Spinal Muscular Atrophy

Spinal muscular atrophy is a genetic condition that causes progressive muscle weakness and wasting, affecting movement, breathing, and sometimes swallowing. While there is no cure, new treatments are helping people with this condition live longer and better lives.

Table of contents

• What is Spinal Muscular Atrophy?
• Types of Spinal Muscular Atrophy
• Signs and Symptoms
• What Causes SMA?
• How is SMA Diagnosed?
• Treatment Options
• Living with SMA
• Outlook and Life Expectancy

What is Spinal Muscular Atrophy?

Spinal muscular atrophy (SMA) is a genetic condition that affects the nerves that control muscle movement. The disease causes certain muscles to become weak and waste away over time^[1]. The nerve cells that control muscles, called motor neurons (specialized nerve cells in the brain and spinal cord that control movement), break down and stop working properly^[2].

When motor neurons don’t work, muscles don’t receive the signals they need to move. Without these signals, muscles become weak and get smaller, a process called atrophy (the medical term for getting smaller)^[1]. The weakness in SMA tends to be more severe in muscles close to the center of the body, such as the shoulders, hips, and back, compared to muscles farther away like the hands and feet^[1].

SMA affects muscles throughout the body, including those used for feeding and swallowing, as well as those involved in breathing and coughing^[4]. It’s important to understand that SMA does not affect a person’s intelligence or ability to learn^[4].

Although SMA is considered uncommon, it is the second most common severe hereditary disease of infancy and childhood after cystic fibrosis^[1]. The condition affects approximately 1 in 6,000 to 1 in 10,000 live births worldwide^[6].

5q spinal muscular atrophy, autosomal recessive proximal spinal muscular atrophy

Types of Spinal Muscular Atrophy

There are five main types of SMA, traditionally classified based on the age when symptoms begin and how severe they are^[1]. The earlier symptoms start, the more severe the condition tends to be. Each type affects people differently in terms of muscle function and life expectancy.

SMA Type 0 (Congenital SMA)

This is a very rare and severe form that affects a baby before birth. During pregnancy, the mother may notice decreased fetal movements^[2]. At birth, infants have severe muscle weakness and difficulty breathing^[1]. Sadly, babies with type 0 usually do not survive beyond the first month of life^[1].

SMA Type 1 (Severe SMA)

Type 1 SMA is the most common form, accounting for about 60% of all SMA cases^[1]. It is also known as Werdnig-Hoffmann disease or infantile-onset SMA. Symptoms appear before a baby is 6 months old, with most showing signs by 3 months^[7].

Babies with type 1 SMA have limited head control, decreased muscle tone (they appear “floppy”), and lack of reflexes^[1]. They cannot sit without support and have difficulty swallowing, breathing, and feeding^[2]. Without breathing support, children with type 1 SMA rarely live beyond their second birthday^[1]. However, new treatments are helping children with type 1 SMA live longer than before^[7].

SMA Type 2 (Intermediate SMA)

Type 2 SMA, also called Dubowitz disease, begins to affect children between 6 and 18 months of age^[1]. Children with this type may be able to sit without support at some point but cannot walk on their own^[9].

The muscle weakness tends to affect the legs more than the arms. Children with type 2 often develop a curved spine (scoliosis) and may have weak respiratory muscles^[1]. Around 70% of people with type 2 survive until age 25, with some living into their 30s^[1]. Respiratory problems are the major cause of death^[1].

SMA Type 3 (Mild SMA)

Type 3 SMA, also known as Kugelberg-Welander disease, causes symptoms after 18 months of age^[1]. Children with type 3 can usually walk on their own, though they may have difficulty doing so^[2]. They may struggle with running, getting up from a chair, or climbing stairs^[2].

People with type 3 SMA generally don’t develop breathing problems, and the condition typically doesn’t affect life expectancy^[1]. Some may eventually need to use a wheelchair later in life^[9].

SMA Type 4 (Adult SMA)

Type 4 is the mildest and rarest form of SMA, affecting less than 5% of people with the condition^[9]. Symptoms typically don’t appear until after age 21, and sometimes not until age 30 or older^[1].

