Presentation: Pregnancy at risk of spinal muscular atrophy

A woman attends her booking appointment and mentions that her sister has recently had a baby who died of spinal muscular dystrophy (SMA) type 1 in infancy. She knows that her sister has had genomic testing and is a carrier of the condition. The woman’s partner has no known family history of SMA.

• When there is a family history of SMA (maternal, paternal or both); for example, when one partner is at risk of being, or is a known carrier, and the other partner has no known family history.
• When both parents are known to be carriers of SMA variants.

• Collect a detailed family and personal history from the couple.
• Refer to clinical genetics for review by a clinical geneticist or genetic counsellor.
• The clinical genetics team will review the NHS England 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 our dedicated Knowledge Hub resource.
• Testing options include those listed below.
  • Carrier screening of the patient:
    • R252 SMA carrier testing for patients with a background population risk – that is, no personal family history of SMA. This test is performed on partners of known carriers, and can currently only be requested by clinical genetics. R252 will confirm whether the partner is a carrier of the condition with a known variant.
  • Prenatal testing in a pregnancy with a known familial disease-causing variant:
    • invasive testing; and
    • R311 Non-invasive prenatal diagnosis (NIPD) for SMA: this is available when both parents are confirmed to be carriers of SMA (R311.1 NIPD single-gene testing) and can currently be requested by both clinical genetics and fetal medicine (the testing laboratory must be informed in advance of the request to ensure the necessary samples/validation work can take place).
  • If the patient presents pre-conceptually, pre-implantation genomic testing for monogenic disorders may be available. Referral via clinical genetics is required.
• For NIPD, a blood sample in a Streck tube (or EDTA tube) is required. For many of the tests, partner samples are also needed or are helpful. Please refer to your local Genomic Laboratory Hub (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, 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.
• A record of discussion form, or another appropriate local consent form, is required for testing.
• 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
• Birmingham Women’s and Children’s NHS Foundation Trust: NIPD for spinal muscular atrophy (SMA) – R311.1 (PDF, one page)

For patients

• Spinal Muscular Atrophy UK