Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by muscle weakness. SMA symptoms exist along a continuum and vary greatly in their impact on physical function, quality of life, and life expectancy. Type of SMA and age of diagnosis are two of the most important variables that determine SMA symptom severity.
Depending on the severity of symptoms, a person with SMA may require aid to complete acts of daily living like bathing, dressing, and eating.
Muscle weakness, also referred to as hypotonia or lack of muscle tone, is the primary symptom of all types of SMA. Muscle weakness in spinal muscular atrophy is caused by the loss of nerve cells that transmit signals from the brain and spinal cord to the muscles. A mutation on the SMN1 gene is responsible for SMA types 0-4, which accounts for nearly all cases of the condition. The SMN2 gene determines which type of SMA a person develops. The degree of weakness, which parts of the body it affects, and how it impacts physical function and quality of life depend on the type of SMA a person has and age of onset.
In most types of SMA, muscle weakness affects the proximal muscles (those closest to the center of the body) and lower extremities. Weakness is usually present on both sides of the body. Muscle weakness can impact the development of motor skills, mobility functions like walking, and other functions like swallowing and breathing. Muscle weakness generally worsens over time, meaning people may lose functionality as spinal muscular atrophy progresses.
Muscle weakness is most profound in type 0 and type 1 (Werdnig-Hoffmann disease), the most severe forms of SMA. Babies with types 0 and 1 have no head control and do not reach developmental milestones. Severe muscle weakness impacts their breathing ability and in turn, their life expectancy.
In some types of SMA, muscle weakness comes with hyporeflexia (lack of, or severely reduced, muscle reflexes). Babies and children with types 0 and 1 show symptoms of hyporeflexia. Lack of muscle reflexes is also common in type 2 — about 70 percent of children with SMA type 2 lack muscle reflexes.
Depending on the type and severity of SMA, a child or adult may have mobility limitations ranging from the inability to lift their head to slight difficulty walking.
Problems sucking and swallowing are caused by weak muscles in the throat and mouth and are commonly seen in babies with type 1 SMA. Poor ability to suck and swallow can prevent infants from receiving adequate nutrition and can also cause problems related to aspiration (inhaling food or liquid into the lungs). Older babies and toddlers with SMA type 2 may struggle with chewing in addition to sucking and swallowing. Infants and children with SMA may need to be fed using a feeding tube to receive adequate nutrition.
Infants and children with SMA types 0 and 1 never develop the ability to sit up unsupported. Babies and toddlers with SMA type 2 will develop the muscle strength the sit up unaided. However, because of the degenerative nature of SMA, individuals with type 2 often lose the ability to sit up by themselves by their mid-teen years.
Children with SMA type 2 rarely develop the ability to stand, whereas those with type 3 (Kugelberg-Welander disease) will be able to stand. Children with type 3a (diagnosed before age 3) will likely have delayed development of standing ability. In types 3a and 3b, the ability to stand may degenerate over time. Sometimes people with SMA type 3 will have problems moving from a sitting to a standing position.
Babies and children with types 0-2 will never develop the ability to walk. Depending on age of diagnosis, young children with type 3a generally learn to walk but may start experiencing falls or difficulty with stairs around 2 to 3 years old. People with type 3b may also have problems with falling and stairs as SMA progresses and muscles weaken. They may develop foot deformities or abnormal walking patterns (gait) that can make walking more challenging. Adults with type 4 may also develop walking problems as they age and SMA progresses.
Walking difficulties are a major symptom in adults who develop SMA with lower extremity predominance (SMA-LED), which is among the rarest forms of SMA. SMA-LED causes muscle weakness in the legs, especially the thighs.
Problems with respiratory function can occur in spinal muscular atrophy because of weakness in the muscles that control breathing. Weakness in the respiratory muscles can be the most dangerous aspect of SMA. Complications related to breathing can be responsible for reduced life expectancy, especially in the more severe types of SMA.
