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 there is any genomic testing available.

Genomic testing should be considered if:

• an autosomal recessive condition is suspected or diagnosed in either the maternal or paternal family;
• either parent is a known carrier for an autosomal recessive condition; or
• clinical features in the fetus (found during a fetal echocardiogram or an anomaly scan, for example) are suggestive of an autosomal recessive condition.

• Collect a detailed family and personal history from the couple, including details of previous genomic testing in the family (if known).
• Refer one or both parents to a clinical genetics department for review by a clinical geneticist or genetic counsellor. If either the pregnant woman or her partner has already received genomic testing and counselling for a known recessive condition in the family and was found not to be a carrier, a referral is not routinely required. If this is uncertain, referral is advised.
• The clinical genetics team will review the National Genomic Test Directory eligibility criteria to determine which tests are available. The directory itself provides a list of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• Testing options may include the following.
  • Where there is a known maternal and paternal disease-causing variant:
    • R448 Prenatal testing (this is targeted variant testing): amniocentesis or chorionic villus sampling may be offered to test a pregnancy for an autosomal recessive condition in cases in which non-invasive prenatal diagnosis (NIPD) is not appropriate or available, or where it is the individual’s preference;
    • R249 NIPD using paternal exclusion testing for very rare conditions where familial variant is known:
      • may be an option if the mother and father carry different disease-causing variants in the same gene;
      • may only report the presence of the paternal variant, depending on the type of NIPD (please contact your local Genomic Laboratory Hub (GLH) in advance of testing to confirm).
    • Note that certain conditions (such as cystic fibrosis, spinal muscular atrophy and congenital adrenal hyperplasia) have specific test directory indications and associated codes.
• • Where there is a known maternal and paternal disease- causing variant, 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