Spinal muscular atrophy (SMA) is a rare genetic disease characterized by a deterioration of motor neurons in the spinal cord, which disrupts the communication between the central nervous system and muscles. Loss of spinal nerve cells leads to muscle weakness, decreased muscle tone (hypotonia), and, in some cases, reduced life expectancy.
SMA affects 1 in 11,000 people in the United States. Around 1 out of 54 people are asymptomatic carriers of an abnormal survival motor neuron 1 (SMN1) gene, which can cause SMA. The age of onset for the disease ranges from before birth (type 0) to about 10 years old and into adulthood (type 4). Genetic testing typically confirms the presence of these neuromuscular diseases.
To illustrate the different ways SMA is inherited, we’ll follow Taylor, a hypothetical child with SMA.
There are three types of SMA inheritance patterns: autosomal recessive, autosomal dominant, and X-linked recessive. Let’s learn more about each.
The most common types of SMA, types 0-4, are confirmed with a genetic diagnosis based on the chromosomes that are inherited from both parents. All of these types are known as autosomal recessive disorders. The genetic difference that causes SMA types 0-4 is located in the SMN1 gene, which leads to reduced levels of functional survival motor neuron protein. This means that a person must inherit two nonworking (mutated) copies of the SMN1 gene, one from each parent.
Two other types of SMA — SMA with respiratory distress (SMARD) and SMA with progressive myoclonic epilepsy (SMA-PME) — are caused by different gene mutations than SMA types 0-4, but they are also autosomal recessive disorders.
If Taylor was diagnosed with SMA type 0-4, SMARD, or SMA-PME, it would mean that Taylor inherited a nonworking gene from both parents. It does not mean that Taylor’s parents also have SMA.
The genetics of SMA can vary depending on which genes are mutated. Less common forms of the disease, such as distal SMA and SMA with lower extremity predominance, are caused by mutations in genes with an inheritance pattern called autosomal dominance. This means that a person only needs to inherit one copy of a nonworking gene from either parent to develop SMA. Very rarely, a child can have a de novo (new, spontaneous) genetic change. In this case, neither parent would have the nonworking gene.
If Taylor was diagnosed with autosomal dominant SMA, it would mean they received just one copy of the mutated gene. This also means that the parent who passed the abnormal gene to Taylor also has SMA. Only one parent must have SMA for Taylor to inherit the genetic disorder.
Another type of SMA, spinal and bulbar muscular atrophy — also known as Kennedy’s disease — is an X-linked recessive disorder. Similar to the recessive forms of SMA, this form only occurs in a person with the genetic change in all available copies of the X chromosome.
Since males typically only have one X chromosome, they just need one mutated copy of this gene from their mother. Females, on the other hand, would usually not show signs of disease unless there was a problem with one of their X chromosomes, or if the nonworking gene was passed on from both parents.
Now, let’s assume Taylor has been diagnosed with an X-linked variety of SMA. If Taylor is female, the inheritance is similar to the autosomal recessive pattern. Taylor would have to inherit a copy of this mutation from both parents. In this case, Taylor’s father would also have SMA, because he likely only has one X chromosome to offer Taylor, and it must have the mutation. There are few other ways a female might show symptoms. Whether or not Taylor’s mother is diagnosed with SMA, she may also be a carrier of this mutation.
If Taylor is male, only one mutated copy from his mother is required. Although Taylor’s parents may not have SMA, his mother must be a carrier of the gene.
The risk of an SMA diagnosis is the same for each child born to a couple that carries these genetic changes. Taylor’s parents are now expecting a second child, and they are discussing the baby’s chances of developing SMA with a health care professional.
Since the autosomal recessive SMA gene is the most common inheritance pattern, it’s likely that Taylor’s parents are both carriers of the SMA gene but don’t have SMA themselves. In this case, Taylor’s new sibling has a 25 percent chance of being born with SMA.
If the form of SMA that is in the family has an autosomal dominant inheritance pattern, the new child’s risk increases to 50 percent. Furthermore, if Taylor has an X-linked recessive form of SMA, then the new baby’s SMA risk could range from less than 1 percent to 50 percent, depending on the baby’s sex.
SMA risk is difficult to predict. The baseline chance of being a carrier for SMA depends on the genetic ancestry of the parents. Carrier testing is available to determine if someone is a carrier before planning a pregnancy.
Taylor is now an adult who wants to start a family. Taylor worries about whether SMA will be inheritable. This, again, is complicated. It depends on Taylor’s type of SMA and both parents’ genetic status.
For recessive types of SMA, Taylor’s children would need to inherit the nonworking SMN1 gene from both parents to be diagnosed with SMA. If Taylor’s partner is not a carrier of a nonworking SMN1 gene, none of their children will have SMA. Conversely, if Taylor’s partner is a carrier, there is a 50 percent chance that their child will have SMA.
However, if Taylor’s child does inherit SMA, the severity of the disease could vary. This is because SMA severity is dependent on a different gene. A partially active backup SMN gene — the SMN2 gene — can replace some of the SMN protein that a person loses from an inactive SMN1 gene. A person can have up to eight copies of the SMN2 gene. The more copies they have, the less severe the disease is. So, for example, even though Taylor has SMA type 1, the type of SMA that Taylor could pass on will range from type 0 to type 4, depending on the number of SMN2 genes their child has.
If both parents are SMA carriers, prenatal genetic testing can tell them which type of SMA their child has.
Read more about types of SMA.
If you have SMA or carry the gene, the decision to start a family can be a complex and personal one. Genetic counseling and carrier testing are available to people with SMA or with a family history of the disorder. The test requires a single blood sample. With these results, a genetic counselor can help parents understand their chances of passing SMA to their children.
On mySMAteam, the social network for people with SMA, members come together to ask questions, give advice, and share their stories with others who understand life with spinal muscular atrophy.
Do you still have questions about the genetics of SMA? Share your questions in the comments below or by posting on mySMAteam.