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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 types.
In most cases, 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 more than 95% of cases of SMA, the mutation is a common deletion; less commonly, there are spelling errors, also called point mutations, in SMN1 or other genetic variants. Symptomatic individuals of all ages can be tested through DNA studies typically done from a blood sample.
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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 SMA based on symptoms and age of onset:
SMA is caused not by an absence of SMN protein, like many other disorders, but by a deficiency. Everyone still makes some SMN protein, from a gene called SMN2. However, each SMN2 gene functions about 10-15% as well as a SMN1 gene. The copy number of SMN2 genes correlates with disease severity, and is responsible for some of the broad variety in clinical presentation.
The symptoms of spinal muscular atrophy may resemble other problems or medical conditions. Always consult your child's doctor for a diagnosis.
Many states, including Pennsylvania and New Jersey, have recently mandated screening of all newborn babies for SMA. Other times, the diagnosis of spinal muscular atrophy is made after the sudden or gradual onset of specific symptoms and after diagnostic testing. During a physical examination, your child's doctor will obtain a complete medical history of your child and may ask if there is a family history of any medical problems.
Diagnostic tests that may be redone to confirm the diagnosis of spinal muscular atrophy include:
Current Access to treat spinal muscular atrophy
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, rehabilitation/physical therapy/occupational therapy, pulmonology, orthopedics, endocrinology, anesthesiology, nutrition/gastroenterology and others.
There are two goals of treatment for SMA. The first goal 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 spinal muscular atrophy treatment will be determined by your child's care team based on:
There is no cure for spinal muscular atrophy. The key to medically managing the condition is through early detection and proactive management of associated symptoms.
Supportive care for SMA will focus on:
In addition to a multidisciplinary approach to care, there are also new specific treatments for SMA, which are described in more detail below.
Another recent advancement in spinal muscular atrophy treatment is gene replacement therapy. In May 2019, gene replacement therapy for SMA, called onasemnogene abeparvovec-xioi (brand name Zolgensma®), was approved by the FDA for treatment of children under age 2 years with genetically confirmed SMA.
If your child meets these criteria, we will complete a clinical evaluation and additional testing to determine if they are a candidate to receive SMA gene therapy.
Clinical trials have shown clear efficacy in young children with SMA type 1, resulting in a decreased need for respiratory support as well as improvement in motor skills. Research trials have also shown that the earlier children receive gene therapy, the better the results.
Additional clinical trials with Zolgensma are ongoing. We encourage you to ask your child’s medical team any questions you may have, and we will share new information as it becomes available.
Deformities of the spine, chest wall, and hips are common in children with SMA. These Deformities can result in decreased space for the lungs and can negatively affect lung function.
Scoliosis is a deformity of the spine that is brought on by the muscular weakness that develops in children with the condition. The age of onset of scoliosis can vary dramatically depending on the severity of the disease, but can be as early as age 1 even in newborns who undergo gene therapy treatment.
Children with SMA should be evaluated for a spinal deformity beginning before age 1. Current treatment involves surgically implanting growing rods to control and manage the progressive and detrimental effects of scoliosis. Our surgical team is mindful to leave an area of the child’s spine unfused to allow for genetically-targeted therapy injections, when needed.
Chest wall deformities such as the parasol rib deformities can exist with or without a spinal deformities in children with SMA. In the parasol rib deformities, the ribs are collapsed, preventing proper respiratory mechanics. At CHOP, treatment of this condition involves surgery to reposition the ribs in order to maintain or preserve lung function and prevent further collapse. Ours is one of only a few programs in the country to offer this unique approach to managing this condition.
Pelvic issues in children with SMA can lead to hip deformities and hip dysplasia. Evaluation and management of the condition of the pelvis and the hips is important to preserve a child’s mobility.
