Spinal muscular atrophy (SMA), the leading genetic cause of death in infants and toddlers, is caused by the progressive loss of specialized nerve cells that control voluntary movement.
The common symptoms of most types of SMA include progressive muscle weakness and poor muscle tone that mainly affect motor function, but can also cause breathing problems, fatigue, scoliosis, nutritional deficiencies, along with other symptoms.
The age of onset, occurrence, and severity of symptoms vary across the different disease types, particularly the main five types — 0, 1, 2, 3, and 4 — which are based on the age of symptom onset and the highest motor milestone achieved.
In type 0, the most severe form of the disease, some symptoms first appear before birth, in the womb, while in type 1, symptoms usually begin in the first six months after birth. Symptoms usually appear between six and 18 months in type 2, and between 1.5 and 3 years of age in type 3. Symptom onset during adulthood is typical of type 4, the mildest form.
The most severe forms are associated with a shorter lifespan, while patients with the milder types have a normal life expectancy.
Muscle weakness and poor muscle tone
SMA is characterized by progressive muscle weakness and atrophy, poor muscle tone (a lack of tension in the muscles, which can cause floppiness), and loss of muscle control — all of which impairs motor development and/or future mobility.
Muscle weakness is usually the same on both sides of the body, and affects the proximal muscles more, or those closer to the center of the body — such as those of the shoulders, thighs, and pelvis — than the most distant muscles, such as those in the hands and feet. Normal growth and development can place additional stress on muscles that are already weakened.
Given that proximal muscles enable activities such as crawling, head control, sitting, standing, and walking, SMA patients may never acquire these motor milestones or may gradually lose these functions. Delayed achievement, and failure to meet or loss of milestones are typically the first signs leading to a suspicion of SMA. In types 0 and 1, there may also be an absence or reduction of fetal movements during pregnancy.
Besides impaired mobility and muscle control, patients’ posture often worsens over time as muscles shrink, resulting in balance problems.
Patients with types 0, 1, or 2 typically have breathing difficulties due to severe weakness of the intercostal muscles (those supporting the chest wall), leaving the diaphragm as the main breathing muscle. The diaphragm is the thin muscle that sits at the base of the chest and separates it from the abdomen.
This may lead to lung underdevelopment, reduced lung function, and difficulty in coughing and clearing respiratory secretions, which increases the risk of hypoventilation (shortness of oxygen and carbon dioxide build-up) and of lung infections. Aspiration pneumonia, a lung infection that develops due to food or liquid being aspirated into the lungs, is common in SMA.
Breathing problems and hypoventilation are usually worse at night, since in a lying position, the abdominal contents push up against the diaphragm and gravity is reduced, making it harder for patients to take deep breaths. This may lead to sleep problems, such as obstructive sleep apnea, and to daytime sleepiness and headaches.
Most patients with the milder forms of SMA may never experience breathing problems.
Fatigue is a common symptom of SMA, with patients describing it as an overwhelming sense of tiredness and exhaustion during repetitive daily activities such as lifting an arm during eating or walking even short distances. It can decrease motivation and affect a patient’s everyday activities, work, and social life.
SMA patients report both muscle fatigue and perceived fatigue, a subjective impression that might be aggravated by the inability to perform everyday tasks.
While is not entirely understood what causes muscle fatigue in SMA, previous studies suggest that it may be related to abnormal development and maturation of the neuromuscular junction, the site of communication between a nerve cell and a muscle cell.
Fatigue may also be intensified by daytime tiredness due to hypoventilation during sleep.
Scoliosis and other bone/joint problems
Most SMA patients also develop scoliosis, an abnormal and progressive sideways curvature of the spine (forming an “S” shape when viewed from behind) that’s caused by weakness in the back muscles that support the spine’s position. Other abnormal curvatures may also occur, such as lordosis, an excessive inward bend of the spine, and kyphosis, an outward curve, sometimes called hunchback.
Scoliosis usually develops from an early age, and it can progressively worsen even after patients have reached adulthood and growth has stopped. Patients with SMA type 1 or 2 are likely to develop scoliosis, as are about 50% of those with type 3. Patients affected by milder forms of SMA typically have milder and slower scoliosis progression.
This spine curvature can cause breathing difficulties, because the lungs have less room to expand and allow for deep breathing, as well as problems at the joints placed under stress by the bending spine.
Other common bone and joint defects include hip dislocation, joint contractures (limited range of motion caused by shortening of muscles or tendons around a joint), and weak and fracture-prone bones. Deformation of the hands, feet, chest, and joints is also common, particularly in more severe forms.
People with SMA often experience tremors, particularly in the hands and fingers, and reduced or absent deep tendon reflexes, such as the reflex that occurs when a person’s knee is tapped. Involuntary tongue movements are common among infants with type 1. Speech problems may also occur due to severe weakness in the muscles involved in speaking.
People with SMA may experience a number of gastrointestinal issues, as well as swallowing and/or chewing difficulties in the more severe types, making getting adequate nutrition a challenge.
Last updated: July 19, 2021
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