The muscle weakness progresses slowly, and most people with type 4 remain mobile^[1]. This type usually causes mild to moderate leg muscle weakness and doesn’t affect life expectancy^[2].

Signs and Symptoms

The main symptom of SMA is muscle weakness, typically in the muscles closest to the center of the body^[1]. However, symptoms vary considerably based on the type of SMA and when it begins.

Common symptoms across different types may include^[9]:

• Muscle weakness and decreased muscle tone
• Limited mobility and difficulty with movement
• Breathing problems
• Problems eating and swallowing
• Delayed motor skills (such as sitting, crawling, or walking)
• Trembling or shaking muscles (tremors)
• Curved spine (scoliosis)

In severe forms that affect infants, additional symptoms include limited head control, a weak cry, and an abnormal breathing pattern with a bell-shaped chest^[1]. Babies may appear “floppy” and don’t move much^[7].

For people with later-onset SMA, early signs might be subtle and include dropping things, falling, and feeling tired^[23]. These symptoms can sometimes be overlooked for years, being mistaken for clumsiness or normal aging^[23].

It’s crucial to note that people with SMA may experience respiratory infections more easily. They may also develop joint problems where muscles and tendons become chronically shortened^[2].

What Causes SMA?

Most cases of SMA are caused by changes (mutations) in a gene called SMN1 (survival motor neuron gene 1)^[2]. This gene provides instructions for making a protein called SMN, which motor neurons need to survive and work properly^[6].

When the SMN1 gene doesn’t work correctly, the body can’t make enough SMN protein. Without enough of this protein, motor neurons break down and can’t send signals to muscles^[7]. In about 95% of SMA cases, both copies of the SMN1 gene are missing^[9].

There is another similar gene called SMN2 that also makes SMN protein, but it produces much less than SMN1^[2]. All people with SMA have some copies of the SMN2 gene. The number of SMN2 gene copies a person has can affect how severe their SMA is — having more copies of SMN2 is generally associated with milder forms of the disease^[3].

How SMA is Inherited

SMA is usually passed down through families in what’s called an autosomal recessive pattern. This means that both parents must carry the altered gene for a child to have the condition^[9]. Parents who carry the gene typically don’t have SMA themselves — they are called “carriers.”

When both parents are carriers, with each pregnancy there is^[9]:

• A 1 in 4 (25%) chance their child will have SMA
• A 2 in 4 (50%) chance their child will be a carrier but not have SMA
• A 1 in 4 (25%) chance their child will not carry the altered gene or have SMA

About 1 in 40 people carry a copy of the altered gene that causes SMA, although they don’t have the condition themselves^[4]. In around 2% of cases, the mutation occurs during early development and is not inherited from parents^[6].

How is SMA Diagnosed?

Diagnosing SMA can sometimes be challenging, especially for later-onset types, as symptoms can resemble other neuromuscular conditions^[9]. If a doctor suspects SMA based on symptoms and physical examination, several tests may be used to confirm the diagnosis.

Genetic Testing

A blood test for genetic testing is the definitive way to diagnose SMA^[5]. This test checks for specific changes in the SMN1 gene. Genetic testing became more widely available in the 1990s after researchers identified the gene responsible for SMA^[23].

Other Diagnostic Tests

Before genetic testing or to rule out other conditions, doctors may use additional tests^[9]:

• Electromyography (EMG) — a test that measures electrical activity in muscles and nerves
• Muscle biopsy — taking a small sample of muscle tissue to examine
• Motor function testing — measuring fine motor skills or walking ability

Prenatal and Newborn Testing

If you’re at risk of having a child with SMA, tests are available before, during, and after pregnancy^[5]:

• Genetic blood testing can determine if you carry the altered gene
• Chorionic villus sampling (CVS) or amniocentesis can check if a baby has SMA during pregnancy
• Blood tests can be done after a baby is born

Many U.S. states now screen newborns for SMA^[9]. Early diagnosis is important because starting treatment as soon as possible can improve outcomes^[12].

Treatment Options

While there is currently no cure for SMA, several treatment options are now available that can help manage symptoms and improve quality of life^[1]. The introduction of new therapies since 2016 has significantly improved outcomes for people with SMA^[6].

