Spinal muscular atrophy

Spinal muscular atrophy is a disorder that affects the control of muscle movement. It is caused by a loss of specialized nerve cells, called motor neurons, in the spinal cord and the part of the brain that is connected to the spinal cord (the brainstem). The loss of motor neurons leads to weakness and shrinkage (atrophy) of muscles used for activities such as crawling, walking, sitting up, and controlling head movement. In severe cases of spinal muscular atrophy, the muscles used for breathing and swallowing are affected.

Spinal muscular atrophy is divided into subtypes based on the severity and age of onset of symptoms. Three types of this disorder affect children before the age of 1 year. Type 0 is a very severe form of spinal muscular atrophy that begins before birth. Usually, the initial sign of type 0 is reduced movement of the fetus that is first noticed between 30 and 36 weeks of gestation. After birth, newborns show little movement and have difficulties swallowing and breathing. Type I spinal muscular atrophy (also called Werdnig-Hoffman disease) is a severe form of the disorder that is evident at birth or within the first few months of life. Typically, affected infants have difficulty breathing and swallowing, and they are unable to sit without support. Children with type II spinal muscular atrophy usually develop muscle weakness between ages 6 and 12 months. Children with type II can sit without support, although they cannot stand or walk unaided.

Type III spinal muscular atrophy (also called Kugelberg-Welander disease or juvenile type) is a milder form of the disorder than types 0, I or II. Symptoms appear between early childhood (older than age 1 year) and early adulthood. Individuals with type III spinal muscular atrophy can stand and walk unaided, but usually lose this ability later in life. Two types of spinal muscular atrophy, type IV and Finkel type, occur in adulthood, usually after age 30. Symptoms of adult-onset spinal muscular atrophy are typically mild to moderate and include muscle weakness, tremor, and twitching.

Spinal muscular atrophy affects 1 in 6,000 to 1 in 10,000 people.

Mutations in the SMN1 and VAPB genes cause spinal muscular atrophy.

Extra copies of the SMN2 gene modify the course of spinal muscular atrophy.

Mutations in the SMN1 gene cause spinal muscular atrophy types 0, I, II, III, and IV. SMN1 mutations lead to a shortage of a protein, called SMN protein, which is needed for the survival of motor neurons. Without SMN protein, motor neurons die, and nerve impulses are not passed between the brain and muscles. As a result, some muscles cannot perform their normal functions, leading to weakness and impaired movement.

Some people with type II, III, or IV spinal muscular atrophy have three or more copies of the SMN2 genes in each cell. These multiple copies of the SMN2 gene can modify the course of spinal muscular atrophy. On a limited basis, extra SMN2 genes can help replace the shortage of SMN protein caused by mutations in the SMN1 genes. In general, symptoms are less severe and begin later in life as the number of copies of the SMN2 gene increases.

Finkel type spinal muscular atrophy is caused by a mutation in the VAPB gene. It is unclear how a VAPB mutation leads to the loss of motor neurons.

Read more about the SMN1, SMN2, and VAPB genes.

Spinal muscular atrophy types 0, I, II, III, and IV are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Finkel type spinal muscular atrophy is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.