Spinal muscular atrophy (SMA) is a rare inherited condition that affects the nerves controlling muscles. It causes muscle weakness that gets worse over time. Depending on the type and age when it starts, other symptoms of SMA can include breathing trouble, an inability to stand or walk, and bulbar dysfunction (difficulties with chewing, swallowing, and speaking).

Severe breathing problems are common in infant or child-onset SMA and can contribute to a reduced life expectancy. Disease-modifying therapies (DMTs) are treatments that can slow the course of a disease. These new therapies are helping improve the outlook for children with SMA. Most forms of adult-onset SMA do not significantly affect life expectancy.

Read on to learn facts about which genes are involved in SMA and how these genes are inherited.

1. Mutations in the SMN Gene Cause Most SMA

SMA types 0 through 4, which account for nearly all cases of SMA, are caused by a mutation (or change) in both copies of the survival motor neuron 1 (SMN1) gene.

Most people have two sets of 23 chromosomes.

Which Deficiency Causes Spinal Muscular Atrophy?

SMN genes tell the body to make SMN protein, which is needed for motor neurons to work properly. Motor neurons are nerve cells that transmit signals from the brain and spinal cord to the muscles. Without enough SMN protein, motor neurons die, and the brain cannot signal the muscles to function. The result is progressive muscle weakness that affects walking and breathing.

2. How Many Copies of the Gene Determine the Severity

There are two SMN genes on chromosome 5, SMN1 and SMN2. In a person without SMA, the SMN1 gene is the main one. It makes most of the protein that muscles need to stay strong and work properly. The SMN2 gene only produces a minor amount of SMN protein.

People without SMA have two SMN1 gene copies and one or two SMN2 copies. Some people have multiple SMN2 gene copies. It’s extremely rare for someone to have none.

In nearly all cases of SMA, a child must inherit an altered gene from both parents to develop the condition.

Babies with type 0, the most severe form of SMA, may have only one SMN2 copy. Those with SMA type 1 (Werdnig-Hoffmann disease) usually have one or two copies, and people with SMA type 2 often have three copies.

In comparison, those with SMA type 3 (Kugelberg-Welander disease) might have three or four SMN2 copies, and those with type 4 may have four or more SMN2 copies.

Gene therapy is available for some individuals with SMA types 0 through 4, depending on age and genetic factors. Learn more about treatments for SMA.

3. Other SMA Types Are Related to Different Genes

Other SMA types are caused by variations in different genes. Here’s what you need to know about these types and their causes.

SMA With Respiratory Distress

SMA with respiratory distress (SMARD) is caused by changes in the immunoglobulin mu-binding protein 2 (IGHMBP2) gene. The SMARD variant causes faulty proteins that damage motor neurons.

Distal SMA

Distal SMA can be caused by a genetic change on the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2), glycyl-tRNA synthetase (GARS1), or receptor accessory protein 1 (REEP1) genes. Mutations in the BSCLR2 gene lead to malformed proteins within cells that may damage or kill motor neurons. The GARS1 gene helps the body create certain enzymes needed for producing proteins.

Kennedy Disease

According to the Muscular Dystrophy Association, Kennedy disease, also known as X-linked spinal and bulbar muscular atrophy (SBMA), primarily affects men. It’s caused by a variation in the androgen receptor (AR) gene on the X chromosome. The AR gene tells the body to make androgen receptors. Androgen receptors are important for the development of male sex characteristics and are also important for human hormonal function.

SMA With Progressive Myoclonic Epilepsy

SMA with progressive myoclonic epilepsy (SMA-PME) is a rare autosomal recessive disorder. It is the result of a variation on the N-acylsphingosine amidohydrolase 1 (ASAH1) gene. This gene makes ceramides, fats that contribute to the creation of myelin. Myelin protects nerve cells. The altered ASAH1 gene functions at less than one-third of the capacity of a normal ASAH1 gene, which is believed to be the reason for the nerve cell damage that causes SMA-PME.

SMA With Lower Extremity Predominance

SMA with lower extremity predominance (SMA-LED) can be caused by changes in the dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) or BICD cargo adaptor 2 (BICD2) genes. Both of these genes help make dynein proteins, which are needed for neurons to grow and work properly. When this growth is disrupted, motor neurons may start to break down, mainly affecting the legs.

X-Linked Infantile SMA

X-linked infantile SMA is caused by a change in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene on the X chromosome. The UBA1 gene provides instructions for creating an enzyme that helps maintain the body’s balance of protein creation and breakdown. If old proteins aren’t broken down, they can impair the function of other cells, such as motor neurons.

4. A Child Must Usually Inherit SMA From Both Parents

For most types of SMA, a genetic variation on both copies of a person’s SMN1 gene determines whether they will have SMA. As explained above, the type of SMA, how severe it is, and life expectancy often depend on the number of SMN2 copies a person has.

As of 2024, all 50 U.S. states screen newborns for SMA at birth.

If you’ve wondered how SMA is inherited, here’s what you need to know. Nearly all cases of SMA are autosomal recessive. This means that a child must inherit an altered gene from both parents to develop SMA. For types 0-4, a child must inherit two mutated copies of the SMN1 gene. If both parents are carriers of the variant that causes SMA, their child has a 25 percent chance of developing SMA, a 50 percent chance of being a carrier of SMA, and a 25 percent chance of inheriting two normal copies of the gene. If someone is a carrier, they can pass the gene on to their children but won’t develop SMA.

Some Types Are Passed Down From Only One Parent

Some types of spinal muscular atrophy, including distal SMA and SMA-LED, follow an autosomal dominant inheritance pattern — meaning one altered gene copy can cause the condition. According to MedlinePlus, X-linked forms of SMA, like Kennedy disease and X-linked infantile SMA, occur almost exclusively in males. This happens when a specific genetic change on the X chromosome is inherited from the mother.

5. Screening for SMA Genes Is Available

Genetic testing via a blood test is used to screen for and diagnose SMA in babies, children, and adults who show symptoms of SMA. As of 2024, all 50 U.S. states screen all newborns for SMA at birth. Prenatal testing for SMA is usually only recommended when both parents are carriers.

Carrier screening before pregnancy can show if potential parents carry the SMA gene change, and it is especially recommended for those with a family history of SMA. It’s also offered for many other genetic conditions. Talk to your healthcare provider if you want to learn more about these options.

Since early treatment improves symptoms and outcomes, it’s vital to find out an SMA diagnosis as soon as possible.

Find Your Team

On mySMAteam, people share their experiences with spinal muscular atrophy, get advice, and find support from others who understand.

Have you discussed the causes of SMA with your care team? What did they recommend for you or your family? Share your story in the comments below.