spinal muscular atrophy

What Is Spinal Muscular Atrophy?

Spinal muscular atrophy (SMA) is a condition that causes a loss (atrophy) of motor neurons, which are specific nerves in the brain and spinal cord that control movement. It is caused by a deficiency of the SMN protein, which is most often the result of a deletion (or loss) of part of the SMN1 gene. Without motor neurons, messages cannot be passed from the brain to the muscles of the body. In severe cases, a patient will not be able to sit independently, and their breathing and swallowing may be impaired. In the mildest cases, symptoms begin in adulthood and independent movement-such as walking-may become more difficult (but still possible). With all types of SMA, there may be difficulties with sleeping and gaining weight (failure to thrive). Frequent pneumonia is common, as is curvature of the spine (scoliosis) and stiff joints (joint contractures). Intelligence is generally unaffected in individuals with SMA. Women with the milder forms of the condition have been known to give birth to healthy children, although many of the pregnancies have complications.

There are four main subtypes of SMA, each described below. It is not always possible to predict which type of SMA an individual will have based on their genetic testing results.

Type 0

Type 0 is the most severe form of SMA. Symptoms can often be seen in the later stages of pregnancy, as the fetus is less active than expected. Once born, the infant will have little ability to move and may not be able to breathe and swallow independently. Infants with SMA type 0 often die before six months of age.

Type I, Also Called Werdnig-Hoffmann Disease

Type I is another severe form of the condition. Symptoms typically develop within the first six months of life. Infants with type I SMA often have trouble breathing and swallowing. Their muscle tone and strength are extremely poor (hypotonia and muscle weakness, respectively); they cannot sit without support and will not achieve any motor skill milestones.

Type II, Also Called Dubowitz Disease

In children with type II SMA, muscle weakness becomes apparent between the ages of six and twelve months. When placed in a sitting position, children with the condition can usually maintain the position without support; however, they often lose this ability by their mid-teens. Individuals with type II SMA cannot stand or walk without assistance. They have poor muscle tone and strength, and their fingers usually tremble uncontrollably.

Type III, Also Called Kugelberg-Welander Disease

Type III is a milder form of the condition. Symptoms begin sometime between the age of one year and early adulthood. As young children, these individuals may fall repeatedly and have trouble walking downstairs. While their muscles are weaker than normal, individuals with type III SMA can usually stand and walk without assistance, although they may lose this ability later in life. The legs are often more severely affected than the arms.

Type IV

Type IV is the mildest form of SMA. With this form of the condition, muscle weakness does not begin until the twenties or thirties, or potentially even later. This weakness is often mild to moderate, and the individual is generally able to walk and move independently. They may also experience mild to moderate tremors and/or twitching of the muscles.

How Common Is Spinal Muscular Atrophy?

The incidence of SMA in the population is between 1 in every 6,000 to 10,000 individuals. The incidence of SMA is more common among individuals of Caucasian descent.

How Is Spinal Muscular Atrophy Treated?

There is no cure for SMA. Many available treatments are supportive in nature and are aimed at improving the symptoms that are present in individuals with the condition. For children with the more severe forms of SMA, mechanical breathing aids may help with sleep and prolong lifespan. In addition, placement of a feeding tube may ensure proper nutrition in those with swallowing problems or feeding difficulties. For individuals with milder forms of SMA, certain types of respiratory assistance may help with sleep problems and surgery may be used to treat orthopedic issues.

In addition to the treatments for SMA symptoms, medications are now available that have been shown to improve motor development in individuals with the condition. These medications, known as nusinersen (market name Spinraza®), onasemnogene abeparvovec (market name Zolgensma®), and risdiplam (market name Evrysdi®), have been approved in the United States for use in patients with SMA.

What Is the Prognosis for an Individual with Spinal Muscular Atrophy?

The prognosis for an individual with SMA varies greatly depending on which type they have and their treatment course.

Type 0

Type 0 SMA is typically fatal between two and six months of age. These infants do not develop any motor skills expected of infants their age.

Type I

This type of SMA is usually fatal within two years. However, children with type I SMA may live longer with the aid of mechanical breathing aids and other available therapies. There are a few known cases in which the individual survived to adolescence or early adulthood.

Type II

With type II SMA, 75% of those affected live to the age of 25. They are often able to sit independently when placed in a sitting position but lose this ability by their mid-teens.

Type III

Individuals with type III SMA may have a normal lifespan. Many learn to walk independently, although most lose the ability to do so by their thirties or forties.

Type IV

A normal lifespan is also possible for individuals with type IV SMA. They do not develop symptoms until their twenties or thirties and usually retain the ability to walk independently.