Spinal Muscular Atrophy: The Genetic Neuromuscular Condition You’ve Probably Never Heard Of

What is Spinal Muscular Atrophy?

Spinal muscular atrophy is a genetic neuromuscular disorder affecting both the peripheral and central nervous systems,  as well as skeletal muscle. The condition is a motor neuron disease because neurons, the specialized nerve cells that send chemical messages to and from the nervous system, die off. The loss of motor neurons initiates progressive muscle wasting (atrophy). There are not enough neurons to stimulate the muscles. Over time, someone with spinal muscular atrophy experiences weakness and other symptoms from decreasing muscle mass throughout the body.

Causes of Spinal Muscular Atrophy

Spinal muscular atrophy is a genetic condition caused by a genetic mutation. According to the Muscular Dystrophy Association, 94% of spinal muscular atrophy cases are the result of a deletion mutation on chromosome 5—the chromosome harboring the genes responsible for motor neuron function. This creates a deficiency in the SMN protein. Motor neurons cannot survive without SMN.

Symptoms of Spinal Muscular Atrophy

As motor neurons are lost and muscle atrophy progresses, the symptoms of spinal muscular atrophy are widespread. Any function from mobility to vital processes such as breathing are affected. Each patient may have a similar set of symptoms, yet with varying severities.

• Muscle weakness—Muscle weakness is the primary symptom. This weakness can span from an infant struggling to hold themselves upright to functions like problems sucking, chewing, breathing, and swallowing.  
• Limited mobility—Mobility, such as walking and standing, is limited due to muscle wasting and tremors.
• Spinal curvatures—With little muscle to support the bones, spinal curvatures may develop. When the spine curves to the side, it is known as scoliosis. Bracing the back or surgical intervention prevents the spine from interfering with the organs.
• Difficulty breathing—Difficulty breathing can result from a weak diaphragm, poor lung function, or from severe scoliosis. Patients are prone to pneumonia.
• Trouble swallowing—Swallowing is another process controlled by muscles. Problems eating can arise from trouble swallowing.
• Tongue fasciculation—Studies (Giannopoulou et al., 2015) show that uncontrolled movement of the tongue, also referred to as tongue fasciculation, occurs in approximately one-third of patients.
• Delayed motor skills—Motor skills are the movements that allow the movement of the muscles. The motor skills that are delayed depends on the type and age of onset of spinal muscular atrophy. For example, an infant with type 1 is unable to hold their head up or rollover at the typical age a healthy child would be able to perform those movements with ease.
• Muscle aches—Already weak muscles cause widespread muscle aches and pains, as an extra burden is placed on less weak muscles to compensate.
• Tremors or twitching—A sign of spinal muscular atrophy is tremors or twitching of the muscles.

Types of Spinal Muscular Atrophy

The four types of spinal muscular atrophy are classified by their symptom severity and onset. Spinal muscular atrophy is evident prior to birth in severe cases or symptoms may not develop until later in adulthood. Knowing which type is important for treatment and prognosis.

Spinal Muscular Atrophy Type 1

Werdnig-Hoffmann disease is another name for spinal muscular atrophy type 1. It has a very early onset between birth and six months of age. With symptoms appearing early in life, this is typically the most severe form. Infants with the disorder present with significant developmental delays and generalized muscle weakness. They experience general muscle weakness, are unable to hold themselves upright unassisted, exhibit a weak cry, and show respiratory distress. The majority of those with spinal muscular atrophy type 1 have two to three copies of the SMN2 gene.

Spinal Muscular Atrophy Type 2

Spinal muscular atrophy type 2 occurs between the ages of 6 months to a year and goes by the names of intermediate SMA and Dubowitz disease. Three copies of the SMN2 gene tend to cause this type. The weakness in spinal muscular atrophy type 2 is proximal and affects the lower limbs of the body more than the upper body. Mobility for tasks such as standing or sitting without assistance is difficult.   

