What is Spinal Muscular Atrophy (SMA)?

 
Spinal Muscular Atrophy (SMA) refers to a group of diseases which affect the motor neurons of the spinal cord and brain stem. These critically important cells are responsible for supplying electrical and chemical messages to muscle cells. Without the proper input from the motor neurons, muscle cells can not function properly. The muscle cells will, therefore, become much smaller (atrophy) and will produce symptoms of muscle weakness. There are dozens of diseases which affect the motor neurone.
 
*Spinal Muscular Atrophy kills more babies than any other genetic disease.
 
Degeneration and death of the motor neurons (also called Anterior Horn Cells) in the brain stem and spinal cord produces weakness in the muscles of swallowing, breathing, and limbs. This disease afflicts infants, children, and adults worldwide. It is estimated that spinal muscular atrophy occurs in between one-in-6,000 and one-in-20,000 births. Recent advances in our understanding of the genetics of this disorder confirm that the majority of children and adults afflicted with SMA, have inherited this disorder by receiving one gene from both their mother and their father. This is termed autosomal recessive genetic transmission.
 
Between one-in-40 and one-in-80 “normal” men and women carry the gene for spinal muscular atrophy. If both a man and woman carry the gene, the chances are 25% that any of their children will manifest SMA.
 
Despite the fact that SMA was described many decades ago, there is still a great deal of confusion among patients, parents, and physicians as to the diagnosis, treatment, and genetic counseling which should be provided for those affected with this disease. Some of these questions have been answered by advances in the science of molecular genetics. We now know that the common forms of SMA are the result in a change in a gene located on chromosome #5. Even though we refer to “different types of SMA”, most of these are the result of a number of alterations (mutations) in the gene which are ultimately responsible for the degeneration or premature death of the anterior horn cells. It is still useful to think in terms of several different types of SMA to assist in guiding appropriate treatment, depending on whether the disease is severe or relatively benign. In virtually all cases of SMA, the symptoms are dominated by muscle weakness. There are no problems with sensation of the face, arms, or legs. Intelligence is unaffected, and in fact many physicians who have worked with hundreds of children with SMA are impressed that these children tend to be unusually alert, interactive, and socially gifted.
 

Types of Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) Type 1

 
Spinal Muscular Atrophy Type I, also known as Infantile Spinal Muscular Atrophy was initially described by Drs. Werdnig and Hoffman. Many texts still refer to this as Werdnig-Hoffman Disease. This is the most severe form of SMA. Some children are affected even before birth and mothers may note that during the last three months of pregnancy that fetal movements are weak. Virtually all children with Type I SMA show symptoms of weakness before age eight months. The disease tends to affect the muscles of chewing and swallowing, the chest wall muscles, and the muscles of the arms and legs. As a result, children may experience great difficulties with feeding and may even breathe milk or formula into their lungs. This places these youngsters at high risk of respiratory infections and pneumonia.
 
*Spinal Muscular Atrophy Type I is the Most Lethal Form of SMA
 
The weakness of the chest wall muscles (intercostal and accessory respiratory muscles) makes it difficult for these youngsters to breathe deeply or to generate a strong cough. Some of the breathing muscles, especially the diaphragm, are relatively unaffected. This may produce an unusual shape of the chest with a sunken appearance and a bell-like configuration of the chest wall. Each inspiration seems to be generated from the abdomen and “belly breathing” is often noted by parents and physicians.
 
Weakness in the arms and legs makes it difficult for the children to roll over and children with Type I SMA are never able to sit without assistance.
 
Weakness of the neck muscles makes it difficult for these children to achieve head control. Quivering of the tongue is often noticed. This has been termed tongue fasciculation. This clinical sign is seen in virtually no other disease in children except for spinal muscular atrophy.
 
Children with Type I SMA face a difficult battle. They are constantly at risk of respiratory infection and pneumonia. Feeding difficulties make it a real challenge for parents to give their children adequate nutrition and supplemental feedings may be required. Tubes placed through the nose or directly onto the stomach may be necessary. Recurrent respiratory problems usually result in death before two years of age. However, a small number of children with Type I SMA may survive into their teens or early adulthood.

Spinal Muscular Atrophy (SMA) Type 2

 
Children with Spinal Muscular Atrophy Type II manifest less severe weakness than children with SMA Type I. Symptoms are usually noticed later in life, usually between the age of 6 to 18 months. The clinical features are similar to those found in children with Type I; in fact, there are many children for whom the characterization of Type 1 or Type 2 Spinal Muscular Atrophy becomes a “best guess”.
 
*Spinal Muscular Atrophy Type 2 is the “Intermediate” Form of SMA
 
Children with Type II SMA usually achieve the ability to sit independently, however, they almost never achieve the ability to walk or stand without support. Some children with SMA Type II have a relatively static course and remain free of life threatening complications such as pneumonia. Other children, have progressive weakness of their swallowing and respiratory muscles. Many youngsters with Spinal Muscular Atrophy Type 2 develop curvature of the spine (Kyphoscoliosis) and other orthopedic problems. Skillful management by a team of physical therapists and orthopedic surgeons is usually needed to manage these problems.

Spinal Muscular Atrophy (SMA) Type 3

 
Children with Spinal Muscular Atrophy Type III (also known as Kugelberg-Welander Disease) typically have the onset of symptoms after 18 months of age. Many of these children may appear “normal” until they are five or 10 or even older. These children achieve independent walking and their weakness may be so mild that medical attention is not sought for years!
 
*Many Spinal Muscular Atrophy Type 3 Victims Remain Undiagnosed for Years
 
Many children have a very benign course and may remain ambulatory for decades after the onset of symptoms. Other patients exhibit slowly progressive symptoms resulting in a loss of independent walking. Respiratory complications are uncommon and swallowing problems are rarely encountered.

Adult (Type 4) Spinal Muscular Atrophy (SMA)

 
Many authorities add an additional form of SMA termed Spinal Muscular Atrophy Type IV, also known as Adult Onset Spinal Muscular Atrophy. This disorder begins in adulthood with most patients noticing symptoms in their mid-30′s.
 
*Spinal Muscular Atrophy Type 4 Rarely Leads to Total Loss of Mobility
 
The course is benign with only a small number of patients eventually requiring wheelchair assistance. Some, but not all of the adult cases, are due to genetic abnormalities on chromosome #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 TYPE IV.
 
Although the preceding classification of spinal muscular atrophy is useful to patients, families, and the medical team working with them, it must be emphasized that SMA Types I, II, and III (and in some cases SMA Type – IV) represent a continuum. Additional understanding of the gene defects will undoubtedly explain the tremendous clinical variation that children and young adults with SMA demonstrate.

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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