In spinal muscular atrophy (SMA) lung infections can cause respiratory difficulty and are a common cause of hospitalization. For this reason, it is critical to support a patient’s ability to cough and clear his/her mucus. In addition, as muscle weakness progresses it can become difficult for patients to breathe in oxygen and remove carbon dioxide. This respiratory compromise can first appear during sleep when there is an overall decrease in muscle strength. The pulmonary team works with the child and his/her guardian(s) to assess the muscles involved in breathing and overall lung function regularly through the use of such testing as:
Chromosome 5 (SMN-related) SMA (Types 0-IV), the most common type of SMA, is caused by a mutation in the SMN1 gene (survival motor neuron 1) that produces a protein in the body called Survival Motor Neuron (SMN) protein. A deficiency of this protein affects the health of the motor neurons, causing them to shrink and eventually die. SMA is inherited in an autosomal recessive pattern, which means that for a child to be affected both parents must be carriers of the abnormal gene, and both must pass this gene on to their child.
In unaffected people, the SMN1 gene produces full length and fully functional SMN protein, but when it has mutations, insufficient levels of SMN protein are produced. However, a neighbouring gene on chromosome 5, SMN2, also produces SMN protein and a small percentage of the protein is functional. People can have multiple copies of the SMN2 gene (normally between 0-8 copies) and the more SMN2 gene copies a person has the more functional SMN protein is available. The more copies of the SMN2 gene a person with SMA has, the milder the disease course is likely to be.
The severity of the disease is dependent on type and age of onset. SMA can be a fatal disease, however, children with SMA Type II usually live to at least young adulthood and those with Type III or Type IV (or late on-set) don’t have respiratory issues and their life expectancy is not affected.
Duchenne muscular dystrophy (DMD) is a genetic condition which causes progressive muscle degeneration and weakness. DMD is caused by mutations in the Dystrophin gene and is one of four diseases known as the dystrophinopathies. The condition usually only affects males, and symptoms are usually observed in early childhood – typically between the ages of 2 and 3.
DMD is caused by a mutation in the gene called Dystrophin located on the X-chromosome. The mutation prevents the production of dystrophin protein, and its absence results in progressive muscle weakness as muscle cells break down and are gradually lost.
DMD is a genetic condition which can be inherited from the mother or be caused by a spontaneous mutation in a child’s genes (de novo mutation). As the dystrophin gene is on the X-chromosome, DMD almost only affects males (females have two X-chromosomes and the second copy can compensate for the faulty one). Females with one affected gene (called carriers) can pass the mutated gene to their children; Females with one affected gene (called carriers) can pass the mutated gene to their children; female carriers are at risk of developing heart problems and, therefore, should be monitored by a cardiologist.
It is common for boys diagnosed with DMD to begin using a wheelchair by the age of 11. At first, a wheelchair may only be used for long distances; however, later, it is likely that affected boys will need to use a wheelchair full time.
As the disease progresses, muscle weakness means that maintaining a good posture is increasingly difficult; therefore, complications are more likely. DMD is a severe disease that shortens life expectancy; however, the high standards of care now available for patients mean that many young men with DMD reach adulthood.
The first signs and symptoms of DMD usually occur in early childhood: growth rate is typically slower than normal and those with DMD are usually late walkers. In toddlers, enlarged calf muscles may be evident due to abnormalities in muscle tissue.
Young children may have difficulty running, climbing stairs, and getting up from the floor to an upright position. When walking, affected boys may display a waddling gait and walk on their toes or the balls of their feet. Difficulties with balance and raising upper limbs may also be a sign of muscle weakness.
A lack of dystrophin can weaken the muscles that operate the lungs and diaphragm which can lead to respiratory issues and symptoms such as shortness of breath, headaches, and difficultly concentrating or staying awake. Children who use wheelchairs tend to have poor pulmonary function.
DMD causes heart problems including cardiomyopathy and conduction abnormalities. The heart should be closely monitored by a paediatric cardiologist as problems can occur without any symptoms.
Although serious cognitive disability is not common, boys with DMD may have some degree of learning disability affecting attention focusing, verbal learning and memory and/or emotional interaction. If a child is diagnosed with a learning disability, educational and psychological intervention can be put in place to support boys and their families.