Disease-Modifying Medications

Three medications have been approved by the U.S. Food and Drug Administration (FDA) to treat SMA. These medications target the genetic cause of the disease and work to increase production of the SMN protein^[15]:

Nusinersen (Spinraza) — This medication modifies the SMN2 gene to increase production of functional SMN protein^[15]. It is given as an injection into the spinal canal (intrathecal injection). Nusinersen is approved for both pediatric and adult patients^[17].

Onasemnogene abeparvovec-xioi (Zolgensma) — This is a gene therapy that delivers a working copy of the SMN1 gene to the body^[15]. It was the first-ever FDA-approved gene therapy for any neuromuscular disease^[15]. Zolgensma is given as a one-time intravenous (into the vein) infusion for pediatric patients younger than age 2^[12].

Risdiplam (Evrysdi) — This is an oral medication taken by mouth that also works to increase SMN protein production^[6].

The most suitable treatment depends on a person’s age and symptoms. Healthcare providers can discuss the risks and benefits of different treatment options^[5].

Supportive Care and Therapies

In addition to disease-modifying medications, supportive care is essential for managing SMA symptoms. A team of specialists may be involved in care, including neurologists, respiratory therapists, physical therapists, and dietitians^[1].

Supportive treatments may include^[5]:

• Physical therapy, exercises, and stretches to maintain strength and prevent joints from becoming stiff
• Mobility equipment such as walking frames and wheelchairs
• Supports for arms or legs (splints or braces)
• Breathing support when needed
• Nutritional support and help with feeding
• Treatment for scoliosis (curved spine)

These supportive measures help maintain comfort and function and can prolong life^[15].

Living with SMA

Living with SMA requires balancing self-care needs with daily responsibilities and relationships throughout different life stages^[18]. With proper support and care, many people with SMA can lead fulfilling lives.

Healthy Lifestyle Habits

Good nutrition is essential for keeping energy levels up and promoting regular bowel movements^[18]. If you have difficulty eating, you may need to include more pureed or liquid foods in your diet. A registered dietitian can help find foods you enjoy that meet your nutritional needs.

Exercise can reduce muscle weakness and improve quality of life^[18]. Physical therapy with appropriate exercises can be beneficial. Exercise can also be a positive outlet for stress that often comes with having a chronic condition.

Smoking is especially dangerous for people with SMA because it increases the risk of breathing problems and respiratory infections^[18]. If you currently smoke, it’s important to try to stop.

Building a Healthcare Team

Since SMA can affect multiple body systems, you may need a network of specialists who work together to coordinate care^[18]. Your healthcare team might include a neurologist, respiratory specialist (pulmonologist), respiratory therapist, dietitian, physical therapist, and other professionals.

To build your healthcare team, start by asking for referrals from your doctor. You can also request information from organizations like the Muscular Dystrophy Association to find specialized clinics in your area^[18].

Managing Daily Life

People with SMA have developed various strategies to adapt and be successful as they manage work, errands, family time, social activities, and leisure^[18]. Focusing on self-care first helps everything else fall into place. Many people find support through connecting with others who understand what they’re going through.

Outlook and Life Expectancy

The outlook for people with SMA varies greatly depending on the type and when treatment begins. In the natural course of the disease without treatment, outcomes range from death within weeks after birth in the most severe cases to normal life expectancy in milder forms^[6].

Type 1 SMA is the most severe form. Without treatment, children rarely live past early childhood due to respiratory failure^[8]. However, new treatments are significantly improving outcomes, and children with type 1 SMA are now living longer^[7].

For type 2 SMA, life span varies, but many people live into their twenties or thirties^[8]. Depending on the severity of symptoms, some may have a normal life span^[9].

People with type 3 and type 4 SMA generally have an almost normal life expectancy^[1][8]. While they may experience mobility challenges, they can often lead full and active lives.

The introduction of new treatments in 2016 has significantly improved outcomes for people with SMA^[6]. People with SMA today will likely have different experiences than people with SMA years ago^[23]. Early diagnosis and treatment are important factors in improving long-term outcomes.

With appropriate medical care, supportive therapies, and the newer disease-modifying medications, many people with SMA can enjoy improved quality of life and extended life expectancy. The outlook continues to improve as research advances and new treatments are developed.