Spinal Muscular Atrophy

A genetic condition in which muscles become weakened is called spinal muscular atrophy (SMA). In general, there are 5 subtypes of SMA that range in severity and age of onset. While this disorder cannot be cured, there are multiple treatments that can help ease the symptoms and improve your quality of life.

This condition causes a loss of specific types of nerve cells in the spinal cord (called lower motor neurons or anterior horn cells). These neurons control muscle movement. Without them, the muscles cannot receive nerve signals to make them move.

This genetic disorder can be more severe if it affects the muscles close to the center of the body (proximal muscles) compared to muscles in other parts of the body (also known as distal muscles). Usually, the weakness of the muscles worsens over time.

Types of Spinal Muscular Atrophy

Healthcare providers have categorized this disorder into 5 subtypes based on severity, life expectancy, and age of onset. Examples include:

Type 0 SMA (congenital SMA) – This subtype of SMA is often present at birth (congenital). While it occurs very rarely, it may reduce fetal movements by causing severe muscle weakness. Sometimes, it may even lead to respiratory failure. Commonly, congenital SMA is fatal.
Type 1 SMA (severe SMA) – About 60% of all diagnosed SMA cases are type 1. It is also known as Werdnig-Hoffmann disease. The symptoms usually appear in the first 6 months of age and may include hypotonia (reduced muscle tone), difficulty swallowing, breathing problems, and others. Usually, babies who experience trouble breathing live up to 2 years old.
Type 2 SMA (intermediate SMA) – This subtype of SMA is also called Dubowitz disease. It often appears between 6 and 18 months of age and causes the following symptoms. For example, hypotonia, muscle weakness, inability to walk or sit, and others. However, roughly 70% of people with this type of SMA survive until 25, and some of them may survive into their 30s.
Type 3 SMA (mild) – This type is also known as Kugelberg-Welander disease, and it often appears at 18 months of age. While people with type 3 of SMA may also develop breathing problems, they do not affect their life expectancy.
Type 4 SMA – While it is the mildest form of SMA, it does not appear until after 21 years old. The symptoms include muscle weakness that worsens gradually. This type also does not affect life expectancy.

While it occurs quite rarely, it is the 2^nd most common severe hereditary disease of infancy and childhood after cystic fibrosis. According to some research, it affects approximately 1 in 6,000 to 1 in 11,000 people. Furthermore, White and Asian people are more likely to develop it compared to Black and Hispanic people.

Symptoms

While the primary symptom of SMA is muscle weakness, people may also experience other symptoms. It depends on the type of SMA, overall health, age, and other factors. Check below some examples:

0 Type SMA Symptoms

Reduced fetal movements
Arthrogryposis
Hypotonia
Severe muscle weakness
Shortness of breath

1 Type SMA Symptoms

Reduced head control
Areflexia (lack of reflexes)
Inability to sit without support
Breathing problems
Difficulty swallowing (which may lead to malnutrition)
Facial muscle weakness

2 Type SMA Symptoms

Scoliosis
Progressive muscle weakness that mostly affects legs and arms
Abnormal movements in the hands (also known as polyminimyoclonus)
Jaw joint stiffness caused by bone fusion (ankylosis)
Joint contractures

The third and fourth type of SMA often causes progressive muscle weakness.

Causes

This is a genetic disorder, which means it occurs due to a mutation of a specific gene. These abnormal genes are usually passed from biological parents to their children. Commonly, SMA occurs when changes (mutations) in the SMN1 (survival motor neuron 1) gene cause all types of this disorder. However, the number of copies that you have of the SMN2 gene may change the severity of the condition.

In normal circumstances, the SMN1 gene produces the SMN protein that is needed by motor neurons to survive and function properly. When the body does not produce enough SMN protein, the motor neurons may shrink and even die. Therefore, the brain cannot send signals to the muscles, which may lead to involuntary movements (especially in the head, neck, chest, and legs).

Furthermore, the SMN2 gene also produces a small amount of the same protein. For instance, if a person has up to 8 copies of an SMN2 gene, he/she often develop a less severe form of SMA because the SMN2 gene compensates for a part of the missing protein.

Usually, babies get the abnormal genes from both biological parents during pregnancy. In most cases, parents of a child with an autosomal recessive disorder carry one abnormal SMN1 gene. However, these carriers do not experience symptoms of SMA. Generally, mutations of the SMN1 gene are quite common. For example, 1 in 50 white people may be a carrier of this abnormal gene.

Rarely, you may get only one gene from a biological parent and acquire a new mutation in the other copy during pregnancy.

