Spinal Muscular Atrophy

What is 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 (motor neurones) in the spinal cord and the part of the brain that is connected to the spinal cord (brain stem). The loss of motor neurones leads to weakness and shrinkage (atrophy) of voluntary muscles used for activities such as crawling, walking, sitting up, and controlling head movement.

Spinal muscular atrophy is divided into subtypes based on the severity and age of onset of symptoms. Type I (also called Werdnig-Hoffman disease) is the most severe form of spinal muscular atrophy. Symptoms are 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 or stand. Children with type II spinal muscular atrophy usually develop muscle weakness between 6 and 12 months of age. Children with type II can sit, although they cannot stand or walk unaided.

Type III spinal muscular atrophy (also called Kugelberg-Welander disease or juvenile type) is the least severe form, and patients are able to stand and walk unaided. Symptoms appear between early childhood (after 1 year of age) and early adulthood. 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.

How common is spinal muscular atrophy?

Spinal muscular atrophy affects approximately 1 in 10,000 people.

What genes are related to spinal muscular atrophy?

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

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

Mutation in the SMN1 gene cause spinal muscular atrophy, types I-IV. SMN1 mutations lead to a shortage (deficiency) of a protein needed for the survival of motor neurones. Without this protein, motor neurones die, and nerve impulses cannot pass between the brain and muscles. As a result, some muscles cannot perform their normal functions, leading to weakness and impaired movement.

In some people with spinal muscular atrophy, the number of copies of the SMN2 gene increases from two to three or four. Changes that add copies of the SMN2 gene can modify the severity of symptoms. On a limited basis, extra SMN2 genes can help replace the protein needed for the survival of motor neurones. 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 remains unclear how a VAPB mutation leads to the loss of motor neurones.

How do people inherit spinal muscular atrophy?

Most cases of spinal muscular atrophy are inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

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.

What other names do people use for spinal muscular atrophy?

• hereditary motor neuroneopathy
• Progressive Muscular Atrophy
• SMA