Some, but not all of the adult cases, are due to genetic abnormalities on chromosome number 5. However, it is a certainty that adult SMA is not a single disease. Different forms of genetic transmission have been documented in different families with SMA IV. The most common form of genetic transmission, however, is known as Autosomal recessive inheritance. Autosomal recessive inheritance requires that both the mother and father have at least one copy of an altered gene located on one of the 22 autosomes (that is, not the X or Y chromosomes). These parents may be carriers who show no signs of the disease (i.e., each has one copy of an altered gene), but they have a 25% chance of producing either a normal child or a child with the disease; they have a 50% chance of producing offspring who are carriers with no signs of disease. Two affected parents (i.e., each has two copies of an altered gene) usually produce children who are all affected. Males and females are at equal risk for being affected

At this stage, the cause of difference in severity of all of the different forms of SMA is not completely known. Additional understanding of the gene defects will undoubtedly explain the tremendous clinical variation that children and young adults with SMA demonstrate.

Symptoms include generalized weakness and muscle wasting with muscle twitches common, atrophy of distal leg muscles, thigh muscle weakness, arm muscle weakness, impaired vibratory sense, diminished leg reflexes, no cortical spinal tract dysfunction. The bulbar muscles used for swallowing and respiratory function are rarely affected in SMA IV.

SMA IV is a relatively mild form of SMA. Progression is slow and life expectancy is normal. Women with SMA may experience increased muscle weakness with pregnancy.

The process of finding a diagnosis of SMA IV is very similar to other forms of SMA.

There are four key elements to establishing a firm diagnosis of SMA: (1) the clinical history and physical examination, (2) electromyography and nerve conduction studies; (3) muscle biopsy, (4) genetic testing.

The initial step in diagnosing SMA begins when an individual becomes concerned with their strength and gross motor abilities. It is important that a physician knowledgeable about  neuromuscular diseases when performing the examination. Many other neuromuscular diseases can present with clinical symptoms identical to those expressed in SMA. Some of these alternative diagnoses required different diagnostic tests and may warrant different forms of treatment. 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. Sensation is generally normal with individuals able to feel very 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 other Muscular Dystrophies. Most people with muscular dystrophy have very high CPK levels, where as individuals with SMA have normal or only slightly elevated CPK levels.

The EMG test consists of two parts. The physician administers a small electrical stimulus to the nerves of the 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 can found in an individual 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.

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 millimetres 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.

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.