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Diseases

Genetic and Rare Diseases Information Center (GARD)

Spinal muscular atrophy


Your Question

My brother's daughter was recently diagnosed with spinal muscular atrophy. What can you you tell me about this condition, particularly as it relates to the SMN genes? Can this condition be treated? What is the prognosis?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is spinal muscular atrophy?

Spinal muscular atrophy (SMA) refers to a group of inherited conditions that affect the muscles. The severity of the condition; the associated signs and symptoms; and the age at which symptoms develop varies by subtype. In general, people with SMA experience progressive weakness and atrophy of muscles involved in mobility, the ability to sit unassisted, and head control. Breathing and swallowing may also be affected in severe cases.[1][2][3] SMA is generally caused by changes (mutations) in the SMN1 gene and is inherited in an autosomal recessive manner. Extra copies of the SMN2 gene modify the severity of SMA. Rare autosomal dominant (caused by mutations in DYNC1H1 or VAPB) and X-linked (caused by mutations in UBA1) forms of SMA exist.[4] Treatment is based on the signs and symptoms present in each person.[5][2]
Last updated: 1/7/2016

What are the signs and symptoms of spinal muscular atrophy?

Spinal muscular atrophy (SMA) is primarily characterized by progressive muscle weakness and atrophy. Depending on the type, onset may range from before birth to adolescence or young adulthood.[6]

SMA type 0 (the prenatal form) is the most severe form and begins before birth. Usually, the first symptom of type 0 is reduced movement of the fetus that is first seen between 30 and 36 weeks of the pregnancy. After birth, these newborns have little movement and have difficulties with swallowing and breathing.[1] Life span is approximately 2-6 months.[6]

There are 3 types of SMA that tend to affect children before the age of one (SMA type I, SMA type II, and X-linked SMA). SMA type 1 is a severe form that may be apparent at birth or the first few months of life. Features may include difficulty swallowing or breathing and inability to sit without support.[4] The life span is usually less than 2 years.[6] SMA type II typically becomes apparent between 6 and 12 months of age; affected children may sit without support, although they cannot stand or walk unaided.[4] About 70% of people with this type live to be at least 25 years of age.[6] X-linked infantile SMA is similar to SMA type I; additional features may include joint deformities (contractures) or even broken bones at birth in very severe cases.[4]

Three other types of SMA can affect people in early childhood and adulthood.[4] SMA type III (also called Kugelberg-Welander disease or juvenile type) is a milder form of spinal muscular atrophy with symptoms that generally appear between early childhood (older than age 1 year) and early adulthood. People with type III are able to stand and walk without help, although they usually lose this ability later in life.[1] SMA type IV and Finkel type occur in adulthood, usually after age 30. Symptoms of adult-onset SMA are usually mild to moderate and include muscle weakness, tremor and twitching.[1]
Last updated: 1/7/2016

What genes are related to spinal muscular atrophy?

Changes (mutations) in the SMN1, UBA1, VAPB, and DYNC1H1 genes cause spinal muscular atrophy. Extra copies of the SMN2 gene modify the severity of spinal muscular atrophy.[4]
Last updated: 1/7/2016

What can you tell me about the SMN genes and their relationship to spinal muscular atrophy?

The SMN1 and SMN2 genes encode a protein that is important for the maintenance of motor neurons (specialized cells located in the spinal cord and the brainstem that control muscle movement). The SMN1 gene makes most of the body's functional form of this protein, although a small amount is produced by the SMN2 gene. Changes (mutations) in the SMN1 gene causes reduced levels of the protein which leads to the death of motor neurons. Consequently, nerve impulses are not passed between the brain and muscles, leading to the many signs and symptoms associated with spinal muscular atrophy types I, II, III, and IV.[4]

Normally, each cell has two copies of the SMN1 gene and up to two copies of the SMN2 gene.[7][8] However, in some cases, people have three or more copies of the SMN2 gene. In those with spinal muscular atrophy, additional copies of the SMN2 gene are associated with a milder course of the disease (less severe symptoms that begin later in life).[8]
Last updated: 1/7/2016

How is spinal muscular atrophy inherited?

Most forms of spinal muscular atrophy (types I, II, III, and IV, specifically) are inherited in an autosomal recessive pattern.[4] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Finkel type spinal muscular atrophy is inherited in an autosomal dominant pattern, which means an affected person only needs a mutation in one copy of the responsible gene in each cell.[4]

X-linked infantile spinal muscular atrophy is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.[4]
Last updated: 1/7/2016

How might spinal muscular atrophy be treated?

Unfortunately, there is currently no cure for spinal muscular atrophy. Treatment is supportive and based on the signs and symptoms present in each person.[1]

The Spinal Muscular Atrophy Foundation offers many patient resources regarding the treatment and management of people with spinal muscular atrophy. To access these resources, please click on the link.

CureSMA has a Web page entitled "Living with SMA" which includes management options for some of the key medical issues associated with spinal muscular atrophy and strategies for daily care.
Last updated: 1/8/2016

What is the long-term outlook for people with spinal muscular atrophy?

The long-term outlook (prognosis) for people with spinal muscular atrophy varies by subtype. Even within a subtype, lifespan can vary based on the severity of the case, the associated symptoms and the response to treatment (i.e. respiratory therapy, nutrition support, and physical therapy).[9]

In general, the lifespan in spinal muscular atrophy type 1 is often less than two years due to respiratory problems and infections. Although survival time with type II is often longer, many affected people pass away during childhood. Children with type III disease may survive into adulthood. Affected people who do not develop symptoms of SMA until adulthood generally have a normal life expectancy.[2][9]
Last updated: 1/8/2016

References
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