Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder that primarily affects young children and infants. This hereditary disease causes weakness in the muscles through degeneration of the motor nerves at the base of the brain and in the spinal cord. The presentation of SMA varies by type, but signs and symptoms generally include problems with motor function (movement and muscle control), breathing difficulties, trouble walking, standing, swallowing, or chewing. Currently, genetic testing for SMA is the best way to diagnose this condition. Genetic testing can provide the answers that families need about SMA.
SMA is an inherited disease, meaning that it is passed along in families. SMA is caused by a very specific genetic mutation in a gene called the SMN1 gene. The SMN1 gene codes for survival motor neuron (SMN) protein. SMN proteins play a critical role in the survival of the nerve cells that control muscles. SMA is an autosomal recessive disorder, which means that both parents need to carry a copy of the mutated SMN1 gene and pass it along to their child. When a child receives two copies of the mutant SMN1 gene, the child’s body can’t make enough of this crucial protein and muscular degeneration begins. In fact, symptoms of SMA can begin before the baby is born.
SMN1 doesn’t work alone to influence the course of SMA. Another gene, SMN2, which is closely located to SMN1 on the 5q chromosome, influences the severity of the disease. SMN1 and SMN2 work together to make functional SMN protein. A person can have between zero and eight copies of the SMN2 gene, and studies show that the number of SMN2 copies and the amount of functional SMN protein produced correlate with disease severity. The more copies of SMN2 a child has, the better the outlook and prognosis will be.
Although a defect or deficit in SMN1 is the cause of SMA type 1, type 2, type 3, and type 4, other genetic mutations have been associated with other types of SMA. For example, spinal muscular atrophy with respiratory distress (SMARD) is characterized by a mutation in the IGHMBP2 gene, which codes for immunoglobulin μ-binding protein 2. Like SMA (types 1-4), SMARD can also be diagnosed through a genetic test.
Carrier screening for SMA is a part of the family-planning process. Through a simple blood test, a doctor can determine if a parent is a carrier of the mutant SMN1 gene. Performing this test evaluates the risk of a child developing SMA.
Genetic testing is a little different. Genetic testing is done to confirm suspected cases of SMA. Unlike carrier screening, genetic testing is not preventive, but rather diagnostic testing.
A genetic test is the primary way to diagnose SMA. Genetic testing usually involves taking a blood sample to test in a laboratory. This laboratory test is usually a real-time polymerase chain reaction (RT-PCR) assay that detects the genetic deletion. These laboratory tests can determine whether an infant or child inherited mutant SMN1 genes from their parents. A genetic test will confirm the disease in approximately 94 percent of individuals with SMA.
A fetus can also be tested in utero for SMA. In cases when the parent is still pregnant, a doctor can extract amniotic fluid from inside the amniotic sac that holds the unborn child. This process is called amniocentesis and can be conducted at 15 to 20 weeks of pregnancy. Another test, chorionic villus sampling (CVS), can be done as early as 10 weeks. CVS involves removing placental tissue, which is analyzed in this genetic test.
If a child is displaying symptoms associated with SMA, they should be tested as early as possible in order to receive a diagnosis and begin treatment. Testing is particularly important if the parents know that they have a family history of SMA or if they tested positive for a mutant SMN1 gene during SMA carrier testing. Symptoms of SMA vary depending on the type, but generally include:
Infants and children who display these symptoms should complete genetic testing to determine if the disease is in fact SMA. If SMA is diagnosed, families should seek treatment and genetic counseling.
Genetic counseling is an important component of support for families with SMA. Genetic counseling can help families become more informed about the pathogenesis (disease development) of SMA. It can also help families determine whether they want to have more children who would also be at risk for SMA.
One study found that most people received some form of genetic counseling from a neurologist instead of a genetic counselor. This study also found that families who gained knowledge about the genetics of SMA through the use of the internet and support groups understood the genetics of SMA just as well as those who received similar information from health care professionals.
Although there are challenges in genetic counseling, individuals affected by SMA should strive to learn as much as they can about the disease in order to make informed choices about their own family’s future.
On mySMAteam, the social network for people with spinal muscular atrophy and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with SMA.
Have you or a loved one undergone genetic testing for SMA? Share your experience in the comments below, or start a conversation by posting on mySMAteam.