Spinal Muscular Atrophy Type 3

A milder form of the disorder is type 3. Symptoms of spinal muscular atrophy type 3 appear in childhood and adolescence. Like type 2, weakness is proximal and impacts the lower limbs. While these patients can eventually walk independently, they struggle with climbing stairs or raising from a seated position. Tremors are a predominant symptom along with the muscle weakness. As their condition progresses, they are prone to falls and most have spinal curvatures and respiratory distress.

Spinal Muscular Atrophy Type 4

Infants, children, and adolescence are not the only populations that have spinal muscular atrophy. When symptoms present in adulthood after the age of thirty, the disorder is classified as spinal muscular atrophy type 4. The disorder is caused by four to eight copies of the mutated gene. Although they have generalized muscle weakness and tremors, adults with spinal muscular atrophy reach their developmental milestones on time. They are not as limited in mobility. However, some develop minor respiratory symptoms.

Cognitive Development In Spinal Muscular Atrophy

Cognition is the process of thinking. It is how we acquire knowledge from the environment through the five senses. Much emphasis has been placed on the physical symptoms of spinal muscular atrophy. However, researchers have been curious as to if children with spinal muscular atrophy follow the same patterns of cognitive development in comparison to their healthy counterparts. Poor oral communication, the inability to freely explore the environment, and a lack of social interaction are all factors (Polido et al., 2019).  

Social Interaction

Studies published in the Journal of Neuromuscular disorders suggest that poor social interaction impedes proper cognitive development in children with spinal muscular atrophy. Children with spinal muscular atrophy did not perform as well and took longer to complete matching tasks during cognitive testing. These delays are likely related to social interaction.

While spinal muscular atrophy does not directly affect cognition and patients have normal intelligence levels, their physical states have indirect consequences. Dealing with a chronic medical condition sets these children apart from their peers. They are not exposed to the same environmental stimuli, and if they are, they exhibit poor motor control that prevents them from exploring their surroundings and communicating.

Spinal Muscular Atrophy Related Depression

Depression is a mood disorder characterized by unexplained sadness lasting longer than two weeks. Feelings of hopelessness, apathy, and a lack of interest in regular activities all accompany the disorder. Depression is commonly reported in patients with spinal muscular atrophy, especially adolescents and adults. Studies (Laufersweiler-Plass et al., 1992) document that depression, amongst other psychiatric conditions like separation anxiety, phobias, and behavioral disorders, occur in 12% of the patient population with spinal muscular atrophy. A lack of and difficulties with social interaction is a central component of spinal muscular atrophy related depression.

How To Diagnose Spinal Muscular Atrophy

The diagnosis of spinal muscular atrophy begins with a physical evaluation and a thorough family history. A physician suspecting a patient has spinal muscular atrophy looks for signs such as muscle weakness, motor delays, diminished reflexes, and a weak cry and feeding difficulties in babies. The initial evaluation rules out other muscle disorders that share similar symptoms.

The physician will likely perform a blood test that measures the level of creatine kinase (CK). Creatine kinase is an enzyme released into the bloodstream. Elevated levels are indicative of muscle damage. Types 2 and 3 often have high levels, while creatine kinase is normal in type 1.

The least invasive option to test for spinal muscular atrophy is to take a blood sample for genetic sequencing. This test identifies genetic mutations on chromosome 5 to confirm the diagnosis. If genetic testing is not sufficient, like for the types unassociated with mutations on chromosome 5, a muscle biopsy and nerve conduction studies are helpful diagnostic tools.

Treating Spinal Muscular Atrophy

There is no cure for spinal muscular atrophy. Treatment involves managing the symptoms. Someone with spinal muscular atrophy relies on a team of therapists, a strong support system for coping, medications, and assistive devices.

