maternal and paternal family.
• When a history of an autosomal recessive condition is confirmed in both the maternal and paternal family.
• When clinical features in the fetus (found during, for example, a fetal echocardiogram or an anomaly scan) are suggestive of an autosomal recessive condition.

• Collect a detailed family and personal history from the couple, taking careful note of any consanguinity (being related prior to becoming a couple) and including details of any previous genomic testing done within the family.
• Refer the case to a clinical genetics department for review by a clinical geneticist or genetic counsellor. If one member of the couple has been screened for a known recessive condition in the partner’s family and was found not to be a carrier, a referral is not required.
• The clinical genetics team will review the NHS England National Genomic Test Directory eligibility criteria to determine which tests are available to your patients. The directory itself provides a list of all available tests.
  • For those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• Testing options may include the following:
  • Where there is a known maternal and paternal disease-causing variant:
    • offer prenatal targeted testing;
    • invasive testing is usually offered; and
    • if the mother and father carry different disease-causing variants in the same gene, non-invasive prenatal diagnosis (NIPD) may be an available option. Depending on the type of NIPD, the test may only report the presence of the paternal variant or it may be able to report on both the paternal and maternal variants. Please contact your local Genomic Laboratory Hub (GLH) in advance of testing to confirm.
  • Where there are known variants, pre-implantation genomic testing for monogenic disease may be available in a future pregnancy. Referral via clinical genetics is required.
  • Where there is a suspected maternal and paternal disease-causing variant:
    • try to confirm the disease-causing variant in each family;
    • test each partner for their family’s disease-causing variant;
    • if unable to confirm the family’s disease-causing variant, consider the appropriate genomic test according to the features of the affected individual (this may be a gene panel test or a test for common variants); and
    • offer testing to other family members if the index patient has a disease-causing variant.
  • If there are clinical features in the fetus suggestive of an autosomal recessive condition, the test is R21 Fetal anomalies with a likely genetic cause: fetal exome sequencing. Referral to clinical genetics is required.
  • A record of discussion form is required.
• For NIPD, a blood sample in a Streck tube (or EDTA tube) is required. For many of the tests, parental samples are also needed or are helpful. Please refer to your local GLH for details of test request forms and where to send samples.
• For invasive tests, an amniocentesis or chorionic villus sample or fetal blood sample (in an EDTA tube) is required, as well as a sample from the mother to test for maternal cell contamination. For many of the tests (particularly whole genome and exome sequencing), parental samples are also needed or are helpful. Please refer to your local GLH for details of test request forms and where to send samples.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• NHS England: National Genomic Test Directory

For patients

• Genetic Alliance UK: Autosomal recessive conditions