A person without SMA breathes using their intercostal muscles, the muscles that cause the chest to expand and contract when breathing, and the diaphragm, the muscle that moves the rib cage up and down. SMA can cause weakness in the intercostal muscles – mostly in types 0-2 and rarely in type 3. The diaphragm is forced to compensate for ineffective intercostal muscles. Weakness in the intercostal muscles and overcompensation from the diaphragm leads to abnormal breathing patterns and lung underdevelopment. Breathing problems can also be related to scoliosis (curvature of the spine), which is a very common complication of SMA types 1-3. The changed shape of the spine can reduce the capacity of the lungs. The resulting breathing problems are the leading cause of illness and reduced life span in babies and children with SMA. Nearly every baby or child with respiratory weakness will require respiratory care to support breathing.
Weak respiratory muscles can make it difficult for people with SMA to effectively cough and clear secretions or mucus from the lungs. The inability to clear the lungs can make breathing more difficult and, in some cases, lead to complete or partial lung collapse. A weak cough also increases the risk of chest infections. A cough machine or manual cough assistance are options for clearing the lungs.
Respiratory weakness, aspiration of food or liquids, or inability to effectively cough can lead to pneumonia and other chest infections. Chest infections like pneumonia are most common in SMA types 1 and 2 and SMA with respiratory distress (SMARD). Respiratory infections can be managed with various methods that help to clear the lungs, including manual methods and mechanical cough machines.
Scoliosis is the curvature of the spine to the side. Instead of the spine being held by muscles in a normal curve, the spine creates an abnormal ‘S’ shape. Scoliosis impacts nearly all children with SMA types 1 and 2 and about half of people with type 3. The change in the shape of the spine occurs because of muscle weakness and can cause breathing problems and limited mobility. SMA-related scoliosis is often treated with surgery. People with SMA may also have kyphosis, a forward bend in the spine.
Tremors in the hands are often the first noticeable symptom of SMA type 4 and Kennedy's disease (X-linked spinal and bulbar muscular atrophy). Tremors in the fingers can also occur in SMA type 2 and type 3a.
Tongue fasciculations, or tongue quivering, is common in severe types of SMA and can also occur in Kennedy's disease. Tongue fasciculations occur because of the involvement of the bulbar motor neurons, which impact the muscles that control speech, swallowing, and chewing.
Joint contracture is a deformity caused by the shortening or tightening of muscles or tendons. Joint contractures in the lower limbs are common in SMA and occur more often than contractures in the upper limbs. The hips, knees, and ankles are common sites of contractures in the lower body and the elbows, shoulders, and wrists are common sites in the upper body. Contractures can be treated with physical therapy or surgery, though surgery is more likely to be recommended for lower body contractures.
Sleep problems are common in children with types 1 and 2 because of respiratory weakness. Weak respiratory muscles can cause sleep time breathing to be too slow or too shallow (hypoventilation). As a result, the person with SMA isn’t breathing in enough oxygen or breathing out enough carbon dioxide. A mechanical breathing machine like a BiPAP (bilevel positive airway pressure) can be used to support breathing at night.
Headaches sometimes occur because of hypoventilation. Using a breathing machine at night can help ensure a person with SMA gets sufficient oxygen which can prevent headaches.
Hip dislocation and other problems with the hip joints are common in SMA types 1-3. Problems with the hip joints generally occur because of weakened muscles and lack of use. Surgery to correct hip problems is not usually recommended due to limited effectiveness and risks associated with operating.
Bone fractures occur frequently in types 2 and 3. Fractures in the femur near the knee and in the ankle are common in type 2, and fractures in the arms are common in type 3. In some cases, infants born with SMA may have congenital fractures (bone breaks present at birth). Treatment for bone breaks will depend on a person’s level of mobility.
Depression and mood disorders are common in people with chronic conditions and can affect people with SMA and their families. In a series of interviews with 19 young people with SMA, several reported experiencing depression or feelings of sadness related to loss of functional ability or concerns around the possibility of losing function. The researchers concluded that more efforts should be made to integrate mental health care into overall health care for people with SMA. If you’re experiencing symptoms of depression, speak to your health care provider about treatment options, including therapy or medication.
Parents of babies and children with SMA can experience depression following diagnosis and as they face the challenges of caring for a child with a severe disability. Seeking support from a mental health professional can help caregivers manage their emotional well-being. In-person or online support groups like mySMAteam can also be beneficial.