Who Is SMA Carrier Screening Recommended For?

Spinal muscular atrophy (SMA) is a group of autosomal recessive conditions most often caused by disease-associated changes in the SMN1 gene. Carriers are usually healthy, but when both reproductive partners are carriers there is a chance of an affected child. Carrier screening helps assess this reproductive chance before or during pregnancy.

Who should be offered SMA carrier screening?

ACOG recommends that SMA carrier screening be offered, after appropriate counselling, to all women who are considering pregnancy or are already pregnant. ACMG also supports an equitable, broad carrier screening approach in the preconception and prenatal periods. The decision to test should be informed and voluntary.

Timely assessment is particularly relevant when:

a relative has SMA or a suspected diagnosis,
one reproductive partner is known to be an SMA carrier,
there is unexplained infantile muscle weakness or early death in the family,
pregnancy is being planned and carrier screening has not been performed,
the couple wishes to clarify reproductive chance during an ongoing pregnancy.

What does the test analyse?

Routine SMA carrier screening generally assesses the copy number of SMN1. Finding one SMN1 copy is consistent with carrier status. Some people, however, have two copies on one chromosome and none on the other. This “silent carrier” configuration, as well as rare variants that do not alter copy number, may not be detected by a standard dosage method.

A negative result reduces but does not eliminate carrier probability. Residual risk should be interpreted using the method, copy number, any additional markers and ancestry. When there is a family history, reviewing the affected relative’s molecular report is especially important.

What if one partner is a carrier?

If one partner is identified as a carrier, testing should be offered to the other. When both are carriers, each pregnancy has a 25% chance of an affected child, a 50% chance of a carrier child and a 25% chance of a child who inherited neither familial change. These probabilities apply independently to every pregnancy.

Genetic counselling can provide balanced information about prenatal diagnosis in a natural pregnancy, IVF with preimplantation genetic testing, donor gametes or pregnancy without further testing. The decision belongs to the couple according to their values and medical circumstances.

Does carrier status mean disease?

Being a carrier does not mean that the person has SMA. Carrier screening is also not the diagnostic test used to investigate current muscle weakness. Symptomatic individuals require a separate diagnostic assessment by neurology and medical genetics.