Presentation: Pregnancy at risk of Duchenne or Becker muscular dystrophy

A young, fit and healthy woman presents to her GP as she is planning a pregnancy. She has a family history of Duchenne muscular dystrophy (DMD) and is concerned that there is a risk of a future pregnancy being affected.

Genomic testing should be considered if:

• there is a maternal family history of DMD or Becker muscular dystrophy (BMD) (this may be genetically confirmed or clinically likely); and/or
• the mother is known to be a carrier for DMD or BMD and the pregnancy has been confirmed to be male. DMD and BMD are both X-linked recessive conditions. A male fetus will therefore have a one-in-two chance of developing the condition if their mother is a carrier.

• Collect a detailed family and personal history from the couple.
• Refer the patient to clinical genetics for review by a clinical geneticist or genetic counsellor.
• The clinical genetics team will review the National Genomic Test Directory eligibility criteria to determine which tests are available to your patient. The directory itself provides a list of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• Testing options may include the following.
  • Carrier screening of the patient.
    • R244 Carrier testing for known familial variant(s): This is carrier screening for women who have a family history of DMD or BMD with an identified genetic cause. This test can currently only be requested by clinical genetics.
    • R73 Duchenne or Becker muscular dystrophy: This is carrier testing for women in whose family there is a clinical diagnosis (or likely diagnosis) of DMD or BMD without an identified genetic cause.
  • Prenatal testing in a pregnancy in which one or both parents has a known familial disease-causing variant.
    • Sex determination:
      • R251 Non-invasive prenatal sexing: This involves non-invasive prenatal diagnosis (NIPD) for fetal sex determination to inform management in pregnancy. NIPD can be performed after seven weeks’ gestation. Contact your local Genomic Laboratory Hub (GLH) in advance to determine the local process.
    • Non-invasive testing available for male pregnancies includes:
      • R310 NIPD for Duchenne and Becker muscular dystrophy – haplotype testing. This testing is available when the mother is confirmed to be a carrier of one of the conditions and R251 has confirmed that the pregnancy is a single XY fetus. It can currently be requested by clinical genetics and fetal medicine teams. The testing laboratory must be informed in advance of the request to ensure the necessary samples and/or validation work can take place.
    • Invasive testing available for male pregnancies includes:
      • R448 Prenatal testing: This involves amniocentesis or chorionic villus sampling and may be offered to test a male pregnancy for DMD or BMD; and
      • R320 Invasive prenatal diagnosis requiring fetal sexing: This is available if the use of NIPD to determine fetal sex has not been possible.
• If a patient presents prior to conception, pre-implantation genomic testing may be available. Referral via clinical genetics is required.
• None of the tests outlined above use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order form and consent (record of discussion) form.
• Parental samples may be needed for interpretation of the proband’s result. Parental samples can be taken alongside that of the proband, and their DNA stored, or can be requested at a later date if needed.
• Most tests are DNA based and require an amniocentesis or chorionic villus sample, or a fetal blood sample in an EDTA (typically purple-topped) tube. For NIPD, a blood sample in a Streck tube is required. For more information about different sample types, see Samples for genomic testing in rare disease.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• 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

• Birmingham Women’s and Children’s NHS Foundation Trust: NIPD for Duchenne/Becker muscular dystrophies – R310.1
• NHS England: National Genomic Test Directory

For patients

• Muscular Dystrophy UK
• NHS Health A to Z: Muscular dystrophy