Spinal muscular atrophy (SMA) is a genetic condition that affects 1 in 6,000 to 10,000 people. It impairs a person’s ability to control their muscle movement. Though everyone with SMA has a gene mutation, the onset, symptoms, and progression of the disease vary considerably.
For this reason, SMA is often broken down into four types. Other rare forms of SMA are caused by different gene mutations.
Read on to learn about the different types of SMA.
What causes SMA?
All four types of SMA result from a deficiency of a protein called SMN, which stands for “survival of motor neuron.” Motor neurons are nerve cells in the spinal cord that are responsible for sending out signals to our muscles.
When a mutation (mistake) occurs in both copies of the SMN1 gene (one on each of your two copies of chromosome 5), it leads to a deficiency in SMN protein. If little or no SMN protein is produced, it leads to motor function problems.
Genes that neighbor SMN1, called SMN2 genes, are similar in structure to SMN1 genes. They can sometimes help offset the SMN protein deficiency, but the number of SMN2 genes fluctuates from person to person. So the type of SMA depends on how many SMN2 genes a person has to help make up for their SMN1 gene mutation. If a person with chromosome 5–related SMA has more copies of the SMN2 gene, they can produce more working SMN protein. In return, their SMA will be milder with a later onset than someone who has fewer copies of the SMN2 gene.
Type 1 SMA
Type 1 SMA is also called infantile-onset SMA or Werdnig-Hoffmann disease. Usually, this type is due to having only two copies of the SMN2 gene, one on each chromosome 5. More than half of new SMA diagnoses are type 1.
When symptoms start
Babies with type 1 SMA start showing symptoms in the first six months after birth.
The symptoms of type 1 SMA include:
- weak, floppy arms and legs (hypotonia)
- a weak cry
- problems moving, swallowing, and breathing
- an inability to raise the head or sit without support
Babies with type 1 SMA used to not survive for more than two years. But with new technology and the advancements of today, children with type 1 SMA may survive for a number of years.
Type 2 SMA
Type 2 SMA is also called intermediate SMA. In general, people with type 2 SMA have at least three SMN2 genes.
When symptoms start
The symptoms of type 2 SMA usually begin when a baby is between 7 and 18 months old.
Symptoms of type 2 SMA tend to be less severe than type 1. They include:
- inability to stand up on their own
- weak arms and legs
- tremors in the fingers and hands
- scoliosis (curved spine)
- weak breathing muscles
- difficulty coughing
Type 2 SMA may shorten life expectancy, but most people with type 2 SMA survive into adulthood and live long lives. People with type 2 SMA will have to use a wheelchair to get around. They may also need equipment to help them breathe better at night.
Type 3 SMA
Type 3 SMA can also be referred to as late-onset SMA, mild SMA, or Kugelberg-Welander disease. The symptoms of this type of SMA are more variable. People with type 3 SMA generally have between four and eight SMN2 genes.
When symptoms start
The symptoms begin after 18 months of age. It’s usually diagnosed by age 3, but the exact age of onset can vary. Some people may not begin to experience symptoms until early adulthood.
People with type 3 SMA can usually stand and walk on their own, but they may lose the ability to walk when they get older. Other symptoms include:
- difficulty getting up from seated positions
- balance problems
- difficulty going up steps or running
Type 3 SMA doesn't generally alter a person’s life expectancy, but people with this type are at risk of becoming overweight. Their bones may also become weak and break easily.
Type 4 SMA
Type 4 SMA is also called adult-onset SMA. People with type 4 SMA have between four and eight SMN2 genes, so they can produce a reasonable amount of normal SMN protein. Type 4 is the least common of the four types.
When symptoms start
Symptoms of type 4 SMA usually begin in early adulthood, typically after age 35.
Type 4 SMA may gradually worsen over time. Symptoms include:
- weakness in the hands and feet
- difficulty walking
- shaking and twitching muscles
Type 4 SMA doesn't alter a person’s life expectancy, and the muscles used for breathing and swallowing usually aren’t affected.
Rare types of SMA
These types of SMA are rare and caused by different gene mutations than those affecting the SMN protein.
- Spinal muscular atrophy with respiratory distress (SMARD) is a very rare form of SMA caused by a mutation of the gene IGHMBP2. SMARD is diagnosed in infants and causes severe breathing problems.
- Kennedy's disease, or spinal-bulbar muscular atrophy (SBMA), is a rare kind of SMA that usually only affects males. It often starts between the ages of 20 and 40. Symptoms include tremors of the hands, muscle cramps, limb weakness, and twitching. While it can also cause difficulty walking later in life, this type of SMA doesn't usually alter life expectancy.
- Distal SMA is a rare form caused by mutations in one of many genes, including UBA1, DYNC1H1, and GARS. It affects nerve cells in the spinal cord. Symptoms usually start during adolescence and include cramps or weakness and wasting of the muscles. It doesn’t affect life expectancy.
There are four different types of chromosome 5–related SMA, roughly correlating with the age at which symptoms start. The type depends on the number of SMN2 genes a person has to help offset a mutation in the SMN1 gene. In general, an earlier age of onset means fewer copies of SMN2 and a greater impact on motor function.
Children with type 1 SMA typically have the lowest level of functioning. Types 2 through 4 cause less severe symptoms. It’s important to note that SMA doesn’t affect a person’s brain or ability to learn.
Other rare forms of SMA, including SMARD, SBMA, and distal SMA, are caused by different mutations with an entirely different pattern of inheritance. Talk with your doctor to find out more about the genetics and outlook for a particular type.