What Is SMA (Spinal Muscular Atrophy)?
What Is SMA?
Spinal muscular atrophy (SMA) is a genetic disorder that can cause progressive muscle weakness and wasting by affecting the lower motor neurons in the spinal cord. SMA is not a muscular dystrophy; it affects the nerve cells that control muscle movement. In the most common form, 5q SMA, loss of function of both copies of the SMN1 gene results in insufficient production of SMN protein.
SMA is usually inherited in an autosomal recessive pattern. If both parents are carriers, there is a 25% chance of having a child with SMA in each pregnancy. Carrier screening may be considered before pregnancy or when planning a pregnancy. Carrier tests differ from tests used to diagnose the disease; a negative result does not completely eliminate the risk, as some tests may not detect conditions such as silent carrier status.
What Causes SMA?
The most common form of SMA is caused by disease-causing changes in the SMN1 gene. The SMN2 gene also produces SMN protein; a higher SMN2 copy number is often associated with a milder disease course. However, SMN2 copy number alone does not definitively indicate disease severity.
SMA Types and Disease Course
SMA has historically been classified into types 0–4 based on the age at symptom onset and the motor milestones achieved. This classification can provide a general understanding of the disease; however, the disease course may vary between individuals. Early diagnosis and disease-modifying treatments have reduced the predictive value of this traditional classification, particularly in individuals diagnosed in infancy. Therefore, motor function, age at symptom onset, SMN2 copy number and clinical findings are considered together during assessment.
What Are the Symptoms of SMA?
Symptoms may vary depending on the age at onset and disease severity. Possible signs and symptoms include:
- Muscle weakness and low muscle tone (hypotonia)
- Delay in or loss of motor skills such as head control, sitting, standing or walking
- Reduced reflexes
- Difficulty sucking, swallowing or feeding
- Difficulty coughing and breathing
- Spinal curvature and restricted joint movement
Sensation and cognitive function are generally preserved in SMA; however, symptoms may vary from person to person. If newborn screening yields a result suggestive of SMA, confirmatory testing and specialist assessment should not be delayed, even if the baby has no symptoms.
How Is SMA Diagnosed?
When SMA is suspected, diagnosis is primarily investigated through genetic testing of the SMN1 gene. Newborn screening helps identify suspected SMA early; a screening result is not a diagnosis, and a positive or suspicious result must be evaluated with confirmatory genetic tests. In addition to SMN1 changes, SMN2 copy number may contribute to disease assessment during the diagnostic process.
EMG, nerve conduction studies, CK testing or muscle biopsy are not necessary for every patient. A physician may request additional tests when genetic testing does not establish the diagnosis or when another neuromuscular disorder is suspected. Assessment of suspected SMA should be planned with input from paediatric or adult neurology specialists and clinical geneticists.
Important: Carrier screening does not replace genetic testing performed to diagnose SMA. If symptoms or a suspicious newborn screening result are present, a physician's assessment is required for diagnostic testing. You can find information about carrier screening at Wellcare here.
Is There Treatment for SMA?
There are treatments that can modify the course of SMA. Nusinersen and risdiplam aim to increase the production of functional SMN protein through SMN2. Onasemnogene abeparvovec is a gene therapy option. The appropriate treatment is determined by a specialist physician, taking into account age, clinical condition, genetic findings, access to treatment and the licensing/reimbursement conditions in the relevant country. Treatment options and approved age indications may vary between countries.
Treatment may be most effective when given as early as possible, before symptoms begin. However, treatment may not completely eliminate the disease and does not remove the need for follow-up. Multidisciplinary follow-up remains important in areas such as breathing, nutrition and swallowing, physiotherapy and rehabilitation, mobility and spinal health.
Supportive Care in SMA
The needs of people with SMA vary according to age, motor function and symptoms. The follow-up plan may include monitoring respiratory health, assessing nutrition and swallowing, rehabilitation to maintain range of motion and orthopaedic support when needed. Individual recommendations on vaccinations and protection against infections should be planned with the physician overseeing the patient's care.
If SMA is suspected, there is a family history of SMA or a test result indicates carrier status, genetic counselling and specialist assessment help ensure accurate interpretation of test results and determine the next steps.