Spinal muscular atrophy

background

Spinal muscular atrophy (SMA) is a group of inherited diseases that cause muscles to lose function. The progressive muscle deterioration causes weakness and eventually leads to death.
SMA affects the motor neurons, especially those in the spinal cord and brain stem. Motor neurons help convey electrical and chemical signals to and from the voluntary muscles in the body that are used for physical activities such as crawling, walking, head and neck control, and swallowing.
There are four types of SMA, which are distinguished by the age of disease onset and specific motor functions that the patient is capable of performing, indicating the severity of the disease.
SMA disorders are caused by a genetic mutation (abnormal gene) or deletion (missing gene). The gene affected is known as the survival motor neuron gene (SMN1), which is normally responsible for creating a protein necessary for motor neurons to function correctly. When SMN1 is mutated or missing, this protein is not produced, causing motor neurons to degenerate and die. When motor neurons die, they no longer signal the muscle cells, and then the muscle cells cannot function properly. When muscle cells are not being used, they become very small and begin to break down (atrophy). This is what causes the muscle weakness associated with SMA.
SMA is inherited through autosomal recessive genetic transmission, meaning that two abnormal genes are needed to result in the disease.
There are a number of diseases that involve loss of function in motor neurons. SMA is considered a rare disorder, but is more common than other disorders in this category, such as Werdnig-Hoffmann disease. About one out of every 15,000-20,000 babies born in the United States is affected by SMA. Infants, children, and adults are affected worldwide.
Various muscles throughout the body may be affected by SMA. The proximal muscles, those closest to the trunk of the body, such as in the neck, back, shoulders, or hips, are the most severely affected by the disease. The legs are generally more severely affected than the arms.
Muscle degeneration causes weakness and eventually loss of function. SMA patients experience more weakness in the legs than the arms. If the muscles in the neck or throat are affected, feeding and swallowing may become difficult. Respiratory muscles may also be affected, causing difficulties breathing and coughing and increasing the patient's risk of developing pneumonia and other lung problems.
There is currently no known cure for SMA. Generally, the younger the onset of disease, the shorter the patient's life expectancy. Treatment consists of managing the symptoms and preventing complications.

Related Terms

Adult onset spinal muscular atrophy, Autosomal recessive disorder, chronic SMA, hypotonia, infantile-onset SMA, intermediate SMA, juvenile SMA, Kugelberg-Welander disease, mild SMA, muscle weakness, muscular dystrophy, progressive muscle degeneration, SMARD1, SMN1 gene mutation, type I SMA, type II SMA, type III SMA, Werdnig-Hoffman disease, Wolhlfart-Kugelberg-Welander disease, X-linked infantile spinal-muscular atrophy, XL-SMA.

types of the disease

General: Spinal muscular atrophy (SMA) patients are classified into having one of four main types of disorders. Classification is based on the age of onset of the disease and specific motor functions that the patient is capable of performing, which indicate the severity of SMA. Type I and II are the most commonly observed types.
Patients with SMA typically lose muscle function over time. This may occur rapidly in association with a growth spurt or illness, or much more gradually, as seen in adult-onset SMA. Patients have been observed to maintain stable motor and muscle function for prolonged time periods, sometimes over the course of several years. However, almost all cases of SMA experience continued loss of function as they age.
Type I: Type I is also called Werdnig-Hoffmann Disease and is the most severe form of SMA. This type is first apparent in infants between birth and six months of age. Diagnosis is usually made before three months and mothers may even note that the child has decreased movement during the final months of pregnancy. Fifty percent of children with type I SMA do not live past two years of age.
Most children with type I SMA do not achieve normal motor skill milestones. Patients with SMA are not able to lift their own heads or sit up without support. They do not usually kick their legs with as much strength as healthy infants do and they cannot hold up any weight using their legs.
Type I patients may have difficulties swallowing and feeding and as the tongue weakens, it may show rippling movements (fasciculations). They may also have trouble breathing, as type I patients may have a smaller than usual sized chest, which may appear caved in (concave) and the muscles between the ribs (intercostal muscles) that expand the chest are generally weak.
Type II: Type II SMA is also called juvenile SMA, intermediate SMA, or chronic SMA. This type of SMA typically affects infants between seven and 18 months of age, and diagnosis is almost always made before two years of age. Type II patients differ in motor function from type I patients in that they may be able to sit without support, though only if they are placed in position. Some patients with type II SMA may even be able to stand with support.
Although difficulty swallowing is not usually characteristic of type II SMA, some patients may require a feeding tube because it is difficult to consume the quantity of food by mouth that is necessary to maintain weight and to grow. Children with type II SMA also have tongue fasciculations.
Children with type II have weak intercostal muscles and breathe with their diaphragms. They are at increased risk for complications from respiratory infections.
Type II SMA patients are also at increased risk of bone fractures due to decreased bone density. As children with type II SMA grow, almost all patients develop scoliosis (side-to-side spinal curvature). This requires either bracing, spinal surgery, or both.
Type III: Type III SMA is also known as Kugelberg-Welander disease or juvenile SMA and is the mildest form of childhood-onset SMA. Type III usually becomes apparent in children as early as the age of eighteen months, but may develop as late as adolescence. Diagnosis is usually made before age three. Unlike patients with types I and II, type III patients are able to walk, although most experience weakness. Eventually, most type III patients require the use of a wheelchair.
Early motor development is often normal in type III SMA. However, once the patient begins walking, they may fall frequently, have difficulty standing up from a seated or bent position, and may be incapable of running. These individuals often lose their ability to walk later in childhood, adolescence, or even adulthood. This is usually associated with a growth spurt.
Type III patients also have a tremor in their outstretched fingers, but do not usually have tongue fasciculations.
Feeding or swallowing difficulties in childhood are very uncommon in type III patients.
Type IV (adult onset): Type IV SMA is the adult form of the disease and the most uncommon. Symptoms tend to begin after age 35. It is rare for SMA symptoms to develop between ages 18 and 30.
Adult-onset SMA is typically characterized by onset without warning signs and very slow progression.
In contrast to types I, II, and III, the muscles used for swallowing and respiratory function are rarely affected in type IV.