Spinal Muscular Atrophy (SMA)

What Is Spinal Muscular Atrophy (SMA)? What Causes Spinal Muscular Atrophy?

Spinal muscular atrophy (SMA) is a collection of different muscle diseases. Grouped together, it is the second leading cause of neuromuscular disease. Most of the time, a person must get the defective gene from both parents to be affected. Approximately 4 out of every 100,000 people have the condition.

One in every 6,000 babies is born with spinal muscular atrophy, or SMA. It is the number one genetic killer of children under the age of 2, but can affect people of any age and gender. The disease destroys the nerves that control voluntary muscle movement. This severely limits people's abilities to walk, swallow, crawl and hold their head up.

According to Medilexicon's medical dictionary:

Spinal Muscular Atrophy is a heterogeneous group of degenerative diseases of the anterior horn cells in the spinal cord and motor nuclei of the brainstem; all are characterized by weakness. Upper motor neurons remain normal. These diseases include Werdnig-Hoffmann disease, spinal muscular atrophy types I and II (SMA1, SMA2); and Kugelberg-Welander disease, spinal muscular atrophy type III (SMA3).

Also called Werdnig-Hoffmann disease, SMA type I is evident before birth. There may be a reduction in fetal movement during the final months of pregnancy or within the first few months of life. Children with SMA type I never sit or stand and usually die before the age of two.

SMA type II usually becomes apparent between 3 and 15 months of age. These children may learn to sit but will never be able to stand or walk. Life expectancy varies.

Kugelberg-Welander disease, or SMA type III, appears between 2 and 17 years of age with an abnormal way of walking, difficulty running, climbing steps, or rising from a chair and slight tremor of the fingers.

Kennedy syndrome is also known as progressive spinobulbar muscular atrophy. Kennedy syndrome has its clinical onset between 15 and 60 years of age. It is inherited in an X-linked recessive manner. Women carry the gene on one of their two X chromosomes, but the disorder only occurs in their sons. The risk to each son of a carrier mother is one-half to receive the gene and manifest the disease. The disorder is slowly progressive.

Congenital SMA with Arthrogryposis is a rare disorder characterized by persistent contracture of joints (arthrogryposis) evident at birth. Features include the severe contractures, curvature of the spine, chest deformity, respiratory problems, an unusually small jaw, and drooping upper eyelids.

Adult SMA may begin between 40 and 60 years of age and progresses rapidly, with an average life expectancy of about 5 years from the onset of symptoms. Most cases prove to be variants of amyotrophic lateral sclerosis (ALS, commonly called Lou Gehrig's disease).

What are the symptoms of Spinal Muscular Atrophy?

A symptom is something the patient senses and describes, while a sign is something other people, such as the doctor notice. For example, drowsiness may be a symptom while dilated pupils may be a sign.
Infants with SMA type 1 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 is normally transmitted from motor neurons in the spinal cord to muscle via the motor neuron's axon, but either the motor neuron with its axon, or the axon itself, is lost in all forms of SMA.

The features of SMA are strongly related to its severity and age of onset. SMA caused by mutation of the SMN (survival motor neuron) gene has a wide range, from infancy to adult, fatal to trivial, with different affected individuals manifesting every shade of impairment between these two extremes. Many of the symptoms of SMA relate to secondary complications of muscle weakness, and as such can be at least partially remediated by prospective therapy.

What are the causes of Spinal Muscular Atrophy

SMA is a recessive genetic disease. There are parts of every cell in the human body that receives instructions from genes. The parts of the cell that get the instructions are, by nature, protein.

When the instructions contain a mistake, this is called a deletion. In SMA, the instructions given to nerves that control muscles contain a deletion that causes a protein deficiency. The gene responsible for the instruction to motor neurons is called SMN 1, or survival motor neuron.

Each person has 2 pairs of genes for each instruction given. One gene is inherited from mother and one from father. Some diseases will show up if only one of the inherited genes contains an instruction error. Other diseases, such as SMA, need both mother's and father's inherited genes to contain a mistake before the disease will present itself.

The SNM 1 gene, which is responsible for SMA, is one of those types of genes. This means that for a child to have SMA, both parents must have contributed an SMN 1 with faulty instructions. Even then, the chance is 1 in 4 per pregnancy that the child will have SMA. One in 40 adults are carriers of the gene that causes SMA.

Diagnosing Spinal Muscular Atrophy

The first step in obtaining a diagnosis is for parents or caretakers to notice SMA symptoms in their child. A physician should take a detailed medical history of the child, including a family history and a physical exam.

There are several types of tests used to diagnose SMA including blood tests, muscle biopsy, genetic tests and potentially an EMG. Testing is possible prenatally with amnioscetises or chorionic villus samples.

A health care provider should take a careful history and perform a neurologic examination to find out if there is a family history of neuromuscular disease.

A doctor will also look out for floppy or flaccid muscles, no deep tendon reflexes and muscle fasciculation of the tongue muscle.

A lot of issues are generated regarding testing for SMA in children, as well as testing parents for carrier status. In 1997, a DNA test, called the quantitative PCR test for the SMN 1 gene, came out on the market to help parents determine if they carry the mutant gene that causes SMA. The test is done by taking a blood sample. Testing the general population is too difficult, so it is reserved for those who have had people with SMA in their family.

What are the treatment options for Spinal Muscular Atrophy?

Individuals with SMA are living longer and fuller lives with the help of assistive technology such as ventilators, power wheelchairs, and modified access to computers. These mitigate the effects of SMA upon the individuals' daily lives, allowing them to participate in the community like everyone else.

Ventilation is especially important. The course of SMA is directly related to the severity of weakness. Infants with the severe form of SMA frequently succumb to respiratory disease due to weakness of the muscles that support breathing. Children with milder forms of SMA naturally live much longer although they may need extensive medical support, especially those at the more severe end of the spectrum.

Due to molecular biology, there is a better understanding of SMA. Many experimental treatments are being tested, including gene replacement, stem-cell replacement of motor neurons, and most promising therapies intended to increase the expression of the SMN 2 gene or increase the percentage of mRNA transcript from SMN 2 that is spliced to the full length form.

Other potential therapies are directed to drugs that might enhance residual SMN function, or compensate for its loss. Significant progress has been made in preclinical research towards an effective treatment.

Several drugs have been identified in laboratory experiments that hold promise for patients. To evaluate if these drugs benefit SMA patients, clinical trials are needed. In a clinical trial a new medication is tested while the patients are carefully monitored for their safety and for any possible drug effects, positive or negative.

In 2007, the SMA Treatment Acceleration Act was introduced in the United States Congress to authorize the Secretary of Health and Human Services to conduct activities to rapidly advance treatments for spinal muscular atrophy, neuromuscular disease, and other pediatric diseases.

Preventing Spinal Muscular Atrophy

Due to the fact that SMA is genetic, there are no prevention methods available.

Genetic counseling is recommended for prospective parents with a family history of spinal muscular atrophy.