Spinal muscular atrophy type 4

Last updated Feb. 2, 2023, by Marisa Wexler, MS
Fact-checked by Ana de Barros, PhD

Type 4 is the mildest form of spinal muscular atrophy (SMA), a rare genetic disease that leads to muscle weakness and wasting. SMA is characterized by the progressive loss of motor neurons, the nerve cells that control voluntary movement, and consists of five main types.

One of the rarest forms of this rare disease, SMA type 4 accounts for less than 1% of all cases. It is also called adult-onset or late-onset SMA, because symptoms appear at a much later age than in other SMA types.

Like the other four key forms of SMA, type 4 is caused by mutations in both copies of the SMN1 gene — one inherited from each biological parent. This gene provides instructions to produce SMN, a protein essential for motor neuron and muscle health.

What are the symptoms of SMA type 4?

Symptoms of SMA type 4 develop in adulthood, most commonly after age 35. This is different than other SMA types, in which the first signs are typically seen in infancy or, in some cases, during adolescence.

The disease is mainly characterized by muscle weakness, which usually affects the legs and hips first. Such weakness starts off as mild, but as the disease progresses, it worsens and often starts to affect the upper limbs as well. Most people with SMA type 4 retain the ability to walk independently, though they may need an aid like a cane or a crutch in the latter decades of life.

Other common SMA type 4 symptoms include:

• muscle twitching and aching
• fatigue
• numbness
• cramping
• mild hand and finger tremors.

Unlike the other four main types of SMA, type 4 rarely affects patients’ swallowing and breathing functions.

How is SMA type 4 diagnosed?

Because symptoms of SMA type 4 start off as mild and can appear similar to other neuromuscular conditions, it’s common for a diagnosis of SMA to take some time, with initial tests ruling out other more common conditions.

If SMA is suspected and/or there is a history of SMA in the family, a diagnosis can be made through genetic testing that looks for disease-causing mutations in the SMN1 gene. This testing is typically done on a blood sample.

Genetic testing also can be used to measure the number of copies a person has of a “backup” SMN2 gene that influences disease severity. Typically, a higher number of SMN2 copies is associated with less severe SMA, and most type 4 patients carry four or more copies, relative to the two copies usually present in healthy people. Combining these genetic results with the age of symptom onset and symptom severity helps to confirm the type of disease.

DNA testing also works to identify SMA carriers — individuals who will not develop SMA, but carry one mutated SMN1 copy and could pass the disorder on to their children. If both parents carry one mutated copy of SMN1, they will have a 25% chance of having a biological child with any of the most common SMA types, and a 50% risk of each of their biological children being a carrier of SMA like them. There also is a 25% chance any offspring could be born without the disease.

A person with SMA will pass one mutated copy of SMN1 to their biological children, so if a person with SMA type 4 has biological children with a carrier, there is a 50% chance that the child will have SMA, and a 50% chance the child will be a carrier.

Further tests, such as an electromyogram or muscle biopsy, may be considered if there is any uncertainty about the diagnosis, but are usually not needed to confirm whether an individual has SMA.

Electromyography assesses the health of muscles and motor neurons that control them; the technique measures muscles’ responses to electrical stimulations by motor neurons. In a muscle biopsy, a small section of muscle tissue is removed, usually from the upper thigh, and examined to see whether it has SMA-associated features.

What are the treatment options for SMA type 4?

There are a few disease-modifying therapies approved in the U.S. to treat type 4 SMA. These therapies are believed to slow the progression of the disease, although it remains unclear if people with this milder form of SMA also will benefit.

Each of the current treatments for SMA was developed within the last decade. They include:

• Spinraza (nusinersen), which is approved to treat patients of all ages with all main types of SMA. It is administered via injections into the spine every four months.
• Evrysdi (risdiplam), approved to treat all main types of SMA in patients who are at least 2 months old. It is a once daily oral therapy.

Supportive care and assistive devices

In addition to disease-modifying therapies, many people living with SMA type 4 use other forms of supportive care to help maintain their health and improve their quality of life. Among the alternatives for supportive care are:

• physical therapy, exercise, and stretching, which can help improve motor function
• occupational therapy, which works to find strategies for making life with a chronic illness easier
• dietary counseling, to promote good nutrition and digestive health
• supportive therapies to help manage pain and fatigue.

People with SMA type 4 typically retain the ability to walk, though they often need an aid such as a cane, crutch, or walker to help them get around in later stages of disease.

What is the life expectancy for people with SMA type 4?

SMA type 4 life expectancy is the same as that found for the general population. This is one reason type 4 is the mildest form of SMA; other more severe types (0, 1, and 2)are associated with a shortened lifespan.

SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.