What Are The Possible Complications of Spinal Muscular Atrophy?

People with SMA may experience some complications, especially if they do not get treatment. Check below some examples:

Bone fractures
Hip dislocation
Scoliosis
Malnutrition and dehydration
Chest infections (including aspiration pneumonia)
Weak lungs and trouble breathing
Respiratory failure
Hypoglycemia (low blood sugar levels)
Vitamin deficiencies
Heart problems (including irregular heart rhythm or heart failure)
Peripheral vascular disease

Moreover, those who develop SMA are at increased risk of developing metabolic acidosis. In any case, you can consult with your healthcare professional about ways to reduce the risk or prevent previous complications.

Prevention

Typically, this is a genetic disorder that cannot be prevented. However, you can perform some genetic tests before pregnancy to make sure you do not have this abnormal gene. It is important to understand the risks of having children with SMA.

Additionally, you can take certain steps before becoming pregnant to reduce the risk of SMA. One of them is preimplantation genetic diagnosis (PGD). This procedure eliminates the embryos with mutated genes and then doctors implant healthy embryos during IVF (in vitro fertilization).

Diagnosis

Physicians typically initiate the diagnosis of SMA by asking questions about symptoms and medical history, conducting a physical examination, and performing a neurological examination. However, to confirm this disorder, doctors often perform a genetic test. This test has confirmed approximately 95% of all SMA cases by identifying the abnormal SMN1 gene.

Furthermore, SMA may cause some symptoms similar to other neuromuscular disorders (such as muscular dystrophy). Check below some symptoms that are used to rule out other diseases:

Creatine kinase blood test – This test is used to check for some enzymes that are released when a muscle is deteriorating.
Electromyogram (EMG) and nerve conduction study – Physicians usually perform these tests to measure the electrical activity of the nerves and muscles.
Muscle biopsy – During this procedure, doctors will take a small sample of the affected muscle for testing.

In addition, there are some tests that can check the developing fetus for SMA, especially if you have a family history of this disorder. These include:

Amniocentesis – This procedure involves a thin needle to get a small sample of amniotic fluid to check for the abnormal gene that causes SMA. Commonly, amniocentesis is performed after the 14^th week of pregnancy.
Chorionic villus sampling (CVS) – During this procedure, physicians will remove a small sample of the placenta through the cervix or belly (abdomen). Thereafter, a pathologist will check this sample for an abnormal SMN1 gene. In most cases, this test is performed after the 10^th week of pregnancy.

Treatment

This genetic disorder cannot be cured. That’s why treatment focuses on relieving the symptoms and preventing life-threatening complications. Check below some examples:

Physical therapy – This treatment is used to improve posture, prevent joint immobility, and slow down the progression of muscle weakness.
Occupational therapy – This procedure is used to improve the ability to perform daily activities.
Speech Therapy – This treatment is recommended by doctors to improve swallowing difficulties.
Feeding tube – It helps get nutrients when the patient experiences swallowing problems.
Assisted ventilation (used for breathing problems)
Assistive devices – These include crutches, walkers, wheelchairs, and orthopedic braces.

In addition, the FDA (Food and Drug Administration) has approved some treatments that significantly slow down the progression of SMA. These include:

Disease-modifying therapy – This treatment helps improve the production of SMN2 protein. Physicians often prescribe Nusinersen injections or Risdiplam tablets that are taken orally.
Gene replacement therapy – Physicians often recommend this procedure for children under 2 years old. It involves intravenous (IV) medications called onasemnogene abeparvovec-xioi. This therapy may help replace a missing or abnormal SMN1 gene.

Frequently Asked Questions

What is the prognosis for someone with SMA?

Generally, the prognosis of this disease varies among people because it depends on several factors. These include the subtype of the disease, response to the treatment, age, and preferences.

What is the life expectancy of someone with SMA?

The life expectancy also varies depending on the subtype of SMA you develop. For example:

Type 0 SMA – This condition is almost always fatal within one month of life.
Type 1 SMA – People who develop the first subtype of the disease may live up to 2 years old.
Type 2 SMA – The life expectancy often varies among people with this subtype of disease. However, some people may live until their 20s, 30s, or 40s.
Type 3 and 4 SMA – These subtypes of the disease usually do not affect lifespan.

For more details, discuss it with your physician.

What is the cause of spinal muscular atrophy?

Commonly, this disorder occurs due to an abnormal gene (SMN1 gene) that is passed from biological parents to their biological children during pregnancy. Ask your healthcare provider if you have additional questions.