SMA and the Desire for a Healthy Baby: When Should Testing Be Recommended?”
Spinal Muscular Atrophy (SMA) is a disease caused by a congenital genetic disorder that affects the alpha motor neurons located in the anterior horn of the spinal cord. These neurons are responsible for movement and directly control the skeletal muscles.
SMA is an inherited single-gene disorder and belongs to the group of autosomal recessive diseases. In autosomal recessive disorders, both copies of the gene must carry a mutation for the disease to appear. Individuals with only one altered copy are called carriers. If both parents are carriers, there is a 25% chance that the child will have SMA, a 50% chance that the child will be a carrier, and a 25% chance that the child will inherit two normal copies of the gene.
SMA is caused by mutations in the SMN1 gene on chromosome 5. Approximately 1 in every 40–60 people is a carrier of the SMA-causing gene variant. The SMN1 gene produces the SMN protein. If there is not enough SMN protein, the motor neurons begin to shrink and die, leading to weakness in the arms, legs, neck, swallowing muscles, and breathing muscles.
The frequency of SMA is approximately 1 in 10,000 births. There are 5 subtypes of SMA, classified from Type 0 to Type 4. Type 0 is the most severe, while Type 4 is the mildest. Type 1 SMA is the most common form.
The SMN2 gene is almost identical to the SMN1 gene and can also produce SMN protein, although in much smaller amounts. The higher the number of SMN2 copies, the milder the disease usually becomes.
About 95% of SMA patients have a deletion in exon 7 of the SMN1 gene. The remaining 5% have point mutations. Therefore, genetic testing usually begins by looking for exon 7 deletion, but if clinical findings strongly suggest SMA, the entire SMN1 gene should also be examined.
Newborn Screening
There is currently no routine newborn screening program for SMA in Türkiye, although a few countries have already included SMA in their newborn screening programs. SMA meets all the criteria for newborn screening because it is a serious disease, can be detected early, and early treatment is very effective.
Carrier Testing
Carrier testing is especially recommended in countries where consanguineous marriage is common, such as Türkiye. It is also strongly recommended if there is a family history of SMA. If one partner is found to be a carrier, the other partner should also be tested.
What Should Carrier Couples Do?
If both partners are carriers, there are two main options:
- Prenatal diagnosis during pregnancy, performed by chorionic villus sampling (CVS) at 11–13 weeks or amniocentesis at 16–18 weeks. These tests can determine whether the baby has SMA with approximately 99.7% accuracy.
- IVF with preimplantation genetic testing. Embryos are tested on the fifth day, and only healthy or carrier embryos are transferred, allowing the birth of a healthy child.
Although SMA has been known for more than a century, advances in genetic testing, newborn screening, and treatment are making this disease increasingly manageable.