Physical Therapy

Physical therapy is intended to improve, maintain, and rehabilitate physical function through physical activity. It entails a therapist creating an exercise plan personalized to the patient’s needs. In those with spinal muscular atrophy, physical therapy is beneficial to slow the progression of muscle atrophy, improve motor function, and maintain mobility for as long as possible. Resistance training is found to be an effective exercise. Studies show that children with type 2 and 3 displayed benefits after exercising three times per week using ankle and wrist weights (Lewelt et al., 2015). Swimming, exercise bikes, and walking (for those that can) also have positive results.

Assistive Devices

Several assistive devices are used in the treatment of spinal muscular atrophy. They incude:

• Motorized wheelchairs—Wheelchairs that are motorized require the push of a button to move and navigate. They allow patients to mobilize independently.
• Walkers—Many with types 3 and 4 spinal muscular atrophy maintain significant mobility. A walker lends support to prevent falls.  
• Non-invasive ventilators—Patients have respiratory symptoms. Non-invasive ventilators like a bi-bap machine support breathing when the respiratory muscles are weak.
• Orthotics—Orthotic devices are worn feet, ankles, and knees to support the muscles. For example, ankle-foot orthoses (AFOs) maintain joint alignment and knee splints support the knees.
• Back bracing—If spinal curvatures are present, a back brace straightens the spine and reduces pain.
• Feeding tubes—Swallowing difficulties and weakness of the jaw makes eating a challenge. Patients aspirate, which causes pneumonia. A feeding tube is a device inserted into the stomach to deliver a formula that provides nutrition when the patient cannot sustain themselves by eating orally.

Medication

experimental phase. However, two medications used for gene therapy are thought to slow motor neuron death. Spinraza (nusinersen) targets the SMN2 gene to trigger the body to release the lacking protein. Zolgensma increases the amount of SMN protein through a genetically engineered virus.  

Coping Skills

Coping with spinal muscular atrophy is stressful for the patient and the caregiver. Implementing coping skills into the treatment regimen is essential for balancing mental and physical health. A psychologist is a mental health professional that guides patients through these burdens. Cognitive behavioral therapy is one way therapists accomplish overcoming the developmental difficulties and the resulting depression that can arise. The therapist changes destructive or unhelpful behaviors by identifying negative thought patterns. Family therapy is beneficial for parents, siblings, or other caregivers.

Prognosis of Spinal Muscular Atrophy

The overall prognosis of spinal muscular atrophy is contingent on the type and age of onset. With type 1 being the most severe, these patients are at risk of death from respiratory failure before the age of two. They require ventilators and feeding tubes to manage symptoms. Type 2 carries similar risks, yet at a later age in childhood. Adolescents and adults with spinal muscular atrophy live a normal lifespan.

References

Giannopoulou, E. Z., Martin, T., Wirth, B., Yilmaz, U., Gortner, L., & Meyer, S. (2015). Tongue fasciculations in an infant with spinal muscular atrophy type 1. Clinical case reports, 3(10), 832–834. https://doi.org/10.1002/ccr3.359

Lewelt, A., Krosschell, K. J., Stoddard, G. J., Weng, C., Xue, M., Marcus, R. L., Gappmaier, E., Viollet, L., Johnson, B. A., White, A. T., Viazzo-Trussell, D., Lopes, P., Lane, R. H., Carey, J. C., & Swoboda, K. J. (2015). Resistance strength training exercise in children with spinal muscular atrophy. Muscle & nerve, 52(4), 559–567. https://doi.org/10.1002/mus.24568

Polido, G. J., de Miranda, M., Carvas, N., Mendonça, R. H., Caromano, F. A., Reed, U. C., Zanoteli, E., & Voos, M. C. (2019). Cognitive performance of children with spinal muscular atrophy: A systematic review. Dementia & neuropsychologia, 13(4), 436–443. https://doi.org/10.1590/1980-57642018dn13-040011

Cheyanne Perry

Cheyanne is currently studying psychology at North Greenville University. As an avid patient advocate living with Ehlers Danlos Syndrome, she is interested in the biological processes that connect physical illness and mental health. In her spare time, she enjoys immersing herself in a good book, creating for her Etsy shop, or writing for her own blog.