Alternative Names
hereditary motor neuronopathy; Progressive Muscular Atrophy; SMA
Symptoms & Characteristics
Spinal muscular atrophy (also known as SMA) is a group of genetic conditions that affect the control of muscle movement and causes progressive muscle degeneration and weakness. SMA 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 SMA, the muscles used for breathing and swallowing are affected.
SMA is divided into subtypes based on the severity and age of onset of symptoms. The age of onset of symptoms ranges from before birth to adolescence or young adulthood.
SMA Type 0: prenatal onset, reduced movement of fetus in utero (first noticed between 30 and 36 weeks of pregnancy); severe joint contractures (known as arthrogryposis multiplex congenital); facial weakness; difficulties with swallowing and breathing, muscle present at birth. Lifespan is usually 2-6 months old.
SMA Type I (also known as Werdnig-Hoffman disease): onset before 6 months of age; mild joint contractures; poor muscle tone (hypotonia); difficulties breathing and swallowing; facial weakness; fasciculation of the tongue; lack of motor development and unable to sit without support; absence of tendon reflexes. Lifespan is usually up to 2 years old.
SMA Type II: onset between 6 months and 12 months of age; able to sit without support; cannot stand or walk without support; finger trembling; low muscle tone (flaccidity); absence of tendon reflexes in 70% of people. About 70% of affected people are alive at 25 years old.
SMA Type III (also known as Kugelberg-Welander disease): onset in childhood (after 12 months of age); more mild form of SMA than types 0, I or II; can stand and walk unaided, but usually lose this ability later in life. Lifespan is usually normal.
SMA Type IV: adult onset (usually after age 30 years); mild to moderate symptoms that include muscle weakness, tremor and twitching; motor milestones are normal. Lifespan is usually normal.
Treatment
There is no cure for SMA. However, early diagnosis and routine surveillance can help to manage some of the symptoms and sometimes prevent related problems, depending upon the subtype.
How Common Is It?
SMA is the second leading cause of neuromuscular disease. About 1 in 6,000 to 1 in 10,000 people worldwide are affected with SMA.
Genetics & Inheritance
The primary cause of SMA is believed to be mutations in a gene called SMN1, which is located on chromosome 5 at the location q13.
We all have two copies of the SMN1 gene - one from each parent. In SMA, it is necessary to have two mutations, one in each gene copy, to be affected. This is called autosomal recessive inheritance.
- Both parents of an affected person are usually carriers (have only one mutation). Two carriers have a 25% chance with each pregnancy to have an affected child, but typically do not have symptoms themselves. Of note, approximately 2% of people affected with SMA have one de novo mutation in the SMN1 gene, meaning that one mutation occurs sporadically, while the other is inherited from a carrier parent.
- About 95% of individuals affected with SMA have a deletion in a portion of the SMN1 gene called exon 7 in both copies of the gene. These individuals are said to be homozygous for this deletion. In about 5% of people affected with SMA, only one copy of the SMN1 gene is missing exon 7, and the other copy of the gene has a different type of mutation in the gene. Thus far, researchers have identified nearly 30 such disease-causing mutations.
Extra copies of a gene called SMN2 appear to modify the severity and age of symptom onset of SMA. The SMN2 gene is located adjacent to the SMN1 gene on chromosome 5 at the location q13.
- Some people affected with SMA type II, III, or IV have three or more copies of the SMN2 gene in each cell of their body. These multiple copies of the SMN2 gene can modify the course of SMA. In general, symptoms are less severe and begin later in life as the number of copies of the SMN2 gene increases.
There are many other genetic conditions, which have symptoms that overlap with SMA. A genetic consultation with a trained genetic professional is important for a complete evaluation, accurate diagnosis, as well as discussion of the benefits and limitations of testing and recurrence risk.
Genetic Testing
Clinical genetic testing for spinal muscular atrophy can be broken down into two categories: diagnostic testing and carrier testing.
- Diagnostic testing may be used to confirm or rule out a clinical diagnosis in a person suspected to have the disorder.
- Carrier testing is available for the common mutations. In 2008, The American College of Medical Genetics (ACMG) recommended that all couples who are pregnant or planning to become pregnant are offered SMA carrier testing.
Carrier testing for spinal muscular atrophy is available online (over the internet). Go to the Tests tab to link to the best providers, compare providers and read provider reviews.
Diagnostic testing and carrier testing for spinal muscular atrophy is available through an in person genetic consultation. Use our find a genetic professional directory to locate a trained genetic professional in your area.
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