All about spinal muscular atrophy (SMA)
Muscle wasting and weakness results, making it difficult to stand, walk, control head movements, and even, in some cases, to breathe and to swallow.
Spinal muscular atrophy (SMA) is not just one condition but a range of diseases. Grouped together, the different types of SMA form the second leading cause of neuromuscular disease.
If SMA affects an infant under the age of 2 years, it is usually fatal. If the patient is older when the disease appears, they will have a different type of SMA, and life expectancy may be normal.
There is no cure for SMA, but in December 2016, the first drug to treat it was approved: Spinraza.
Here are some key points about spinal muscular atrophy (SMA). More detail is in the main article.
- There are different types of SMA. They vary in severity.
- It is a genetic condition.
- The main symptom is muscle weakness and muscle loss. In severe cases, respiratory problems may occur.
- Treatments include supportive devices to help the patient breathe, and a new drug, Spinraza.
- SMA cannot be prevented, but prospective parents can request genetic testing if they may be carriers.
There are different types of SMA. They vary in terms of when they start to appear in an individual, and in the life expectancy that a person with the disorder will have.
SMA type I
Spinal muscular atrophy affects physical function but not necessarily intellectual ability.
SMA type I is a serious condition. Children with this disorder never manage to sit or stand. It is usually fatal before the age of 2 years.
It can be detected before birth, as there may be a reduction in fetal movement during the final months of pregnancy. If not, it will become evident within the first few months of life.
Infants with SMA type I never sit or stand, and they do not usually survive to the age of two years. SMA type I is also known as Werdnig-Hoffmann disease.
SMA type II
SMA type II usually appears between the ages of 3 and 15 months. The infant may learn to sit, but will never be able to stand or walk.
Life expectancy depends on whether or not the patient develops breathing problems. Most people with SMA type II survive into adulthood.
SMA type III
SMA type III, or Kugelberg-Welander disease, appears between 2 and 17 years of age.
Symptoms include an unusual gait and difficulty running, climbing steps, or rising from a chair. There may be a slight tremor of the fingers. Some people may lose the ability to walk, and they may also develop scoliosis. Complications include obesity and osteoporosis.
Kennedy syndrome is also known as progressive spinobulbar muscular atrophy. Kennedy syndrome is a slowly progressive, inherited condition that usually appears between 20 and 40 years of age, but it can appear later.
Women carry the gene, but only a son will inherit the disorder.
Congenital SMA with arthrogryposis
Congenital SMA with arthrogryposis is a rare disorder. People with this condition will have a persistent contracture of joints, known as arthrogryposis.
The condition is evident at birth. Features include severe contractures, curvature of the spine, chest deformity, respiratory problems, an unusually small jaw, and drooping upper eyelids.
Adult SMA, or SMA IV, begins after the age of 18 years. People with this condition can walk, and they do not have problems with breathing or eating.
The symptoms of SMA depend on its severity and the person's age when it starts. Infants with SMA type I are born with very little muscle tone, weak muscles, and feeding and breathing problems. With SMA type III, symptoms may not appear until the second year of life.
In all of its forms, the primary feature of SMA is muscle weakness, accompanied by atrophy of muscle. This is the result of denervation, or loss of the signal to contract, that is transmitted from the spinal cord.
This signal is normally transmitted from motor neurons in the spinal cord to muscle via the motor neuron's axon. In SMA, either the motor neuron with its axon, or the axon itself, becomes non-functioning. It stops working.
Many of the symptoms of SMA relate to secondary complications of muscle weakness. These can be relieved partly by therapy.
SMA happens when motor neurons in the spinal cord and the brainstem either do not work or stop working, because of genetic changes. Motor neurons are the nerve cells that control movement.
Every human cell contains a part that receives instructions from genes, and when the instructions contain a mistake, this is called a deletion. The part that receives the instructions is normally a protein.
In SMA, the instructions that are given to the motor neurons, or nerves that control motion, contain a deletion that causes a protein deficiency. The gene responsible for the instruction to motor neurons is a survival motor neuron, normally SMN 1.
Each person has 2 pairs of genes for each instruction given. One gene is inherited from the mother and one from the father. Some diseases will appear if only one of the inherited genes contains an instruction error. Other diseases, such as SMA, will only emerge if there is a mistake in both the mother's and the father's inherited genes.
For a child to have SMA, both parents must contribute an SMN 1 with faulty instructions.
However, even if both parents have the faulty gene, the child will not always inherit it. Even among this population, the chance is only 1 in 4 per pregnancy that the child will have SMA. One in 40 adults are carriers of the gene that causes SMA.
Diagnosis usually starts when parents or caregivers notice symptoms of SMA in a child.
A physician will carry out a detailed medical history, a family history, and a physical exam. They will see if the muscles are floppy or flaccid, to check for deep tendon reflexes and muscle fasciculation of the tongue muscle.
Tests used to diagnose SMA include blood tests, muscle biopsy, genetic tests, and potentially electromyography (EMG). EMG is used to assess the health of muscles and the nerve cells, or motor neurons, that control them. Amniocentesis or chorionic villus sampling can evaluate the fetus during gestation.
There is, as yet, no cure for SMA, and there is no way to prevent it, as it is an inherited condtion. However, treatment can help people live fuller lives.
In December 2016, the United States (U.S.) Food and Drug Administration (FDA) approved a drug, nusinersen (Spinraza) to treat SMA. It is the first drug to be approved for this condition.
It is given by injection, the first three doses at 14-day intervals, the fourth after 30 days, and then every 4 months.
Spinraza targets the underlying defect in SMA, so it may help delay, prevent, or even reverse the symptoms. Common side effects include a higher risk of respiratory tract infection and constipation. There may also be a risk of bleeding and kidney problems.
Assistive technology such as ventilators, power wheelchairs, and modified access to computers are enabling individuals with SMA to live longer, be more active, and to participate in the community.
Ventilation is especially important. The severity of the individual's weakness directly affects the course of the disease. Infants with severe SMA may experience respiratory disease, because the muscles that support breathing are weak.
Children with milder forms of SMA can expect to have a longer lifespan, although they may need extensive medical support.
Molecular biology has improved our understanding of SMA. Many experimental treatments are being tested, including gene replacement, stem-cell replacement of motor neurons, and therapies to increase the expression of the SMN 2 gene.
SMA is genetic, and there is no way to prevent it.
Parents with a family history of SMA are encouraged to seek genetic counseling before starting a family.