Spinal muscular atrophies are hereditary disorders in which nerve cells that originate in the spinal cord and brain stem degenerate, causing progressive muscle weakness and wasting.
- The five main types of spinal muscular atrophies cause various degrees of muscle weakness and wasting.
- Depending on the type, people may be confined to a wheelchair, and life span may be shortened.
- The diagnosis, suggested by symptoms, is based on family history, tests of muscle and nerve function, and blood tests to detect the defective gene.
- There is no cure, but physical therapy and use of braces can help.
(See also Overview of the Peripheral Nervous System.)
Spinal muscular atrophies are usually inherited as an autosomal (not sex-linked) recessive trait. That is, two genes for the disorder are required, one from each parent. These disorders may affect the brain and spinal cord (central nervous system), as well as peripheral nerves.
There are five main types of spinal muscular atrophy.
Symptoms of the first four types of spinal muscular atrophy first appear during infancy and childhood.
Spinal muscular atrophy type 0, the most severe form, begins to affect the fetus before birth. The fetus does not move as much as expected during late pregnancy. Once born, the baby has severe weakness and lacks muscle tone. Reflexes are absent, and joint movement is limited. Both sides of the face are paralyzed. Birth defects of the heart are also present. The muscles that control breathing are very weak. Infants often die within the first months because they cannot breathe adequately, resulting in respiratory failure.
In spinal muscular atrophy type 1 (infantile spinal muscular atrophy or Werdnig-Hoffmann disease), muscle weakness is often apparent at or within a few days of birth. It is virtually always apparent by age 6 months. Infants lack muscle tone and reflexes and have difficulty sucking, swallowing, and eventually breathing. Death occurs in 95% of children within the first year and in all by age 4 years, usually due to respiratory failure.
In spinal muscular atrophy type 2 (intermediate form of Dubowitz disease), weakness typically develops between age 3 and 15 months. Fewer than one fourth of children learn to sit. None can crawl or walk. Reflexes are absent. Muscles are weak, and swallowing may be difficult. Most children are confined to a wheelchair by age 2 to 3 years. The disorder is often fatal in early life, usually because of respiratory problems. But some children survive with permanent weakness that does not continue to worsen. These children often have severe curvature of the spine (scoliosis).
Spinal muscular atrophy type 3 (juvenile form or Wohlfart-Kugelberg-Welander disease) begins between age 15 months and 19 years and worsens slowly. Consequently, people with this disorder usually live longer than those with type I or II spinal muscular atrophy. Some of them have a normal life span. Weakness and wasting of muscles begin in the hips and thighs and later spread to the arms, feet, and hands. How long people lives depends on whether respiratory problems develop.
Spinal muscular atrophy type 4 first appears during adulthood, usually between the ages of 30 and 60 years. Muscles, mainly in the hips, thighs, and shoulders, slowly become weak and waste away.
- A doctor's evaluation
- Electromyography and nerve conduction studies
- A blood test for the abnormal gene
- Sometimes biopsy of a muscle
Doctors usually test for spinal muscular atrophies when unexplained weakness and muscle wasting occur in young children. Because these disorders are inherited, a family history may help doctors make the diagnosis.
Electromyography and nerve conduction studies help confirm the diagnosis. The specific defective gene can be detected by blood tests in 95% of affected people (genetic testing).
Occasionally, biopsy of a muscle is done.
If there is a family history of one of the disorders, amniocentesis can be done to help determine whether an unborn child has the defective gene.
- Physical and occupational therapy
- Braces and assistive devices
- Drugs that may improve muscle function and delay disability and death
There is no cure for spinal muscular atrophies.
Physical therapy and wearing braces can sometimes help. Physical and occupational therapists can provide adaptive devices to enable children to feed themselves, write, or use a computer.
Nusinersen may slightly improve muscle movement and may delay disability and death. Nusinersen is injected into the space around the spinal cord. Before injecting the drug, doctors often numb the injection site with a small amount of local anesthetic. Then they insert a needle between two vertebrae in the lower spine, as is done for a spinal tap (lumbar puncture). Nusinersen is initially given in four doses over a period of 2 months. Then it is given at regular intervals every 4 months.
Two new drugs have been developed.
Onasemnogene abeparvovec-xioi is used to treat some children under 2 years old. Only one dose is given. It is given intravenously over 1 hour. It appears to help children meet developmental milestones, such as sitting without support, eating, rolling over, and walking independently.
Risdiplam is used to treat adults and children 2 years old and over. It is given as a liquid or through a feeding tube once a day. It may delay death and reduce the need for mechanical ventilation to help with breathing.
Gene therapy for spinal muscular atrophy has recently become available. It is injected into a vein. Only one injection is required.
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