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One of the leading causes of infant death is a genetic disease called spinal muscular atrophy, also known as SMA. While SMA is genetic, most people are unaware of the risk of having a child with SMA until they either have a child with this disorder or their SMA carrier screening result is positive. Many couples opt for preimplantation genetic testing (PGT) if they test positive for SMA in a carrier screening.

What Is Spinal Muscular Atrophy?

SMA is a genetic disorder in which nerves and muscles deteriorate over time. Symptoms first appear in newborns or during infancy. SMA is a recessive disease caused by variants in the SMN1 gene. Infants with SMA must inherit two malfunctioning SMN1 genes — one from each parent — in order to have SMA. When both parents are carriers for SMA, they each have one nonworking SMN1 gene, and there is 25 percent chance that a pregnancy will produce a child with SMA. Approximately 350-700 infants are born with SMA each year in the United States alone. Between 1-3 percent of the population carries a nonworking SMN1 gene, and over 10 million people worldwide are carriers for SMA.

Because this disease affects infants of all races and occurs so frequently, the American College of Obstetrics and Gynecology recommends that all individuals who are pregnant or thinking about getting pregnant should consider having an SMA carrier screening test.

What Causes SMA?

The SMN1 gene provides instructions for the body to make the survival motor neuron (SMN) protein, which is responsible for keeping the spinal motor neurons (specific nerves located in the spine that control muscles) working. When both copies of the nonworking SMN1 gene are passed on and their infant cannot make enough SMN protein.

A lack of adequate SMN protein causes the spinal motor neurons to slowly stop working. When the spinal motor neurons stop working, the muscles they control can’t move, and grow weaker and shrink (atrophy) over time. The muscles controlled by the spinal motor neurons in the spine are responsible for helping us breathe, eat and move.

Many infants with SMA either never develop the ability to breathe independently or lose that ability over time; most will need a machine to help them breathe. A child with SMA will also have trouble moving and may never learn to sit up, crawl or walk.

While there is no cure for SMA, in 2016 the Food and Drug Administration approved the first drug found to treat the disease called Spinraza (nusinersen), which showed an improvement in motor milestones in 40% of treated patients. Spinraza is a life-long treatment, which requires an injection administered into the fluid surrounding the spinal cord. There are side effects associated with the treatment such as respiratory infection. By some estimates, this drug is among the most expensive treatments in the world. In early December, Novartis announced that its new single-dose gene therapy for SMA could be approved as early as May of 2019. If approved, the medication dubbed Zolgensma is rumored to launch as one of the most expensive therapies on the market with a price tag of $4 million to $5 million. For patients with SMA and their families, the hope is that this treatment will improve quality of life.

What Are the Different Types of SMA?

Doctors classify SMA into five different types based on when symptoms begin and the severity of the symptoms.

Type 0, 1, 2 and 3 are the most severe forms of the disorder and affect newborns and infants. Newborn babies with SMA type 0 may have decreased movements during pregnancy. After birth, they have very little ability to move and may not be able to breath and swallow by themselves. Unfortunately, because of the severity of their medical problems, most infants with SMA type 0 die before six months of age.

Infants with SMA types 1-3 generally have some ability to move but this decreases over time. Infants with SMA type 1 have problems earlier than those with type 2 and type 3. Infants with SMA type 1 have trouble breathing and swallowing, have decreased muscle function and cannot sit up without support. Infants with SMA type 2 develop symptoms at 6 to 12 months of age and can typically sit but cannot stand or walk. Infants with SMA type 3 develop symptoms after one year of age and before adulthood. They may learn to stand and to walk, but over time lose these skills.

SMA type 4 is the mildest form and develops in adulthood.

Because of the severity of the medical problems associated with SMA, couples at risk to have a child with SMA type 0-3 often look for options to decrease their risk of having a child with SMA, including PGT.

Preimplantation Genetic Testing and SMA

PGT for SMA is done by using in vitro fertilization (IVF) to collect and make fertilized eggs. Once the embryos have developed to the blastocyst stage, a small number of cells are biopsied and sent to a genetics lab to test for SMA. Since such a small amount of DNA is being tested, DNA from other family members may be needed as well. Once the lab results are received, embryos that do not have the SMN1 gene variant are chosen for transfer and implanted.

Because of the severity of SMA symptoms and the risk for early death, talking with a genetic counselor about PGT for SMA if you’ve tested positive in a carrier screening may be the first step in learning about your family planning options.