Spinal Muscular Atrophies (SMAs)
The four 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 four main types of spinal muscular atrophy.
Symptoms of the first three types first appear during infancy and childhood.
In type I spinal muscular atrophy (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 type II (intermediate) spinal muscular atrophy, 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).
Type III spinal muscular atrophy (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.
Type IV spinal muscular atrophy 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.
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.
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, a new drug, 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.
Gene therapy for spinal muscular atrophy has recently become available. It is injected into a vein. Only one injection is required.