Fight SMA Spinal Muscular Atrophy Guidebook

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 neuron.

*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.

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.

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 counseling.

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.

Spinal Muscular Atrophy Symptoms and Treatment

Each Spinal Muscular Atrophy patient is an individual. The physical and emotional impact of this diagnosis on the patient and family are as different as people themselves. There are some problems, however, which can be anticipated and addressed before they become a threat to the child with SMA.

1) Swallowing

This is a particularly sensitive issue in children with Type I (and some children with Type II) spinal muscular atrophy. Difficulty with chewing and swallowing may predispose to aspiration and pneumonia. A skilled speech pathologist may be able to identify certain foods which pose a particular hazard to the child. This is often done with the assistance of a special x-ray study called a "swallowing study and cine esophagram". Direct observation of how a child swallows thin liquids, semisolid and solid foods often guide the therapist and parents to the safest diet. It is critical for children with neuromuscular disease to maintain adequate nutrition; a body deprived of calories and protein will often turn to its own muscles as a source of nourishment. Those children who can not safely swallow liquids or semisolids may be helped with alternative means of feeding including nasogastric (NG) tubes and gastrostomy tubes. The NG tube is inserted through the nose, down the esophagus (food pipe), and into the stomach. Parents can often learn how to place these tubes to assist their children's nutrition. A gastrostomy tube (or PEG) is inserted by a surgeon or gastroenterologist. These devices allow nourishing liquids to be placed directly into the stomach. Although many parents find the concepts of an NG or PEG tube frightening, they are actually simple means of dealing with a potentially serious problem.

2) Arm and leg weakness

Progressive weakness and immobility of the arms and legs in spinal muscular atrophy patients may predispose to other orthopedic problems including tightness of the joints (contractures). Physical therapists can instruct children and their families in range of motion techniques to help prevent these problems. Night splints of the ankles and wrist may also be useful in preventing contractures. Facilitated independent sitting or standing with a special chair or a standing frame may be an important part of the child's daily therapy program.

3) Mobility

Children with Type I and Type II Spinal Muscular Atrophy virtually never achieve independent standing or walking. Their independent mobility invariably requires wheelchair assistance, Because most children lack the upper body strength to propel a manual wheelchair, a power chair is the logical choice. Many youngsters can be taught to safely operate a power chair when they are only two or three years of age! This enables them to participate in household and outdoor activities with their family and peers.

4) Respiratory support

Children with Spinal Muscular Atrophy Type I and Type II are especially vulnerable to respiratory complications. A regular program of respiratory therapy and breathing exercises may be very helpful for these youngsters. Precautions to avoid illness such as yearly influenza immunization should be given to most of these youngsters. The most emotionally charged issues in the management of children with SMA concern whether or not to initiate aggressive mechanical support when the breathing muscles begin to fail. Although the medical options are reasonably simple, the emotional turmoil of placing a child on a "breathing machine" is invariably painful for parents. Although many parents (and physicians alike) carry an image of a mechanical ventilator as a huge and unwieldy device, advances in technology have made ventilator use considerably easier and more convenient. Less invasive means of dealing with respiratory problems include many options. Parents should be trained in simple chest physiotherapy to help tide youngsters through their usual "coughs and colds". Because of difficulty with coughing, even a simple cold may result in saliva and mucous obstructing a child's airway. Techniques of postural drainage and chest percussion may prevent this complication.

Some children benefit from supplemental oxygen usually delivered through a small nasal tube. This is often helpful at night. Before initiating oxygen treatment, however, it must be determined that the brain is not using low concentrations of oxygen in the blood to determine how rapidly a child must breathe. Some of the normal regulation of breathing may be altered in children with chronic neuromuscular diseases. The decision to use supplemental oxygen should, therefore, be preceded by an evaluation by a pulmonary specialist.

Although the "standard" means of mechanical breathing support involves the surgical placement of a tube in the wind pipe (trachea), other less invasive means of breathing support are now being used. This includes devices termed "negative pressure" ventilators and external positive airway pressure support systems. The use of a BI-PAP has been especially helpful for many of our children with SMA. Instead of a tracheostomy, air is mechanically directed through the nostrils through a firmly, but gently fitted mask. This affords many of the benefits of a mechanical ventilator. It can only be emphasized that the decision to use any or all of these forms of respiratory support are emotionally charged and highly personal. Parents and children would be well advised to speak with other parents who have made this decision and to visit with children who have opted to utilize BI-PAP or tracheostomy based respiratory support.

The above was written for Fight SMA by: Robert T. Leshner, M.D., Professor, Neurology and Pediatrics, Children’s National Medical Center.