Spinal muscular atrophy (SMA) is a genetic disease that affects the spinal cord and nerves, resulting in muscle wasting and weakness. Untreated, it is a neurodegenerative, progressive disease, which can be fatal in its more severe forms.
SMA is an autosomal recessive disease. This means that both males and females are equally affected, and that two mutated copies of the gene, one inherited from each parent, are necessary to have the condition.
SMA is caused by mutations in a gene called survival motor neuron 1 (or SMN1). In over 95 percent of cases of SMA, the mutation is a common deletion; less commonly, there are spelling errors, also called point mutations, in SMN1. Symptomatic individuals of all ages can be tested through DNA studies typically done from a blood sample.
When both parents are carriers (or they each have one abnormal copy of the gene and one normal copy), there is a one in four (25 percent) chance, with each pregnancy, to have a child with SMA. Carrier testing for the general population is being offered more commonly as part of routine prenatal care, but still has some limitations due to the complex genetics of SMA.
Spinal muscular atrophy is sometimes difficult to diagnose, as symptoms can resemble other conditions or medical problems. Each child may experience symptoms differently. There are four types of spinal muscular atrophy based on symptoms and age of onset. The child may have the following symptoms:
Type I SMA (also called Werdnig-Hoffman or infantile-onset SMA).This is the most severe type of SMA and may be present at birth. Infants have problems holding their head, sucking, feeding, swallowing, and typically move very little. The muscles of the chest are also affected. The motion of the tongue is described as having "worm-like" movements. Untreated patients typically require full-time ventilator support by the age of 2, and life expectancy is often shortened.
Type II SMA (juvenile SMA or intermediate SMA). This form of SMA presents initially in children from six months to 18 months of age. These children, without treatment, never attain the ability to walk independently, and may need respiratory and feeding support when symptoms first appear, or later in life. They typically have generalized muscle weakness and may require braces, walkers, or a wheelchair for assistance. Life-expectancy often extends into adulthood.
Type III SMA (mild SMA). This form of SMA affects children older than 18 months of age or as late as adolescence. These children show signs of clumsiness, difficulty walking, mild muscle weakness, and if untreated, may lose the ability to walk independently. These children live long into their adult years.
Type IV SMA. This form of SMA affects adults from age 18 years onwards, resulting primarily in a walking disability.
The symptoms of spinal muscular atrophy may resemble other problems or medical conditions. Always consult your child's doctor for a diagnosis.
The diagnosis of spinal muscular atrophy is made after the sudden or gradual onset of specific symptoms and after diagnostic testing. During the physical examination, your child's doctor will obtain a complete medical history of your child, and he or she may also ask if there is a family history of any medical problems.
Diagnostic tests that may be performed to confirm the diagnosis of spinal muscular atrophy include the following:
Genetic tests: Diagnostic tests that evaluate for conditions that have a tendency to run in families.
Electromyogram (EMG)/Nerve conduction studies (NCS): A test that measures the electrical activity of a nerve, muscle or a group of muscles. An EMG/NCS can detect abnormal electrical nerve and muscle activity due to diseases and neuromuscular conditions.
Muscle ultrasound (US): A test to look at the activity and quality of the muscle. This test can help see fasciculations, or abnormal muscle movements, that are classic in spinal muscular atrophy.
Newborn screening: Newborn screening is testing performed at birth for a variety of treatable inherited disorders. SMA is now on the Recommended Uniform Screening Panel (RUSP), and Pennsylvania and other states are working hard on initiating this process.
Treatment for spinal muscular atrophy is very complex, and requires coordinated care from many different subspecialists. Your child’s care team may include experts from neurology, pulmonology, orthopaedics, endocrinology, anesthesiology, gastroenterology and others.
There are two goals of treatment for SMA. The first goal of spinal muscular atrophy treatment is to proactively manage anticipated issues that may arise with multi-systemic supportive care. The second goal is targeted treatments to help slow down, and in some cases stop, the progression of SMA.
Specific treatment for spinal muscular atrophy will be determined by your child's care team based on:
- Your child's age, overall health, and medical history
- The extent of the condition
- The type of spinal muscular atrophy
- Your child's tolerance for specific medications, procedures, or therapies
- Expectations for the course of the condition
- Your opinion or preference
Managing symptoms of SMA
There is no cure for spinal muscular atrophy. The key to medically managing spinal muscular atrophy is through early detection and proactive management of associated symptoms.
