Spinal Muscular Atrophy Diagnosis and Tests

There are four key elements to establishing a firm diagnosis of spinal muscular atrophy:
1. the clinical history and physical examination,
2. electromyography and nerve conduction studies;
3. muscle biopsy,
4. genetic testing
1. Clinical Tests for Spinal Muscular Atrophy

The initial step in diagnosing SMA begins with parental concerns about their children’s strength and gross motor abilities. These concerns usually occur early in life in children with SMA Type I and II, where as children with SMA III may not show any clinical symptoms for many years. It is important that a physician knowledgeable about pediatric neuromuscular diseases examine these youngsters. Many other neuromuscular diseases can present with clinical symptoms identical to those expressed by children with SMA. Some of these alternative diagnoses required different diagnostic tests and may warrant different forms of treatment. Typically, the child with SMA Type I and II will exhibit his or her most dramatic weakness in the proximal muscles of the legs and arms. A quivering tongue (fasciculations of the motor units in the tongue muscle), is a very important clinical sign and often guides the physician to the diagnosis of SMA. Most children with SMA lose their deep tendon reflexes (the reflexes physicians check when they strike the knees or ankles with a rubber hammer). Sensation is normal and children always appreciate feelings like tickling and light touch. Although the clinical examination is critically important, the fact that other neuromuscular disease can present with the same symptoms and show some of the same physical features makes additional diagnostic testing necessary. Often the physician will order a blood test such as a muscle enzyme test (creatine kinase – CPK), to distinguish SMA and Muscular Dystrophy. Most children with muscular dystrophy have very high CPK levels, where as children with SMA have normal or only slightly elevated CPK levels.

2. Electromyography Testing (EMG) for Spinal Muscular Atrophy
The EMG test consists of two parts. The physician administers a small electrical stimulus to the nerves of a child’s arm and legs to determine how quickly electrical messages are carried by the motor and sensory nerves. This test is necessary to differentiate some forms of nerve disease from SMA. The second part of the test requires the insertion of a very fine electrical probe into several muscles. Characteristic abnormalities show that the muscle has lost nerve supply because of the malfunction of the motor neuron. These EMG findings are called “abnormalities of denervation” and are found in all children with symptomatic SMA. The testing is very sensitive, but should be performed by an electromyographer experienced in pediatric neuromuscular disease. This test involves a small amount of discomfort; an experienced electromyographer can minimize the pain of the procedure with a rapid and skillful interpretation of the results.
3. Muscle Biopsy Tests for Spinal Muscular Atrophy
The examination of muscle tissue is commonly used to confirm the diagnosis of SMA. Muscle tissue may be obtained in one of two ways: A surgeon may make a one or two inch incision in the skin to remove a piece of muscle for microscopic examination. Alternatively, a less invasive technique termed a punch muscle biopsy has become popular among many pediatric neuromuscular specialists. This involves a skin incision of only a few millimeters and can often be done without general anesthesia. Many experts believe that this is the biopsy procedure of choice for infants and younger children because it avoids the risk of heavy sedation or anesthesia. Although the muscle biopsy may be highly specific for SMA, many authorities feel comfortable in deferring a biopsy when the clinical, EMG findings, and genetic studies all confirm the diagnosis of SMA. When the genetic investigations are not confirmatory, muscle biopsy is absolutely essential.
4. Genetic Testing for Spinal Muscular Atrophy
The past few years have witnessed remarkable advances in our understanding of the genetic defects underlying SMA. The gene determining SMA has been localized to a small region of chromosome #5. The actual identification of the gene has been hindered by the extreme complexity of this portion of the chromosome. At least two different genes in this area have been proposed as the “offenders” producing SMA. One is termed the “survival motor neuron gene” (SMN) and the other is the “neuronal apoptosis inhibitory protein gene” (NAIP). These genes are located next to each other; in fact, there are copies of each of these genes forming a near mirror image of one another. The major candidate gene is the SMN gene. This very complex picture has hampered a full and complete understanding of how the genes work and how their malfunction may produce SMA. Although we do not fully understand how the gene abnormality produces the disease, the discovery of the SMN gene has proved extremely helpful in both establishing a diagnosis of SMA, and offering precise genetic counselling.
In over 95% of patients with SMA, changes in the SMN gene are identified which confirm the diagnosis and allow screening for the carrier state in parents and asymptomatic relatives.
It is our hope that additional understanding of the gene and its functions will provide insights into SMA and clues for future treatments.
The information on this page was written for Fight SMA by: Robert T. Leshner, M.D., Professor, Neurology and Pediatrics, Children’s National Medical Center.
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