What tests can diagnose spinal muscular atrophy?

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To function properly, motor neurons rely on the SMN protein. Two genes, SMN1 and SMN2, contribute to the production of SMN. Whereas SMN1 controls nearly all of our body’s SMN production, SMN2 makes around 10% of what SMN1 produces.

SMA occurs when both copies of a person’s SMN1 gene have a mutation. And it occurs only as a result of mutations to the SMN1 gene and not the SMN2 gene.

All people with SMA have at least one copy of the SMN2 gene, and some people have multiple copies of the gene. People with more copies of the SMN2 gene appear to have a less severe type of SMA.

One of the treatments for SMA targets the SMN2 gene to direct it to make more SMN protein.

Spinal muscular atrophy testing can identify SMA in around 95% of people who have SMA types 1, 2, or 3. Standard SMA tests can also identify whether someone carries the abnormal gene linked to SMA, even if they do not have the condition themselves.

A person should consider getting tested for the SMA gene mutation if any of the following are true:

• They have a family history of SMA: Having a family history of SMA increases the risk of person developing the condition or passing the related gene mutation to their offspring. As such, a person with a family history of SMA may want to find out whether they have the gene mutation, particularly if they plan on having children.
• They develop symptoms of SMA: People who experience any of the following symptoms of SMA should talk with a doctor about being tested for the condition:
  • progressive muscle weakening
  • progressive difficulty controlling the arms, legs, or trunk
  • progressive difficulty breathing and swallowing
• The person is a newborn or infant, and they are not meeting developmental milestones: Missing certain developmental milestones, such as sitting up or walking unaided, can be a sign of SMA.

People who are considering becoming pregnant can undergo SMA blood testing to see whether they have an abnormal or faulty copy of the SMN1 gene associated with the condition. This is recommended for people who are at risk.

Around 1 in 40 to 1 in 60 people have the SMN1 gene mutation. If both parents carry the mutation, there is a 1 in 4 chance their child will inherit both copies of the mutated SMN1 gene and develop SMA.

Prenatal SMA testing checks for abnormal SMN genes in the amniotic fluid or placenta. The amniotic fluid is the fluid in the sac that surrounds the fetus. The placenta is a disc of tissue that connects the uterus to the umbilical cord.

Amniotic fluid testing involves drawing out the fluid using a long needle, whereas placenta testing, or chronic villus sampling (CVS), involves taking cells from the placenta. In both cases, the doctor will send the samples to the lab for analysis.

Doctors will usually recommend testing a fetus for SMA if either of the following is true:

• Both parents carry the gene mutation for SMA.
• Fetal ultrasounds show abnormal findings, such as reduced fetal movement or contractures.

As of 2021, 39 American states perform SMA blood testing as a routine part of newborn screening. This process enables early SMA diagnosis and treatment, which leads to the best outcomes.

A newborn, infant, or child should also undergo testing for SMA if they do not meet development milestones, such as being able to hold their head up and sit up.

If a newborn or infant tests positive for SMA, they may receive treatments to help boost healthy SMN proteins. Two treatments that doctors may use for this purpose are nusinersen and gene replacement therapy.

People may also undergo supportive therapy to help manage SMA symptoms and improve quality of life.

Nusinersen

Nusinersen is a disease-modifying medication that doctors inject into the fluid surrounding the spine. The drug targets the SMN2 gene. This causes it to make a more complete SMN protein.

If successful, nusinersen may help slow or stop the onset of SMA symptoms and can even reverse the disease in some cases.

Gene replacement therapy

Children under 2 years of age may also benefit from undergoing a procedure called gene replacement therapy (GRT). During this procedure, children receive a one-time intravenous infusion of the medication onasemnogene abeparvovec. The medication works by delivering a functional SMN1 gene copy into motor neuron cells.

Supportive therapy

Newborns, infants, and children with SMA may also receive supportive therapy from a team of medical professionals to help manage SMA symptoms and improve quality of life. Examples of supportive therapy for SMA include:

• physical therapy
• speech therapy
• respiratory therapy
• nutritional monitoring

If a person carries the gene mutation for SMA, it does not mean they cannot have children. However, it does mean that their children have an increased risk of having the disease.

A person with SMA will give a copy of the mutated SMN1 gene to all of their offspring, so all of them will be carriers. If the person with SMA has a partner who carries the mutation, their offspring have a high chance of developing SMA. If both partners have SMA, then their children will develop SMA.

There are options for people who wish to have children but carry the gene mutation for SMA and are worried about passing it on to their children. They may consider:

• undergoing prenatal testing for SMA
• testing an embryo for SMA before implanting it into the uterus as part of in vitro fertilization
• undergoing intrauterine insemination with sperm from a donor that does not carry the SMA gene mutation
• pursuing surrogacy
• adopting

Spinal muscular atrophy (SMA) is a genetic condition that leads to a progressive loss of lower motor neurons. People can undergo genetic testing to see whether they have SMA or carry a copy of the SMN1 gene mutation responsible for the disease. Those who carry the mutation are at risk of passing it on to their offspring.

People who plan on having children should undergo screening for SMA, especially if they have a family history of the disease. Ideally, they should undergo screening before the pregnancy. Prenatal screening is also possible, and doctors may recommend this if fetal ultrasounds show abnormal or reduced fetal development.

Many states screen newborns for SMA, since early SMA detection and treatment improves outcomes. Otherwise, newborns, infants, and children should undergo screening if they do not meet certain developmental milestones.