Spinal muscular atrophy (SMA) is a rare genetic disorder that affects about 1 out of every 11,000 people. People with SMA have a change in the SMN1 gene that prevents it from making enough of the protein — called survival motor neuron protein or SMN protein — that nerve cells need to survive. Some people make enough of this protein with a related gene called SMN2.

There are different types of SMA. SMA type 0, 1, 2, 3, and 4 are caused by changes (pathogenic variants, also know as mutations) in the SMN1 gene and are inherited in an autosomal recessive manner. Extra copies of the nearby related gene, SMN2, modify the severity of SMA. There are other rarer types of SMA caused by changes in different genes.

SMA type 0 can cause miscarriage or death by 6 months of age. Most children have SMA type 1, which causes weakness and, without treatment, can worsen quickly and lead to death.

SMA testing looks for changes in your SMN1 gene that may increase your risk of carrying an abnormal SMN1 gene. When it is done before or during pregnancy, it allows you to find out your chances of having a child with a spinal muscular atrophy (SMA).

Newborn screening for SMA can be included with routine newborn screening for other disorders during the first few days of your baby's life. This process uses the same dried blood spots already collected for screening of other disorders.

SMA testing is done to check if you or your child has SMA, or if you're at risk of having a child with the condition. There is no cure for SMA yet, but early diagnosis allows early monitoring and treatment.

SMA testing looks for unusual changes in the SMN1 gene. Your doctor may want to order this test in the following situations:

• If you have a family member who was diagnosed with SMA.
• If you are planning a pregnancy.
• If you are pregnant, as a part of prenatal diagnosis.
• When certain abnormalities are found on fetal ultrasound.
• As a part of routine newborn screening during the first few days of your baby's life.

Genetic carrier screening usually involves testing a sample of blood, saliva (spit), or cells from the inside of the cheek.

• For a blood test: A health care professional will take a blood sample from a vein in your arm, using a small needle. After the needle is inserted, a small amount of blood will be collected into a test tube or vial. You may feel a little sting when the needle goes in or out. This usually takes less than five minutes.
• For a saliva test: You'll spit into a container or use a cotton pad to soak up some saliva.
• For a cheek swab: A health care professional will wipe the inside of your cheek with a small tool to remove some cells. You may have the option of doing it yourself.

When the test is done in a pregnant woman, a sample of the placenta or amniotic fluid may be used.

• For amniocentesis: A provider inserts a hollow needle through your belly and into your uterus to withdraw a sample of amniotic fluid.
• For chorionic villus sampling (CVS): A provider collects a sample of tissue from the placenta with either a needle that's inserted through your belly or a tube that's inserted through your vagina.

In a routine newborn screening, dried blood spots collected from a baby’s heel within the first 24-48 hours of birth are used to detect genetic disorders including SMA.

You don't need any special preparations for a blood test.

A half hour before a saliva test, you may need to stop eating, drinking, or smoking. Follow all the instructions your provider gives you or the instructions in an at-home kit.

For a cheek swab, you may be asked to rinse your mouth before the test.

For a CVS or amniocentesis, you may need to drink extra fluid and not urinate before your test so that your bladder is full.

There is very little risk to having a blood test. You may have slight pain or bruising at the spot where the needle was put in, but most symptoms go away quickly.

There are no risks linked to providing a saliva sample or having a cheek swab.

During amniocentesis or CVS, you may feel mild stinging or cramping. Both tests are safe, but they do have a slight risk of causing a miscarriage.

Most forms of SMA are inherited in an autosomal recessive pattern. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell.

SMA testing results are reported as the number of healthy copies of SMN1 a person has:

• Zero healthy copies of SMN1. 95-98% of individuals with SMA have zero copies of the SMN1 gene. This result is consistent with a diagnosis of spinal muscular atrophy. If the SMN1 gene is found to be abnormal, further studies will be done to identify the number of copies of the SMN2 gene. SMN2 also produces SMN protein but in smaller quantities that will not compensate for the amount missing due to the abnormal SMN1. As a result, when an affected individual has more than three copies of SMN2, SMA will likely develop later in life and typically in a milder form.

• One healthy copy of SMN1. People who inherit one faulty copy and one functioning copy of SMN1 are called carriers, and they usually don’t develop SMA symptoms. However, they can still pass on the faulty gene to their children. When both partners are carriers, their chance of having a child with SMA is 1 in 4 (25%).

• Two or more healthy copies of SMN1. People who inherit two or more SMN1 copies have a significantly reduced risk of being an SMA carrier.

In some cases, interpreting results of carrier testing for SMA is difficult. Approximately 6% of parents of a child with SMA due to deletions in each copy of the gene have normal results of SMN1 carrier testing for one of two reasons. Most people have one copy of SMN1 on each chromosome. However, about 4% of carriers have two copies of SMN1 on a single chromosome and a deletion on the other chromosome. These carriers with two copies of SMN1 on one chromosome are misdiagnosed as non-carriers by the SMN1 carrier test (they have a false negative test result). The second reason is that a new (de novo) deletion on one copy of the SMN1 gene occurs in 2% of people with SMA; in these cases, only one parent is a carrier.

About 95% of individuals with SMA have the mutations that delete a specific section of the SMN1 gene in both copies of the gene. In about 5% of people with this genetic disorder, however, one copy of the SMN1 gene has the deletion and the other copy has a different mutation; researchers have identified at least 65 mutations in the SMN genes that cause spinal muscular atrophy.