Types of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a group of related disorders that cause muscle weakness that gets worse over time. Four major types of SMA are caused by changes in the SMN1 gene. People with higher levels (3 or more) of the back-up SMN2 gene have less severe symptoms. Other rare types of SMA are caused by other genes.¹

Classifying SMA types helps doctors make treatment decisions. However, SMA varies from person to person, even between people who have the same type. As new treatments impact the course of the disease, it may change how doctors classify SMA types.

How are the types of spinal muscular atrophy defined?

SMA is classified into types based on the age symptoms begin and the highest physical milestone achieved. However, the severity of SMA symptoms is more like a continuous spectrum, without distinct classifications. About 25 percent of people with SMA do not fall into a distinct type.¹

New drug treatments have changed expected health outcomes for many people with SMA. For example, some children with SMA who show symptoms before 6 months old (typical for type 1 SMA) may be able to sit (typical for type 2 SMA) if they start treatment early enough. These new disease outcomes have forced us to change how we classify SMA types. To make treatment decisions, doctors instead rely on:²

• Age when symptoms start
• Number of SMN2 copies
• Age at the start of drug treatment

What are the most common types of SMA?

The 4 major types of SMA are caused by an altered SMN1 gene. Because this gene is on chromosome 5q, these types are called “5q SMAs.”³

Type 1

This is the most common type of SMA. It accounts for about half of all SMA cases. It is also known as Werdnig-Hoffmann disease.^4-6

Symptoms usually appear within the first 6 months of life. Infants may not have noticeable symptoms but then quickly develop reduced muscle tone and severe weakness. Infants are usually never able to sit. Lung muscle weakness leads to respiratory failure. Most infants die from respiratory failure before they are 2 years old.^4-6

Type 2

This is also called Dubowitz disease. About 20 percent of all SMA cases are type 2.^3,4,6
Symptoms usually appear between 7 and 18 months old. Children are able to sit but usually cannot stand or walk. Common symptoms include:^3,4,6

• Tongue twitches
• Low reflexes
• Difficulty swallowing and breathing
• Skeletal problems

Life expectancy is usually 20 to 40 years. Some reports say that 2 out of 3 people with type 2 SMA live to age 25.^6,7

Type 3

This is also called Kugelberg-Welander disease. About 30 percent of all SMA cases are type 3.^3-5

Symptoms usually appear between 18 months old and adulthood. People can walk independently and have a normal lifespan. Some common symptoms include:^3-5

• Weakness in the legs
• Loss of ability to stand or walk with age
• Foot abnormalities

Type 4

This is an adult form of SMA. It accounts for less than 5 percent of all SMA cases.^3-5

Symptoms appear during adulthood, usually after 30 years old. People keep the ability to walk throughout life and have a normal lifespan.^3-5

What are other less common types?

Expanded classifications also include a type 0 SMA. This is the rarest and most severe type. Symptoms appear before birth. Mothers may notice loss of fetal movement in late pregnancy. At birth, infants with type 0 have severe weakness and low muscle tone. Infants with type 0 usually die within a month due to respiratory failure.^3,6

Many rare forms of SMA are not caused by altered SMN1 genes. These forms are called “non-5q SMAs.” Some examples include:

Spinal muscular atrophy with respiratory distress (SMARD)

SMARD is a form of distal SMA. In this form, weakness starts in the hands and feet before spreading to other muscles. SMARD is caused by changes in the IGHMBP2 gene. Babies with SMARD have arm weakness and severe respiratory distress. Other distal SMAs are linked to other gene alterations.^3,4,8

Scapuloperoneal spinal muscular atrophy (SPSMA)

SPSMA is caused by changes in the TRPV4 gene. Symptoms start in childhood or adulthood, with the shoulders and lower legs being the most affected. The disease progresses slowly, and most people can walk until after age 50.^3,8

Spinal and bulbar muscular atrophy (SBMA)

SBMA is a form of X-linked SMA. This means that the altered gene is located on the X-chromosome. X-linked SMA types are more common in men than women. SBMA is also known as Kennedy’s disease. It is caused by changes in the AR gene. SBMA symptoms appear between 30 and 50 years old. It causes muscle weakness and wasting in the legs, arms, face, and throat.^4,8