Spinal Muscular Atrophy Fact Sheet

Spinal muscular atrophy (SMA) Types I, II, and III belong to a group of hereditary diseases that cause weakness and wasting of the voluntary muscles in the arms and legs of infants and children.

The disorders are caused by an abnormal or missing gene known as the survival motor neuron gene (SMN1), which is responsible for the production of a protein essential to motor neurons. Without this protein, lower motor neurons in the spinal cord degenerate and die.

The type of SMA (I, II, or III) is determined by the age of onset and the severity of symptoms. Type I has the earliest onset, usually at birth, and the most severe symptoms. Type II usually happens in early childhood and is less severe but still disabling. Type III can happen as late as adolescence and may be only moderately disabling.

There are other types of SMA disorders with similar symptoms, but different causes. Infantile SMA disorders, such as X-linked infantile SMA, SMA with cerebellar hypoplasia, diaphragmatic SMA, and SMA with congenital bone fractures are linked to genes other than SMN1. Kennedy syndrome (X-linked spinal and bulbar muscular atrophy, SMAX1), a disease of adult males, has symptoms similar to the childhood SMAs, but is caused by a different gene and genetic mutation.

• SMA Type I, also known as Werdnig-Hoffman disease, or infantile-onset SMA, is evident at birth or within the first few months. Symptoms include floppy limbs and trunk, feeble movements of the arms and legs, swallowing difficulties, a weak sucking reflex, and impaired breathing. A baby with SMA Type I will not be able to sit without support. The majority of babies with SMA Type I die of respiratory failure within the first two years.
• SMA Type II, also known as juvenile SMA, intermediate SMA, or chronic SMA, has an onset between 6 and 18 months. Legs tend to be more impaired than arms. The first indication that a baby may have the disease is when he or she fails to crawl or walk. Children with Type II are usually able to sit without support if placed in position. Some may be able to stand or walk with help. Although children with SMA Type II may not need artificial assistance to breathe, they are still at an increased risk for respiratory infections. These children often survive into adulthood, but with significant motor disability.
• SMA Type III, also called Wolhlfart-Kugelberg-Welander disease, or mild SMA, can begin as early as the toddler years or as late as adolescence. Children can stand alone and walk, but may have difficulty getting up from a sitting position. Their fingers may tremble. Children with SMA Type III usually remain mobile well into adulthood. Like children with Type II, they are at an increased risk for respiratory infections.

A blood test is available that can indicate whether there are deletions or mutations of the SMN1 gene. This test identifies at least 95 percent of SMA Types I, II, and III. Other diagnostic tests may include electrodiagnosis with nerve conduction velocities (EMG), and muscle biopsy.

There is no cure for SMA. Treatment consists of managing the symptoms and preventing complications. Treatment for specific symptoms and common complications are described below.

Breathing issues: Babies with SMA (especially those with Type I) may need help breathing, especially at night, using non-invasive methods that include negative pressure ventilators and bi-level positive airway pressure support, which direct air through the nostrils via a small, gently-fitted mask. Children who survive their first two years are at risk for complications involving the lungs, which may not be fully developed. A regular program of respiratory therapy and breathing exercises is helpful. Parents should be instructed in chest physiotherapy (CPT), a series of physical maneuvers that clear the lungs and airway.

Failure to thrive: Infants with SMA I may have difficulties getting adequate nutrition because they have a weak sucking reflex and tendency to tire easily. Their unprotected air passage makes it difficult for older babies to chew and swallow; they may inhale and choke on their food. Some babies may require feeding with naso-gastric or gastric tubes.

Weak arms and legs: Children with SMA Types I and II are not likely to stand or walk on their own. They can be taught to operate a power wheelchair at two to three years of age. Less handicapped children may benefit from a standing frame, vertical stander, or standing wheelchair. Physical therapy and exercise may also help improve mobility and joint movement, brighten mood, and improve sleep patterns. Stretching exercises can preserve and increase flexibility.

Orthopedic complications. Scoliosis (curvature of the spine) occurs at some point in the majority of children with SMA Types I and II, and some with Type III. Custom seating systems, seating aids, and a body jacket can be used to prevent severe scoliosis. Spinal fusion surgery may be necessary for some children.

The prognosis is poor for babies with SMA Type I. Most die within the first two years. For children with SMA Type II, the prognosis for life expectancy or for independent standing or walking roughly correlates with how old they are when they first begin to experience symptoms - older children tend to have less severe symptoms. Some children may have a normal life expectancy and learn to walk with the aid of a brace. Others may die from respiratory infections, such as pneumonia. Children with onset after 18 months are often able to walk and are fully functional for years before they need assistance. They may have a normal life expectancy.

The National Institute for Neurological Disorders and Stroke (NINDS) conducts research on SMA in laboratories at the NIH and also supports research through grants to major medical institutions across the country.

• Several basic science studies are looking at ways to stimulate the production of the SMN protein from the SMN2 gene, a gene that is almost identical to SMN1. Most children with SMA have functional SMN2 genes. Researchers are beginning to test (in animal models) chemical compounds that have the potential to stimulate SMN protein production from the SMN2 gene.
• Ongoing clinical trials are testing the benefits in children of hydroxyurea, riluzole, valproic acid, and phenylbutyrate -- drugs that have promise in treating the symptoms of SMA. Researchers are following the trial participants to determine how well the drugs are tolerated, the optimal dosage, and the best mode of administration.
• The Spinal Muscular Atrophy (SMA) Project is an NINDS-funded collaborative program focused on the development of drug therapies for the treatment of SMA. The program is guided by experts from industry, academia, NINDS, and the U.S. Food and Drug Administration. The Project is accelerating the research process by identifying drugs already in use that increase the level of SMN protein in cultured cells, which are then used as potential leads for further drug discovery and clinical testing.