Spinal Muscular Atrophy

Spinal muscular atrophy is an inherited disorder caused by loss of nerve cells in the spinal cord. These nerve cells control the ability to sit up, crawl, and walk. Activities such as feeding, breathing, and swallowing can also be affected. SMA leads to muscle weakness and wasting away, which become worse over time. Intelligence is not affected by SMA. Age of onset varies from infancy for the most severe form of SMA to adult for the milder late onset form. It is not possible to predict which form of SMA a person might have but the infantile form is the most common. SMA is the most common genetic cause of infant death. Children affected with SMA often have severe muscle weakness before 6 months and die due to respiratory failure before two years of age. There is no cure for SMA. Some of the muscle weakness may respond to treatment. SMA is primarily caused by a common deletion pathogenic variant in the SMN1 gene.

SMA is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers. In about 98% of SMA cases, both parents of an affected child are pathogenic variant carriers while about 2% of affected children have a new pathogenic variant in one copy of the SMN1 gene. In this situation, the pathogenic variant will only be detected in one parent.

There are generally no signs or symptoms associated with being a carrier for SMA Carriers are at an increased risk of having a child with SMA. Testing of reproductive partners is recommended for SMA carriers. Typically a person who is not a carrier of SMA will have two copies of the SMN1 gene, one on each chromosome. Some carriers will have both of their copies of the SMN1 gene on the same chromosome and a deletion on the other chromosome and will go undetected with our current level of testing. This, however, is a rare occurrence.

SMA occurs in approximately 1 in 6,000 to 10,000 newborns in the United States. SMA occurs in people of every race and ancestry, but is more common in the Caucasian (White) population, with a carrier frequency of 1 in 35.

Genetics Home Reference: Spinal muscular atrophy (SMA) (http://ghr.nlm.nih.gov/)
Genetic Alliance: Spinal muscular atrophy (http://www.diseaseinfosearch.org/)

OMIM [SMN1: 600354] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Spinal Muscular Atrophy (SMA) (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Copy number analysis of exon 7. In addition to copy number analysis, detection of g.27134T>G is used to determine the presence of an SMN1 duplication on a single allele (2+0).