Supportive care for SMA will focus on:
- Physical and occupational therapy, avoiding contractures and enhancing safe independent mobility and daily function
- Breathing supports as needed
- Maximizing nutritional status
- Improving bone health
- Management of musculoskeletal issues, such as scoliosis
In addition to a multidisciplinary approach to care, there are also new specific treatments for SMA, which are described in more detail below.
Medication used to treat spinal muscular atrophy
One of the latest breakthroughs in care for patients with spinal muscular atrophy is the FDA approval of a new medicine called nusinersen (brand name Spinraza) for the treatment of SMA in children and adults.
Your child’s doctor will determine if your child is a candidate for the drug based on genetic factors, disease type, and symptoms. Currently, nusinersen is approved for use in all patients who are confirmed to have the SMN gene mutation that causes the disease.
Early results of SMA treatment with Spinraza are promising. Clinical trials have shown some patients experience improvement in motor skills. Many others will stabilize and not experience any further loss or deterioration of skills.
Research trials show that the earlier patients start the medication, the better the results.
How does nusinersen work?
Nusinersen is a medication that is used to increase production of the survival of motor neuron (SMN) protein. While individuals with SMA do not have functional copies of SMN1, they typically have multiple copies of the SMN2 gene. The SMN2 gene is not as functional as SMN1, and makes a much smaller amount of functioning protein.
Nusinersen alters how SMN2 is processed, increasing the amount of functional protein produced from this gene. Because the primary site of injury is in the motor neurons in the spinal cord, the medication is injected into the spinal fluid to specifically target the cells that are most affected.
How is nusinersen given?
Nusinersen is injected directly into the fluid surrounding the spine using a needle. This procedure is called a lumbar puncture.
During a lumbar puncture, it is very important for your child to remain still. Many older children and teens are able to have this procedure performed without sedation, with only local anesthetics, or numbing medications. Some children will need sedation to help them stay calm and still.
At Children’s Hospital of Philadelphia, our expert pediatric anesthesiologists will work closely with the rest of the team to provide the safest possible care and make sure your child has the breathing support they need when under sedation. For individuals with severe scoliosis or prior spinal fusion, interventional radiology may be necessary to provide imaging guidance.
Depending on the individual needs of the child, this procedure can be done either in a regular procedure room, a sedation room, an operating room, or an interventional radiology suite.
In the first two months, your child will receive four doses. After that, you’ll return once every four months for maintenance doses. Patients typically receive the drug during an outpatient visit. While the procedure time is short (typically around 15 minutes), the visit can last several hours, as monitoring labs are checked prior to the injection, and patients are observed for a minimum of one hour after the procedure is completed.
Our dedicated child life specialists are also available to work with your child and provide age-appropriate and therapeutic activities to make them feel comfortable and familiar with the procedure.
Nusinersen is currently the only approved therapy for SMA. However, there are many other medications currently being studied, with the hope that they may also become treatment options. These include other medications that work to increase SMN protein, such as gene replacement therapy, as well as medications that may help improve body function in ways not directly related to SMN protein.
CHOP has long been a site for many of these research studies. In addition to interventional trials, we are also a site for natural history studies that allow us to learn more about the disorder and how treatment is altering its natural history. We work with colleagues in pulmonology, orthopaedics, and physical and occupational therapy to help learn more about how to best manage this disorder.
A child with spinal muscular atrophy requires frequent medical evaluations throughout their lifespan. Your child’s healthcare team will work closely with your family on how to best care for your child at home. We will also outline specific clinical problems that require immediate medical attention by their doctor.
Being cared for in a top-ranked Children’s Hospital means your child will have immediate access to the many clinical specialists and pediatric-focused care they need to manage their SMA. We have the experts, support services, facilities and technology in place to ensure your child receives the best possible care.
It is our goal to deliver cutting-edge treatment to as many patients as possible. We have the resources required to provide access to new SMA therapies and medications in a timely manner. We are equipped to tailor dosing to each individual patient and provide the support services that can help make the experience easier on your child and family. These are important factors to look for in any SMA treatment center.
Our team is also involved in ongoing research studies and clinical trials, continually seeking to find the next breakthrough in the treatment of SMA.