What is spinal muscular atrophy?

Spinal muscular atrophy (SMA) is a genetic disorder that causes muscle weakness and paralysis. It primarily affects the muscle cells of the spinal cord, and it’s one of the leading causes of infant mortality.

SMA is classified as either type 1 or type 2, depending on which motor neuron degenerates first. Type 1 SMA usually develops before 6 months of age, while type 2 SMA typically develops after age 2. Both types can vary in severity and symptoms.

There’s no cure for SMA, but treatments can help manage symptoms and improve mobility.

What are the types?

Spinal muscular atrophy (SMA) is a progressive disease that causes muscle weakness and loss of motor control due to degeneration of neurons in the spinal cord. The disease primarily affects children younger than 2 years old, but it may also affect adults with weakened immune systems.

SMA type 1: the most severe form, with onset in infancy and death usually occurring by age 2

SMA type 2: onset in early childhood, slow progression to disability

SMA type 3: onset between ages 5 and 8 years, slower progression than type 2 (most children have walking ability at age 10)

SMA type 4: onset during adolescence or adulthood, often with milder symptoms than types 1, 2 or 3.

What causes SMA?

The exact cause of SMA is not yet known. However, it is thought to be caused by a combination of genetic and environmental factors.

SMA affects about one in 10,000 babies born in the UK. It can affect both males and females of all races, but is most common in Caucasians and Ashkenazi Jewish people.

The best way to understand SMA is as a spectrum disorder – meaning that there are different types of SMA with varying severity. The different types are listed below:

Spinal muscular atrophy type 1 (SMA1) is the most severe form of SMA and affects one in 10 children born with SMA. Children born with this form of SMA will begin to show signs such as weakness within their first year of life and will eventually require round-the-clock care. There is no cure for this form of SMA, but there are treatments available which aim to relieve symptoms and improve quality of life.

Spinal muscular atrophy type 2 (SMA2) is less severe than SMA1, but can still be debilitating due to muscle weakness and loss of function in key areas such as swallowing or breathing. Most children born with this form of disease live into their teenage years and some into adulthood.

What are the symptoms of SMA?

The symptoms of SMA are due to the loss of motor neurons, which are nerve cells that control muscle movement. The muscles that work the hips, legs and shoulders are affected first, followed by those that work the arms.

Weakness usually begins in early infancy and progresses over time. Infants with SMA may not be able to lift their heads or sit unsupported as early as other babies. As they grow older, they may have trouble standing on their own, walking or crawling. They may have difficulty breathing when they get tired or when they laugh hard or cry loudly.

The severity of symptoms varies from one person to another and among affected siblings or family members.

What is the progression of SMA?

The progression of SMA is different for each individual. Some people with SMN1 mutations will never lose the ability to walk, while others will require a wheelchair by the time they are in their teens.

The most common age of onset is between 3 and 6 months. However, it can be later if the mutation is mild or if other factors such as environmental exposures or prenatal factors have an impact on development.

Symptoms start with weakness in the muscles that control breathing, swallowing and speaking (motor functions). Symptoms then progress to weakness in the neck, trunk and limbs (sensory functions). Loss of muscle tone (spasticity) can also occur.

Some children with SMA1 may not show any symptoms until they are between 6 months and 2 years old, but most kids with SMA1 show signs before their first birthday.

What is the status of research on SMA?

The SMN2 gene, which was discovered in 1999, was the first to be identified as a gene responsible for SMA.

The SMA Foundation funded research that confirmed that the SMN2 gene is a “hit-or-miss” gene; it produces either too little or no functional protein. The amount of functional protein produced depends on how many copies a person has of the normal (wild-type) SMN1 gene. People who have one copy of SMN1 are called carriers; they have enough functional protein and do not develop symptoms of SMA. Those with two copies of SMN1 are called non-carriers; they do not have enough functional protein and develop symptoms of SMA.

How treat SMA?

There is currently no cure for SMA. However, there are treatments that can help manage symptoms and improve quality of life.

For some types of SMA, there are drugs that may help slow the progression of symptoms. These include:

Glucocorticoids, such as prednisone or methylprednisolone, which are steroid hormones that can reduce muscle damage and promote muscle growth.

Spinal cord stimulation, which delivers electrical impulses to specific areas of the spinal cord through electrodes implanted in the epidural space near the spinal cord. This blocks nerve signals from reaching certain muscles, reducing pain and allowing more efficient use of remaining muscles. It does not correct weakness or paralysis but may be effective for some people with lower limb involvement who cannot walk independently with conventional mobility aids such as crutches or wheelchairs. Some patients experience significant side effects from spinal cord stimulation, including headaches, muscle pain and chest pain due to abnormal heart rhythms caused by interference with electrical impulses within their hearts (cardiac pacemakers).