Spinal Muscular Atrophy
Spinal muscular atrophy is a genetic disorder characterized by weakness and wasting (atrophy) in muscles used for movement (skeletal muscles). It is caused by a loss of specialized nerve cells, called motor neurons that control muscle movement. The weakness tends to be more severe in the muscles that are close to the center of the body (proximal) compared to muscles away from the body's center (distal). The muscle weakness usually worsens with age.
There are many types of spinal muscular atrophy that are caused by changes in the same genes. The types differ in age of onset and severity of muscle weakness; however, there is overlap between the types. Other forms of spinal muscular atrophy and related motor neuron diseases, such as spinal muscular atrophy with progressive myoclonic epilepsy, spinal muscular atrophy with lower extremity predominance, X-linked infantile spinal muscular atrophy, and spinal muscular atrophy with respiratory distress type 1 are caused by mutations in other genes.
Spinal muscular atrophy type 0 is evident before birth and is the rarest and most severe form of the condition. Affected infants move less in the womb, and as a result they are often born with joint deformities (contractures). They have extremely weak muscle tone (hypotonia) at birth. Their respiratory muscles are very weak and they often do not survive past infancy due to respiratory failure. Some infants with spinal muscular atrophy type 0 also have heart defects that are present from birth (congenital).
Spinal muscular atrophy type I (also called Werdnig-Hoffmann disease) is the most common form of the condition. It is a severe form of the disorder with muscle weakness evident at birth or within the first few months of life. Most affected children cannot control their head movements or sit unassisted. Children with this type may have swallowing problems that can lead to difficulty feeding and poor growth. They can also have breathing problems due to weakness of respiratory muscles and an abnormally bell-shaped chest that prevents the lungs from fully expanding. Most children with spinal muscular atrophy type I do not survive past early childhood due to respiratory failure.
Spinal muscular atrophy type II (also called Dubowitz disease) is characterized by muscle weakness that develops in children between ages 6 and 12 months. Children with this type can sit without support, although they may need help getting to a seated position. However, as the muscle weakness worsens later in childhood, affected individuals may need support to sit. Individuals with spinal muscular atrophy type II cannot stand or walk unaided. They often have involuntary trembling (tremors) in their fingers, a spine that curves side-to-side (scoliosis), and respiratory muscle weakness that can be life-threatening. The life span of individuals with spinal muscular atrophy type II varies, but many people with this condition live into their twenties or thirties.
Spinal muscular atrophy type III (also called Kugelberg-Welander disease) typically causes muscle weakness after early childhood. Individuals with this condition can stand and walk unaided, but over time, walking and climbing stairs may become increasingly difficult. Many affected individuals require wheelchair assistance later in life. People with spinal muscular atrophy type III typically have a normal life expectancy.
Spinal muscular atrophy type IV is rare and often begins in early adulthood. Affected individuals usually experience mild to moderate muscle weakness, tremors, and mild breathing problems. People with spinal muscular atrophy type IV have a normal life expectancy.
Spinal muscular atrophy (SMA) is sometimes difficult to diagnose, as symptoms can resemble other conditions or medical problems. Doctors usually diagnose SMA after a child has muscle weakness and decreased muscle tone.
If your clinician suspects SMA, they may use the following tests to diagnose the condition:
genetic blood tests, which can confirm the diagnosis of SMA
an electromyography (EMG) test that measures the electrical activity of a muscle or a group of muscles (in some cases)
a creatine kinase (CPK) test (to distinguish from other types of neuromuscular diseases, if necessary)
The FDA has approved three medications to treat SMA: nusinersen (Spinraza), onasemnogene abeparvovec-xioi (Zolgensma) and risdiplam (Evrysdi). Both are forms of gene therapy that affect the genes involved in SMA. The SMN1 and SMN2 genes give your body instructions for making a protein that helps with controlling muscle movement.
Nusinersen (Spinraza). This treatment adjusts the SMN2 gene and lets it make more protein. It's used for both children and adults with SMA. Your child's medical team will inject the drug into the fluid around their spinal cord. Including preparation and recovery time, this can take at least 2 hours and will need to be done several times, followed by another dose every 4 months. Studies show it helps about 40% of people who use it by making them stronger and slowing the disease.
Onasemnogene abeparvovec-xioi (Zolgensma). This involves replacing the problem SMN1 gene. It's used for children under 2 years old. Your child's medical team will put a tiny tube called a catheter directly into a vein in their arm or hand (an IV). Then, they'll send a copy of the SMN gene through the tube into a specific group of motor neuron cells. This will need to be done only one time. In studies, onasemnogene abeparvovec-xioi helped children with SMA reach certain developmental milestones faster, like controlling their heads or sitting without support.
Risdiplam (Evrysdi). This treatment works to stop the SMN2 genes from disrupting the protein production, allowing the protein to reach the nerve cells as needed. Your child takes it orally once a day after a meal. The dosage is determined by their weight.Clinical trials showed improved muscle function after 12 months in 41% of those taking it.
Besides gene therapy, your doctor may suggest a few other ways to help manage symptoms:
Breathing. With SMA, especially types 1 and 2, weak muscles keep air from moving easily in and out of the lungs. If this happens to your child, they may need a special mask or mouthpiece. For severe problems, your child may use a machine that helps them breathe.
Swallowing and nutrition. When muscles in the mouth and throat are weak, babies and children with SMA can have a hard time sucking and swallowing. In that situation, your child may not get good nutrition and may have trouble growing. Your doctor may suggest working with a nutritionist. Some babies may need a feeding tube.
Movement. Physical and occupational therapy, which use exercises and regular daily activities, can help protect your child's joints and keep muscles strong. A therapist may suggest leg braces, a walker, or an electric wheelchair. Special tools can control computers and phones and help with writing and drawing.
Back issues. When SMA starts in childhood, children can get a curve in their spine. A doctor may suggest that your child wear a back brace while their spine is still growing. When they’ve stopped growing, they may have surgery to fix the problem.
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