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 for the condition. The woman’s partner has no known family history of SMA.

Genomic testing should be considered when:

• there is a confirmed history of a previous pregnancy or child diagnosed with SMA;
• there is a family history of SMA, be it maternal, paternal or both; and/or
• either or both parents are known to be carriers of SMA.

• 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. 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 below.
• • For carrier screening of the parent(s):
• • • R242 Predictive testing for known familial variant(s): This may be offered to a parent when they have a family history of SMA but have not yet had carrier testing themselves. Testing can only be requested by clinical genetics teams. If they are a carrier, carrier testing for their partner is recommended (if it has not already been done).
• • • R252 SMA carrier testing at population risk for partners of known carriers: This is for partners of known carriers where there is no personal or family history of SMA. Testing can only be requested by clinical genetics teams. The test also confirms whether the partner is a carrier of the condition with a known variant and will also advise regarding the chance of a pregnancy being affected.
• • For prenatal testing in a pregnancy with a known familial disease-causing variant:
• • • R311 Non-invasive prenatal diagnosis (NIPD) for spinal muscular atrophy – variant testing: NIPD may be available if both parents are confirmed to be carriers for SMA with known variants in the SMN1 gene. R311 can be requested by clinical genetics and fetal medicine teams after eight weeks of pregnancy (as confirmed by dating scan). Note that the testing laboratory must be informed in advance of the request to ensure the necessary samples and/or validation work can take place.
• • • R448 Prenatal testing: This may be offered, with amniocentesis or chorionic villus sampling, to test a pregnancy for SMA where NIPD is not appropriate or available, or where it is the individual’s preference.
• • If an individual does not want testing for SMA prior to or during pregnancy, their infant can be tested after birth.
• • • R242 Predictive testing for known familial variant(s): This may be offered if the infant does not show any clinical signs of SMA. Testing can only be requested by clinical genetics teams.
• • • R70 Spinal muscular atrophy type 1 diagnostic test: This can be arranged if the infant/child shows clinical signs of SMA. Testing can be requested by clinical genetics, neonatology, neurology and paediatrics teams.
• • If an individual presents prior to conception:
• • • Pre-implantation genomic testing may be available. Referral via clinical genetics is required.
• For NIPD, a blood sample in a Streck tube is required. The testing laboratory can confirm their specific sample requirements. 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 sample, 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, partner samples are also needed or are helpful (this is called trio testing). 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