Spinal muscular atrophy diagnosis and testing
Medically reviewed by Edward Smith, MD
Due to the progressive nature of spinal muscular atrophy (SMA) — a rare genetic disease — an early diagnosis is critical. People with SMA who receive a timely diagnosis can start treatment immediately.
Most cases of SMA are caused by mutations in the SMN1 gene, leading to a deficiency of a protein called SMN or survival motor neuron protein. The deficiency of this protein leads to the progressive loss of motor neurons — the specialized nerve cells that control voluntary movements — and ultimately loss of muscle strength and function.
Several treatments are now available, but early diagnosis is critical as these treatments can be more effective when started early.
Genetic testing is the standard and most accurate method of diagnosis for SMA. Other tests also may be used in the diagnostic workup of the disease.
When should someone be tested for SMA?
Testing for SMA is generally recommended when:
- an individual starts to show muscle weakness and other symptoms that are indicative of the disease. Depending on the type of SMA, this may manifest as weak or floppy limbs, a failure to hit motor development milestones in early life, or difficulty walking.
- a person has a family history of SMA. Because SMA is a genetic condition and SMA-causing mutations may be passed from parents to their biological children, testing is recommended when there is a family history of the disorder.
Genetic testing also can be done on prospective parents to determine the likelihood they will pass on any SMA-causing mutation to their biological children. This may be particularly helpful for parents who have a child with SMA or if either parent has a family history of the disease.
Newborn screening, when babies are tested for SMA and other disorders shortly after birth, is becoming increasingly common in the U.S. — programs are active in all 50 states — and in some other countries. Such screening can facilitate an SMA diagnosis even when there is no known family history of the disease.
Genetic tests for SMA
The gold standard for an SMA diagnosis is genetic testing to identify whether a potential patient has the disease-causing mutations. A number of technologies may be used for this type of testing, ranging from techniques that look for common mutations in the SMN1 gene, which assesses the entirety of the gene.
The main forms of SMA — type 0, type 1, type 2, type 3, and type 4 — are all caused by mutations in the SMN1 gene located on chromosome 5.
The most common type of SMA-causing mutation in SMN1 is a deletion of exon 7, essentially meaning that a chunk of the code for the SMN1 gene is missing. This specific mutation is present in both parental copies of the SMN1 gene in approximately 94% of patients, so first-line tests for SMA usually specifically check for this deletion.
- If both copies of SMN1 carry the deletion, the diagnosis of SMA is confirmed.
- When one copy of SMN1 carries the deletion but the other does not, additional testing is used to check for rarer mutations in the gene that does not harbor the exon 7 deletion.
- If both copies do not have the deletion but the patient shows signs indicative of SMA, a more detailed assessment of SMN1 may be performed. Testing also may be done to look for mutations in other genes that are associated with rarer forms of SMA, also called “non-chromosome 5 SMA,” including the IGHMBP2, VAPB, DYNC1H1, BICD2, AR, and UBA1 genes. None of these rarer SMA types will respond to currently available SMA treatments.
Genetic testing also can be used to identify the number of copies of the “backup” gene, called SMN2, a person has. This gene is able to lead to the production of SMN protein, but only in very small amounts. Knowing the “SMN2 copy number” can help predict disease type as, generally, more copies of the SMN2 gene are associated with milder disease.
Testing before pregnancy
When one or both prospective parents have a family history of SMA, genetic testing and counseling can be used to determine the risk that any children could inherit the disease. Such testing can help inform family planning decisions.
The main types of SMA are inherited in an autosomal recessive manner, meaning that the disease will only develop if both copies of the SMN1 gene (one inherited from each biological parent) carry a mutation. A person who only has one mutated copy of SMN1 and one healthy copy will not develop SMA, but they may pass the mutated gene on to their biological children — this person is known as an SMA carrier. In the U.S., it is estimated that about 1 in 50 people carry an SMN1 mutation.
If two people who are both carriers conceive a child, there is a:
- 25% chance the child will have SMA
- 50% chance the child will be a carrier
- 25% chance the child will not have SMA or be a carrier.
If there is a chance of conceiving children with SMA, steps can be taken prior to pregnancy to reduce the risk. For example, donor sperm or egg cells from a noncarrier may be used for conception.
It also is possible for clinicians to perform pre-implantation diagnostic testing. In such tests, sperm and egg cells are collected from patients/carriers and used to develop embryos in a laboratory setting. The resulting embryos can be tested for SMA before they are implanted in the womb.
Testing during pregnancy
The mutations that cause SMA are present from the moment of conception, or when a sperm cell fertilizes an egg cell. It is therefore possible to test for SMA in a developing fetus during pregnancy, a method referred to as prenatal testing.
The most common techniques used for prenatal SMA testing are chorionic villus sampling and amniocentesis. These procedures each take about 10-30 minutes to perform, though the results may take a few days to several weeks to be available.
Both procedures are usually described as uncomfortable but not painful, and there is a small but notable risk of miscarriage with both techniques. Other complications like infection are rare, but can occur. It is recommended that people considering these tests should discuss the potential risks and benefits in detail with their care team.
Chorionic villus sampling
Chorionic villus sampling, or CVS, is a technique that uses a small sample of cells taken from the placenta, a structure made of fetal tissue that supports the developing fetus during pregnancy. The cells are tested to determine whether the fetus has SMA-causing mutations.
CVS is most commonly done using a needle inserted through the abdomen; less commonly it may be performed with a tube or forceps inserted through the cervix. CVS is usually performed between the 10th and up to the 14th weeks of pregnancy, though it can be done later in some cases.
Amniocentesis
Amniocentesis involves collecting a sample of amniotic fluid — the fluid that surrounds a developing fetus in the womb. Cells collected from the fluid can be used for genetic testing.
