Overview of SMA
Spinal muscular atrophy (SMA) is a rare, inherited disorder that occurs on average in one of every 6,000 to 12,000 babies born per year (Johns Hopkins, 2020), affecting an estimated 40 to 60 infants in Texas per year. SMA affects nerve cells (motor neurons) of the spinal cord and brain stem. Over time, more motor neurons are lost, resulting in progressive muscular weakness and atrophy. Muscle weakness is more severe in an individual’s trunk, upper legs, and arms than in muscles in the hands and feet. The disease progressively destroys muscles that normally allow an individual to crawl, sit, walk, turn the head, speak, breathe and swallow.
SMA does not affect involuntary muscles, such as those in the heart, blood vessels and digestive tract. Sensation, learning and thinking also are not affected by SMA. In fact, “it has been observed that many patients with SMA are highly intelligent” (Johns Hopkins, 2020).
Individuals with SMA have inadequate amounts of the spinal motor neuron (SMN) protein, leading to progressive motor neuron death and subsequent muscle weakness that, without treatment, can lead to death in the first months or years of life.
Two genes provide the instruction for creation of the SMN protein:
- Survival motor neuron one (SMN1)
- Survival motor neuron two (SMN2)
Most functional SMN protein is produced from the SMN1 gene, with a small amount produced from the SMN2 gene. Normally, individuals have two copies of the SMN1 gene, but the number of SMN2 copies can vary greatly. For example, some individuals have as many as eight copies of the SMN2 gene. Pathogenic variants in the SMN1 gene cause all five types of SMA, which are described below. The number of copies of the SMN2 gene modifies the severity of the condition and helps determine which type of SMA develops. In general, the condition is milder when an individual has more copies of the SMN2 gene.
Individuals with SMA have alterations in both of their SMN1 genes. Individuals with one functional SMN1 gene do not have SMA.
This diagram shows possible gene combinations that carrier parents—those who have one non-functioning SMN1 gene—can pass down each time they have a baby.
Fast Facts: SMA inheritance by the numbers
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Depending on race or ethnicity, one in every 40 to 60 people is a genetic carrier for SMA.
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SMA occurs in all races and ethnicities, however white infants have the highest incidence.
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95 percent of SMA cases are caused by deletions in the SMN1 gene.
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5 percent of SMA cases are caused by specific mutations in the SMN1 gene.
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A newborn whose biological parents both carry one non-functioning SMN1 gene has a 25 percent chance of having SMA.
Sources: American College of Obstetricians and Gynecologists, GeneReviews,National Organization for Rare Disorders (2020), Cleveland Clinic, (2015)
Types of SMA
Clinically, SMA has been divided into five categories—type 0 through type 4—based on an individual’s age when SMA symptoms appear. SMA symptoms can begin before birth or during infancy, childhood or adulthood. The most severe types of SMA begin either before birth or very early in life. Type 1, which occurs in the first six months of life, accounts for more than half of all cases.
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