Spinal Muscular Atrophy (SMA) Carrier Screening
What is SMA?
Spinal Muscular Atrophy (SMA) is a disease that causes abnormally functioning motor neurons, which control voluntary movements such as walking, talking, and swallowing. SMA leads to progressive muscle weakness and atrophy, especially in the muscles of the torso, upper legs, and upper arms. Symptoms can begin prior to six months of age, in childhood, and, more rarely, in adulthood. In the most common form of the disease, lifespan is often less than two years of age.
SMA is caused by changes in the survival motor neuron 1, or SMN1, gene. Approximately 95-98% of affected individuals have deletions in the SMA1 gene and 2-5% have specific mutations in the SMA1 gene that result in a decreased production of the SMN protein. When three or more copies of the SMA2 gene are also present, the disease may be milder.1
How is SMA Inherited?
SMA is inherited in an autosomal recessive manner. In most cases, both parents must be carriers of the condition in order to have a child with SMA. Carriers are not themselves affected by the disease, but have a chance of having a child with the disease. If one parent is found to be a carrier, screening is recommended for their partner. If the partner screens negative, then the couple’s risk of having an affected child is reduced (but not eliminated). If both parents are carriers of SMA, there is a 25% chance in each pregnancy of having a child with SMA, a 50% chance of having a child who is an unaffected carrier of the condition, and a 25% chance of having a child who is not a carrier and is unaffected.
Reporting of SMA Carrier Screen Results:
| Copies | Results |
|---|---|
| 0 | Affected with SMA |
| 1 | Carrier for SMA |
| 2 | Reduced carrier risk |
| 3 | Significantly reduced carrier risk |
Is There Still a Risk to be a Carrier if a Patient Has Two Copies of SMN1?
Yes. Although testing for SMA is very accurate, there are limitations. Most individuals with two SMN1 copies have one copy of the gene on each of their chromosomes. However, some individuals will have two copies on the same chromosome and no copies on the other. Since it is possible for these individuals to pass the chromosome without SMN1 copies to their children, these individuals are carriers of SMA. This test will not be able to identify these carriers. In addition, this test does not detect other disease-causing mutations in the SMN1 gene. This is why the risk of being a carrier in individuals with two or three copies of the SMN1 gene is reduced but not eliminated.
| Ancestry | Carrier Risk | Detection Rate | Carrier Rate if Negative (Two Copies) | Carrier Rate if Negative (Three Copies) |
|---|---|---|---|---|
| Caucasian | 1/35 | 95% | 1/632 | 1/3,500 |
| Ashkenazi Jewish | 1/41 | 90% | 1/350 | 1/4,000 |
| Asian | 1/53 | 93% | 1/628 | 1/5,000 |
| African American | 1/66 | 71% | 1/121 | 1/3,000 |
| Hispanic | 1/117 | 91% | 1/1,061 | 1/11,000 |
Who Should Be Offered SMA Testing?
Since SMA is a common and severe genetic condition, ACMG and ACOG recommend that SMA carrier testing be offered to all couples prior to conception or early in pregnancy. However, testing is voluntary.
Is There Prenatal Testing for Spinal Muscular Atrophy?
Yes. Prenatal testing by chorionic villi sampling or amniocentesis can be performed to determine whether or not a fetus is affected with SMA.
References
- National Organization for Rare Disorders. Spinal Muscular Atrophy. Causes. https://rarediseases.org/rare-diseases/spinal-muscular-atrophy/. Accessed September 10, 2019.