A needle is inserted through the abdomen and into the amniotic fluid during the amniocentesis procedure. It is typically done between the 15th and 20th weeks of pregnancy, alhough, if necessary, it can be performed earlier or later than this time window.
Testing after birth
An SMA test may be done after birth if a person begins to experience symptoms indicative of the disease, if there is a family history of the condition, or if the person’s parents are known to be carriers.
All U.S. states and many other countries now include SMA in newborn screening programs, in which all babies born are systematically checked for SMA and other congenital conditions within the first few days after birth.
Historically, electromyography, nerve conduction tests, and muscle biopsy were the main methods used to diagnose the disease. In the modern era, genetic testing is considered the gold standard to test for SMA, though these other assessments also may be included in the diagnostic workup when genetic tests are inconclusive, or when used to evaluate disease severity.
Electromyography
Electromyography (EMG) is a test that assesses the health of muscles and motor neurons — the nerve cells that control voluntary muscle movement, which die off in SMA. Motor neurons send out electrical signals to muscles, which in turn contract and give off electrical signals that can be measured via EMG.
In people with SMA, findings from EMG are generally indicative of motor neuron loss, the hallmark of the disease.
The test involves the insertion of a needle-like electrode into the muscle, which can record electrical signals at rest and when the patient is asked to slowly contract the muscle. These recordings can help to determine if the muscle cells are responding appropriately to stimulation from the motor neurons, as well as check if the muscles are inactive when they aren’t being stimulated.
The insertion of the needle-like electrode can cause similar pain to receiving an injection, and the electrical current that is sent through the needle also can cause some discomfort to the patient. Patients or their parents can ask technicians to take a short break as a way to mitigate any pain or discomfort during the procedure.
Nerve conduction tests
A nerve conduction test is typically always performed along with an EMG, and it is used to measure the speed and strength of electrical signals traveling through the specific nerve being analyzed. In people with SMA, the nerve response is usually weakened, and it may be slower at advanced stages of the disease.
Nerve conduction tests use electrode stickers that are applied at various points to the surface of the skin over a nerve. One or more electrodes deliver mild electric pulses to the nerve, while the others record the nerve’s responses. The test may cause a mild tingling feeling.
When EMG tests and nerve conduction studies are done together, they help assess whether symptoms are due to motor nerve impairment, muscular problems, or problems with nerve-to-muscle signal transmission.
Muscle biopsy
A muscle biopsy involves the collection of a small section of muscle tissue, usually from the upper thigh. That sample is examined under a microscope to see whether it has SMA-associated features that indicate motor neuron loss.
Following the application of a local anesthetic, and depending on the amount of sample needed, the healthcare provider may insert a biopsy needle into the muscle, or make a small cut in the skin and into the muscle to collect the tissue. Some local pain and discomfort can be felt on the skin and muscle involved in the biopsy, but physicians can help relieve the pain by prescribing appropriate medication.
Next steps after diagnosis
After a diagnosis of SMA is confirmed, patients, their families, and the healthcare team will work together to develop a care strategy.
For those diagnosed with the main types of SMA (types 0 to 4), there are approved disease-modifying therapies that can slow or stop disease progression. It is recommended that these treatments be started as early as is feasible, as early treatment initiation can help improve motor development and SMA life expectancy.
In the U.S., there are three therapies approved for types 0 to 4, although some are only approved for patients in certain age ranges. These medicines also are available in many other countries, but specific indications may vary. These approved therapies are not indicated for the treatment of rarer SMA forms (non-chromosome 5 SMA types).
In addition to disease-modifying treatment, care for people with SMA commonly involves other interventions and support devices aiming to maximize the patient’s functional capacity and quality of life. Among these treatments are physical therapy, occupational therapy, and the use of adaptive equipment.
Across the SMA News Today website, information and resources can be found to help people become more familiar with the disease. Support also is available on the website. This includes learning from the experiences of other patients and caregivers through our columns.
SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about SMA diagnosis
The gold standard for diagnosing spinal muscular atrophy (SMA) is genetic testing to identify disease-causing mutations. The main forms of SMA are caused by mutations in the SMN1 gene, but mutations in other specific genes can result in less common forms of the disease. Other tests may be performed as part of a diagnostic workup.
Spinal muscular atrophy (SMA) can be diagnosed at any age. Because the mutations that cause SMA are present from the moment of conception, or when a sperm cell fertilizes an egg cell, testing and diagnosis of the disease may be performed even while a developing fetus is still in the womb. However, many patients are only diagnosed at the time of symptom onset, which differs between SMA types, or as part of newborn screening programs for the main types of SMA (types 0 to 4).
Genetic testing for spinal muscular atrophy (SMA) is a medical laboratory technique that checks whether a person carries mutations that are known to cause SMA. Genetic testing also can be used to identify SMA carriers — people who will not develop SMA themselves, but who carry the disease-causing mutation and may pass it on to their biological children.
Genetic disorders such as spinal muscular atrophy (SMA) can be detected during pregnancy by taking a small sample of cells from the fetus and performing genetic testing to look for disease-causing mutations. The most common strategies used to obtain fetal cells for this testing are chorionic villus sampling (CVS), which collects a sample of cells from the placenta, and amniocentesis, which takes a sample of the fluid surrounding the developing fetus.
Without an accurate diagnosis, it is impossible to administer the appropriate treatment. Consequently, patients who have spinal muscular atrophy (SMA) but are not diagnosed will continue to experience disease progression, with symptoms such as muscle weakness and breathing problems continually getting worse over time. Once SMA is diagnosed, therapies are available for the main types of SMA (types 0 to 4) that can be administered to help slow or stall the progression of the disease.
Related Articles
